Naturally developed HPV16 antibodies and risk of newly detected cervical HPV infection outcomes.

Little is known about the protection conferred by antibodies from natural human papillomavirus (HPV) infection. Our objective was to evaluate the association between HPV16 seroreactivity and HPV16 redetection, newly detected HPV infections, and loss of HPV DNA detection during follow-up. We analyzed data from 2462 unvaccinated Brazilian women. HPV16 IgG and neutralizing antibodies at baseline were assessed by enzyme-linked immunosorbent assay (n = 1975) and by the pseudovirus-based papillomavirus neutralization assay (n = 487). HPV detection, genotyping, and viral load were assessed by PCR-based methods. The associations were analyzed by Cox proportional hazards models. We observed a positive association between HPV16 IgG seroreactivity and redetection of HPV16 infections. Age-adjusted hazard ratios (HR) with 95% confidence intervals (CI) ranged from 2.45 (1.04-5.74) to 5.10 (1.37-19.00). Positive associations were also observed between HPV16 IgG antibodies and (1) newly detected HPV infections by genotypes unrelated to HPV16 (age-adjusted HR [95% CI] = 1.32 [1.08-1.2]) and (2) loss of detection of HPV infections by genotypes unrelated to HPV16 (age-adjusted HR [95% CI] = 1.24 [1.03-1.50]). Naturally developed HPV16 antibodies do not prevent recurrent HPV infections. Overall HPV16 IgG and neutralizing antibodies seem to be serological markers for latent or past infections.

Human Papillomavirus Intermittence and Risk Factors Associated With First Detections and Redetections in the Ludwig-McGill Cohort Study of Adult Women.

BACKGROUND: We assessed the incidence and risk factors for first detection and redetection with the same human papillomavirus (HPV) genotype, and prevalence of cytological lesions during HPV redetections. METHODS: The Ludwig-McGill cohort study followed women aged 18-60 years from São Paulo, Brazil in 1993-1997 for up to 10 years. Women provided cervical samples for cytology testing and HPV DNA testing at each visit. A redetection was defined as a recurring genotype-specific HPV positive result after 1 or more intervening negative visits. Predictors of genotype-specific redetection were assessed using adjusted hazard ratios (aHR) with Cox regression modeling. RESULTS: In total, 2184 women contributed 2368 incident HPV genotype-specific first detections and 308 genotype-specific redetections over a median follow-up of 6.5 years. The cumulative incidence of redetection with the same genotype was 6.6% at 1 year and 14.8% at 5 years after the loss of positivity of the first detection. Neither age (aHR 0.90; 95% confidence interval [CI], .54-1.47 for ≥45 years vs < 25 years) nor new sexual partner acquisition (aHR 0.98; 95% CI, .70-1.35) were statistically associated with genotype-specific redetection. High-grade squamous intraepithelial lesion prevalence was similar during first HPV detections (2.9%) and redetection (3.2%). CONCLUSIONS: Our findings suggest many HPV redetections were likely reactivations of latent recurring infections.

CD4/CD8 Ratio Outcome According to the Class of the Third Active Drug in Antiretroviral Therapy Regimens: Results From the Quebec Human Immunodeficiency Virus Cohort Study.

BACKGROUND: The impact of different therapeutic classes of drugs in antiretroviral therapy (ART) regimens on the CD4/CD8 ratio is not well documented in people treated for HIV. The objective of this study was to analyze the long-term effect of exposure to integrase strand transfer inhibitor (INSTI) on CD4/CD8 ratio compared with nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) among ART-treated persons with HIV (PWH). METHODS: Data from the Quebec HIV Cohort collected from 31 August 2017 were used. Our analysis included all patients in the cohort who received a first or subsequent ART regimen composed of 2 nucleoside reverse transcriptase inhibitors (NRTIs) and a third active drug of a different class (NNRTI, PI, or INSTI) for at least 16 weeks. Marginal structural Cox models were constructed to estimate the effect of different therapeutic classes on the CD4/CD8 ratio outcome. RESULTS: Among the 3907 eligible patients, 972 (24.9%), 1996 (51.1%), and 939 (24.0%) were exposed to an ART regimen whose third active agent was an NNRTI, PI, or INSTI, respectively. The total follow-up time was 13 640.24 person-years. The weighted hazard ratio for the association between the third active class and CD4/CD8 ratio ≥1 was .56 (95% confidence interval [CI]: .48-.65) for patients exposed to NNRTI + 2 NRTIs and .41 (95% CI: .35-.47) for those exposed to PI + 2 NRTIs, compared with those exposed INSTI + 2 NRTIs. CONCLUSIONS: For people treated for HIV, INSTI-based ART appears to be associated with a higher CD4/CD8 ratio than NNRTI and PI-based ART.

Prevalence and determinants of anemia at discharge in pediatric intensive care survivors.

