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por&#233;m essa an&#225;lise ainda &#233; lenta e limitada por resultados falsos negativos&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">A prote&#237;na C reativa &#40;PCR&#41;&#44; uma importante prote&#237;na de fase aguda&#44; &#233; um membro da fam&#237;lia pentraxina e desempenha um papel central na imunidade inata e adaptativa&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> Apesar do desenvolvimento de novos biomarcadores&#44; at&#233; o momento a PCR &#233; um dos testes de laborat&#243;rio mais estudados e mais usados para diagn&#243;stico de sepse neonatal&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> A PCR leva de 10&#8208;12 horas para surgir significativamente ap&#243;s o in&#237;cio da infec&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a> Como a PCR mostra um aumento em v&#225;rias doen&#231;as&#44; ela &#233; preferencialmente usada em combina&#231;&#227;o com outros biomarcadores&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Um problema relevante na abordagem cl&#237;nica atual de neonatos doentes &#233; a disponibilidade limitada de ferramentas simples&#44; seguras e n&#227;o invasivas com alta precis&#227;o de diagn&#243;stico&#46; A saliva dos neonatos supera os obst&#225;culos associados &#224; pesquisa neonatal e oferece ao investigador uma nova fonte de amostras n&#227;o invasivas para explora&#231;&#227;o da biologia neonatal&#46; A PCR foi detect&#225;vel na saliva dos neonatos e pode prever limites anormais de PCR no soro&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Recentemente&#44; certos par&#226;metros de hemograma completo &#40;HC&#41; foram usados como marcadores de inflama&#231;&#227;o e infec&#231;&#245;es&#46; O volume m&#233;dio de plaquetas &#40;VMP&#41; tem sido usado no diagn&#243;stico&#44; no acompanhamento e na previs&#227;o de gravidade da sepse neonatal em neonatos a termo e prematuros&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#8211;8</span></a> A propor&#231;&#227;o de neutr&#243;filos&#8208;linf&#243;citos &#40;PNL&#41; &#233; um simples biomarcador de inflama&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a> Al&#233;m disso&#44; a propor&#231;&#227;o de plaquetas&#47;linf&#243;citos &#40;PPL&#41; tamb&#233;m &#233; um marcador &#250;til de inflama&#231;&#227;o sist&#234;mica&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">O presente estudo visou a avaliar a aplicabilidade da PCR salivar&#44; do VMP&#44; da PNL e da PPL como marcadores de diagn&#243;stico em neonatos a termo com sepse neonatal&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">M&#233;todos</span><p id="par0035" class="elsevierStylePara elsevierViewall">O presente estudo foi conduzido na unidade de terapia intensiva neonatal &#40;UTIN&#41; de Suez Canal University Hospital&#44; Ismailia&#44; Egito&#44; entre janeiro de 2016 e junho de 2016&#46; Durante esses seis meses&#44; 320 neonatos foram internados na unidade&#46; Foram inscritos 35 neonatos com sepse neonatal de in&#237;cio precoce ou tardio e 35 neonatos saud&#225;veis de controle&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Crit&#233;rios de inclus&#227;o&#58; foram inscritos neste estudo os nascidos a termo de ambos os sexos&#44; do nascimento a 28 dias&#44; internados na UTIN de Suez Canal University com caracter&#237;sticas cl&#237;nicas de sepse neonatal de in&#237;cio precoce ou tardio&#46; O diagn&#243;stico de sepse cl&#237;nica foi feito por hist&#243;rico&#44; achados cl&#237;nicos&#44; achados laboratoriais e hemocultura&#46; Os achados cl&#237;nicos incluem presen&#231;a de tr&#234;s ou mais do que segue&#58; &#40;1&#41; instabilidade de temperatura &#40;hipotermia&#44; hipertermia&#41;&#59; &#40;2&#41; problemas respirat&#243;rios &#40;grunhidos&#44; retra&#231;&#245;es intercostais&#44; apneia&#44; taquipneia&#44; cianose&#41;&#59; &#40;3&#41; cardiovasculares &#40;bradicardia&#44; taquicardia&#44; fraca perfus&#227;o&#44; hipotens&#227;o&#41;&#59; &#40;4&#41; neurol&#243;gicos &#40;hipotonia&#44; letargia&#44; convuls&#245;es&#41; e &#40;5&#41; gastrointestinais &#40;intoler&#226;ncia alimentar&#44; distens&#227;o abdominal&#41;&#46; O valor de PCR de<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>mg&#47;L foi considerado positivo&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#44;11</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Crit&#233;rios de exclus&#227;o&#58; foram exclu&#237;dos neonatos prematuros e neonatos com pneumonia confirmada ou outras condi&#231;&#245;es inflamat&#243;rias&#44; malforma&#231;&#245;es do sistema nervoso central &#40;SNC&#41;&#44; disfun&#231;&#245;es metab&#243;licas&#44; anomalias cromoss&#244;micas&#44; restri&#231;&#227;o do crescimento intrauterino&#44; asfixia ao nascer&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Por&#233;m&#44; os 35 neonatos saud&#225;veis sem sintomas&#44; sinais ou fatores de risco para infec&#231;&#245;es internados por icter&#237;cia fisiol&#243;gica na unidade neonatal e todos os neonatos sem fatores de risco infecciosos internados em cl&#237;nicas ambulatoriais do hospital foram inscritos de forma prospectiva como controles&#46; O n&#237;vel de PCR no soro dos neonatos nesse grupo foi negativo &#40;PCR de menos de 10<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">As amostras foram coletadas de neonatos com sepse entre 4&#8208;12 horas ap&#243;s o diagn&#243;stico cl&#237;nico para a medi&#231;&#227;o dos n&#237;veis de PCR no soro e antes do in&#237;cio do tratamento com antibi&#243;ticos&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Para o HC&#44; o sangue perif&#233;rico foi coletado em um tubo EDTA a v&#225;cuo e analisado por um contador de c&#233;lulas sangu&#237;neas automatizado &#40;Cell&#8208;Dyn 3700&#44; Abbott Laboratories&#44; IL&#44; EUA&#41;&#46; A PNL e a PPL foram calculadas como propor&#231;&#227;o de neutr&#243;filos&#47;linf&#243;citos e plaquetas&#47;linf&#243;citos&#44; respectivamente&#46; Os n&#237;veis deles foram obtidos das mesmas amostras de sangue&#46; Para o c&#225;lculo preciso do VMP&#44; as amostras foram analisadas at&#233; 60 minutos ap&#243;s a amostragem para evitar falso aumento do VMP&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Para determina&#231;&#227;o do n&#237;vel de PCR no soro&#44; foi usado o autoanalisador automatizado Cobas c501 &#40;Roche Diagnostics&#44; Manheim&#44; Alemanha&#41;&#46; Para a PCR salivar&#44; as amostras foram coletadas aproximadamente uma hora antes da alimenta&#231;&#227;o para evitar contamina&#231;&#227;o do leite&#46; A saliva foi coletada ao inclinar a cabe&#231;a para frente para juntar saliva na parte do ch&#227;o da boca&#46; As amostras foram ent&#227;o obtidas com uma seringa de 1<span class="elsevierStyleHsp" style=""></span>mL anexada em um aspirador para rede canalizada &#40;LWS&#41; &#40;&#60; 20<span class="elsevierStyleHsp" style=""></span>mm Hg&#41;&#46; Isso garante que a saliva continue na seringa e n&#227;o entre no tubo ou no aspirador nasal&#46; A saliva foi aspirada das l&#237;nguas dos neonatos e de seus sulcos gengivais&#46; A suc&#231;&#227;o foi mantida por aproximadamente 10&#8208;15 segundos&#44; coletaram&#8208;se cerca de 0&#44;5<span class="elsevierStyleHsp" style=""></span>mL&#46; A seringa foi ent&#227;o separada da suc&#231;&#227;o e o &#234;mbolo foi novamente posicionado na seringa&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Ap&#243;s a coleta&#44; as amostras foram colocadas em tubos de polipropileno para evitar contamina&#231;&#227;o e falhas anal&#237;ticas de reten&#231;&#227;o&#46; As amostras foram armazenadas a &#8208;20<span class="elsevierStyleHsp" style=""></span>&#176;C at&#233; o uso&#46; A PCR salivar foi medida por Elisa&#46; As hemoculturas foram feitas para o grupo com sepse&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Este estudo foi aprovado por nosso comit&#234; de &#233;tica institucional local e foi obtido o consentimento informado dos pais de todos os neonatos durante todo o estudo&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">An&#225;lises estat&#237;sticas</span><p id="par0080" class="elsevierStylePara elsevierViewall">Foram feitas com o pacote estat&#237;stico SPSS para Windows&#44; vers&#227;o 20 &#40;SPSS&#44; Chicago&#44; IL&#44; EUA&#41;&#46; Foram avaliadas as diferen&#231;as entre os grupos com rela&#231;&#227;o aos dados quantitativos n&#227;o param&#233;tricos por meio do teste