Pluripotent Very Small Embryonic-Like Stem Cells in Adult Testes – An Alternate Premise to Explain Testicular Germ Cell Tumors

Developmental exposure to endocrine disruptors has resulted in the increased incidence of infertility and testicular germ cell tumors (T2GCT) in young men residing in developed countries. Unlike T1GCT (infants and young children) and T3GCT (aged men), T2GCT arise from CIS/GCNIS that develops from pre-CIS. Pre-CIS represents undifferentiated, growth-arrested gonocytes that persist in fetal testes due to endocrine disruption. However, whether pre-CIS truly exist, do CIS develop into T2GCT, why no CIS in T1GCT/T3GCT, why germ cell tumors (GCT) also occur along midline at extra-gonadal sites, why T1GCT show partial erasure and T2GCT show complete erasure of genomic imprints are open questions that are awaiting answers. We propose that rather than pre-CIS, pluripotent, very small embryonic-like stem cells (VSELs) get affected by exposure to endocrine disruption. Since VSELs are developmentally equivalent to primordial germ cells (PGCs), T2GCT cells show complete erasure of genomic imprints and CIS represents growth-arrested clonally expanding stem/progenitor cells. PGCs/VSELs migrate along the midline to various organs and this explains why GCT occur along the midline, T1GCT show partial erasure of imprints as they develop from migrating PGCs. T3GCT possibly reflects effects of aging due to compromised differentiation and expansion of pre-meiotic spermatocytes. Absent spermatogenesis in pre-pubertal and aged testes explains absence of CIS in T1GCT and T3GCT. Endocrine disruptors possibly alter epigenetic state of VSELs and thus rather than maintaining normal tissue homeostasis, VSELs undergo increased proliferation and compromised differentiation resulting in reduced sperm count, infertility and TGCT. This newly emerging understanding offers alternate premise to explain TGCT and warrants further exploration.     

Use of Tunneled-Cuffed Central Catheters in Patients with Cancer: A Single-Center Experience

Background

Effective and reliable venous access is among the cornerstones of modern medical therapy in oncology.

Angelman syndrome in adolescence and adulthood: A retrospective chart review of 53 cases

Angelman syndrome is a neurogenetic disorder with varying clinical presentations and symptoms as the individual ages. The goal of this study was to characterize changes over time in the natural history of this syndrome in a large population. We reviewed the medical records of the 53 patients who were born prior to 2000 and seen at the Angelman Syndrome Clinic at Massachusetts General Hospital to assess neurological, sleep, behavioral, gastrointestinal, orthopedic, and ophthalmologic functioning. The average age of this cohort was 24 years. Active seizures were present in 35%, nonepileptic myoclonus in 42%, and clinically significant tremors in 55%. Anxiety was present in 57%, increasing to 71% in those ages 26–43 years. In terms of sleep, 56% reported 8 hr of sleep or more, although 43% reported frequent nocturnal awakenings. Gastrointestinal issues remain problematic with 81% having constipation and 53% gastroesophageal reflux. The majority lived in a parent's home and remained independently mobile, though scoliosis was reportedly present in 30%, and 20% had reported low bone density/osteoporosis. The results of this study suggest that the prevalence of active seizures may decrease in adulthood but that the prevalence of movement disorders such as tremor and nonepileptic myoclonus may increase. Anxiety increases significantly as individuals age while defiant behaviors appear to decrease. Sleep dysfunction typically improves as compared to childhood but remains a significant issue for many adults. Other areas that require monitoring into adulthood include gastrointestinal dysfunction, and orthopedic/mobility issues, such as reported scoliosis and bone density, and ophthalmologic disorders.     

The Diagnostic Dilemma of a Parasympathetic Schwannoma in the Submandibular Gland

Schwannomas are benign soft tissue tumours that arise from nerve sheath cells. They are rare in the salivary glands and are thought to arise from the parasympathetic nerves. We report the case of a 69-year-old man who presented with a painless right submandibular mass that appeared to resemble a pleomorphic adenoma on ultrasonography and, on this basis, proceeded to surgical excision of the gland. We review the relevant literature and highlight the diagnostic pitfalls.     

Transnasal Humidified Rapid‐Insufflation Ventilatory Exchange (THRIVE): a physiological method of increasing apnoea time in patients with difficult airways

Emergency and difficult tracheal intubations are hazardous undertakings where successive laryngoscopy–hypoxaemia–re‐oxygenation cycles can escalate to airway loss and the ‘can't intubate, can't ventilate’ scenario. Between 2013 and 2014, we extended the apnoea times of 25 patients with difficult airways who were undergoing general anaesthesia for hypopharyngeal or laryngotracheal surgery. This was achieved through continuous delivery of transnasal high‐flow humidified oxygen, initially to provide pre‐oxygenation, and continuing as post‐oxygenation during intravenous induction of anaesthesia and neuromuscular blockade until a definitive airway was secured. Apnoea time commenced at administration of neuromuscular blockade and ended with commencement of jet ventilation, positive‐pressure ventilation or recommencement of spontaneous ventilation. During this time, upper airway patency was maintained with jaw‐thrust. Transnasal Humidified Rapid‐Insufflation Ventilatory Exchange (THRIVE) was used in 15 males and 10 females. Mean (SD [range]) age at treatment was 49 (15 [25–81]) years. The median (IQR [range]) Mallampati grade was 3 (2–3 [2–4]) and direct laryngoscopy grade was 3 (3–3 [2–4]). There were 12 obese patients and nine patients were stridulous. The median (IQR [range]) apnoea time was 14 (9–19 [5–65]) min. No patient experienced arterial desaturation < 90%. Mean (SD [range]) post‐apnoea end‐tidal (and in four patients, arterial) carbon dioxide level was 7.8 (2.4 [4.9–15.3]) kPa. The rate of increase in end‐tidal carbon dioxide was 0.15 kPa.min^?1. We conclude that THRIVE combines the benefits of ‘classical’ apnoeic oxygenation with continuous positive airway pressure and gaseous exchange through flow‐dependent deadspace flushing. It has the potential to transform the practice of anaesthesia by changing the nature of securing a definitive airway in emergency and difficult intubations from a pressured stop–start process to a smooth and unhurried undertaking.     

Preserving Residual Renal Function in Dialysis: What We Know

Residual renal function confers a survival benefit among dialysis patients thought to be related to greater volume removal and solute clearance. Whether the presence of residual renal function is protective or merely a marker for better health is not clear. The basic mechanisms governing the decline or persistence of residual renal function are poorly understood and few studies have examined the role of medical therapy in its preservation. Dialysis modality, inflammatory processes often associated with comorbid diseases (including diabetes mellitus and obesity), volume dysregulation, and vitamin D deficiency are predictive of residual renal function decline. We review potential mechanisms for preservation of remaining glomerular filtration rate among chronic dialysis patients.