BACKGROUND: Restrictive transfusion practices are increasingly being followed in pediatric intensive care units (PICU); consequently, more patients are discharged anemic from PICU. Given the possible impact of anemia on long-term neurodevelopmental outcomes, we aim to describe the epidemiology of anemia at PICU discharge in a mixed (pediatric and cardiac) cohort of PICU survivors and to characterize risk factors for anemia. STUDY DESIGN AND METHODS: We performed a retrospective cohort study in the PICU of a multidisciplinary tertiary-care university-affiliated center. All consecutive PICU survivors for whom a hemoglobin level was available at PICU discharge were included. Baseline characteristics and hemoglobin levels were extracted from an electronic medical records database. RESULTS: From January 2013 to January 2018, 4750 patients were admitted to the PICU (97.1% survival); discharge hemoglobin levels were available for 4124 patients. Overall, 50.9% (n = 2100) were anemic at PICU discharge. Anemia at PICU discharge was also common in the cardiac surgery population (53.3%), mainly in acyanotic patients; only 24.6% of cyanotic patients were anemic according to standard definitions of anemia. Cardiac surgery patients were transfused more often and at higher hemoglobin levels than medical and non-cardiac surgery patients. Anemia at admission was the strongest predictor of anemia at discharge (odds ratios (OR): 6.51, 95% confidence interval (CI:5.40;7.85)). DISCUSSION: Half of PICU survivors are anemic at discharge. Further studies are required to determine the course of anemia after discharge and to ascertain whether anemia is associated with adverse long-term outcomes.

Perioperative clinical practice in liver transplantation: a cross-sectional survey.

PURPOSE: The objective of this study was to describe some components of the perioperative practice in liver transplantation as reported by clinicians. METHODS: We conducted a cross-sectional clinical practice survey using an online instrument containing questions on selected themes related to the perioperative care of liver transplant recipients. We sent email invitations to Canadian anesthesiologists, Canadian surgeons, and French anesthesiologists specialized in liver transplantation. We used five-point Likert-type scales (from "never" to "always") and numerical or categorical answers. Results are presented as medians or proportions. RESULTS: We obtained answers from 130 participants (estimated response rate of 71% in Canada and 26% in France). Respondents reported rarely using transesophageal echocardiography routinely but often using it for hemodynamic instability, often using an intraoperative goal-directed hemodynamic management strategy, and never using a phlebotomy (medians from ordinal scales). Fifty-nine percent of respondents reported using a restrictive fluid management strategy to manage hemodynamic instability during the dissection phase. Forty-two percent and 15% of respondents reported using viscoelastic tests to guide intraoperative and postoperative transfusions, respectively. Fifty-four percent of respondents reported not pre-emptively treating preoperative coagulations disturbances, and 91% reported treating them intraoperatively only when bleeding was significant. Most respondents (48-64%) did not have an opinion on the maximal graft ischemic times. Forty-seven percent of respondents reported that a piggyback technique was the preferred vena cava anastomosis approach. CONCLUSION: Different interventions were reported to be used regarding most components of perioperative care in liver transplantation. Our results suggest that significant equipoise exists on the optimal perioperative management of this population.

RéSUMé: OBJECTIF: L'objectif de cette étude était de décrire certaines composantes de la pratique périopératoire en transplantation hépatique telles que rapportées par les cliniciens. MéTHODE: Nous avons mené un sondage transversal sur la pratique clinique à l'aide d'un instrument en ligne comportant des questions sur des thèmes sélectionnés liés aux soins périopératoires des receveurs de greffe du foie. Nous avons envoyé des invitations par courriel à des anesthésiologistes canadiens, des chirurgiens canadiens et des anesthésiologistes français spécialisés en transplantation hépatique. Nous avons utilisé des échelles de type Likert à cinq points (de « jamais ¼ à « toujours ¼) et des réponses numériques ou catégorielles. Les résultats sont présentés sous forme de médianes ou de proportions. RéSULTATS: Nous avons obtenu des réponses de 130 participants (taux de réponse estimé à 71 % au Canada et à 26 % en France). Les répondants ont déclaré utiliser rarement l'échocardiographie transœsophagienne de routine, mais l'utiliser fréquemment pour l'instabilité hémodynamique, souvent en utilisant une stratégie de prise en charge hémodynamique peropératoire axée sur les objectifs, et jamais en utilisant une phlébotomie (médianes des échelles ordinales). Cinquante-neuf pour cent des répondants ont déclaré utiliser une stratégie restrictive de gestion liquidienne pour prendre en charge l'instabilité hémodynamique pendant la phase de dissection. Quarante-deux pour cent et 15 % des répondants ont déclaré utiliser des tests viscoélastiques pour guider les transfusions peropératoires et postopératoires, respectivement. Cinquante-quatre pour cent des répondants ont déclaré ne pas traiter préventivement les troubles préopératoires de la coagulation, et 91 % ont déclaré les traiter en peropératoire uniquement lorsque les saignements étaient importants. La plupart des répondants (48-64 %) n'avaient pas d'opinion sur les temps ischémiques maximaux du greffon. Quarante-sept pour cent des répondants ont déclaré qu'une technique de 'piggyback' (anastomose latéroterminale) était l'approche préférée pour l'anastomose de la veine cave. CONCLUSION: Différentes interventions ont été signalées pour la plupart des composantes des soins périopératoires dans la transplantation hépatique. Nos résultats suggèrent qu'il existe une incertitude significative concernant la prise en charge périopératoire optimale de cette population.