U de Mann&#8208;Whitney&#46; O teste de qui&#8208;quadrado foi usado para testar as diferen&#231;as significativas das vari&#225;veis qualitativas&#46; A sensibilidade&#44; a especificidade e o ponto de corte ideal da PCR salivar foram determinados com a curva ROC&#46; Para toda a an&#225;lise estat&#237;stica&#44; o n&#237;vel de relev&#226;ncia considerado foi<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Resultados</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Dados demogr&#225;ficos e pr&#233;&#8208;natais</span><p id="par0085" class="elsevierStylePara elsevierViewall">Houve diferen&#231;as estat&#237;sticas entre os dois grupos com rela&#231;&#227;o &#224; idade&#44; ao hist&#243;rico de infec&#231;&#227;o do trato urin&#225;rio &#40;ITU&#41; materna e ao tipo de parto&#46; Sepse de in&#237;cio tardio &#40;SIT&#41; foi diagnosticada em 74&#44;3&#37; dos neonatos com sepse&#44; ao passo que sepse de in&#237;cio precoce &#40;SIP&#41; foi diagnosticada em apenas 25&#44;7&#37; deles &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Quadro cl&#237;nico&#44; resultados do HC e hemocultura no grupo de sepse</span><p id="par0090" class="elsevierStylePara elsevierViewall">No momento da apresenta&#231;&#227;o dos neonatos com sepse&#44; 19 &#40;54&#44;3&#37;&#41; apresentaram baixa atividade e recusa de alimenta&#231;&#227;o&#44; ao passo que nove &#40;25&#44;7&#37;&#41; apresentaram febre e baixa atividade&#44; sete &#40;20&#37;&#41; apresentaram recusa de alimenta&#231;&#227;o e insufici&#234;ncia respirat&#243;ria&#46; Houve diferen&#231;as significativas entre os dois grupos nos n&#237;veis do HC&#46; Dos neonatos com sepse 12 &#40;34&#44;3&#37;&#41; apresentaram anemia&#44; ao passo que quatro &#40;11&#44;4&#37;&#41; dos controles apresentaram anemia&#46; A contagem de gl&#243;bulos brancos mostrou diferen&#231;a entre os neonatos com sepse e os controles&#44; leucocitose em 11 &#40;31&#44;4&#37;&#41; dos neonatos com sepse em compara&#231;&#227;o com um &#40;2&#44;9&#37;&#41; dos controles&#46; Trombocitopenia foi encontrada em nove &#40;25&#44;7&#37;&#41; do grupo com sepse e um &#40;2&#44;9&#37;&#41; dos controles&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">No grupo com sepse&#44; a hemocultura foi positiva em 25 &#40;71&#44;5&#37;&#41;&#44; estafilococos coagulase negativa foram os pat&#243;genos isolados mais frequentes&#44; seguidos de <span class="elsevierStyleItalic">E&#46; coli</span>&#44; <span class="elsevierStyleItalic">Klebsiella pneumonia</span> e <span class="elsevierStyleItalic">Serratia marcescens</span>&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Valores de PCR no soro&#44; PCR salivar&#44; VMP&#44; PNL e PPL</span><p id="par0100" class="elsevierStylePara elsevierViewall">Houve diferen&#231;as significativas entre os dois grupos na PCR no soro&#44; PCR salivar&#44; VMP e PNL&#46; Os valores de PCR no soro mostraram diferen&#231;a significativa entre os dois grupos &#40;m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>27&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#44;3<span class="elsevierStyleHsp" style=""></span>mg&#47;L em compara&#231;&#227;o com 4&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;8<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41;&#44; respectivamente&#46; A m&#233;dia de PCR no soro dos neonatos com SIP foi de 23&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#44;3&#44; ao passo que a m&#233;dia em neonatos com SIT foi de 29&#44;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46; A PCR salivar mostrou diferen&#231;a significativa entre os dois grupos &#40;m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;6<span class="elsevierStyleHsp" style=""></span>ng&#47;L em compara&#231;&#227;o com 2&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;2<span class="elsevierStyleHsp" style=""></span>ng&#47;L&#41;&#44; respectivamente&#46; O VMP mostrou diferen&#231;a significativa entre os dois grupos &#40;m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;2 fL em compara&#231;&#227;o com 8&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;5 fL&#41;&#44; respectivamente&#46; A PNL mostrou diferen&#231;a significativa entre os dois grupos &#40;m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;7 em compara&#231;&#227;o com 1&#44;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;4&#41;&#44; respectivamente&#46; A diferen&#231;a da PPL entre os dois grupos n&#227;o foi significativa &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Correla&#231;&#227;o entre a PCR salivar e PCR no soro&#44; VMP&#44; PNL e PPL</span><p id="par0105" class="elsevierStylePara elsevierViewall">Houve correla&#231;&#245;es estatisticamente significativas entre PCR salivar e PCR no soro &#40;0&#44;66&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; VMP &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;45&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; e PNL &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;408&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; A correla&#231;&#227;o entre PCR salivar e PPL n&#227;o foi estatisticamente significativa &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Compara&#231;&#227;o na curva de caracter&#237;stica de opera&#231;&#227;o do receptor &#40;ROC&#41; da PCR soro&#44; PCR salivar&#44; VMP&#44; PNL e PPL como marcadores de sepse neonatal</span><p id="par0110" class="elsevierStylePara elsevierViewall">A an&#225;lise das curvas ROC mostrou que a PCR no soro em um valor de corte de 10<span class="elsevierStyleHsp" style=""></span>mg&#47;L tem sensibilidade de 83&#44;1&#37; e especificidade de 85&#44;9&#37;&#46; A PCR salivar em um valor de corte de 3&#44;48<span class="elsevierStyleHsp" style=""></span>ng&#47;L tem sensibilidade de 94&#44;3&#37; e especificidade de 80&#37;&#46; O VMP mostrou sensibilidade de 80&#37; e especificidade de 80&#37; em um valor de corte de 10&#44;2 fL&#46; A PNL em um valor de corte de 2&#44;7<span class="elsevierStyleHsp" style=""></span>ng&#47;L tem sensibilidade de 80&#37; e especificidade de 57&#44;1&#37;&#46; A PPL mostrou baixa sensibilidade e especificidade ao prever sepse neonatal &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">A PCR salivar em um valor de corte de 3&#44;4<span class="elsevierStyleHsp" style=""></span>ng&#47;L mostrou sensibilidade de 94&#37; e especificidade de 91&#44;3 na previs&#227;o de PCR no soro &#8805; 10<span class="elsevierStyleHsp" style=""></span>mg&#47;L em neonatos com sepse&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discuss&#227;o</span><p id="par0120" class="elsevierStylePara elsevierViewall">A sepse neonatal &#233; uma das principais causas de morbidade e mortalidade em unidades de terapia intensiva neonatais&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a> Adicionalmente&#44; tem morbidades de longo prazo&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">13&#44;14</span></a> Por outro lado&#44; manobras simples&#44; como o uso de &#225;lcool em gel e treinamento sobre higieniza&#231;&#227;o das m&#227;os&#44; podem reduzir a SIT&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Em todo o mundo&#44; as infec&#231;&#245;es representam dois ter&#231;os dos seis milh&#245;es de &#243;bitos anuais em crian&#231;as com menos de cinco anos&#46; O per&#237;odo neonatal representa o maior risco de vida de infec&#231;&#245;es graves&#44; com uma estimativa de 400&#46;000 &#243;bitos de rec&#233;m&#8208;nascidos anualmente&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> No Egito&#44; as taxas de sepse ultrapassam 50&#37; em unidades de terapia intensiva neonatal&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Recentemente&#44; a an&#225;lise da saliva para monitoramento cl&#237;nico e detec&#231;&#227;o de biomarcadores em neonatos representa uma &#243;tima promessa de melhoria nos cuidados de sa&#250;de dessa popula&#231;&#227;o fr&#225;gil&#46; A saliva representa um biofluido ideal e facilmente acess&#237;vel para exames n&#227;o invasivos de morbidades neonatais comuns&#44; como prematuridade&#44; infec&#231;&#245;es e insultos cerebrais&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">18&#8211;20</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">At&#233; agora&#44; a PCR &#233; o reagente de fase aguda mais amplamente estudado e&#44; apesar da detec&#231;&#227;o de novos marcadores de infec&#231;&#227;o&#44; sua ampla disponibilidade e sua determina&#231;&#227;o