A retrospective multi-center experience of renal transplants from India during COVID-19 pandemic.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) pandemic led to a sudden drop in renal transplant numbers across India in the initial months of 2020. Although the transplant numbers increased with easing of lockdown, the outcome of these transplants remains unknown. METHODS: This was a retrospective, observational, multi-center study done across eight different transplant centers in India. All the transplants done from January 30, 2020 to December 31, 2020 were included. The primary outcomes studied were patient and death censored graft survival as well as incidence of COVID-19 infection and its outcomes. RESULTS: During the study period a total of 297 kidney transplants were done. After a median follow up of 265 days the patient and death censored graft survival was 95.3% and 97.6%, respectively. Forty-one patients (13.8%) developed COVID-19 post-transplant. Majority (58.5%) were asymptomatic to mildly symptomatic and the case fatality ratio was 14.6%. On multivariable logistic regression analysis older age was associated with higher likelihood of COVID-19 infection (odds ratio 1.038; CI 1.002-1.077). CONCLUSIONS: Patient and graft outcome of kidney transplants done during the COVID-19 pandemic in India was acceptable. The incidence of COVID-19 was 13.8% with a high case fatality ratio.

Ferritinophagy is not required for colon cancer cell growth.

Ferritinophagy is a form of selective autophagy responsible for degrading intracellular ferritin, mediated by nuclear receptor coactivator 4 (NCOA4). NCOA4 plays significant roles in systemic iron homeostasis, and its disruption leads to simultaneous anemia and susceptibility to iron overload. The importance of iron colorectal cancer pathogenesis is well studied; however, the role of ferritinophagy in colon cancer cell growth has not been assessed. Disruption of ferritinophagy via NCOA4 knockout leads to only marginal differences in growth under basal and iron-restricted conditions. Moreover, NCOA4 played no significant role in cell death induced by 5-fluorouracil and erastin. Western blotting analysis for ferritin and transferrin receptor 1 found a dose-dependent effect on expression in both proteins in wild-type and NCOA4 knockout cell lines, but further investigation revealed no difference in growth response when treated at both high and low doses. Our data demonstrate a marginal role for ferritinophagy in growth both under normal and cytotoxic conditions in colon cancer cells, as well as a possible compensatory mechanism in colon cancer cells in response to ferroptosis induction.

A Rationally Designed Multifunctional Antibiotic for the Treatment of Drug-Resistant Acne.

Acne is a multifactorial skin disease, underpinned by colonization of Propionibacterium acnes and inflammation. The emergence of resistant P. acnes strains has affected the current acne treatment algorithm. This setback served as an impetus for rationally designing a library of next-generation antibiotics that exhibit a bactericidal effect on resistant P. acnes and exert an immunomodulatory function to reduce inflammation. In silico screening showed that one of the molecules, VCD-004, exhibits improved mode of binding to bacterial DNA gyrase. VCD-004 shows high potency against clinical isolates of resistant P. acnes and excellent efficacy in vivo. Furthermore, VCD-004 exhibits a superior mutant prevention index, suggesting that it impedes the development of resistance better than clindamycin. Additionally, it shows optimal skin penetration and has a potent anti-inflammatory effect via reduction of proinflammatory cytokines (IL-6) independent of its antibacterial action. VCD-004 affects P. acnes-induced nuclear accumulation of NF-κB in THP-1 cells. The in vitro viability of human keratinocytes in the presence of VCD-004 indicates a desirable therapeutic window for topical use. Such rationally designed bactericidal and immunomodulatory dual pharmacophore-based lipophilic molecule(s) can emerge as the next-generation topical therapy for acne with underlying resistant P. acnes etiology.

Unexplained post-renal transplant tolerance: a case report.

Achievement of an immunosuppression-free condition defined as clinical operational tolerance is an ideal goal. We hereby report a case of clinical operational tolerance in a patient whose allograft is functioning normally, without immunosuppression, for more than 3 years. The patient withdrew from immunosuppression in 2011 following which his serum creatinine was 1.34 mg/dl and proteinuria was 178 mg/24 h. Flowcytometric studies showed an elevated number of B lymphocytes and NK cells. IL-10 cytokine levels had increased, whereas those of IFN-γ decreased, suggesting that both B lymphocytes and NK cells, with their immunoregulatory function, contribute to the maintenance of long-term graft function. Consequently, further studies in understanding the interactions of NK cells and B lymphocytes may give us a better insight into the underlying mechanisms that underpin organ tolerance.

[The hepatorenal syndrome - a review]. / La sindrome epato-renale: una revisione della letteratura.