Risk factors for placental human papillomavirus infection.

OBJECTIVE: Human papillomavirus (HPV) has been associated with adverse pregnancy outcomes but placental HPV infection has been rarely studied. The objective was to determine the proportion of HPV-positive placentas and the associated risk factors among HPV-positive women during pregnancy. METHODS: We analysed data from pregnant women enrolled in HERITAGE cohort study between 2010 and 2016 with positive vaginal HPV infection during the first trimester of pregnancy (n=354). Placental swabs and biopsies were collected. HPV genotyping was performed using Linear Array. The predictors of placental HPV detection were identified by generalised estimating equations models. RESULTS: HPV was detected in 78 placentas (22.0%) (one among 96 caesarean sections and 77 among 258 vaginal deliveries). Overall, 91% of HPV-positive placentas were positive for a genotype that was detected in vaginal samples during pregnancy. Among women who delivered vaginally, abnormal cytology (adjusted OR (aOR) 1.78 (95% CI 1.02 to 3.10)), other genitourinary infection (aOR 2.41 (95% CI 1.31 to 4.44)), presence of multiple HPV genotypes in the first trimester (aOR 2.69 (95% CI 1.76 to 4.12)) and persistence of high-risk HPV infections during pregnancy (HPV-16/18: aOR 3.94 (95% CI 2.06 to 7.55) and other than HPV-16/18: aOR 2.06 (95% CI 1.05 to 4.02)) were independently associated with placental HPV. CONCLUSIONS: HPV was frequently detected in the placenta of women who delivered vaginally and may be associated with host immune response characteristics.

Intraoperative phlebotomies and bleeding in liver transplantation: a historical cohort study and causal analysis.

BACKGROUND: Liver transplantation is associated with major bleeding and red blood cell (RBC) transfusions. No well-designed causal analysis on interventions used to reduce transfusions, such as an intraoperative phlebotomy, has been conducted in this population. METHODS: We conducted a historical cohort study among liver transplantations performed from July 2008 to January 2021 in a Canadian centre. The exposure was intraoperative phlebotomy. The outcomes were blood loss, perioperative RBC transfusions (intraoperative and up to 48 hr after surgery), intraoperative RBC transfusions, and one-year survival. We estimated marginal multiplicative factors (MFs), risk differences (RDs), and hazard ratios by inverse probability of treatment weighting both among treated patients and the whole population. Estimates are reported with 95% confidence intervals (CIs). RESULTS: We included 679 patients undergoing liver transplantations of which 365 (54%) received an intraoperative phlebotomy. A phlebotomy did not reduce bleeding, transfusion risks, or mortality when estimated among the treated but reduced bleeding and transfusion risks when estimated among the whole population (MF, 0.85; 95% CI, 0.72 to 0.99; perioperative RD, -15.2%; 95% CI, -26.1 to -0.8; intraoperative RD, -14.7%; 95% CI, -23.2 to -2.8). In a subgroup analysis on 584 patients with end-stage liver disease, slightly larger effects were observed on both transfusion risks when estimated among the whole population while beneficial effects were observed on the intraoperative transfusion risk when estimated among the treated population. CONCLUSION: The use of intraoperative phlebotomy was not consistently associated with better outcomes in all targets of inference but may improve outcomes among the whole population. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT04826666); registered 1 April 2021.

RéSUMé: CONTEXTE: La transplantation hépatique est associée à des saignements importants et à de multiples transfusions de globules rouges (GR). Aucune analyse causale bien conçue sur l'effet d'interventions servant à réduire les transfusions, comme une phlébotomie peropératoire, n'a été menée dans cette population. MéTHODE: Nous avons mené une étude de cohorte historique incluant toutes les transplantations hépatiques réalisées dans un centre canadien de juillet 2008 à janvier 2021. L'exposition d'intérêt était une phlébotomie peropératoire. Les critères d'évaluation étaient le saignement peropératoire, les transfusions de GR périopératoires (peropératoires et jusqu'à 48 heures après la chirurgie), les transfusions de globules rouges peropératoires et la survie à un an. Des facteurs multiplicatifs (FM), des différences de risque (DR) et des rapports de risques instantanés marginaux ont été estimés en utilisant une pondération par l'inverse de la probabilité de traitement parmi les patients traités et parmi l'ensemble de la population. Les effets estimés ont été rapportés avec des intervalles de confiance (IC) à 95 %. RéSULTATS: Nous avons inclus 679 transplantations hépatiques dont 365 (54 %) ont bénéficié d'une phlébotomie peropératoire. La phlébotomie n'a pas réduit les saignements, le risque de transfusion ou la mortalité lorsque ses effets ont été estimés parmi les patients traités, mais a réduit les risques de saignement et de transfusion lorsque ses effets ont été estimés parmi l'ensemble de la population (FM = 0,85 (IC 95 %, 0,72 à 0,99); DR périopératoire = −15,2 % (IC 95 %, −26,1 % à −0,8 %); DR peropératoire = −14,7 % (IC 95 %, −23,2 % à −2,8 %)). Dans une analyse de sous-groupe portant sur 584 patients atteints d'une hépatopathie terminale, des effets légèrement plus importants ont été observés sur les deux risques transfusionnels lorsqu'estimés dans l'ensemble de la population, tandis que des effets bénéfiques ont été observés sur le risque transfusionnel peropératoire lorsqu'estimés parmi les patients traités. CONCLUSION: L'utilisation de la phlébotomie peropératoire n'a pas été systématiquement associée à de meilleurs résultats dans toutes les populations cibles, mais semble améliorer les résultats lorsque les effets sont estimés dans l'ensemble de la population. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT04826666); enregistrée le 1er avril 2021.