r&#225;pida&#44; simples e com bom custo&#8208;benef&#237;cio a tornam um dos &#237;ndices preferenciais em muitas unidades de terapia intensiva neonatal&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Na literatura relatada&#44; a PCR no soro mostrou diferente cin&#233;tica e valores de corte que variam de 1&#44;5 a 20<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; tamb&#233;m com sensibilidades e especificidades de grande alcance que variam de 74 a 98&#37; e de 71 a 94&#37;&#44; respectivamente&#44; nas determina&#231;&#245;es de PCR serial ou uma &#250;nica medi&#231;&#227;o de pelo menos 12 horas ap&#243;s o in&#237;cio dos sintomas de sepse neonatal&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#44;11&#44;21&#8211;23</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Essas diferen&#231;as nos valores de corte podem ser explicadas por diferentes idades gestacionais&#44; pesos no nascimento e cin&#233;tica fisiol&#243;gica da PCR ap&#243;s o nascimento nos neonatos estudados&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> H&#225; um debate sobre o ponto de corte da PCR em casos de SIP e SIT&#44; com certa concord&#226;ncia sobre o uso de 10<span class="elsevierStyleHsp" style=""></span>mg&#47;L como um corte confi&#225;vel&#44; principalmente na SIP&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#44;11</span></a> No presente estudo&#44; a m&#233;dia da PCR no soro foi de 27&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#44;3<span class="elsevierStyleHsp" style=""></span>mg&#47;L em neonatos com sepse&#44; com sensibilidade de 83&#44;1&#37; e especificidade de 85&#44;9&#37; em um valor de corte de 10<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">As medi&#231;&#245;es seriais do n&#237;vel de PCR tamb&#233;m podem ser &#250;teis na identifica&#231;&#227;o de neonatos com infec&#231;&#227;o bacteriana&#44; no monitoramento da resposta ao tratamento em neonatos infectados e na determina&#231;&#227;o da dura&#231;&#227;o da terapia antibi&#243;tica&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">21&#44;24</span></a> Por&#233;m&#44; o monitoramento da PCR no soro na popula&#231;&#227;o neonatal a coloca em riscos m&#233;dicos de amostragem frequente&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">A detec&#231;&#227;o da PCR salivar &#233; um novo m&#233;todo de diagn&#243;stico na popula&#231;&#227;o neonatal&#46; Em 2014&#44; Iyengar et al<span class="elsevierStyleItalic">&#46;</span> publicaram o primeiro trabalho sobre detec&#231;&#227;o e utilidade da PCR salivar em neonatos&#44; considerado o primeiro estudo para detectar&#44; quantificar e demonstrar que a PCR salivar &#233; um bom &#237;ndice dos limites clinicamente relevantes de PCR no soro&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Neste estudo&#44; investigamos pela primeira vez at&#233; onde sabemos que a PCR salivar &#233; um marcador de diagn&#243;stico n&#227;o invasivo em neonatos com sepse&#46; A m&#233;dia da PCR salivar mostrou diferen&#231;a estatisticamente significativa entre os neonatos com sepse e controles&#44; com m&#233;dia de 12&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;6<span class="elsevierStyleHsp" style=""></span>ng&#47;L em neonatos com sepse&#44; ao passo que a dos controles foi de 2&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;2<span class="elsevierStyleHsp" style=""></span>ng&#47;L&#46; Um ponto de corte de 3&#44;48<span class="elsevierStyleHsp" style=""></span>ng&#47;L na PCR salivar mostrou alta sensibilidade &#40;94&#44;3&#37;&#41; e especificidade &#40;80&#44;0&#37;&#41;&#46; Em nosso estudo&#44; a PCR salivar mostrou boa precis&#227;o na previs&#227;o de altos n&#237;veis de PCR no soro&#46; Foi observado que a PCR salivar no ponto de corte 3&#44;4<span class="elsevierStyleHsp" style=""></span>ng&#47;L apresentou sensibilidade correspondente &#40;94&#37;&#41; e especificidade &#40;91&#44;3&#37;&#41; na previs&#227;o de forma precisa de um n&#237;vel de PCR no soro de &#8805; 10<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Iyengar et al<span class="elsevierStyleItalic">&#46;</span> mostraram que a concentra&#231;&#227;o bruta de PCR salivar de 4&#44;84<span class="elsevierStyleHsp" style=""></span>ng&#47;L apresentou uma sensibilidade e especificidade correspondentes de 64&#37; e 94&#37; na previs&#227;o de forma precisa de um n&#237;vel de PCR no soro de 5<span class="elsevierStyleHsp" style=""></span>mg&#47;L e sensibilidade e especificidade correspondente de 54&#37; e 95&#37; na previs&#227;o de forma precisa de PCR no soro de 10<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> Essa discrep&#226;ncia pode retornar &#224; natureza da doen&#231;a investigada&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">O HC &#233; um dos tratamentos simples e rotineiros para determinar infec&#231;&#227;o em neonatos&#46; A baixa contagem de leuc&#243;citos&#44; a contagem absoluta de neutr&#243;filos e a alta propor&#231;&#227;o de neutr&#243;filos imaturos&#47;total de neutr&#243;filos foram os &#237;ndices mais comumente usados na detec&#231;&#227;o de infec&#231;&#227;o em neonatos&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Recentemente&#44; outros &#237;ndices de HC&#44; como VMP&#44; PNL e PPL&#44; foram usados como marcadores de inflama&#231;&#227;o sist&#234;mica em crian&#231;as e adultos&#46; Em neonatos&#44; est&#227;o dispon&#237;veis dados muito limitados sobre o uso de PNL e PPL no diagn&#243;stico de infec&#231;&#227;o neonatal ou outras doen&#231;as inflamat&#243;rias&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Em nosso estudo&#44; os valores VMP mostraram uma diferen&#231;a significativa entre os neonatos com sepse e controles&#44; com uma m&#233;dia de 9&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;2 fL e 8&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;5&#44; respectivamente&#44; e mostraram uma correla&#231;&#227;o significativa com PCR no soro e salivar&#46; Oncel et al<span class="elsevierStyleItalic">&#46;</span> relataram tamb&#233;m um maior VMP em neonatos com sepse em compara&#231;&#227;o com os controles&#44; com m&#233;dia de 8&#44;82<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;8 fL e 8&#44;44<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;5 fL&#44; respectivamente&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">O VMP mostrou capacidade de prever neonatos doentes e demonstrou precis&#227;o diagn&#243;stica com sensibilidade de 80&#37; e especificidade no ponto de corte 10&#44;2 fL&#46; Ayd&#305;n et al<span class="elsevierStyleItalic">&#46;</span> relataram que o valor de corte do VMP para diagn&#243;stico em neonatos com sepse foi de 10&#44;4 fL&#44; com sensibilidade e especificidade de 54&#37; e 82&#37;&#44; respectivamente&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> Recentemente&#44; Yao et al<span class="elsevierStyleItalic">&#46;</span> constataram que o ponto de corte ideal do VMP para o diagn&#243;stico de sepse foi 11&#44;4 fL&#44; com sensibilidade e especificidade de 40&#44;5&#37; e 88&#44;4&#37;&#44; respectivamente&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">A PNL &#233; simples e f&#225;cil de calcular com dados laboratoriais de rotina sem t&#233;cnica ou custo adicionais&#44; o que recentemente foi considerado um novo marcador de indica&#231;&#227;o de inflama&#231;&#227;o sist&#234;mica&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">At&#233; onde sabemos&#44; relatamos pela primeira vez uma diferen&#231;a estatisticamente significativa na PNL entre os neonatos com sepse 2&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;7 e os controles&#44; com m&#233;dia de 1&#44;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;4&#44; que tamb&#233;m mostrou uma boa relev&#226;ncia estat&#237;stica na previs&#227;o e diferencia&#231;&#227;o entre os neonatos com sepse e os controles&#44; com sensibilidade de 80&#37; e especificidade de 57&#37; no ponto de corte 2&#44;7&#46; Com rela&#231;&#227;o a infec&#231;&#245;es&#44; a PNL foi relatada como uma vari&#225;vel preditora da gravidade e do resultado cl&#237;nico em pacientes com pneumonia adquirida na comunidade<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a> e bacteremia<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> e pode diferenciar entre meningite bacteriana e viral&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">A PPL &#233; uma taxa sangu&#237;nea amplamente usada em doen&#231;as