Being on hemodialysis during the COVID‐19 outbreak: A mixed‐methods’ study exploring the impacts on dialysis adequacy,analytical data,and patients’ experiences

For individuals with end‐stage renal disease (ESRD), the novel coronavirus can present several additional challenges in disease self‐management. This study aimed to explore the impacts of the COVID‐19 pandemic in non‐COVID‐19 patients with ESRD undergoing in‐center hemodialysis (HD). A mixed‐methods study was conducted with a purposive sample recruited from one dialysis unit in Portugal. Quantitative data were collected retrospectively from patients' medical records from February 2020 (T1—before the outbreak) and from April 2020 (T2—during lockdown). Semi‐structured interviews were conducted with 20 patients (66.9 ± 11.9 years old) undergoing HD for an average of 46.1 months (±39.5) in April 2020. Overall results suggested that dialysis adequacy and serum albumin levels decreased significantly at T2, while phosphorus levels increased. The findings from thematic analysis suggested several psychosocial negative impacts and impacts on disease and treatment‐related health behaviors (eg, difficulties managing dietary restrictions during the lockdown and diminished physical activity), which can partially explain these quantitative results. However, some patients were also able to find positive impacts in this experience and problem‐focused and emotional strategies were identified to cope with the demands of COVID‐19. Several recommendations have been made to mitigate patients’ emotional, relational, and educational unmet needs during the current pandemic and in the event of new outbreaks.     

Human liver stem cell-derived extracellular vesicles reduce injury in a model of normothermic machine perfusion of rat livers previously exposed to a prolonged warm ischemia

Livers from donors after circulatory death (DCD) are a promising option to increase the donor pool, but their use is associated with higher complication rate and inferior graft survival. Normothermic machine perfusion (NMP) keeps the graft at 37°C, providing nutrients and oxygen supply. Human liver stem cell-derived extracellular vesicles (HLSC-EVs) are able to reduce liver injury and promote regeneration. We investigated the efficacy of a reconditioning strategy with HLSC-EVs in an experimental model of NMP. Following total hepatectomy, rat livers were divided into 4 groups: (i) healthy livers, (ii) warm ischemic livers (60 min of warm ischemia), (iii) warm ischemic livers treated with 5 × 10⁸ HLSC-EVs/g-liver, and (iv) warm ischemic livers treated with a 25 × 10⁸ HLSC-EVs/g-liver. NMP lasted 6 h and HLSC-EVs (Unicyte AG, Germany) were administered within the first 15 min. Compared to controls, HLSC-EV treatment significantly reduced transaminases release. Moreover, HLSC-EVs enhanced liver metabolism by promoting phosphate utilization and pH self-regulation. As compared to controls, the higher dose of HLSC-EV was associated with significantly higher bile production and lower intrahepatic resistance. Histologically, this group showed reduced necrosis and enhanced proliferation. In conclusion, HLSC-EV treatment during NMP was feasible and effective in reducing injury in a DCD model with prolonged warm ischemia.     

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.     

Endoscopic internal drainage for the management of leak,fistula, and collection after sleeve gastrectomy: our experience in 617 consecutive patients

BackgroundEndoscopy plays a pivotal role in the management of adverse events (AE) following bariatric surgery. Leaks, fistulae, and post-operative collection after sleeve gastrectomy (SG) may occur in up to 10% of cases.ObjectivesTo evaluate the efficacy and safety of endoscopic internal drainage (EID) for the management of leak, fistula, and collection following SG.SettingRetrospective, observational, single center study on patients referred from several bariatric surgery departments to an endoscopic referral center.MethodsEID was used as first-line treatment for the management of leaks, fistulae, and collections. Leaks and fistulae were treated with double pigtail stent (DPS) deployment in order to guarantee internal drainage and second intention cavity obliteration. Collections were treated with endoscropic ultrasound (EUS)–guided deployment of DPS or lumen apposing metal stents.ResultsA total of 617 patients (83.3% female; mean age, 43.1 yr) were enrolled in the study for leak (n = 300, 48.6%), fistula (n = 285, 46.2%), and collection (n = 32, 5.2%). Median follow-up was 19.5 months. Overall clinical success was 84.7% whereas 15.3% of cases required revisional surgery after EID failure. Clinical success according to type of AE was 89.5%, 78.5%, and 90% for leak, fistula, and collection, respectively. A total of 10 of 547 (1.8%) presented a recurrence during follow-up. A total of 28 (4.5%) AE related to the endoscopic treatment occurred. At univariate logistic regression predictors of failure were: fistula (OR 2.012), combined endoscopic approach (OR 2.319), need for emergency surgery (OR 1.755), and previous endoscopic treatment (OR 4.818).ConclusionEarly EID for the management of leak, fistula, and post-operative collection after SG seems a safe and effective first-line approach with good long-term results.     