Transfusion-related Epstein-Barr virus (EBV) infection: A multicenter prospective cohort study among pediatric recipients of hematopoietic stem cell transplants (TREASuRE study).

BACKGROUND: Epstein-Barr virus (EBV) is carried in the blood of most adults, and transfusion-related infections have been reported. EBV is particularly deleterious in immunosuppressed transplant patients. The aim was to determine if EBV transmission occurred through leukodepleted blood product transfusion in pediatric recipients of hematopoietic stem cell transplants (HSCT). STUDY DESIGN AND METHODS: This prospective Canadian multi-center cohort study includes 156 allogeneic HSCT pediatric recipients. The association between EBV and transfusion was analyzed using Cox regressions. EBV infection, defined by a PCR+ test in the blood of seronegative recipients of an EBV-negative graft, was monitored in order to correlate the recipient EBV strain with that of the blood donors. EBV genotypes were determined by PCR amplification followed by DNA sequencing at two loci (EBNA3b and LMP1). RESULTS: No statistically significant associations were found between transfusions and EBV. One case of post-transplant EBV infection was identified among the 21 EBV-seronegative recipients receiving an EBV-negative graft. A total of 22 blood donors were retraced to determine whether the recipient's EBV strain matched that of a donor. One donor strain showed 100% sequence homology at the EBNA3b locus, but differed by one or two point mutations and by a 132-bp deletion at the LMP1 locus. The blood donor in question was alone among the 22 donors to show amplifiable virus in plasma. Blood from this donor readily produced an immortalized lymphoblastoid cell line in culture. CONCLUSION: While considered a rare event, EBV transmission through transfusion may occur in the context of severe immunosuppression.

Risk factors for post-transplant Epstein-Barr virus events in pediatric recipients of hematopoietic stem cell transplants.

BACKGROUND: Epstein-Barr virus (EBV) can cause severe disease following hematopoietic stem cell transplant (HSCT), including post-transplant lymphoproliferative disorder (PTLD). The objective was to analyze risk factors associated with post-transplant EBV outcomes among pediatric allogeneic HSCT recipients. METHODS: We used data from 156 pediatric allogeneic HSCT recipients enrolled in the Canadian multicenter TREASuRE study. Cox and Prentice-Williams-Petersen models were used to analyze risk factors for post-transplant EBV events including occurrence and recurrence of EBV DNAemia, increase in EBV viral load (EBV-VL), and preemptive use of rituximab, an effective therapy against PTLD. RESULTS: Females were at higher risk for increasing EBV-VL (adjusted hazard ratio (HR) = 2.83 [95% confidence intervals (CI): 1.33-6.03]) and rituximab use (HR = 3.08 [1.14-8.30]), but had the same EBV DNAemia occurrence (HR = 1.21 [0.74-1.99]) and recurrence risks (HR=1.05 [0.70-1.58]) compared to males. EBV DNAemia was associated with recipient pre-transplant EBV seropositivity (HR = 2.47 [1.17-5.21]) and with graft from an EBV-positive donor (HR = 3.53 [1.95-6.38]). Anti-thymocyte globulin (ATG) was strongly associated with all EBV outcomes, including the use of rituximab (HR = 5.33 [1.47-19.40]). Mycophenolate mofetil (MMF) significantly decreased the risk of all EBV events including the rituximab use (HR = 0.13 [0.03-0.63]). CONCLUSION: This study in pediatric allogeneic HSCT patients reveals a reduced risk of all EBV outcomes with the use of MMF. Risk factors for EBV events such as EBV-VL occurrence and recurrence include EBV positivity in the donor and recipient, and use of ATG, whereas risk factors for the most severe forms of EBV outcome (EBV-VL and the use of rituximab) include female sex and ATG use.

Intravenous Immunoglobulin Use In Critically Ill Children.