cr&#244;nicas e malignidades em adultos&#46; Em nosso estudo&#44; a PPL n&#227;o mostrou precis&#227;o significativa na previs&#227;o de neonatos com sepse com baixa sensibilidade &#40;50&#37;&#41; e especificidade &#40;46&#44;7&#37;&#41; no ponto de corte 73&#44;1&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">As principais limita&#231;&#245;es de nosso estudo s&#227;o n&#250;mero relativamente pequeno de neonatos com sepse&#44; percentual pequeno de neonatos com SIP e uso do mesmo valor de corte para PCR no soro em neonatos com SIP e SIT&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Este estudo fornece uma comprova&#231;&#227;o inicial da utilidade da PCR salivar&#44; do VMP e da PNL a serem combinados com outros marcadores no diagn&#243;stico de sepse neonatal&#46; Contudo&#44; esses achados ainda precisam ser confirmados por outros estudos que visem a examinar grandes n&#250;meros de neonatos e diferentes categorias de infec&#231;&#245;es que usam m&#233;todos rigorosos para declarar o papel da PCR salivar e de outros marcadores testados no diagn&#243;stico de sepse neonatal&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflitos de interesse</span><p id="par0215" class="elsevierStylePara elsevierViewall">Os autores declaram n&#227;o haver conflitos de interesse&#46;</p></span></span>"
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              "titulo" => "Dados demogr&#225;ficos e pr&#233;&#8208;natais"
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              "titulo" => "Quadro cl&#237;nico&#44; resultados do HC e hemocultura no grupo de sepse"
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              "titulo" => "Valores de PCR no soro&#44; PCR salivar&#44; VMP&#44; PNL e PPL"
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              "titulo" => "Correla&#231;&#227;o entre a PCR salivar e PCR no soro&#44; VMP&#44; PNL e PPL"
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              "titulo" => "Compara&#231;&#227;o na curva de caracter&#237;stica de opera&#231;&#227;o do receptor &#40;ROC&#41; da PCR soro&#44; PCR salivar&#44; VMP&#44; PNL e PPL como marcadores de sepse neonatal"
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          "palabras" => array:5 [
            0 => "Neonatal sepsis"
            1 => "Salivary CRP"
            2 => "Mean platelet volume"
            3 => "Neutrophil&#47;lymphocyte ratio"
            4 => "Platelets&#47;lymphocytes ratio"
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            0 => "Sepse neonatal"
            1 => "PCR salivar"
            2 => "Volume m&#233;dio de plaquetas"
            3 => "Propor&#231;&#227;o de neutr&#243;filos&#47;linf&#243;citos"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To assess the applicability of salivary C&#8208;reactive protein&#44; mean platelet volume&#44; neutrophil&#8211;lymphocyte ratio&#44; and platelet lymphocyte ratio in the diagnosis of neonatal sepsis&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Prospective case&#8208;control study of 70 full&#8208;term neonates&#44; 35 with sepsis &#40;20 with proven sepsis and 15 with clinical sepsis&#41; and 35 healthy controls&#46; Serum and salivary CRP concentrations were measured by ELISA while MPV&#44; NLR&#44; and PLR were measured by automated blood cell counter&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">This study showed statistically significant difference of mean salivary CRP between septic neonates and controls &#40;12&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;6<span class="elsevierStyleHsp" style=""></span>ng&#47;L <span class="elsevierStyleItalic">vs&#46;</span> 2&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2<span class="elsevierStyleHsp" style=""></span>ng&#47;L&#41; respectively&#46; At a cut&#8208;off point of 3&#46;48<span class="elsevierStyleHsp" style=""></span>ng&#47;L&#44; salivary CRP showed 94&#46;3&#37; sensitivity and 80&#37; specificity&#46; Salivary CRP also showed good predictive accuracy for predicting elevated serum CRP values in septic neonates&#46; MPV and NLR showed significant difference between septic neonates and controls &#40;10&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2<span class="elsevierStyleHsp" style=""></span>fL <span class="elsevierStyleItalic">vs&#46;</span> 8&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;5<span class="elsevierStyleHsp" style=""></span>fL&#59; 2&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;7 <span class="elsevierStyleItalic">vs&#46;</span> 1&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;4&#44; respectively&#41;&#46; At a cut&#8208;off point of 10&#46;2<span class="elsevierStyleHsp" style=""></span>fL&#44; MPV presented 80&#37; sensitivity and specificity&#46; At a cut&#8208;off point of 2&#46;7&#44; NLR presented 80&#37; sensitivity and 57&#46;1&#37; specificity&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">This study provides support for further studies on the usefulness of salivary CPR&#44; MPV&#44; and NLR as diagnostic markers for neonatal sepsis&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Avaliar a aplicabilidade da prote&#237;na C reativa salivar&#44; do volume m&#233;dio de plaquetas&#44; a propor&#231;&#227;o de neutr&#243;filos&#8208;linf&#243;citos e a propor&#231;&#227;o de plaquetas&#47;linf&#243;citos no diagn&#243;stico de sepse neonatal&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudo caso&#8208;controle prospectivo de 70 neonatos a termo&#44; 35 com sepse &#40;20 com sepse comprovada e 15 com sepse cl&#237;nica&#41; e 35 controles saud&#225;veis&#46; As concentra&#231;&#245;es de PCR no soro e salivar foram medidas por ensaio imunossorvente ligado a enzima &#40;Elisa&#41;&#44; ao passo que o VMP&#44; PNL e PPL foram medidos por contador de c&#233;lulas sangu&#237;neas automatizado&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Este estudo mostrou uma diferen&#231;a estatisticamente significativa da m&#233;dia de PCR salivar entre os neonatos com sepse e os controles &#40;12&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;6<span class="elsevierStyleHsp" style=""></span>ng&#47;L em compara&#231;&#227;o com 2&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;2<span class="elsevierStyleHsp" style=""></span>ng&#47;L&#41;&#44; respectivamente&#46; Um ponto de corte 3&#44;48<span class="elsevierStyleHsp" style=""></span>ng&#47;L na PCR salivar mostrou sensibilidade de 94&#44;3&#37; e especificidade de 80&#37;&#46; A PCR salivar mostrou&#44; ainda&#44; boa precis&#227;o preditiva para prever altos valores de PCR no soro em neonatos com sepse&#46; O VMP e a PNL mostraram diferen&#231;a significativa entre os neonatos com sepse e os controles &#40;10&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;2<span class="elsevierStyleHsp" style=""></span>fL em compara&#231;&#227;o com 8&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;5<span class="elsevierStyleHsp" style=""></span>fL&#41;&#44; &#40;2&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;7 em compara&#231;&#227;o com 1&#44;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;4&#41;&#44; respectivamente&#46; O VMP no ponto de corte 10&#44;2<span class="elsevierStyleHsp" style=""></span>fL apresentou 80&#37; de sensibilidade e especificidade&#46; A PNL no ponto de corte 2&#44;7<span class="elsevierStyleHsp" style=""></span>fL apresentou 80&#37; de sensibilidade e 57&#44;1&#37; de especificidade&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#227;o</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Este estudo fornece uma base para outros estudos na utilidade da PCR salivar&#44; VMP e PNL como marcadores de diagn&#243;stico de sepse neonatal&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Como citar este artigo&#58; Omran A&#44; Maaroof A&#44; Mohammad MH&#44; Abdelwahab A&#46; Salivary C&#8208;reactive protein&#44; mean platelet volume and neutrophil lymphocyte ratio as diagnostic markers for neonatal sepsis&#46; J Pediatr &#40;Rio J&#41;&#46; 2018&#59;94&#58;82&#8211;7&#46;</p>"
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Artigo Original
Salivary C‐reactive protein, mean platelet volume and neutrophil lymphocyte ratio as diagnostic markers for neonatal sepsis
Proteína C reativa salivar, volume médio de plaquetas e proporção de neutrófilos/linfócitos como marcadores de diagnóstico de sepse neonatal
Ahmed Omrana,
Autor para correspondência
agomran1@yahoo.com

Autor para correspondência.
