Early and late paternal contribution to cell division of embryos in a time-lapse imaging incubation system

The objective of this study was to investigate the impact of male age, semen quality and days of ejaculatory abstinence on embryo morphokinetics. A total of 1,220 zygotes obtained from 139 couples in a private in vitro fertilisation centre were analysed. The timing of specific events from the point of insemination, such as timings to pronuclei appearance and fading, to two, three, four, five, six, seven and eight cells and to blastulation were recorded. Multivariate linear regression analysis was used to evaluate the influence of paternal factors on embryo morphokinetic events. Paternal age was positively correlated with delayed cell cleavage and blastulation, and negatively associated with implantation rate, and clinical pregnancy and live–birth chances. The ejaculatory abstinence was inversely correlated with the implantation rate. Inverse relationships were observed between semen parameters (sperm count, progressive sperm motility, total motile sperm count and morphology) and the timing of specific events during embryo development. Sperm morphology was also positively associated with implantation rate and pregnancy and live–birth chances. Increased paternal age and ejaculatory abstinence, and poor semen quality correlate with delayed cell cleavage and blastulation and negatively impact intracytoplasmic sperm injection outcomes.     

Ectopic Calcification and Hypophosphatemic Rickets: Natural History of ENPP1 and ABCC6 Deficiencies

Generalized arterial calcification of infancy (GACI) is a rare disorder caused by ENPP1 or ABCC6 variants. GACI is characterized by low pyrophosphate, arterial calcification, and high mortality during the first year of life, but the natural course and possible differences between the causative genes remain unknown. In all, 247 individual records for patients with GACI (from birth to 58.3 years of age) across 19 countries were reviewed. Overall mortality was 54.7% (13.4% in utero or stillborn), with a 50.4% probability of death before the age of 6 months (critical period). Contrary to previous publications, we found that bisphosphonate treatment had no survival benefit based on a start-time matched analysis and inconclusive results when initiated within 2 weeks of birth. Despite a similar prevalence of GACI phenotypes between ENPP1 and ABCC6 deficiencies, including arterial calcification (77.2% and 89.5%, respectively), organ calcification (65.8% and 84.2%, respectively), and cardiovascular complications (58.4% and 78.9%, respectively), mortality was higher for ENPP1 versus ABCC6 variants (40.5% versus 10.5%, respectively; p = 0.0157). Higher prevalence of rickets was reported in 70.8% of surviving affected individuals with ENPP1 compared with that of ABCC6 (11.8%; p = 0.0001). Eleven affected individuals presenting with rickets and without a GACI diagnosis, termed autosomal recessive hypophosphatemic rickets type 2 (ARHR2), all had confirmed ENPP1 variants. Approximately 70% of these patients demonstrated evidence of ectopic calcification or complications similar to those seen in individuals with GACI, which shows that ARHR2 is not a distinct condition from GACI but represents part of the spectrum of ENPP1 deficiency. Overall, this study identified an early mortality risk in GACI patients despite attempts to treat with bisphosphonates, high prevalence of rickets almost exclusive to ENPP1 deficiency, and a spectrum of heterogenous calcification and multiple organ complications with both ENPP1 and ABCC6 variants, which suggests an overlapping pathology. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). This article has been contributed to by US Government employees and their work is in the public domain in the USA.     

500 Consecutive Liver Transplants: The Outcomes of a New Transplantation Program in the Middle West of Brazil

IntroductionLiver transplantation is the standard treatment for end-stage liver disease. Brazil holds the third highest number of liver transplants performed per year, but center maldistribution results in high discrepancies in accessing this treatment. In 2012, an interstate partnership successfully implemented a new liver transplantation program in the middle west of Brazil. Here, we report the results of the first 500 liver transplants performed in this new program and discuss the impacts of a new transplant center in regional transplantation dynamics.MethodsWe reviewed data from the first 500 consecutive deceased donor liver transplants performed in the new program during an 8-year period. We analyzed data on patients’ clinical and demographic profiles, postoperative outcomes, and graft and recipient survival rates. Univariate survival analysis was conducted using log-rank tests to compare the groups.ResultsAlmost half (48%) of the procured organs and 40% of the recipients transplanted in our center were from outside our state. Recipient 30-day mortality was 9%. Overall recipient survival at 1 year and 5 years was 85% and 80%, respectively. Mortality was significantly associated with higher Model for End-Stage Liver Disease (P < .001) but not with the presence of hepatocellular carcinoma (P = .795).DiscussionThe new transplantation program treated patients from different regions of Brazil and became the reference center in liver transplantation for the middle west region. Despite the recent implementation, our outcomes are comparable to experienced centers around the world. This model can inspire the creation of new transplantation programs aiming to democratize access to liver transplantation nationwide.     

Hematoma subdural intracraneal tras punción dural accidental: caso clínico

Intracranial subdural hematoma is a rare, but potentially lethal complication of neuraxial procedures. Considering the high frequency of neuraxial techniques in the obstetric population, parturients are more susceptible to this fearful complication. The diagnosis is often masked and delayed because it shares similar clinical characteristics with posdural puncture headache, with headache being the most common symptom. This case report describes a timely diagnosis and successful management of an intracranial subdural hematoma, after unintentional dural puncture during labour epidural analgesia. Postpartum headache following epidural analgesia, remains a clinical challenge for the caring team, requiring a close follow-up and awareness for non-benign causes that require prompt management, avoiding devastating consequences.     