Purpose: The use of intravenous immunoglobulins (IVIG) has increased significantly in the last decade causing challenges for blood suppliers to respond to the demand. Indications for which IVIG infusion should be given to critically ill children remain unclear. The objective of this study is to characterize the epidemiology of IVIG use in this population. Methods: We performed a single-center retrospective cohort study of all patients aged between 3 days and 18 years who received at least one IVIG infusion while hospitalized in the pediatric intensive care unit of the Centre hospitalier universitaire (CHU) Sainte-Justine, Montréal Quebec (Canada) between January 1, 2013 and December 31, 2018. Results: One hundred and seventy-two patients received a total of 342 IVIG infusions over the study period. Most common indications for IVIG infusions were staphylococcal or streptococcal toxic shock syndrome (n=53/342, 15.5%), immunoglobulin replacement in chylothorax (n=37/342, 10.9%), prophylaxis following bone marrow transplantation (n=31/342, 9.1%), myocarditis (n=25/342, 7.3%) and post-solid organ transplant complications (n=21/342, 6.1%). The median dose of IVIG per infusion was 0.95 g/kg (IQR 0.5-1.0) and median number of IVIG infusions per patient was one (IQR: 1-2). Seventy-nine percent of IVIG infusions given were administrated for off-label indications with regards to Health Canada recommendations. Conclusion: This study identified the most common indications for IVIG infusion in critically ill children in a tertiary care pediatric intensive care unit. Given the costs, the known adverse events associated with IVIG and the pressure that blood suppliers are facing to meet the demands, clinical trials are needed to evaluate the efficacy and safety of IVIG in conditions where use is significant.

Association Between Maternal Human Papillomavirus Infection and Adverse Pregnancy Outcomes: Systematic Review and Meta-Analysis.

BACKGROUND: Experimental studies provide evidence of the harmful effect of human papillomavirus (HPV) infection on pregnancy, but observational studies are inconclusive. We systematically assessed the association between HPV and adverse pregnancy outcomes. METHODS: We searched electronic databases up to December 1, 2019. We included observational studies on the association between HPV and adverse pregnancy outcomes. We conducted a random-effect meta-analysis for each outcome and assessed heterogeneity between studies. RESULTS: From 3034 citations, we included 38 studies and quantitatively synthesized 36 studies. Human papillomavirus was significantly associated with preterm birth (age-adjusted odds ratio [aOR], 1.50; 95% confidence interval [CI], 1.19-1.88), preterm premature rupture of membranes (aOR, 1.96; 95% CI, 1.11-3.45), premature rupture of membranes (aOR, 1.42; 95% CI, 1.08-1.86), intrauterine growth restriction (aOR, 1.17; 95% CI, 1.01-1.37), low birth weight (aOR, 1.91; 95% CI, 1.33-2.76), and fetal death (aOR, 2.23; 95% CI, 1.14-4.37). No significant association was found for spontaneous abortion (aOR, 1.14; 95% CI, 0.40-3.22) and pregnancy-induced hypertensive disorders (aOR, 1.24; 95% CI, 0.80-1.92). Most of the studies were of moderate or low quality, and substantial between-studies heterogeneity remained unexplained. CONCLUSIONS: We found a consistent and significant association between HPV and preterm birth and preterm premature rupture of membranes. Human papillomavirus may also be associated with intrauterine growth restriction, low birth weight, and fetal death, but findings are limited by suboptimal control of biases.

Integrating the prevention of mother-to-child transmission of HIV into primary healthcare services after AIDS denialism in South Africa: perspectives of experts and health care workers - a qualitative study.

BACKGROUND: Integrating Prevention of Mother-to-Child Transmission (PMTCT) programmes into routine health services under complex socio-political and health system conditions is a priority and a challenge. The successful rollout of PMTCT in sub-Saharan Africa has decreased Human Immunodeficiency Virus (HIV), reduced child mortality and improved maternal health. In South Africa, PMTCT is now integrated into existing primary health care (PHC) services and this experience could serve as a relevant example for integrating other programmes into comprehensive primary care. This study explored the perspectives of both experts or key informants and frontline health workers (FHCWs) in South Africa on PMTCT integration into PHC in the context of post-AIDS denialism using a Complex Adaptive Systems framework. METHODS: A total of 20 in-depth semi-structured interviews were conducted; 10 with experts including national and international health systems and HIV/PMTCT policy makers and researchers, and 10 FHCWs including clinic managers, nurses and midwives. All interviews were conducted in person, audio-recorded and transcribed. Three investigators collaborated in coding transcripts and used an iterative approach for thematic analysis. RESULTS: Experts and FHCWs agreed on the importance of integrated PMTCT services. Experts reported a slow and partial integration of PMTCT programmes into PHC following its initial rollout as a stand-alone programme in the aftermath of the AIDS denialism period. Experts and FHCWs diverged on the challenges associated with integration of PMTCT. Experts highlighted bureaucracy, HIV stigma and discrimination and a shortage of training for staff as major barriers to PMTCT integration. In comparison, FHCWs emphasized high workloads, staff turnover and infrastructural issues (e.g., lack of rooms, small spaces) as their main challenges to integration. Both experts and FHCWs suggested that working with community health workers, particularly in the post-partum period, helped to address cases of loss to follow-up of women and their babies and to improve linkages to polymerase-chain reaction (PCR) testing and immunisation. CONCLUSIONS: Despite organised efforts in South Africa, experts and FHCWs reported multiple barriers for the full integration of PMTCT in PHC, especially postpartum. The results suggest opportunities to address operational challenges towards more integrated PMTCT and other health services in order to improve maternal and child health.

No association between early antiretroviral therapy during pregnancy and plasma levels of angiogenic factors: a cohort study.