, Abdallah Maaroofa, Mai H.S. Mohammadb, Amina Abdelwahaba
a Suez Canal University, Faculty of Medicine, Departments of Pediatrics & Neonatology, Ismailia, Egito
b Suez Canal University, Faculty of Medicine, Department of Clinical Pathology, Ismailia, Egito
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        "titulo" => "Prote&#237;na C reativa salivar&#44; volume m&#233;dio de plaquetas e propor&#231;&#227;o de neutr&#243;filos&#47;linf&#243;citos como marcadores de diagn&#243;stico de sepse neonatal"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">A sepse &#233; uma condi&#231;&#227;o grave com risco de vida e uma das principais causas de morbidez e mortalidade em neonatos a termo e prematuros nos pa&#237;ses em desenvolvimento&#46; Ela &#233; amplamente definida como uma resposta inflamat&#243;ria sist&#234;mica&#44; que ocorre nos primeiros 28 dias de vida&#44; como resultado de uma poss&#237;vel infec&#231;&#227;o ou infec&#231;&#227;o comprovada&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Existe um apelo urgente no que diz respeito &#224; detec&#231;&#227;o de biomarcadores confi&#225;veis para diferenciar neonatos infectados e n&#227;o infectados&#46; A hemocultura foi considerada o padr&#227;o de base para diagn&#243;stico&#44; por&#233;m essa an&#225;lise ainda &#233; lenta e limitada por resultados falsos negativos&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">A prote&#237;na C reativa &#40;PCR&#41;&#44; uma importante prote&#237;na de fase aguda&#44; &#233; um membro da fam&#237;lia pentraxina e desempenha um papel central na imunidade inata e adaptativa&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> Apesar do desenvolvimento de novos biomarcadores&#44; at&#233; o momento a PCR &#233; um dos testes de laborat&#243;rio mais estudados e mais usados para diagn&#243;stico de sepse neonatal&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> A PCR leva de 10&#8208;12 horas para surgir significativamente ap&#243;s o in&#237;cio da infec&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a> Como a PCR mostra um aumento em v&#225;rias doen&#231;as&#44; ela &#233; preferencialmente usada em combina&#231;&#227;o com outros biomarcadores&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Um problema relevante na abordagem cl&#237;nica atual de neonatos doentes &#233; a disponibilidade limitada de ferramentas simples&#44; seguras e n&#227;o invasivas com alta precis&#227;o de diagn&#243;stico&#46; A saliva dos neonatos supera os obst&#225;culos associados &#224; pesquisa neonatal e oferece ao investigador uma nova fonte de amostras n&#227;o invasivas para explora&#231;&#227;o da biologia neonatal&#46; A PCR foi detect&#225;vel na saliva dos neonatos e pode prever limites anormais de PCR no soro&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Recentemente&#44; certos par&#226;metros de hemograma completo &#40;HC&#41; foram usados como marcadores de inflama&#231;&#227;o e infec&#231;&#245;es&#46; O volume m&#233;dio de plaquetas &#40;VMP&#41; tem sido usado no diagn&#243;stico&#44; no acompanhamento e na previs&#227;o de gravidade da sepse neonatal em neonatos a termo e prematuros&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6&#8211;8</span></a> A propor&#231;&#227;o de neutr&#243;filos&#8208;linf&#243;citos &#40;PNL&#41; &#233; um simples biomarcador de inflama&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a> Al&#233;m disso&#44; a propor&#231;&#227;o de plaquetas&#47;linf&#243;citos &#40;PPL&#41; tamb&#233;m &#233; um marcador &#250;til de inflama&#231;&#227;o sist&#234;mica&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">O presente estudo visou a avaliar a aplicabilidade da PCR salivar&#44; do VMP&#44; da PNL e da PPL como marcadores de diagn&#243;stico em neonatos a termo com sepse neonatal&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">M&#233;todos</span><p id="par0035" class="elsevierStylePara elsevierViewall">O presente estudo foi conduzido na unidade de terapia intensiva neonatal &#40;UTIN&#41; de Suez Canal University Hospital&#44; Ismailia&#44; Egito&#44; entre janeiro de 2016 e junho de 2016&#46; Durante esses seis meses&#44; 320 neonatos foram internados na unidade&#46; Foram inscritos 35 neonatos com sepse neonatal de in&#237;cio precoce ou tardio e 35 neonatos saud&#225;veis de controle&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Crit&#233;rios de inclus&#227;o&#58; foram inscritos neste estudo os nascidos a termo de ambos os sexos&#44; do nascimento a 28 dias&#44; internados na UTIN de Suez Canal University com caracter&#237;sticas cl&#237;nicas de sepse neonatal de in&#237;cio precoce ou tardio&#46; O diagn&#243;stico de sepse cl&#237;nica foi feito por hist&#243;rico&#44; achados cl&#237;nicos&#44; achados laboratoriais e hemocultura&#46; Os achados cl&#237;nicos incluem presen&#231;a de tr&#234;s ou mais do que segue&#58; &#40;1&#41; instabilidade de temperatura &#40;hipotermia&#44; hipertermia&#41;&#59; &#40;2&#41; problemas respirat&#243;rios &#40;grunhidos&#44; retra&#231;&#245;es intercostais&#44; apneia&#44; taquipneia&#44; cianose&#41;&#59; &#40;3&#41; cardiovasculares &#40;bradicardia&#44; taquicardia&#44; fraca perfus&#227;o&#44; hipotens&#227;o&#41;&#59; &#40;4&#41; neurol&#243;gicos &#40;hipotonia&#44; letargia&#44; convuls&#245;es&#41; e &#40;5&#41; gastrointestinais &#40;intoler&#226;ncia alimentar&#44; distens&#227;o abdominal&#41;&#46; O valor de PCR de<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>mg&#47;L foi considerado positivo&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#44;11</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Crit&#233;rios de exclus&#227;o&#58; foram exclu&#237;dos neonatos prematuros e neonatos com pneumonia confirmada ou outras condi&#231;&#245;es inflamat&#243;rias&#44; malforma&#231;&#245;es do sistema nervoso central &#40;SNC&#41;&#44; disfun&#231;&#245;es metab&#243;licas&#44; anomalias cromoss&#244;micas&#44; restri&#231;&#227;o do crescimento intrauterino&#44; asfixia ao nascer&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Por&#233;m&#44; os 35 neonatos saud&#225;veis sem sintomas&#44; sinais ou fatores de risco para infec&#231;&#245;es internados por icter&#237;cia fisiol&#243;gica na unidade neonatal e todos os neonatos sem fatores de risco infecciosos internados em cl&#237;nicas ambulatoriais do hospital foram inscritos de forma prospectiva como controles&#46; O n&#237;vel de PCR no soro dos neonatos nesse grupo foi negativo &#40;PCR de menos de 10<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">As amostras foram coletadas de neonatos com sepse entre 4&#8208;12 horas ap&#243;s o diagn&#243;stico cl&#237;nico para a medi&#231;&#227;o dos n&#237;veis de PCR no soro e antes do in&#237;cio do tratamento com antibi&#243;ticos&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Para o HC&#44; o sangue perif&#233;rico foi coletado em um tubo EDTA a v&#225;cuo e analisado por um contador de c&#233;lulas sangu&#237;neas automatizado &#40;Cell&#8208;Dyn 3700&#44; Abbott Laboratories&#44; IL&#44; EUA&#41;&#46; A PNL e a PPL foram calculadas como propor&#231;&#227;o de neutr&#243;filos&#47;linf&#243;citos e plaquetas&#47;linf&#243;citos&#44; respectivamente&#46; Os n&#237;veis deles foram obtidos das mesmas amostras de sangue&#46; Para o c&#225;lculo preciso do VMP&#44; as amostras foram analisadas at&#233; 60 minutos ap&#243;s a amostragem para evitar falso aumento do VMP&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Para determina&#231;&#227;o do n&#237;vel de PCR no soro&#44; foi usado o autoanalisador automatizado Cobas c501 &#40;Roche Diagnostics&#44; Manheim&#44; Alemanha&#41;&#46; Para a PCR salivar&#44; as amostras foram coletadas aproximadamente uma hora antes da alimenta&#231;&#227;o para evitar contamina&#231;&#227;o do leite&#46; A saliva foi coletada ao inclinar a cabe&#231;a para frente para juntar saliva na parte do ch&#227;o da boca&#46; As amostras foram ent&#227;o obtidas com uma seringa de 1<span class="elsevierStyleHsp" style=""></span>mL anexada em um aspirador para rede canalizada &#40;LWS&#41; &#40;&#60; 20<span class="elsevierStyleHsp" style=""></span>mm Hg&#41;&#46; Isso garante que a saliva continue na seringa e n&#227;o entre no tubo ou no aspirador nasal&#46; A saliva foi aspirada das l&#237;nguas dos neonatos e de seus sulcos gengivais&#46; A suc&#231;&#227;o foi mantida por aproximadamente 10&#8208;15 segundos&#44; coletaram&#8208;se cerca de 0&#44;5<span class="elsevierStyleHsp" style=""></span>mL&#46; A seringa foi ent&#227;o separada da suc&#231;&#227;o e o &#234;mbolo foi novamente posicionado na seringa&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Ap&#243;s a coleta&#44; as amostras foram colocadas em tubos de polipropileno para evitar contamina&#231;&#227;o e falhas anal&#237;ticas de reten&#231;&#227;o&#46; As amostras foram armazenadas a &#8208;20<span