Why Not Nephrology? A Survey of US Internal Medicine Subspecialty Fellows

There is a decreased interest in nephrology such that the number of trainees likely will not meet the upcoming workforce demands posed by the projected number of patients with kidney disease. We conducted a survey of US internal medicine subspecialty fellows in fields other than nephrology to determine why they did not choose nephrology

Acute kidney injury in patients treated with immune checkpoint inhibitors

Background: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. Methods: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. Results: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. Conclusions: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery

Epigenetic perturbations in the pathogenesis of mustard toxicity; hypothesis and preliminary results

Among the most readily available chemical warfare agents, sulfur mustard (SM), also known as mustard gas, has been the most widely used chemical weapon. SM causes debilitating effects that can leave an exposed individual incapacitated for days to months; therefore delayed SM toxicity is of much greater importance than its ability to cause lethality. Although not fully understood, acute toxicity of SM is related to reactive oxygen and nitrogen species, oxidative stress, DNA damage, poly(ADP-ribose) polymerase (PARP) activation and energy depletion within the affected cell. Therefore several antioxidants and PARP inhibitors show beneficial effects against acute SM toxicity. The delayed toxicity of SM however, currently has no clear mechanistic explanation. One third of the 100,000 Iranian casualties are still suffering from the detrimental effects of SM in spite of the extensive treatment. We, therefore, made an attempt whether epigenetic aberrations may contribute to pathogenesis of mustard poisoning. Preliminary evidence reveals that mechlorethamine (a nitrogen mustard derivative) exposure may not only cause oxidative stress, DNA damage, but epigenetic perturbations as well. Epigenetic refers to the study of changes that influence the phenotype without causing alteration of the genotype. It involves changes in the properties of a cell that are inherited but do not involve a change in DNA sequence. It is now known that in addition to mutations, epimutations contribute to a variety of human diseases. Under light of preliminary results, the current hypothesis will focus on epigenetic regulations to clarify mustard toxicity and the use of drugs to correct possible epigenetic defects

Effects of rosemary and sage tea extract on biogenic amines formation of sardine (Sardina pilchardus) fillets

Natural antimicrobials and antioxidants from rosemary (Rosmarinus officinalis) and sage tea (Salvia officinalis) were produced using solvent extraction method. The effect of two extracts on ammonia (AMN) and biogenic amines (BAs) formation in vacuum packed sardine (Sardina pilchardus) fillets stored at 3±1°C was investigated for 20days. Although the effect of extracts was dependent on specific amine and storage time, phenolic compounds from rosemary and sage tea generally resulted in lower AMN and BAs accumulation in sardine muscle. Putrescine (PUT) and cadaverine (CAD) were the most abundant amines, while histamine (HIS) concentration ranged from 2.05 to 28.77mg100g-1. Rosemary and sage tea extracts significantly reduced HIS, PUT, CAD and trimethylamine accumulation in the fish muscle (P<0.05) while stimulating effect of extracts was observed on serotonin and agmatine formation. At the end of the storage period, PUT and CAD contents of control were 100-fold higher than those of treated groups. © 2011 The Authors. International Journal of Food Science and Technology © 2011 Institute of Food Science and Technology

Effects of rosemary and sage tea extracts on the sensory, chemical and microbiological changes of vacuum-packed and refrigerated sardine (Sardina pilchardus) fillets

The effect of the natural antioxidants and antimicrobials from ethanol extracts of rosemary and sage tea on sensory, chemical [Total volatile basic nitrogen (TVB-N), thiobarbituric acid reactive substances (TBARs), peroxide value (PV), free fatty acid (FFA)] and microbiological (total viable count-TVC and total coliform count) changes of vacuum-packaged sardine (Sardina pilchardus) fillets stored at 3 ± 1 °C was investigated for 20 days. The fish fillets were divided into three groups: untreated group (control, C) and treated groups that were immersed in a 1 L of distilled water containing 10 g rosemary (R group) or sage tea (S group) extracts for 4 min. The shelf life of sardine fillets was found to be 13 days for control (C), 20 days for R and S groups according to sensory assessment results, whose corresponded microbiological assessment showed a shorter shelf life (5 days for C group, 9 for R and S groups). At the end of storage period, TBARs values were 0.98 mg malonaldehyde kg-1 for C group, 0.66 malonaldehyde kg-1 for R group and 1.44 mg malonaldehyde kg-1 for S group. Microbiological results showed that natural compounds from rosemary and sage tea resulted in a lower bacterial growth in fish fillets during the storage period. © 2010 The Authors. International Journal of Food Science and Technology © 2010 Institute of Food Science and Technology