BACKGROUND: Early antiretroviral therapy (ART) during pregnancy has dramatically reduced the risk of perinatal HIV transmission. However, studies have shown an association between premature delivery and the use of ART during pregnancy (particularly protease inhibitor (PI)-based therapies), which could be explained by placental dysfunction. The objective of this study was to evaluate the association of ART (class, duration of exposure and time of initiation) with placental function by using angiogenic factors placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) as biomarkers. METHODS: Clinical and biological data from 159 pregnant women living with HIV were analyzed. Levels of each biomarker were measured in the first and second trimester of pregnancy. After logarithmic transformation, we compared these using generalized estimating equations according to (a) the type of ART; (b) the duration of exposure to ART; and (c) the time of initiation of ART. RESULTS: After adjusting for variables such as ethnicity, maternal age, gestational age, body mass index, parity, smoking status, and sex of the fetus, we found no significant association between the class of ART (PI-based or not) and serum concentrations of PlGF or sFlt-1. Furthermore, no significant association was found between biomarker levels and the duration of ART exposure or the timing of ART initiation (pre- or post-conception). CONCLUSIONS: This study suggests that first and second trimester angiogenic factor levels are not significantly associated with ART, regardless of the duration or type (with or without PI). These observations seem reassuring when considering the use of ART during early pregnancy.

Associations between Maternal Exposure to Bisphenol A or Triclosan and Gestational Hypertension and Preeclampsia: The MIREC Study.

BACKGROUND: Little is known about the association between bisphenol A (BPA) or triclosan (TCS) exposure and hypertension in pregnancy. OBJECTIVE: To investigate potential associations between maternal urinary concentrations of BPA or TCS and gestational hypertension (GH) and preeclampsia. STUDY DESIGN: Among 1,909 pregnant women participating in the maternal-infant research on environmental chemicals (MIREC) study, urinary concentrations of BPA and TCS were measured in the first trimester by liquid chromatography-tandem mass spectrometry using isotope dilution. Blood pressure was measured during each trimester. Multinomial regression was performed to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CI) for the associations between these phenols and GH and preeclampsia. RESULTS: BPA and TCS were not associated with GH or preeclampsia. However, in multiparous women, BPA (0.50-1.30 µg/L) was associated with decreased risk of GH (aOR =0.45; 95%CI: 0.21-0.98) while among nulliparous women, TCS was associated with an increased risk of GH (3.60-32.60 µg/L; aOR = 2.58; 95% CI: 1.09-6.13 and > 32.60 µg/L: aOR = 2.74; 95% CI: 1.15-6.51). CONCLUSION: BPA and TCS urinary concentrations were not associated with GH or preeclampsia; however, our results suggest an association between TCS and GH in nulliparous women. Additional studies are required to confirm our results.

Impact of Acetic Acid on HPV Testing Using Hybrid Capture 2.

As per the American Society for Colposcopy and Cervical Pathology guidelines, human papillomavirus (HPV) testing is currently used as part of cervical cancer screening and during colposcopy follow-up. The present project evaluated if the application of acetic acid (AA) impacts HPV test results. METHODS: We conducted a prospective nonrandomized interventional study. Participants referred for colposcopy were eligible if immunocompetent, older than 18 years, and not pregnant. Women in group A (controls) received 2 consecutive HPV tests without application of AA. Women in group B had a first HPV sample collected before the application of AA and a second sample collected 3 minutes after application of AA. Samples were tested for HPV DNA with Hybrid Capture 2 (HC2) according to the manufacturer's instructions. RESULTS: From October 17, 2012, to January 10, 2013, approximately 101 women were recruited in 2 colposcopy clinics. In each group, concordance was 98%, with only 1 participant having discordant results (testing negative on the first sample and positive on the second sample). We found no statistically significant difference in relative light units(RLUs) between groups (median of difference, - 0.02 vs -0.05 RLU; p = .93). CONCLUSIONS: The results of this study suggest that acetic acid at concentrations of 3% to 5% and sequential cervical sampling do not modify the result of HPV testing by Hybrid Capture 2.

Risk of Human Papillomavirus (HPV) Infection and Cervical Neoplasia after Pregnancy.

BACKGROUND: Parity is well established as a risk factor for cervical cancer. It is not clear, however, how pregnancy influences the natural history of HPV infection and cervical neoplasia. Our objective was to study the risk of HPV infection and cervical squamous intraepithelial lesions (SIL) after pregnancy. METHODS: We used the Ludwig-McGill cohort study which includes 2462 women recruited in Sao Paulo, Brazil in 1993-97 and followed for up to 10 years. Cellular specimens were collected every 4-6 months for Pap cytology and HPV detection and genotyping by a polymerase chain reaction protocol. Study nurses recorded pregnancy occurrence during follow-up. HPV and Pap results from pregnant women were available before and after, but not during pregnancy. The associations between pregnancy and post-partum HPV infection/SIL were studied using generalized estimating equation models with logistic link. Adjusted odds ratios (OR) were estimated with empirical adjustment for confounding. RESULTS: We recorded 122 women with a history of pregnancy during follow-up. Of these, 29 reintegrated the cohort study after delivery. No association between HPV and pregnancy was found. A single SIL case (high grade SIL) occurred post-partum. Likewise, there was no association between pregnancy and risk of low grade SIL or any-grade SIL at the next visit (adjusted OR = 0.84, 95 % CI: 0.46-15.33) after controlling for confounders. CONCLUSIONS: No associations were found between pregnancy and HPV or LSIL. The single observed case of HSIL post-partum was more than would be expected based on the rate of these abnormalities among non-pregnant women. As this association was found with only one case, caution is required in the interpretation of these results.

