Incidence of new onset glomerulonephritis after SARS-CoV-2 mRNA vaccination is not increased.

Numerous cases of glomerulonephritis manifesting shortly after SARS-CoV-2 vaccination have been reported, but causality remains unproven. Here, we studied the association between mRNA-based SARS-CoV-2 vaccination and new-onset glomerulonephritis using a nationwide retrospective cohort and a case-cohort design. Data from all Swiss pathology institutes processing native kidney biopsies served to calculate incidence of IgA nephropathy, pauci-immune necrotizing glomerulonephritis, minimal change disease, and membranous nephropathy in the adult Swiss population. The observed incidence during the vaccination campaign (January to August 2021) was not different from the expected incidence calculated using a Bayesian model based on the years 2015 to 2019 (incidence rate ratio 0.86, 95% credible interval 0.73-1.02) and did not cross the upper boundary of the 95% credible interval for any month. Among 111 patients 18 years and older with newly diagnosed glomerulonephritis between January and August 2021, 38.7% had received at least one vaccine dose before biopsy, compared to 39.5% of the general Swiss population matched for age and calendar-time. The estimated risk ratio for the development of new-onset biopsy-proven glomerulonephritis was not significant at 0.97 (95% confidence interval 0.66-1.42) in vaccinated vs. unvaccinated individuals. Patients with glomerulonephritis manifesting within four weeks after vaccination did not differ clinically from those manifesting temporally unrelated to vaccination. Thus, vaccination against SARS-CoV-2 was not associated with new-onset glomerulonephritis in these two complementary studies with most temporal associations between SARS-CoV-2 vaccination and glomerulonephritis likely coincidental.

Informative value of histological assessment of tissue acquired during aquablation of the prostate.

PURPOSE: To determine the histological validity of the tissue acquired during aquablation of the prostate. PATIENTS AND METHODS: Prostatic tissue of 12 patients that consecutively underwent aquablation for benign prostatic enlargement was systematically examined. Histological examination was performed by two experienced uropathologists using a digital slide scanner and slide viewer software (Pannoramic 250 and Case Viewer 2.3, 3D Histech, Hungary). The surface areas of the assessable glands were examined and set in relation to the total surface area of the material available for histology and to the patient's total prostate volume. Examinations were performed analogously in ten consecutive patients undergoing transurethral resection of the prostate (TURP) to facilitate interpretation of the results. Data were analyzed using descriptive statistics. RESULTS: A median of 4.06% (range 1.43-7.5%) of the preoperative total prostate volume (median 64.5 ml (range 40-80 ml)) was obtained for histological examination by aquablation. Due to severe mechanical destruction and fragmentation, only a proportion of 0.43% (0.06-1.79%) of this tissue represented histologically assessable glands. Therefore, roughly 0.017% of the total prostatic volume was available for a reliable histological examination. In comparison, 32.5% (6.67-37.5%) of the total prostate volume was removed by TURP and 22.86% (7.45-40.57%) of this tissue represented informative prostatic glands, corresponding to 7.43% of the total prostate volume. CONCLUSION: Histological significance of the tissue obtained by aquablation of the prostate is very limited. Costs and effort of the histological examination must, therefore, be weighed critically against the limited informative value.

Initial Diagnosis and Detection of Very Late Local Recurrence of a Ductal Prostate Cancer due to a Ureteral Stone.

We report the case of a 74-year-old patient in whom a ductal prostate cancer was incidentally endoscopically diagnosed in the course of ureteral stenting due to a left distal ureteral stone. The initial PSA was 0.8 µg/l and the digital rectal examination was not suspicious. A radical prostatectomy was performed, and the ensuing follow-up was unremarkable with no signs of recurrence. Fourteen years later, the patient presented with an obstructive pyelonephritis due to a left-sided ureteral stone requiring ureteral stenting. An exophytic tumor was seen in the lining of vesicourethral anastomosis and surgically excised after the pyelonephritis subsided. The histopathological and immunohistochemical analysis revealed a ductal cancer of the prostate consistent with a late local recurrence. Serum PSA was below the limit of detection. Re-staging performed by an MRI of the pelvis, thoracoabdominal CT scan, and gallium-68 PSMA-PET did not reveal any other signs of disease. The ensuing follow-up is planned with regular flexible cystoscopy and computed thoracoabdominopelvic CT scans.

A rare case of an ACTH/CRH co-secreting midgut neuroendocrine tumor mimicking Cushing's disease.

Ectopic ACTH/CRH co-secreting tumors are a very rare cause of Cushing's syndrome and only a few cases have been reported in the literature. Differentiating between Cushing's disease and ectopic Cushing's syndrome may be particularly difficult if predominant ectopic CRH secretion leads to pituitary corticotroph hyperplasia that may mimic Cushing's disease during dynamic testing with both dexamethasone and CRH as well as bilateral inferior petrosal sinus sampling (BIPSS). We present the case of a 24-year-old man diagnosed with ACTH-dependent Cushing's syndrome caused by an ACTH/CRH co-secreting midgut NET. Both high-dose dexamethasone testing and BIPSS suggested Cushing's disease. However, the clinical presentation with a rather rapid onset of cushingoid features, hyperpigmentation and hypokalemia led to the consideration of ectopic ACTH/CRH-secretion and prompted a further workup. Computed tomography (CT) of the abdomen revealed a cecal mass which was identified as a predominantly CRH-secreting neuroendocrine tumor. To the best of our knowledge, this is the first reported case of an ACTH/CRH co-secreting tumor of the cecum presenting with biochemical features suggestive of Cushing's disease. LEARNING POINTS: The discrimination between a Cushing's disease and ectopic Cushing's syndrome is challenging and has many caveats.Ectopic ACTH/CRH co-secreting tumors are very rare.Dynamic tests as well as BIPSS may be compatible with Cushing's disease in ectopic CRH-secretion.High levels of CRH may induce hyperplasia of the corticotroph cells in the pituitary. This could be the cause of a preserved pituitary response to dexamethasone and CRH.Clinical features of ACTH-dependent hypercortisolism with rapid development of Cushing's syndrome, hyperpigmentation, high circulating levels of cortisol with associated hypokalemia, peripheral edema and proximal myopathy should be a warning flag of ectopic Cushing's syndrome and lead to further investigations.

Pembrolizumab-associated minimal change disease in a patient with malignant pleural mesothelioma.

BACKGROUND: Pembrolizumab is an anti- Programmed Death 1 (PD-1) antibody approved in melanoma, non-small cell lung cancer and investigated in malignant pleural mesothelioma. The most frequent immunotherapy related autoimmune reactions include dermatitis, pneumonitis, colitis, hypophysitis, uveitis, hypothyreodism, hepatitis and interstitial nephritis. CASE PRESENTATION: We describe a 62-year old patient diagnosed with malignant pleural mesothelioma who experienced ten days after the second dose of third line therapy with pembrolizumab sudden onset of generalized edema including legs and eyelids and weight gain of 15 kg resulting from nephrotic syndrome and acute renal failure. Pembrolizumab was discontinued and prednisone, diuretics and angiotensin II receptor blocker were initiated with full recovery of symptoms and renal function. Pembrolizumab-associated minimal change disease (MCD) was confirmed by electron microscopy in the renal biopsy. CONCLUSION: We are the first to describe pembrolizumab-related minimal change disease (MCD). Physicians should be aware of this side effect in patients presenting with edema and weight gain and initiate prompt renal function testing, serum albumin and urinalysis followed by steroid treatment if pembrolizumab-related MCD is suspected.