The Hepato Renal Syndrome (HRS) remains a diagnostic and therapeutic conundrum. Controversies persist in the definition, understanding of pathophysiological mechanisms, diagnosis, and therapy of renal dysfunction complicating End Stage Liver Disease (ESLD).While ESLD is complicated by dysfunction in multiple organs, renal disease holds particular bearing on long term outcomes. Liver transplantation is the therapy of choice for ESLD-and co existing renal dysfunction makes it more difficult and challenging. Given that a bare minimum of patients with ESLD will ultimately receive a liver transplant, especially in the developing world, renal dysfunction may ultimately portend untimely death in a many of these patients. It is also critical to recognize the fact that HRS is not the sole cause of renal failure in ESLD. Hence, early recognition and therapy may prolong life even in those who will not receive a transplant for multitude of reasons. Renal Replacement Therapy (RRT) is also a challenge in this patient population, leading to issues with hemodynamics, vascular access and anticoagulation. We take a look at recent literature and advances in the understanding of the pathophysiology of this particularly difficult condition, and its diagnosis and management.

Can tissue PCR augment the diagnostic accuracy in genitourinary tract tuberculosis?

PURPOSE: Conventional methods like smear and culture for Mycobacterium tuberculosis are of limited sensitivity and specificity. Histopathological examination (HPE) for the tissues obtained gives inconclusive diagnosis in the absence of caseous necrosis or stained acid-fast bacilli. This study was conducted to determine the utility of tissue PCR for diagnosing tuberculosis of the genitourinary tract (GUTB) and its comparative evaluation with HPE. PATIENTS AND METHODS: A prospective study was conducted from January 2006 to August 2009 with 78 tissue specimens (renal, prostate, epididymis, penile and soft tissue) from patients with clinically suspected GUTB. All the samples were processed for both PCR and histopathology. RESULTS: In 68 (87.1%) samples, results for both PCR and HPE were coinciding. False positivity and false negativity was observed in 5.1% (4/78) and 7.6% (6/78) samples, respectively. With HPE as the gold standard, PCR has shown sensitivity of 87.5% (95% CI 80.1; 91.9) and specificity of 86.7% (95% CI 74.9; 93.8) and positive agreement between two tests was observed as significant (0.7). PCR results were obtained within a mean period of 3.4 days while those of HPE were obtained in 7.2 days. CONCLUSIONS: Tissue PCR is a sensitive and specific method for obtaining early and timely diagnosis of GUTB. Application of tissue PCR results can augment the diagnostic accuracy in histopathologically labelled granulomatous inflammations.

Duplicated rectum as interlabial mass.

Duplications of the rectum constitute one of the rare congenital anomalies. Presentation as a sequestrated interlabial mass without any associated anomaly has not been reported before. We cannot readily offer any embryological explanation for this congenital distortion. Total extirpation of the lesion was easily achieved ensuring complete cure.

Posterior urethral valve associated with orthotopic ureterocele.

Symptomatic presentation of orthotopic ureterocele in infancy is very rare and its association with posterior urethral valves has not been reported till date. The first such case and a review of the literature on anomalies in association with posterior urethral valves is presented.

Cytomegalovirus ureteritis: an unreported cause of hematuria in an immunocompetent individual.

A middle-aged woman presented with painless hematuria and passage of large clots. Two weeks earlier, she had pyrexia with upper respiratory tract symptoms. Imaging studies revealed no lesions of the urinary tract. Cystoscopy showed clots and oozing of blood from the left ureteric orifice. Urine cytology and mucosal biopsies were normal. Left nephroureterectomy was done as an emergency procedure; the hematuria stopped following the procedure. Histopathology revealed cytomegalovirus inclusion bodies in the mucosa of the excised ureter. This unusual presentation of hematuria has not been reported previously.

Adrenal oncocytoma masquerading as a functional tumor.

Adrenal oncocytoma is a rare entity, with 20 cases reported in literature. A functional oncocytoma is extremely rare. We present a case of adrenal oncocytoma in a hypertensive male who had elevated catecholamine levels, which improved after adrenalectomy with decrease in daily antihypertensive requirement.

Emphysematous pyelonephritis with calculus: Management strategies.

OBJECTIVE: Emphysematous pyelonephritis (EPN) with calculus is well recognized but with very few reports on its treatment. Our aim is to elucidate our experience in its successful management. MATERIALS AND METHODS: Over four years, we diagnosed seven cases (eight renal units) of EPN, out of which two patients (three renal units) had EPN with urinary calculi. After the initial conservative management of EPN, the stones were tackled appropriately. RESULTS: EPN was initially managed effectively with antibiotics and supportive care. Once the patient was stable, the stones were cleared in a step-wise fashion. The associated postoperative complications were also tackled efficiently with preservation of renal function. CONCLUSION: In EPN with stones, nephrectomy is not the sole option available and they can be effectively managed with open / endoscopic measures.

Unexplained systemic hypertension after closure of ductus arteriosus.

Immediately after surgical closure of a patent ductus arteriosus, a 12-year-old boy developed severe systemic arterial hypertension refractory to medication. The cause of hypertension could not be found, but it came under control 3 weeks postoperatively with a combination of angiotensin-converting enzyme inhibitor and chlorothiazide.

Bronchial transection resulting from trivial blunt chest trauma.

A 3-year-old boy with a trivial blunt chest injury presented with a massive bronchopleural leak without any hilar vascular injury. On emergency exploration he had a complete transection of the right main bronchus. An end-to-end anastomosis of the transected bronchial ends was performed. At 1-month clinical and radiologic follow-up, the anastomosis had healed well.