Science behind cisplatin-induced nephrotoxicity in humans: A clinical study

Objective

To investigate the relationship between serum electrolyte changes and cisplatin induced nephrotoxicity.

Methods

We collected data from 18 patients undergoing cisplatin chemotherapy including serum electrolytes, creatinine, blood urea nitrogen (BUN) and urine potassium, sodium and pH levels before and after the cisplatin chemotherapy. All the patients had cancer and were treated with 40-50 mg/day cisplatin. Renal injury was assessed by measuring serum electrolytes, creatinine, BUN levels and urine potassium, sodium and pH levels.

Results

The five cycles of cisplatin based chemotherapy resulted in hypomagnesia (P=0.029), hypocalcaemia (P=0.001*), hypophosphatemia (P=0.003*), hypokalemia (P=0.001*) and increased serum creatinine (P=0.001*) and BUN (P=0.292*) levels. In urine analysis, decrease in potassium (P=0.024*) was found, except potassium there was no significant changes in sodium and urine pH.

Conclusions

The present study demonstrates that, acute nephrotoxicity was observed in patients with different types of cancers undergoing cisplatin based chemotherapy due to electrolyte disturbances, when no corrective measures were initiated.     

Hepatoprotective activity of Hepax-A polyherbal formulation

Objective

To evaluate the hepatoprotective potential of Hepax, a polyherbal formulation, against three experimentally induced hepatotoxicity models in rats.

Methods

Hepatoprotective activity of Hepax was studied against three experimentally induced hepatotoxicity models, namely, carbon tetrachloride (CCl₄), paracetamol and thiocetamide induced hepatotoxicity in rats.

Results

Administration of hepatotoxins (CCl₄, paracetamol and thiocetamide) showed significant morphological, biochemical and histological deteriorations in the liver of experimental animals. Pretreatment with Hepax had significant protection against hepatic damage by maintaining the morphological parameters (liver weight and liver weight to organ weight ratio) within normal range and normalizing the elevated levels of biochemical parameters (SGPT, SGOT, ALP and total bilirubin), which were evidently showed in histopathological study.

Conclusions

The Hepax has highly significant hepatoprotective effect at 100 and 200 mg/kg, p.o. on the liver of all the three experimental animal models.     

Presenting characteristics as predictors of duration of treatment in sarcoidosis

Background: Some sarcoidosis patients never need therapy, butmany still require therapy more than 2 years after initial diagnosis. Aim: To determine what features at initial presentation areassociated with treatment 2 years later. Methods: Patients with biopsy-confirmed sarcoidosis enrolledin the ACCESS (A Case Control Etiologic Study of Sarcoidosis)study were initially evaluated within 6 months of diagnosis.Pulmonary function, chest X-ray and dyspnoea score were measured,and systemic therapy for the sarcoidosis recorded. Organ involvementwas assessed using a standardized instrument. A subset (n =215) were seen 18–24 months later for follow-up, and thesepatients constitute our study group. Results: Ten patients had only received therapy before the firstvisit, with no further therapy, and were excluded from analysis.Of the remaining 205, 95 were not on therapy at the initialvisit and 75 (79%) of these were never treated during follow-up.Of the 110 initially on therapy, 52 (47%) remained on therapyat follow-up. Other initial features associated with continuedtherapy were the level of dyspnoea and predicted vital capacity.On logistic regression, only dyspnoea and therapy at initialvisit remained significant. Patients on systemic therapy atinitial evaluation were more likely to be on therapy at follow-up(OR 3.6, p = 0.003). Neither ethnicity nor gender independentlypredicted therapy at follow-up. Discussion: This study group represents a sample of newly diagnosedsarcoidosis patients. However, this is a referral population,and there was no set protocol for treatment. Use of systemictherapy within the first 6 months after diagnosis appears tobe strongly associated with continued use of therapy 2 yearslater.     

The Dutch founder mutation SDHD.D92Y shows a reduced penetrance for the development of paragangliomas in a large multigenerational family

Germline mutations in SDHD predispose to the development of head and neck paragangliomas, and phaeochromocytomas. The risk of developing a tumor depends on the sex of the parent who transmits the mutation: paragangliomas only arise upon paternal transmission. In this study, both the risk of paraganglioma and phaeochromocytoma formation, and the risk of developing associated symptoms were investigated in 243 family members with the SDHD.D92Y founder mutation. By using the Kaplan–Meier method, age-specific penetrance was calculated separately for paraganglioma formation as defined by magnetic resonance imaging (MRI) and for paraganglioma-related signs and symptoms. Evaluating clinical signs and symptoms alone, the penetrance reached a maximum of 57% by the age of 47 years. When MRI detection of occult paragangliomas was included, penetrance was estimated to be 54% by the age of 40 years, 68% by the age of 60 years and 87% by the age of 70 years. Multiple tumors were found in 65% and phaeochromocytomas were diagnosed in 8% of paraganglioma patients. Malignant paraganglioma was diagnosed in one patient (3%). Although the majority of carriers of a paternally inherited SDHD mutation will eventually develop head and neck paragangliomas, we find a lower penetrance than previous estimates from studies based on predominantly index cases. The family-based study described here emphasizes the importance of the identification and inclusion of clinically unaffected mutation carriers in all estimates of penetrance. This finding will allow a more accurate genetic counseling and warrants a ‘wait and scan'' policy for asymptomatic paragangliomas, combined with biochemical screening for catecholamine excess in SDHD-linked patients.     

The John S. Najarian symposium: The past,present, and future of surgery and transplantation,May 20, 2022, Minneapolis,MN

Dr John S Najarian (1927–2020), chairman of the Department of Surgery at the University of Minnesota from 1967 to 1993, was a pioneer in surgery, clinical immunology and transplantation. A Covid-delayed Festschrift was held in his honor on May 20, 2022. The speakers reflected on his myriad contributions to surgery, transplantation, and resident/fellow training, as well as current areas of ongoing research to improve clinical outcomes. Of note, Dr Najarian was a founder of the journal Clinical Transplantation.