An update on red blood cell storage lesions,as gleaned through biochemistry and omics technologies

Red blood cell (RBC) aging in the blood bank is characterized by the accumulation of a significant number of biochemical and morphologic alterations. Recent mass spectrometry and electron microscopy studies have provided novel insights into the molecular changes underpinning the accumulation of storage lesions to RBCs in the blood bank. Biochemical lesions include altered cation homeostasis, reprogrammed energy, and redox metabolism, which result in the impairment of enzymatic activity and progressive depletion of high‐energy phosphate compounds. These factors contribute to the progressive accumulation of oxidative stress, which in turn promotes oxidative lesions to proteins (carbonylation, fragmentation, hemoglobin glycation) and lipids (peroxidation). Biochemical lesions negatively affect RBC morphology, which is marked by progressive membrane blebbing and vesiculation. These storage lesions contribute to the altered physiology of long‐stored RBCs and promote the rapid clearance of up to one‐fourth of long‐stored RBCs from the recipient's bloodstream after 24 hours from administration. While prospective clinical evidence is accumulating, from the present review it emerges that biochemical, morphologic, and omics profiles of stored RBCs have observable changes after approximately 14 days of storage. Future studies will assess whether these in vitro observations might have clinically meaningful effects.     

Quinidine in the treatment of KCNT1‐positive epilepsies

We report 2 patients with drug‐resistant epilepsy caused by KCNT1 mutations who were treated with quinidine. Both mutations manifested gain of function in vitro, showing increased current that was reduced by quinidine. One, who had epilepsy of infancy with migrating focal seizures, had 80% reduction in seizure frequency as recorded in seizure diaries, and partially validated by objective seizure evaluation on EEG. The other, who had a novel phenotype, with severe nocturnal focal and secondary generalized seizures starting in early childhood with developmental regression, did not improve. Although quinidine represents an encouraging opportunity for therapeutic benefits, our experience suggests caution in its application and supports the need to identify more targeted drugs for KCNT1 epilepsies. Ann Neurol 2015;78:995–999     

Poorly differentiated carcinoma of the rectum with aberrant immunophenotype： A case report

We report a case of a poorly differentiated epithelial tumour of the rectum with a highly pleomorphic morphology and an aberrant immunophenotype, including the expression of epithelial markers, the focal parameter of neuroendocrine differentiation, and the unexpected detection of CD-117 overexpression. A 69-year-old man was admitted to our clinic complaining of rectal bleeding and weight loss. Colonoscopy showed an ulcerative bleeding mass located about 8 cm from the anal verge. Abdominal and pelvis CT scans demonstrated a large low-density lesion with extracanalicular growth from the middle rectum, with local lymph-node spread, and without tumour infiltration of other pelvic organs, or evidence of distant intraabdominal spread. The patient underwent a low anterior resection for rectal cancer together with wide resection of lymph nodes. In immunohistochemical analysis, pankeratin and Epithelial Membrane Antigen （EMA） immunolabeling proved the epithelial nature of the tumor cells. Chromogranin A and Leukocyte Common Antigen （LCA） were negative, whereas CD-56 expression was scanty and Neuron Specific Enolase （NSA） was heavily and diffusely expressed. Ki67 immunoexpression was particularly increased. Interestingly, the intense c-kit immunoreactivity （100%） was a common feature. The above phenotypic and immunohistochemical profile was consistent with an anaplastic carcinoma of the large intestine, with focal neuroendocrine differentiation and diffuse immunoreactivity to c-kit protein. Given the resistance of this tumor to conventional chemotherapy and radiation, the incidence of the c-kit alteration may represent a novel approach to a gene-directed treatment using a c-kit inhibitor （STI571） similar to that which has been proposed in GISTs.     

Perturbations in cortical development and neuronal network excitability arising from prenatal exposure to benzodiazepines in mice

During brain development, many factors influence the assembly and final positioning of cortical neurons, and this process is essential for proper circuit formation and normal brain function. Among many important extrinsic factors that guide the maturation of embryonic cortical neurons, the secreted neurotransmitter GABA has been proposed to influence both their migratory behaviour and their terminal differentiation. The full extent of the short‐term and long‐term changes in brain patterning and function caused by modulators of the GABA system is not known. In this study, we specifically investigated whether diazepam, a commonly used benzodiazepine that modulates the GABA_A receptor, alters neuronal positioning in vivo, and whether this can lead to lasting effects on brain function. We found that fetal exposure to diazepam did not change cell positioning within the embryonic day (E)14.5 mouse cerebral cortex, but significantly altered neuron positioning within the E18.5 cortex. In adult mice, diazepam treatment affected the distribution of cortical interneurons that express parvalbumin or calretinin, and also led to a decrease in the numbers of calretinin‐expressing interneurons. In addition, we observed that neonatal exposure to diazepam altered the sensitivity of mice to a proconvulsant challenge. Therefore, exposure of the fetal brain to benzodiazepines has consequences for the positioning of neurons and cortical network excitability.     

The association of diabetic microvascular and macrovascular disease with cutaneous circulation in patients with type 2 diabetes mellitus

Aims

To study the impact of diabetic neuropathy, both peripheral sensorimotor (DPN) and cardiac autonomic neuropathy (CAN), on transcutaneous oxygen tension (TcPO₂) in patients with type 2 diabetes mellitus (T2DM).

Transthoracic Repair of Asymptomatic Morgagni Hernia in an Adult

Morgagni hernia represents a rare type of diaphragmatic hernia which usually occurs on the right side, in the anterior mediastinum. Predisposing factors of Morgagni hernia include pregnancy, obesity or other causes of increased intraabdominal pressure, and a history of trauma. Most of adults diagnosed with a foramen of Morgagni are asymptomatic. We report a case of an overweight 23-year-old asymptomatic patient with a Morgagni hernia incidentally diagnosed on chest x-ray. There was a satisfactory result after the repair by a transthoracic approach.     

A giant inguinoscrotal bladder hernia as a cause of chronic renal failure: A rare case

INTRODUCTIONGiant inguinoscrotal bladder hernias are very rare and require surgical intervention. They usually do not cause any specific symptoms and thus, they are often misdiagnosed. If left untreated though, they might lead to severe medical conditions, such as renal failure.PRESENTATION OF CASEWe present the case of a 71-year-old male patient suffering from a giant inguinoscrotal mass, accompanied by symptoms of the lower urinary track (LUTS) and chronic renal failure.DISCUSSIONIn our case, the patient presented with bladder hernia causing non specific symptoms of renal failure. In contrast to acute renal failure, a chronic renal impairment most often comes with no specific symptoms and thus, it can be present for many years before the diagnosis is made. It is evident that such serious conditions should be suspected and treated.CONCLUSIONInguinoscrotal bladder hernias may be associated with severe medical conditions, such as renal deterioration, and should be considered in the differential diagnosis of renal failure, when accompanied by any inguinal, scrotal, or low abdominal wall hernia.     

Metachronous early gastric adenocarcinoma presenting coinstantaneously with complete remission of stage IV gastric MALT lymphoma

Adenocarcinoma and lymphoma represent the two most common malignant tumours of the stomach, with both neoplasms being associated with infection by Helicobacter pylori. However, the presence of lymphoma and adenocarcinoma in the same patient is a rare entity with synchronous neoplasms being more common than metachronous types. We report a case of stage IV gastric MALT lymphoma of the gastric angle with infiltration of the bone marrow successfully treated with chemotherapy and the occurrence of metachronous early gastric adenocarcinoma of the fundus presenting 1 year after the diagnosis of the lymphoma.