Clinical Outcomes Associated With RBC Transfusions in Critically Ill Children: A 1-Year Prospective Study.

OBJECTIVE: To identify the potential complications associated with RBC transfusions. DESIGN: Prospective observational study. SETTING: PICU in a tertiary children's hospital. PATIENTS: All children consecutively admitted to our PICU during a 1-year period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were abstracted from medical charts prospectively. Outcomes possibly attributable to RBC transfusions were looked for daily. In transfused cases, it was considered that an outcome was associated with a transfusion only if it was observed after the first RBC transfusion. During the 1-year study period, 913 consecutive admissions were documented, 842 of which were included. Among them, 144 (17%) were transfused at least once. When comparing transfused cases with nontransfused cases, the odds ratio for new or progressive multiple organ dysfunction syndrome was 5.14 (95% CI, 3.28-8.06; p < 0.001). This association remained statistically significant in the multivariable analysis (odds ratio, 3.85; 95% CI, 2.38-6.24; p < 0.001). Transfused cases were ventilated longer than nontransfused cases (14.1 ± 32.6 vs 4.3 ± 9.6 d, p < 0.001), even after adjustment in a Cox model. The PICU length of stay was significantly increased for transfused cases (12.4 ± 26.2 vs 4.9 ± 10.2 d, p < 0.001), even after controlling for potential confounders. The paired analysis for comparison of pretransfusion and posttransfusion values showed that the arterial partial pressure in oxygen was significantly reduced within the 6 hours after the first RBC transfusion (mean difference, 25.6 torr, 95% CI, 5.7-45.4; p = 0.029). The paired analysis also showed an increased proportion of renal replacement therapy. CONCLUSIONS: RBC transfusions in critically ill children were associated with prolonged mechanical ventilation and prolonged PICU stay. The risk of new or progressive multiple organ dysfunction syndrome was also increased in some transfused children. Furthermore, our study questions the ability of stored RBCs to improve oxygenation in critically ill children. Practitioners should take into account these data when prescribing an RBC transfusion to PICU patients.

Respiratory Dysfunction Associated With RBC Transfusion in Critically Ill Children: A Prospective Cohort Study.

OBJECTIVE: Respiratory complications associated with RBC transfusions may be underestimated in PICUs because current definitions exclude patients with preexisting respiratory dysfunction. This study aims to determine the prevalence and characterize the risk factors and outcomes of new or progressive respiratory dysfunction observed after RBC transfusion in critically ill children. DESIGN: Prospective cohort study of all children admitted over a 1-year period. SETTING: A multidisciplinary PICU in a tertiary pediatric university hospital. PATIENTS: Patients who received a RBC transfusion while in PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two independent adjudicators established the diagnosis of respiratory dysfunction. A respiratory dysfunction associated with transfusion was considered new if it appeared after the first RBC transfusion in PICU. A progressive respiratory dysfunction associated with transfusion was diagnosed if the respiratory dysfunction was present before the transfusion and the PaO2/FIO2 or the SpO2/FIO2 ratio dropped by at least 20% thereafter. Among 842 children admitted into the PICU, 136 received at least one RBC transfusion and were analyzed. Fifty-eight cases of respiratory dysfunction associated with transfusion (43% of transfused patients) were detected, including nine new respiratory dysfunction associated with transfusion (7%) and 49 progressive respiratory dysfunction associated with transfusion (36%). Higher severity of illness, multiple organ dysfunction syndrome prior to transfusion, and volume (mL/kg) of RBC transfusion were independently associated with respiratory dysfunction associated with transfusion. A dose-response relationship was observed between transfusion volume (mL/kg) and the prevalence of respiratory dysfunction associated with transfusion. Patients with respiratory dysfunction associated with transfusion had more progressive multiple organ dysfunction and less ventilation-free and PICU-free days at day 28. CONCLUSIONS: Development of respiratory dysfunction associated with transfusion is frequent in PICU and occurs mainly in patients with prior respiratory dysfunction, who would not be identified using current definitions for transfusion-associated complications. A cause-effect relationship cannot be confirmed. However, the high prevalence and the serious adverse outcomes associated with respiratory dysfunction associated with transfusion suggest that this complication should be further studied.

HPV DNA, E6/E7 mRNA, and p16INK4a detection in head and neck cancers: a systematic review and meta-analysis.