Impact of COVID‐19 on wound care in Germany

Recent studies showed that the COVID‐19 pandemic caused collateral damage in health care in terms of reduced hospital submissions or postponed treatment of other acute or chronic ill patients. An anonymous survey was sent out by mail to patients with chronic wounds in order to evaluate the impact of the pandemic on wound care. Sixty‐three patients returned the survey. In 14%, diagnostic workup or hospitalisation was cancelled or postponed. Thirty‐six percent could not seek consultation by their primary care physician as usual. The use of public transport or long travel time was not related to limited access to medical service (P = .583). In ambulatory care, there was neither a significant difference in the frequency of changing wound dressings (P = .67), nor in the person, who performed wound care (P = .39). There were no significant changes in wound‐specific quality of life (P = .505). No patient used telemedicine in order to avoid face‐to‐face contact or anticipate to pandemic‐related restrictions. The COVID‐19 pandemic impaired access to clinical management of chronic wounds in Germany. It had no significant impact on ambulatory care or wound‐related quality of life. Telemedicine still plays a negligible role in wound care.     

Craniofacial Development: Neural Crest in Molecular Embryology

Craniofacial development, one of the most complex sequences of developmental events in embryology, features a uniquely transient, pluripotent stem cell-like population known as the neural crest (NC). Neural crest cells (NCCs) originate from the dorsal aspect of the neural tube and migrate along pre-determined routes into the developing branchial arches and frontonasal plate. The exceptional rates of proliferation and migration of NCCs enable their diverse contribution to a wide variety of craniofacial structures. Subsequent differentiation of these cells gives rise to cartilage, bones, and a number of mesenchymally-derived tissues. Deficiencies in any stage of differentiation can result in facial clefts and abnormalities associated with craniofacial syndromes. A small number of conserved signaling pathways are involved in controlling NC differentiation and craniofacial development. They are used in a reiterated fashion to help define precise temporospatial cell and tissue formation. Although many aspects of their cellular and molecular control have yet to be described, it is clear that together they form intricately integrated signaling networks required for spatial orientation and developmental stability and plasticity, which are hallmarks of craniofacial development. Mutations that affect the functions of these signaling pathways are often directly or indirectly identified in congenital syndromes. Clinical applications of NC-derived mesenchymal stem/progenitor cells, persistent into adulthood, hold great promise for tissue repair and regeneration. Realization of NCC potential for regenerative therapies motivates understanding of the intricacies of cell communication and differentiation that underlie the complexities of NC-derived tissues.     

Validation of the Mayo Adhesive Probability score as a predictor of adherent perinephric fat and outcomes in open partial nephrectomy

BackgroundAdherent perinephric fat (APF) contributes to surgical complexity and can be associated with adverse perioperative outcomes for partial nephrectomy (PN). The Mayo Adhesive Probability (MAP) score accurately predicts the presence of APF during robotic-assisted partial nephrectomy (RAPN). Our primary aim is to validate MAP score as a predictor of APF in open partial nephrectomy (OPNx).MethodsWe reviewed 105 consecutive OPNx (100 patients) performed by a single surgeon with intraoperative determination of APF. We evaluated the ability of the MAP score to discriminate between those with APF and those without APF by estimating the area under the receiver operating characteristic curve (AUROCC). The association of perioperative outcomes with APF was evaluated as well.ResultsForty-three patients [49%; 95% confidence interval (CI), 39–59%] had intraoperative identification of APF. The MAP score had excellent ability to predict APF in OPNx (AUROCC, 0.82; 95% CI, 0.74–0.92). APF was observed in 6% of patients with a MAP score of 0-1, 27% with score 2, 52% with score 3, 75% with score 4, and 90% with score 5. The presence of APF was associated with longer operative times (P=0.004) and higher estimated blood loss (EBL) (P=0.003). Although not statistically significant, our study did suggest that APF may be associated with postoperative complications and prolonged length of stay (LOS) (>3 days).ConclusionsMAP score accurately predicts the presence of APF in patients undergoing OPNx. APF is associated with longer operative time and higher blood loss in OPNx.     

