Immune Checkpoint Inhibitors in Recipients of Renal Allografts.

Kidney transplant recipients are at increased risk of malignancy as a result of immunosuppression and are increasingly exposed to checkpoint inhibitors (CPIs). However, CPI therapy can precipitate allograft rejection. This review aims to summarize the current literature describing the epidemiology, immunological mechanisms, diagnosis, and treatment of CPI-associated allograft rejection.Initial studies of CPIs suggested allograft rejection post commencement of CPIs occured commonly (40-60%), occurring between 2 and 6 weeks after CPI initiation, with a cancer response rate approaching 50%. More recent studies with predefined, structured immunosuppressive regimens have seen rejection rates of 0-12.5%, with rejection occurring later. Allograft biopsy remains the mainstay of diagnosis; however, noninvasive tools are emerging, including donor-derived cell-free DNA, urinary chemokine assessment, and defining alloreactive T-cell clones prior to or during CPI therapy.

Choosing fluids to reduce the risks of acute electrolyte disturbances in children after a kidney transplant.

Intravenous (i.v.) fluid therapy is critically important in pediatric kidney transplantation. Because of the high volumes given perioperatively, transplant recipients can develop significant electrolyte abnormalities depending on the types of fluids used. Current practices in pediatric transplantation aim to balance risks of hyponatremia from traditionally used hypotonic fluids, such as 0.45% sodium chloride, against hyperchloremia and acidosis associated with isotonic 0.9% sodium chloride. Using the balanced solution Plasma-Lyte 148 as an alternative might mitigate these risks.

Metastatic Angiosarcoma Presenting as Ischemic Anterior Circulation Stroke.

BACKGROUND: Angiosarcoma is a rare malignant neoplasm that can arise from vascular endothelium. We report a case of angiosarcoma that presented as thromboembolic stroke, review the current literature, and discuss the management challenges. CASE REPORT: A 77-year-old man presented with a right anterior circulation stroke with a history of multiple, recent transient ischemic attacks. The diagnosis was confirmed on computed tomography and subsequent investigation revealed thrombus within the distal common carotid artery, with an atherosclerotic plaque causing a significant stenosis of the origin of the internal carotid artery above this. In the context of the presentation with recurrent events, carotid endarterectomy was recommended and subsequently performed. At the time of surgery, the common, internal, and external carotid arteries had macroscopic evidence of atherosclerotic disease but appeared otherwise normal. Intraoperatively friable thrombus adherent to the common carotid endothelium was retrieved and sent for histologic assessment. Subsequent immunohistochemistry evaluation revealed changes pathognomic with angiosarcoma. RESULTS: It is unclear in this case whether the pathology originated in the carotid artery or was the result of embolization from a proximal source. There was no extraluminal carotid pathology identified at the time of surgery, and no abnormalities identified on cross-sectional imaging. Similarly, there was no evidence of a proximal source that may have resulted in tumor embolization. As such, it has proved impossible to define an optimal therapeutic pathway for this patient.

Genetic basis of growth adaptation of Escherichia coli after deletion of pgi, a major metabolic gene.

Bacterial survival requires adaptation to different environmental perturbations such as exposure to antibiotics, changes in temperature or oxygen levels, DNA damage, and alternative nutrient sources. During adaptation, bacteria often develop beneficial mutations that confer increased fitness in the new environment. Adaptation to the loss of a major non-essential gene product that cripples growth, however, has not been studied at the whole-genome level. We investigated the ability of Escherichia coli K-12 MG1655 to overcome the loss of phosphoglucose isomerase (pgi) by adaptively evolving ten replicates of E. coli lacking pgi for 50 days in glucose M9 minimal medium and by characterizing endpoint clones through whole-genome re-sequencing and phenotype profiling. We found that 1) the growth rates for all ten endpoint clones increased approximately 3-fold over the 50-day period; 2) two to five mutations arose during adaptation, most frequently in the NADH/NADPH transhydrogenases udhA and pntAB and in the stress-associated sigma factor rpoS; and 3) despite similar growth rates, at least three distinct endpoint phenotypes developed as defined by different rates of acetate and formate secretion. These results demonstrate that E. coli can adapt to the loss of a major metabolic gene product with only a handful of mutations and that adaptation can result in multiple, alternative phenotypes.

Efficient one-pot synthesis of fluorinated benzimidazolines, benzothiazolines, benzoxazolines, and dihydrobenzoxazinones using gallium(III) triflate as a catalyst.

One-pot synthesis of fluorinated benzimidazolines, benzothiazolines, benzoxazolines, and dihydrobenzoxazinones was easily achieved under mild conditions in high yields and purity through gallium(III) triflate mediated condensation-cyclization. Introduction of fluorine atoms favors the formation of the five-membered heterocycles over seven-membered heterocycles. [reaction: see text].