class="elsevierStyleHsp" style=""></span>&#176;C at&#233; o uso&#46; A PCR salivar foi medida por Elisa&#46; As hemoculturas foram feitas para o grupo com sepse&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Este estudo foi aprovado por nosso comit&#234; de &#233;tica institucional local e foi obtido o consentimento informado dos pais de todos os neonatos durante todo o estudo&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">An&#225;lises estat&#237;sticas</span><p id="par0080" class="elsevierStylePara elsevierViewall">Foram feitas com o pacote estat&#237;stico SPSS para Windows&#44; vers&#227;o 20 &#40;SPSS&#44; Chicago&#44; IL&#44; EUA&#41;&#46; Foram avaliadas as diferen&#231;as entre os grupos com rela&#231;&#227;o aos dados quantitativos n&#227;o param&#233;tricos por meio do teste U de Mann&#8208;Whitney&#46; O teste de qui&#8208;quadrado foi usado para testar as diferen&#231;as significativas das vari&#225;veis qualitativas&#46; A sensibilidade&#44; a especificidade e o ponto de corte ideal da PCR salivar foram determinados com a curva ROC&#46; Para toda a an&#225;lise estat&#237;stica&#44; o n&#237;vel de relev&#226;ncia considerado foi<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Resultados</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Dados demogr&#225;ficos e pr&#233;&#8208;natais</span><p id="par0085" class="elsevierStylePara elsevierViewall">Houve diferen&#231;as estat&#237;sticas entre os dois grupos com rela&#231;&#227;o &#224; idade&#44; ao hist&#243;rico de infec&#231;&#227;o do trato urin&#225;rio &#40;ITU&#41; materna e ao tipo de parto&#46; Sepse de in&#237;cio tardio &#40;SIT&#41; foi diagnosticada em 74&#44;3&#37; dos neonatos com sepse&#44; ao passo que sepse de in&#237;cio precoce &#40;SIP&#41; foi diagnosticada em apenas 25&#44;7&#37; deles &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Quadro cl&#237;nico&#44; resultados do HC e hemocultura no grupo de sepse</span><p id="par0090" class="elsevierStylePara elsevierViewall">No momento da apresenta&#231;&#227;o dos neonatos com sepse&#44; 19 &#40;54&#44;3&#37;&#41; apresentaram baixa atividade e recusa de alimenta&#231;&#227;o&#44; ao passo que nove &#40;25&#44;7&#37;&#41; apresentaram febre e baixa atividade&#44; sete &#40;20&#37;&#41; apresentaram recusa de alimenta&#231;&#227;o e insufici&#234;ncia respirat&#243;ria&#46; Houve diferen&#231;as significativas entre os dois grupos nos n&#237;veis do HC&#46; Dos neonatos com sepse 12 &#40;34&#44;3&#37;&#41; apresentaram anemia&#44; ao passo que quatro &#40;11&#44;4&#37;&#41; dos controles apresentaram anemia&#46; A contagem de gl&#243;bulos brancos mostrou diferen&#231;a entre os neonatos com sepse e os controles&#44; leucocitose em 11 &#40;31&#44;4&#37;&#41; dos neonatos com sepse em compara&#231;&#227;o com um &#40;2&#44;9&#37;&#41; dos controles&#46; Trombocitopenia foi encontrada em nove &#40;25&#44;7&#37;&#41; do grupo com sepse e um &#40;2&#44;9&#37;&#41; dos controles&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">No grupo com sepse&#44; a hemocultura foi positiva em 25 &#40;71&#44;5&#37;&#41;&#44; estafilococos coagulase negativa foram os pat&#243;genos isolados mais frequentes&#44; seguidos de <span class="elsevierStyleItalic">E&#46; coli</span>&#44; <span class="elsevierStyleItalic">Klebsiella pneumonia</span> e <span class="elsevierStyleItalic">Serratia marcescens</span>&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Valores de PCR no soro&#44; PCR salivar&#44; VMP&#44; PNL e PPL</span><p id="par0100" class="elsevierStylePara elsevierViewall">Houve diferen&#231;as significativas entre os dois grupos na PCR no soro&#44; PCR salivar&#44; VMP e PNL&#46; Os valores de PCR no soro mostraram diferen&#231;a significativa entre os dois grupos &#40;m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>27&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#44;3<span class="elsevierStyleHsp" style=""></span>mg&#47;L em compara&#231;&#227;o com 4&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;8<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#41;&#44; respectivamente&#46; A m&#233;dia de PCR no soro dos neonatos com SIP foi de 23&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#44;3&#44; ao passo que a m&#233;dia em neonatos com SIT foi de 29&#44;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46; A PCR salivar mostrou diferen&#231;a significativa entre os dois grupos &#40;m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;6<span class="elsevierStyleHsp" style=""></span>ng&#47;L em compara&#231;&#227;o com 2&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;2<span class="elsevierStyleHsp" style=""></span>ng&#47;L&#41;&#44; respectivamente&#46; O VMP mostrou diferen&#231;a significativa entre os dois grupos &#40;m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;2 fL em compara&#231;&#227;o com 8&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;5 fL&#41;&#44; respectivamente&#46; A PNL mostrou diferen&#231;a significativa entre os dois grupos &#40;m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;7 em compara&#231;&#227;o com 1&#44;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;4&#41;&#44; respectivamente&#46; A diferen&#231;a da PPL entre os dois grupos n&#227;o foi significativa &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Correla&#231;&#227;o entre a PCR salivar e PCR no soro&#44; VMP&#44; PNL e PPL</span><p id="par0105" class="elsevierStylePara elsevierViewall">Houve correla&#231;&#245;es estatisticamente significativas entre PCR salivar e PCR no soro &#40;0&#44;66&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#44; VMP &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;45&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; e PNL &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;408&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; A correla&#231;&#227;o entre PCR salivar e PPL n&#227;o foi estatisticamente significativa &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Compara&#231;&#227;o na curva de caracter&#237;stica de opera&#231;&#227;o do receptor &#40;ROC&#41; da PCR soro&#44; PCR salivar&#44; VMP&#44; PNL e PPL como marcadores de sepse neonatal</span><p id="par0110" class="elsevierStylePara elsevierViewall">A an&#225;lise das curvas ROC mostrou que a PCR no soro em um valor de corte de 10<span class="elsevierStyleHsp" style=""></span>mg&#47;L tem sensibilidade de 83&#44;1&#37; e especificidade de 85&#44;9&#37;&#46; A PCR salivar em um valor de corte de 3&#44;48<span class="elsevierStyleHsp" style=""></span>ng&#47;L tem sensibilidade de 94&#44;3&#37; e especificidade de 80&#37;&#46; O VMP mostrou sensibilidade de 80&#37; e especificidade de 80&#37; em um valor de corte de 10&#44;2 fL&#46; A PNL em um valor de corte de 2&#44;7<span class="elsevierStyleHsp" style=""></span>ng&#47;L tem sensibilidade de 80&#37; e especificidade de 57&#44;1&#37;&#46; A PPL mostrou baixa sensibilidade e especificidade ao prever sepse neonatal &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabela 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">A PCR salivar em um valor de corte de 3&#44;4<span class="elsevierStyleHsp" style=""></span>ng&#47;L mostrou sensibilidade de 94&#37; e especificidade de 91&#44;3 na previs&#227;o de PCR no soro &#8805; 10<span class="elsevierStyleHsp" style=""></span>mg&#47;L em neonatos com sepse&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discuss&#227;o</span><p id="par0120" class="elsevierStylePara elsevierViewall">A sepse neonatal &#233; uma das principais causas de morbidade e mortalidade em unidades de terapia intensiva neonatais&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a> Adicionalmente&#44; tem morbidades de longo prazo&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">13&#44;14</span></a> Por outro lado&#44; manobras simples&#44; como o uso de &#225;lcool em gel e treinamento sobre higieniza&#231;&#227;o das m&#227;os&#44; podem reduzir a SIT&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Em todo o mundo&#44; as infec&#231;&#245;es representam dois ter&#231;os dos seis milh&#245;es de &#243;bitos anuais em crian&#231;as com menos de cinco anos&#46; O per&#237;odo neonatal representa o maior risco de vida de infec&#231;&#245;es graves&#44; com uma estimativa de 400&#46;000 &#243;bitos de rec&#233;m&#8208;nascidos anualmente&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> No Egito&#44; as taxas de sepse ultrapassam 50&#37; em unidades de terapia intensiva neonatal&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Recentemente&#44; a an&#225;lise da saliva para monitoramento cl&#237;nico e detec&#231;&#227;o de biomarcadores em neonatos representa uma &#243;tima promessa de melhoria nos cuidados de sa&#250;de dessa popula&#231;&#227;o fr&#225;gil&#46; A saliva representa um biofluido ideal e facilmente acess&#237;vel para exames n&#227;o invasivos de morbidades