Characterization of the Molecular Determinants of Primary HIV-1 Vpr Proteins: Impact of the Q65R and R77Q Substitutions on Vpr Functions

Although HIV-1 Vpr displays several functions in vitro, limited information exists concerning their relevance during infection. Here, we characterized Vpr variants isolated from a rapid and a long-term non-progressor (LTNP). Interestingly, vpr alleles isolated from longitudinal samples of the LTNP revealed a dominant sequence that subsequently led to diversity similar to that observed in the progressor patient. Most of primary Vpr proteins accumulated at the nuclear envelope and interacted with host-cell partners of Vpr. They displayed cytostatic and proapoptotic activities, although a LTNP allele, harboring the Q65R substitution, failed to bind the DCAF1 subunit of the Cul4a/DDB1 E3 ligase and was inactive. This Q65R substitution correlated with impairment of Vpr docking at the nuclear envelope, raising the possibility of a functional link between this property and the Vpr cytostatic activity. In contradiction with published results, the R77Q substitution, found in LTNP alleles, did not influence Vpr proapoptotic activity

Preservation of native esophagus in infants with pure esophageal atresia has good long-term outcomes despite significant postoperative morbidity

Purpose: To evaluate long-term outcomes of pure esophageal atresia (EA) repair with preservation of native esophagus. Methods: Infants with pure EA treated at our institution (2000-2010) and with minimum 5-year follow-up were reviewed (REB:1000046653). Data analysed included demographics, management and outcomes and are reported as mean ± SD/median (range). Results: Of 185 infants with EA, 12 (7 %) had pure EA (gestational age: 36 ± 2.4 weeks, birth weight: 2353 ± 675 g). Ten had associated anomalies, including trisomy-21 (n = 2) and duodenal atresia (n = 1). Surgery: 1 patient (short gap) underwent primary thoracoscopic anastomosis, 11 had gastrostomy (Stamm, n = 5; image-guided, n = 6) as initial procedure. At definitive repair (age: 128 ± 91 days; weight 5.5 ± 2.3 kg): ten had primary anastomosis and 1 had Collis gastroplasty. No patient had esophageal replacement surgery. Outcomes: three patients had gastrostomy dehiscence requiring re-operation. At post-operative esophagram, seven had anastomotic leak successfully treated conservatively. Seven patients developed strictures requiring balloon dilatations (median two dilatations, range 1-10), six received antireflux surgery. At 7-year follow-up (range 5-15 years), all patients had the gastrostomy closed and were on full oral feeds. Conclusions: The management of pure EA continues to be challenging. The preservation of native esophagus is possible with significant morbidity. The long-term outcomes are favourabl

Outcome of esophageal atresia/tracheoesophageal fistula in extremely low birth weight neonates (<1000Â grams)

Purpose To review the outcomes of extremely low birth weight (ELBW, <1000 g) infants with esophageal atresia/tracheoesophageal fistula (EA/TEF). Methods Health records of ELBW EA/TEF infants treated at our institution from 2000 to 2014 were reviewed (REB1000046653). Demographics, operative approach and postoperative complications were analyzed. Data are reported as median (range). Results Of 268 EA/TEF infants, 8 (3 %, five females) were ELBW (930 g, 540–995). Gestational age was 28 weeks (23–32). Seven had type-C EA/TEF and one type B. Outcomes One trisomy 18 infant received no treatment and died; one initially diagnosed as type A had primary repair at 126 days of life (DOL); six underwent TEF ligation (three trans-pleural) with primary repair in one and delayed anastomosis in two (DOL 120 and 178). The remaining three died (gastrostomy dehiscence and peritonitis, liver hemorrhage during peritoneal drain insertion, severe chronic lung disease and brain hemorrhages). At a median follow-up of 3 years (range 15 months–5 years), all survivors are thriving. Conclusion ELBW infants with EA/TEF are rare and result in high morbidity and mortality. Mortality is mainly related to complications not associated with EA/TEF repair. Fistula ligation followed by delayed anastomosis seems to achieve a better outcome in ELBW infants

Survival in very preterm infants with congenital diaphragmatic hernia and association with prenatal imaging markers: A retrospective cohort study

Objectives: To describe the outcomes of preterm born infants with congenital diaphragmatic hernia (CDH; ≤32.0 weeks of gestation) and the associations between prenatal imaging markers and survival. Design: Retrospective cohort study. Setting: Multicentre study in large referral centres. Population: Infants with an isolated unilateral CDH, live born at 32.0 weeks or less of gestation, between January 2009 and January 2020. Methods: Neonatal outcomes were evaluated for infants that were expectantly managed during pregnancy and infants that underwent fetoscopic endoluminal tracheal occlusion (FETO) therapy, separately. We evaluated the association between prenatal imaging markers and survival to discharge. Prenatal imaging markers included observed to expected lung-to-head ratio (o/e LHR), side of the defect, liver position, stomach position grade, and observed to expected total fetal lung volume (o/e TFLV). Main Outcome Measure: Survival to discharge. Results: We included 53 infants born at 30 +4 (interquartile range 29 +1–31 +2) weeks. Survival in fetuses expectantly managed during pregnancy was 48% (13/27) in left-sided CDH and 33% (2/6) in right-sided CDH. Survival in fetuses that underwent FETO therapy was 50% (6/12) in left-sided CDH and 25% (2/8) in right-sided CDH. The o/e LHR at baseline was positively associated with survival in cases expectantly managed during pregnancy (odds ratio [OR] 1.20, 95% CI 1.07–1.42, p < 0.01), but not in cases that received FETO therapy (OR 1.01, 95% CI 0.88–1.15, p = 0.87). Stomach position grade (p = 0.03) and o/e TFLV were associated with survival (p = 0.02); liver position was not (p = 0.13). Conclusions: In infants with CDH born at or before 32 weeks of gestation, prenatal imaging markers of disease severity were associated with postnatal survival