BACKGROUND: We aimed to provide updated information about the global estimates of attributable fraction and type distribution of human papillomavirus (HPV) in head and neck squamous cell carcinomas by doing a systematic review and meta-analysis. METHODS: We did a literature search on PubMed to identify studies that used PCR for detection of HPV DNA in head and neck squamous cell carcinomas with information about HPV genotype distribution. We included studies that tested 20 or more biopsies per cancer site and were published between July 15, 1990, and Feb 29, 2012. We collected information about sex, risk factors, HPV detection methods, and biomarkers of potentially HPV-induced carcinogenesis (E6/E7 mRNA and p16(INK4a)). If it was not possible to abstract the required information directly from the paper, we contacted the authors. We did a meta-analysis to produce pooled prevalence estimates including a meta-regression to explore sources of heterogeneity. FINDINGS: 148 studies were included, contributing data for 12 163 cases of head and neck squamous cell carcinoma from 44 countries. HPV DNA was detected in 3837 cases. HPV16 accounted for 82·2% (95% CI 77·7-86·4) of all HPV DNA positive cases. By cancer site, pooled HPV DNA prevalence estimates were 45·8% (95% CI 38·9-52·9) for oropharynx, 22·1% (16·4-28·3) for larynx (including hypopharynx), and 24·2% (18·7-30·2) for oral cavity. The percent positivity of p16(INK4a) positive cases in HPV-positive oropharyngeal cancer cases was 86·7% (95% CI 79·2-92·9) and of E6/E7 mRNA positive cases was 86·9% (73·2-96·8). The estimate of HPV attributable fraction in oropharyngeal cancer defined by expression of positive cases of E6/E7 mRNA was 39·8% and of p16(INK4a) was 39·7%. Of subsites, tonsils (53·9%, 95% CI 46·4-61·3) had the highest HPV DNA prevalence. HPV DNA prevalence varied significantly by anatomical site, geographic region, but not by sex or tobacco or alcohol consumption. INTERPRETATION: The contribution of HPV prevalence in head and neck squamous cell carcinoma and in particular that of HPV16 in the oropharynx shows the potential benefit of prophylactic vaccines. FUNDING: European Commission.

Prevalence of human papillomaviruses in semen: a systematic review and meta-analysis.

STUDY QUESTION: What is the prevalence of human papillomavirus (HPV) in semen? SUMMARY ANSWER: HPV is present in the semen of asymptomatic men, with a pooled prevalence in a random effects meta-analysis of populations seeking fertility evaluation/treatment of 16%, versus 10% in other populations. WHAT IS KNOWN ALREADY: The main risk of donor insemination (DI) is known to be contamination with an infectious agent. HPV is the necessary cause of cervical cancer, and plays an etiologic role in other anogenital cancers. Although it is known to be prevalent and sexually transmitted, donor semen specimens are not tested for the presence of HPV. STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis of studies published between January 1980 and June 2013 were performed. Variables collected included characteristics of study populations, method of semen preparation, HPV DNA detection and genotyping, HPV types targeted and proportion of HPV positivity. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two investigators independently assessed the studies for inclusion in the review and abstracted the data, while others reviewed the extracted data in detail. Studies were included if they provided data on HPV DNA prevalence in semen and PCR-based methods were used. For the meta-analysis, reports were separated according to the study populations, creating two distinct subgroups: populations seeking fertility evaluation/treatments, and other populations. Data were analysed using a random effects model for each subpopulation. MAIN RESULTS AND THE ROLE OF CHANCE: The literature search identified 285 studies, and in the 27 studies that were included the HPV DNA prevalence in 4029 semen samples varied from 0 to 100%. The three studies focusing on sperm donors identified HPV DNA in 26.3, 7.5 and 16.0% of semen samples. HPV-16 was the most common type overall. The pooled prevalence in a random effects meta-analysis of seven studies focusing on infertile populations was 16% [95% confidence interval (CI): 10-23%] versus 10% (95% CI: 7-14%) in 11 reports focusing on other populations. LIMITATIONS, REASONS FOR CAUTION: First, despite defining clinically relevant subgroups, substantial heterogeneity remained. Secondly, although we retrieved data from reports in English or French only, after reviewing the five reports in other languages only two more could have been added and, as their prevalence estimates were similar to those of studies included in our review, we do not believe that exclusion of these reports biased our results or conclusions. WIDER IMPLICATIONS OF THE FINDINGS: HPV DNA can be found in donor semen and preliminary studies confirm genome activity. For this reason, and although the exact consequences of insemination with HPV-infected semen (cervical infections/lesions, impact on success rate of DI) remain to be clarified, we believe that HPV-infected sperm should be considered a health risk unless well-designed studies prove otherwise. The development and validation of adequate sperm washing techniques before DI appears to be a promising option. STUDY FUNDING/COMPETING INTEREST(S): C.L. and P.M. have no conflicts of interests relevant to the submitted work. H.T. has served as a consultant and on advisory boards and has received speaker fees and travel assistance from Merck-Frosst Canada, Glaxo SmithKline Pharmaceuticals, Belgium and Gilead Sciences. F.C. has received grants through his institution from Merck and Roche, as well as honoraria from Merck and Roche for lectures on HPV. M.-H.M. has received grants though her institution from Merck and Qiagen and lecture honoraria from Merck and GSK for conferences on HPV and best practices in cervical cancer prevention. TRIAL REGISTRATION NUMBER: N/A.