Donor Choriocarcinoma Transmission From Solid Organ Transplantation: A Case Report

Transplantation of any organ has some inherent risk of disease transmission, such as infection and malignancy. The present study aims to describe 2 cases of choriocarcinoma transmission after kidney and liver transplantation originating from the same patient. The donor was a 17-year-old woman who died of cerebral hemorrhage. Both organ recipients died of metastatic choriocarcinoma few months after the transplantation, within days after starting chemotherapy. Retrospective hCG (human chorionic gonadotropin hormone) analysis in donor's blood stored at the time of donation had a result of 9324 mIU/mL. Despite its rarity, clinicians should be aware of the risk of transplant-related choriocarcinoma from female donors in childbearing age. In some cases, hCG dosage should be performed before donation.     

Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice

Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1^asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1^asj/asj mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1^asj/asj mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1^asj/asj mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Surgical resection for non-Asian intrahepatic lithiasis: The Brazilian experience

BackgroundIntrahepatic lithiasis (IHL) is a rare disease in the western world. Complications associated with IHL include acute cholangitis, liver atrophy, secondary biliary cirrhosis, and risk for intrahepatic cholangiocarcinoma. Liver resection is considered the treatment of choice for IHL. The objective of this study was to analyze patients who underwent liver resection for non-Asian hepatolithiasis.Methods127 patients with symptomatic non-Asian hepatolithiasis underwent resection in six institutions. Demographic data, clinical presentation, diagnosis, classification according to stone location, presence of atrophy, bile duct stricture, biliary cirrhosis, incidence of cholangiocarcinoma, treatment and postoperative course were evaluated.Results52 patients (40.9%) were male and the mean age was 46.1 years. Sixty-six patients (51.9%) presented with history of cholangitis. Stones were located in the left lobe in 63 (49.6%), and right lobe in 28 patients (22.0%). Atrophy was observed in 31 patients (24.4%) and biliary stenosis in 18 patients (14.1%). The most common procedure performed was left lateral sectionectomy in 63 (49.6%) patients, followed by left hepatectomy in 36 (28.3%), right hepatectomy in 19 (15.0%), and associated hepaticojejunostomy in 28 (22.0%). Forty-two patients (33.0%) presented postoperative complications and the most common were biliary fistula (13.3%) and surgical site infection (7.0%). Postoperative mortality was 0.7%. Intrahepatic cholangiocarcinoma was observed in 2 patients (1.5%). Recurrence was identified in 10 patients (7.8%), mostly with bilateral stones and/or hepaticojejunostomy.ConclusionLiver resection is the standard treatment for symptomatic unilateral or complicated IHL with good operative results. Risk of cholangiocarcinoma was low in non-Asian patients.     

Safety and immunogenicity of adjuvanted recombinant subunit herpes zoster vaccine in lung transplant recipients

Lung transplant recipients are at high risk for herpes zoster and preventive measures are a significant unmet need. We investigated the safety and immunogenicity of two doses of a recombinant zoster vaccine (RZV) in lung transplant recipients (≥50 years). We enrolled 50 patients of which 49 received at least one vaccine dose. Anti-glycoprotein E (gE) antibody levels (n = 43) increased significantly compared to baseline (median optical density [OD] 1.96; interquartile range [IQR]: 1.17–2.89) after the first (median OD 3.41, IQR 2.54–3.81, p < .0001) and second vaccine dose (median OD 3.63, IQR 3.39–3.86, p < .0001). gE-specific polyfunctional CD4+ T cell frequencies (n = 38) also increased from baseline (median 85 per 10⁶ CD4+ T cells; IQR: 46–180) to the first (median 128 per 10⁶ CD4+ T cells; IQR: 82–353; p = .023) and after the second dose (median 361 per 10⁶ CD4+ T cells; IQR: 146–848; p < .0001). Tenderness (83.0%; 95%CI: 69.2–92.4%) and redness (31.9%; 95%CI: 19.1–47.1%) at injection site were common. One rejection episode within 3 weeks of vaccination was observed. This is the first study demonstrating that RZV was safe and elicited significant humoral and cell-mediated immunity in lung transplant recipients. RZV is a new option for the prevention of shingles in this population.     

Anesthesia using microcannula and sharp needle in upper blepharoplasty: A randomized,double-blind clinical trial evaluating pain,bruising, and ecchymoses

IntroductionWith the emergence of blunt-tipped microcannulas, there is a hypothesis that these could cause less damage and reduce pain as compared to conventional sharp needles in eyelid surgery. The purpose is to determine whether an 18G blunt-tipped cannula can be better than a 26G needle.MethodsThis prospective, observer-blinded, randomized clinical trial was conducted from June 2017 to December 2018. Sixty-eight patients were randomized to receive local anesthesia injections for upper blepharoplasty. Infiltration was performed by using a 26-gauge sharp needle on one side and on the other side, infiltration was performed by using an 18-gauge stainless-steel blunt-tipped microcannula. A numeric rating scale (NRS) from 0 to 10 was used to blindly assess pain in patients receiving anesthesia injections with both needle types. Photographs of the eyelids of each patient were taken in five different periods and used by three blinded observers to identify bruise or ecchymoses.ResultsA total of 136 eyelid operations were performed. There was no statistically significant difference when both groups were compared; however, the average score of pain was higher in patients taking the infiltration through the needle (2.85 versus 2.50). Regarding the evaluation of bruising and ecchymoses, the results showed that, in the five periods evaluated, there was no statistical difference in bruising and ecchymosis in the eyelids when taking the infiltration through a sharp needle when compared with that of the eyelids taking infiltration through a (blunt-tipped) microcannula.ConclusionThe evaluation of the blunt-tipped microcannula showed a lower pain score mean than that obtained for the sharp needle (2.5 versus 2.85) (p > 0.05). There was no statistically significant difference in the bruising and ecchymosis courses.