neonatais comuns&#44; como prematuridade&#44; infec&#231;&#245;es e insultos cerebrais&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">18&#8211;20</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">At&#233; agora&#44; a PCR &#233; o reagente de fase aguda mais amplamente estudado e&#44; apesar da detec&#231;&#227;o de novos marcadores de infec&#231;&#227;o&#44; sua ampla disponibilidade e sua determina&#231;&#227;o r&#225;pida&#44; simples e com bom custo&#8208;benef&#237;cio a tornam um dos &#237;ndices preferenciais em muitas unidades de terapia intensiva neonatal&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Na literatura relatada&#44; a PCR no soro mostrou diferente cin&#233;tica e valores de corte que variam de 1&#44;5 a 20<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#44; tamb&#233;m com sensibilidades e especificidades de grande alcance que variam de 74 a 98&#37; e de 71 a 94&#37;&#44; respectivamente&#44; nas determina&#231;&#245;es de PCR serial ou uma &#250;nica medi&#231;&#227;o de pelo menos 12 horas ap&#243;s o in&#237;cio dos sintomas de sepse neonatal&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#44;11&#44;21&#8211;23</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Essas diferen&#231;as nos valores de corte podem ser explicadas por diferentes idades gestacionais&#44; pesos no nascimento e cin&#233;tica fisiol&#243;gica da PCR ap&#243;s o nascimento nos neonatos estudados&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> H&#225; um debate sobre o ponto de corte da PCR em casos de SIP e SIT&#44; com certa concord&#226;ncia sobre o uso de 10<span class="elsevierStyleHsp" style=""></span>mg&#47;L como um corte confi&#225;vel&#44; principalmente na SIP&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3&#44;11</span></a> No presente estudo&#44; a m&#233;dia da PCR no soro foi de 27&#44;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#44;3<span class="elsevierStyleHsp" style=""></span>mg&#47;L em neonatos com sepse&#44; com sensibilidade de 83&#44;1&#37; e especificidade de 85&#44;9&#37; em um valor de corte de 10<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">As medi&#231;&#245;es seriais do n&#237;vel de PCR tamb&#233;m podem ser &#250;teis na identifica&#231;&#227;o de neonatos com infec&#231;&#227;o bacteriana&#44; no monitoramento da resposta ao tratamento em neonatos infectados e na determina&#231;&#227;o da dura&#231;&#227;o da terapia antibi&#243;tica&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">21&#44;24</span></a> Por&#233;m&#44; o monitoramento da PCR no soro na popula&#231;&#227;o neonatal a coloca em riscos m&#233;dicos de amostragem frequente&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">A detec&#231;&#227;o da PCR salivar &#233; um novo m&#233;todo de diagn&#243;stico na popula&#231;&#227;o neonatal&#46; Em 2014&#44; Iyengar et al<span class="elsevierStyleItalic">&#46;</span> publicaram o primeiro trabalho sobre detec&#231;&#227;o e utilidade da PCR salivar em neonatos&#44; considerado o primeiro estudo para detectar&#44; quantificar e demonstrar que a PCR salivar &#233; um bom &#237;ndice dos limites clinicamente relevantes de PCR no soro&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Neste estudo&#44; investigamos pela primeira vez at&#233; onde sabemos que a PCR salivar &#233; um marcador de diagn&#243;stico n&#227;o invasivo em neonatos com sepse&#46; A m&#233;dia da PCR salivar mostrou diferen&#231;a estatisticamente significativa entre os neonatos com sepse e controles&#44; com m&#233;dia de 12&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;6<span class="elsevierStyleHsp" style=""></span>ng&#47;L em neonatos com sepse&#44; ao passo que a dos controles foi de 2&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;2<span class="elsevierStyleHsp" style=""></span>ng&#47;L&#46; Um ponto de corte de 3&#44;48<span class="elsevierStyleHsp" style=""></span>ng&#47;L na PCR salivar mostrou alta sensibilidade &#40;94&#44;3&#37;&#41; e especificidade &#40;80&#44;0&#37;&#41;&#46; Em nosso estudo&#44; a PCR salivar mostrou boa precis&#227;o na previs&#227;o de altos n&#237;veis de PCR no soro&#46; Foi observado que a PCR salivar no ponto de corte 3&#44;4<span class="elsevierStyleHsp" style=""></span>ng&#47;L apresentou sensibilidade correspondente &#40;94&#37;&#41; e especificidade &#40;91&#44;3&#37;&#41; na previs&#227;o de forma precisa de um n&#237;vel de PCR no soro de &#8805; 10<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Iyengar et al<span class="elsevierStyleItalic">&#46;</span> mostraram que a concentra&#231;&#227;o bruta de PCR salivar de 4&#44;84<span class="elsevierStyleHsp" style=""></span>ng&#47;L apresentou uma sensibilidade e especificidade correspondentes de 64&#37; e 94&#37; na previs&#227;o de forma precisa de um n&#237;vel de PCR no soro de 5<span class="elsevierStyleHsp" style=""></span>mg&#47;L e sensibilidade e especificidade correspondente de 54&#37; e 95&#37; na previs&#227;o de forma precisa de PCR no soro de 10<span class="elsevierStyleHsp" style=""></span>mg&#47;L&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> Essa discrep&#226;ncia pode retornar &#224; natureza da doen&#231;a investigada&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">O HC &#233; um dos tratamentos simples e rotineiros para determinar infec&#231;&#227;o em neonatos&#46; A baixa contagem de leuc&#243;citos&#44; a contagem absoluta de neutr&#243;filos e a alta propor&#231;&#227;o de neutr&#243;filos imaturos&#47;total de neutr&#243;filos foram os &#237;ndices mais comumente usados na detec&#231;&#227;o de infec&#231;&#227;o em neonatos&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Recentemente&#44; outros &#237;ndices de HC&#44; como VMP&#44; PNL e PPL&#44; foram usados como marcadores de inflama&#231;&#227;o sist&#234;mica em crian&#231;as e adultos&#46; Em neonatos&#44; est&#227;o dispon&#237;veis dados muito limitados sobre o uso de PNL e PPL no diagn&#243;stico de infec&#231;&#227;o neonatal ou outras doen&#231;as inflamat&#243;rias&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Em nosso estudo&#44; os valores VMP mostraram uma diferen&#231;a significativa entre os neonatos com sepse e controles&#44; com uma m&#233;dia de 9&#44;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;2 fL e 8&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;5&#44; respectivamente&#44; e mostraram uma correla&#231;&#227;o significativa com PCR no soro e salivar&#46; Oncel et al<span class="elsevierStyleItalic">&#46;</span> relataram tamb&#233;m um maior VMP em neonatos com sepse em compara&#231;&#227;o com os controles&#44; com m&#233;dia de 8&#44;82<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;8 fL e 8&#44;44<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;5 fL&#44; respectivamente&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">O VMP mostrou capacidade de prever neonatos doentes e demonstrou precis&#227;o diagn&#243;stica com sensibilidade de 80&#37; e especificidade no ponto de corte 10&#44;2 fL&#46; Ayd&#305;n et al<span class="elsevierStyleItalic">&#46;</span> relataram que o valor de corte do VMP para diagn&#243;stico em neonatos com sepse foi de 10&#44;4 fL&#44; com sensibilidade e especificidade de 54&#37; e 82&#37;&#44; respectivamente&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> Recentemente&#44; Yao et al<span class="elsevierStyleItalic">&#46;</span> constataram que o ponto de corte ideal do VMP para o diagn&#243;stico de sepse foi 11&#44;4 fL&#44; com sensibilidade e especificidade de 40&#44;5&#37; e 88&#44;4&#37;&#44; respectivamente&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">A PNL &#233; simples e f&#225;cil de calcular com dados laboratoriais de rotina sem t&#233;cnica ou custo adicionais&#44; o que recentemente foi considerado um novo marcador de indica&#231;&#227;o de inflama&#231;&#227;o sist&#234;mica&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">At&#233; onde sabemos&#44; relatamos pela primeira vez uma diferen&#231;a estatisticamente significativa na PNL entre os neonatos com sepse 2&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;7 e os controles&#44; com m&#233;dia de 1&#44;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;4&#44; que tamb&#233;m mostrou uma boa relev&#226;ncia estat&#237;stica na previs&#227;o e diferencia&#231;&#227;o entre os neonatos com sepse e os controles&#44; com sensibilidade de 80&#37; e especificidade de 57&#37; no ponto de corte 2&#44;7&#46; Com rela&#231;&#227;o a infec&#231;&#245;es&#44; a PNL foi relatada como uma vari&#225;vel preditora da gravidade e do resultado cl&#237;nico em pacientes com pneumonia adquirida na comunidade<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a> e bacteremia<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> e pode diferenciar entre meningite bacteriana e viral&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">A