Bystander CD8 T-cell-mediated demyelination is interferon-gamma-dependent in a coronavirus model of multiple sclerosis

Mice infected with the coronavirus mouse hepatitis virus, strain JHM (JHM) develop a disease that shares many histological characteristics with multiple sclerosis. We previously demonstrated that JHM-infected mice that only have CD8 T cells specific for an epitope not in the virus develop demyelination on specific activation of these cells. Herein we show that this process of bystander T-cell-mediated demyelination is interferon-gamma (IFN-gamma)-dependent. The absence of IFN-gamma abrogated demyelination but did not change T-cell infiltration or expression levels of inflammatory cytokines or chemokines in the spinal cord. These results are consistent with models in which IFN-gamma contributes to CD8 T-cell-mediated demyelination by activation of macrophages/microglia, the final effector cells in the disease process.     

An open-randomized clinical trial of selegiline in amyotrophic lateral sclerosis

Based on the hypothesis that free radicals play a general role in the neurodegenerative process in motor neuron disease, we tested selegiline in a group of patients affected by amyotrophic lateral sclerosis (ALS) to examine whether it might modify the progression of the disease. Patients were admitted if they were 25–80 years old and had a confirmed diagnosis of ALS with symptoms lasting no longer than 24 months. Patients with familial ALS, pure progressive bulbar palsy, primary lateral sclerosis or progressive muscle atrophy were excluded; a total of 111 patients were recruited. Fifty-three patients were randomly assigned to receive the drug (selegiline 10 mg/day orally for 6 months) and the remaining 58 were considered ALS controls. Mortality was similar in the two groups (4 and 5 patients respectively), though the difference was not statistically significant. Among the survivors, mean MRC and Norris disability scores and forced vital capacity were fairly similar in the two groups at all times and no statistically significant difference between treated and untreated patients was found. The results did not change when the data were related to age, duration and characteristics of onset of the disease. The rate of progression was significantly more rapid in patients with bulbar symptoms in both groups. Our data do not show any significant effect of selegiline in modifying the progression of ALS.     

Plasma concentrations and renal clearance of orotic acid in argininosuccinic acid synthetase deficiency

Argininosuccinic acid synthetase deficiency (ASD) is a rare disorder of urea cycle metabolism, with pronounced citrullinemia and orotic aciduria being characteristic biochemical features. To further investigate the role of plasma orotic acid and its possible use for monitoring the metabolic status in ASD, we determined plasma orotic acid, amino acid, and ammonium levels in plasma samples collected over a period of 3 years from a patient who is now 8 years of age. Orotic acid plasma concentrations varied widely from less than 1 μmol/l to more than 60 μmol/l. The renal clearance of orotic acid was eightfold the glomerular filtration rate, thus supporting an active mechanism underlying the excretion of this pyrimidine. Data obtained during a metabolic crisis yielded a statistically significant linear correlation of orotic acid plasma levels with those of glutamine and ammonium, which are generally accepted for assessment of the successful treatment of this disorder. Our data revealed no advantage of plasma orotic acid concentrations over the established amino acids (glutamine and arginine) and ammonium for determining acute treatment responses. Since several effects of high levels of orotic acid have been described in mammals, further research is necessary to assess a possible contribution of orotic acid to the pathogenesis of ASD and the use of plasma orotic acid levels in the long-term monitoring of these patients. Received: 3 November 1998 / Revised: 3 May 1999 / Accepted: 3 May 1999