Introduction: Subcutaneous insulin resistance syndrome (SIRS) is a rare condition in which patients poorly respond to subcutaneous (SC) insulin but maintain a normal response to intravenous (IV) insulin. The underlying pathophysiology remains elusive. Several treatment regimens have been tested for the management of SIRS, none of which included a sodium-glucose cotransporter-2 inhibitor (SGLT-2). Case Presentation: Two cases of type 1 diabetes initially achieved adequate glycemic control with subcutaneous insulin. Both cases later progressed into recurrent diabetic ketoacidosis that would resolve following IV insulin administration. Further investigation revealed unresponsiveness to SC, but not IV, insulin and the clinical diagnosis of SIRS was established accordingly. HbA1c values for cases 1 and 2 were 11% on 400 units/day of SC insulin, and 12% on 350 - 400 units/day of SC insulin, respectively. The patients required very high doses of intramuscular (IM) insulin. Subsequently, dapagliflozin as adjunct therapy significantly reduced the patients’ IM insulin requirements beyond the anticipated dose reduction. Ultimately, case 1 achieved an HbA1c of 7 - 8% on 90 units/day of IM insulin and 10 mg/day of dapagliflozin, and case 2 achieved an HbA1c of 7 - 8% on 120 units/day of IM insulin and 10 mg/day of dapagliflozin. Conclusions: These are the first reported cases of SIRS in which dapagliflozin, an SGLT-2 inhibitor, was used. The substantial reduction in the IM insulin dose following the addition of dapagliflozin in our reported cases of SIRS suggests a possible novel mechanism for dapagliflozin beyond its glucosuric effects. In this report, we present a hypothetical basis for this possible novel mechanism.

Background: Individuals with self-declared sarcoidosis are at increased risk of COVID-19 related morbidity and mortality for which vaccination can be lifesaving. Despite this, vaccine hesitancy remains a large barrier to global acceptance of vaccination against COVID-19. We aimed to identify individuals with sar-coidosis who had and had not been vaccinated against COVID-19 vaccine to 1) establish a safety profile of COVID-19 vaccination in those with sarcoidosis and 2) to elucidate factors that contribute to COVID-19 vaccine hesitancy. Methods: A questionnaire inquiring about COVID-19 vaccination status, vaccination side effects, and willingness for future vaccination was distributed from December 2020 to May 2021 to individuals with sarcoidosis living in the US and European countries. Details regarding sarcoidosis manifestations and treat-ment were solicited. Vaccine attitudes were classified as pro or anti-COVID-19 vaccination for subgroup analy-sis. Results: At the time of questionnaire administration, 42% of respondents had already received a COVID-19 vaccination, most of whom either denied side effects or reported a local reaction only. Those not on sarcoidosis therapy were more likely to report systemic side effects. Among subjects who had not yet received a COVID-19 vaccine, 27% of individuals reported they would not receive one once available. Reasons against vaccination were overwhelmingly related to the lack of confidence in vaccine safety and/or efficacy and less related to concerns associated with convenience or complacency. Black individuals, women, and younger adults were more likely to decline vaccination. Conclusions: Among individuals with sarcoidosis, COVID-19 vaccination is well-accepted and well-tolerated. Subjects on sarcoidosis therapy reported significantly less vaccination side effects, and thus the correlation between side effects, vaccine type, and vaccine efficacy requires further investigation. Strategies to improve vaccination should focus on improving knowledge and education regarding vaccine safety and efficacy, as well as targeting sources of misinformation, particularly in young, black, and female subpopulations.

Causes of treatment-refractory hypothyroidism include nonadherence, interference from food or drugs, gastrointestinal disorders, and increased levothyroxine turnover. A practical, stepwise diagnostic approach starts with a detailed history, followed by gastrointestinal and ancillary evaluations. Assay interference and other confounding conditions should also be considered. A trial of levothyroxine formulations other than oral tablets may be useful in select cases.

Bladder cancer (BCa) diagnosis and surveillance rely heavily on invasive cystoscopy and urine cytology, which has limited sensitivity, underscoring the need for reliable non-invasive biomarkers. ENOX2 (tumor-associated NOX) is a candidate pan-cancer biomarker shed from tumor cell membranes into biological fluids, but its utility in BCa remains unexplored. This prospective pilot study enrolled 33 non-muscle-invasive bladder cancer (NMIBC) cases, 32 non-cancer controls for the primary analysis, and 38 other cancer controls. Serum and urinary ENOX2 were measured by ELISA, and ENOX2 gene expression by qPCR. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC). The urinary ENOX2/creatinine ratio was significantly higher in NMIBC cases than controls (median 17.95 vs 0.74 ng/mg, p = 0.018), achieving the highest diagnostic performance among studied markers (AUC 0.670, with sensitivity 53% and specificity 91% at a cutoff of ≥17.85 ng/mg), while serum ENOX2 and qPCR expression showed no diagnostic utility (AUC 0.435 and 0.417, respectively). Further exploratory analyses showed that the urinary ENOX2/creatinine ratio demonstrated comparable AUC across low- and high-grade tumors and correlated with tumor size. Additionally, the levels did not vary across benign urological conditions. The urinary ENOX2/creatinine ratio demonstrates modest but statistically significant diagnostic utility in NMIBC, outperforming serum ENOX2 measures in this pilot study. Further evaluation of ENOX2 in larger, multicenter cohorts, including its potential role within multimarker diagnostic panels, is recommended.

This study shows that the rise in plasma sodium induced by the vasopressin V2-receptor antagonist Tolvaptan can be controlled by regulating water intake to under-replace urine output by a fixed amount per kilogram body weight in healthy subjects. This approach produced increases in plasma sodium that were comparable to hypertonic saline and provides a means to prevent rapid rises in plasma sodium beyond the target rate.