PPL &#233; uma taxa sangu&#237;nea amplamente usada em doen&#231;as cr&#244;nicas e malignidades em adultos&#46; Em nosso estudo&#44; a PPL n&#227;o mostrou precis&#227;o significativa na previs&#227;o de neonatos com sepse com baixa sensibilidade &#40;50&#37;&#41; e especificidade &#40;46&#44;7&#37;&#41; no ponto de corte 73&#44;1&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">As principais limita&#231;&#245;es de nosso estudo s&#227;o n&#250;mero relativamente pequeno de neonatos com sepse&#44; percentual pequeno de neonatos com SIP e uso do mesmo valor de corte para PCR no soro em neonatos com SIP e SIT&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Este estudo fornece uma comprova&#231;&#227;o inicial da utilidade da PCR salivar&#44; do VMP e da PNL a serem combinados com outros marcadores no diagn&#243;stico de sepse neonatal&#46; Contudo&#44; esses achados ainda precisam ser confirmados por outros estudos que visem a examinar grandes n&#250;meros de neonatos e diferentes categorias de infec&#231;&#245;es que usam m&#233;todos rigorosos para declarar o papel da PCR salivar e de outros marcadores testados no diagn&#243;stico de sepse neonatal&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflitos de interesse</span><p id="par0215" class="elsevierStylePara elsevierViewall">Os autores declaram n&#227;o haver conflitos de interesse&#46;</p></span></span>"
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              "titulo" => "Dados demogr&#225;ficos e pr&#233;&#8208;natais"
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              "titulo" => "Quadro cl&#237;nico&#44; resultados do HC e hemocultura no grupo de sepse"
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              "titulo" => "Valores de PCR no soro&#44; PCR salivar&#44; VMP&#44; PNL e PPL"
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              "titulo" => "Correla&#231;&#227;o entre a PCR salivar e PCR no soro&#44; VMP&#44; PNL e PPL"
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              "titulo" => "Compara&#231;&#227;o na curva de caracter&#237;stica de opera&#231;&#227;o do receptor &#40;ROC&#41; da PCR soro&#44; PCR salivar&#44; VMP&#44; PNL e PPL como marcadores de sepse neonatal"
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            0 => "Sepse neonatal"
            1 => "PCR salivar"
            2 => "Volume m&#233;dio de plaquetas"
            3 => "Propor&#231;&#227;o de neutr&#243;filos&#47;linf&#243;citos"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To assess the applicability of salivary C&#8208;reactive protein&#44; mean platelet volume&#44; neutrophil&#8211;lymphocyte ratio&#44; and platelet lymphocyte ratio in the diagnosis of neonatal sepsis&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Prospective case&#8208;control study of 70 full&#8208;term neonates&#44; 35 with sepsis &#40;20 with proven sepsis and 15 with clinical sepsis&#41; and 35 healthy controls&#46; Serum and salivary CRP concentrations were measured by ELISA while MPV&#44; NLR&#44; and PLR were measured by automated blood cell counter&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">This study showed statistically significant difference of mean salivary CRP between septic neonates and controls &#40;12&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;6<span class="elsevierStyleHsp" style=""></span>ng&#47;L <span class="elsevierStyleItalic">vs&#46;</span> 2&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2<span class="elsevierStyleHsp" style=""></span>ng&#47;L&#41; respectively&#46; At a cut&#8208;off point of 3&#46;48<span class="elsevierStyleHsp" style=""></span>ng&#47;L&#44; salivary CRP showed 94&#46;3&#37; sensitivity and 80&#37; specificity&#46; Salivary CRP also showed good predictive accuracy for predicting elevated serum CRP values in septic neonates&#46; MPV and NLR showed significant difference between septic neonates and controls &#40;10&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2<span class="elsevierStyleHsp" style=""></span>fL <span class="elsevierStyleItalic">vs&#46;</span> 8&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;5<span class="elsevierStyleHsp" style=""></span>fL&#59; 2&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;7 <span class="elsevierStyleItalic">vs&#46;</span> 1&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;4&#44; respectively&#41;&#46; At a cut&#8208;off point of 10&#46;2<span class="elsevierStyleHsp" style=""></span>fL&#44; MPV presented 80&#37; sensitivity and specificity&#46; At a cut&#8208;off point of 2&#46;7&#44; NLR presented 80&#37; sensitivity and 57&#46;1&#37; specificity&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">This study provides support for further studies on the usefulness of salivary CPR&#44; MPV&#44; and NLR as diagnostic markers for neonatal sepsis&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Avaliar a aplicabilidade da prote&#237;na C reativa salivar&#44; do volume m&#233;dio de plaquetas&#44; a propor&#231;&#227;o de neutr&#243;filos&#8208;linf&#243;citos e a propor&#231;&#227;o de plaquetas&#47;linf&#243;citos no diagn&#243;stico de sepse neonatal&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudo caso&#8208;controle prospectivo de 70 neonatos a termo&#44; 35 com sepse &#40;20 com sepse comprovada e 15 com sepse cl&#237;nica&#41; e 35 controles saud&#225;veis&#46; As concentra&#231;&#245;es de PCR no soro e salivar foram medidas por ensaio imunossorvente ligado a enzima &#40;Elisa&#41;&#44; ao passo que o VMP&#44; PNL e PPL foram medidos por contador de c&#233;lulas sangu&#237;neas automatizado&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Este estudo mostrou uma diferen&#231;a estatisticamente significativa da m&#233;dia de PCR salivar entre os neonatos com sepse e os controles &#40;12&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;6<span class="elsevierStyleHsp" style=""></span>ng&#47;L em compara&#231;&#227;o com 2&#44;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;2<span class="elsevierStyleHsp" style=""></span>ng&#47;L&#41;&#44; respectivamente&#46; Um ponto de corte 3&#44;48<span class="elsevierStyleHsp" style=""></span>ng&#47;L na PCR salivar mostrou sensibilidade de 94&#44;3&#37; e especificidade de 80&#37;&#46; A PCR salivar mostrou&#44; ainda&#44; boa precis&#227;o preditiva para prever altos valores de PCR no soro em neonatos com sepse&#46; O VMP e a PNL mostraram diferen&#231;a significativa entre os neonatos com sepse e os controles &#40;10&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;2<span class="elsevierStyleHsp" style=""></span>fL em compara&#231;&#227;o com 8&#44;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;5<span class="elsevierStyleHsp" style=""></span>fL&#41;&#44; &#40;2&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;7 em compara&#231;&#227;o com 1&#44;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;4&#41;&#44; respectivamente&#46; O VMP no ponto de corte 10&#44;2<span class="elsevierStyleHsp" style=""></span>fL apresentou 80&#37; de sensibilidade e especificidade&#46; A PNL no ponto de corte 2&#44;7<span class="elsevierStyleHsp" style=""></span>fL apresentou 80&#37; de sensibilidade e 57&#44;1&#37; de especificidade&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#227;o</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Este estudo fornece uma base para outros estudos na utilidade da PCR salivar&#44; VMP e PNL como marcadores de diagn&#243;stico de sepse neonatal&#46;</p></span>"
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                  \t\t\t\t  " colspan="2" align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Intervalo de confian&#231;a de 95&#37;</th><th class="td" title="\n
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                  \t\t\t\t  " rowspan="2" align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Valor de corte</th><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sensibilidade</th><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Especificidade</th></tr><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Limite inferior&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Limite superior&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">PCR no soro&nbsp;\t\t\t\t\t\t\n
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                          "autores" => array:6 [
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                      "titulo" => "Human C&#8208;reactive protein&#58; expression&#44; structure&#44; and function"
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                          "etal" => false
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                      "doi" => "10.1016/s0161-5890(01)00042-6"
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ISSN: 22555536
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