ObjectiveWe aimed to investigate the effect of dosage reduction of four hypoglycemic multidrug regimens on the incidences of acute glycemic complications in people with type 2 diabetes who fast during Ramaḍān.MethodsWe conducted an open-label, parallel-group, randomized controlled trial at a tertiary care center in Amman, Jordan. We recruited adults with type 2 diabetes who expressed an intention to fast during Ramaḍān and were adherent to one of four regimens—namely: metformin and glimepiride; metformin and vildagliptin; metformin and insulin glargine U100; or, metformin, insulin glargine U100, and human regular insulin. We randomly assigned participants in a 2:1 ratio to low- or regular-dosage therapy. The primary outcomes were the incidences of hypoglycemia and hyperglycemia during the 29 days of Ramaḍān 2017, and the secondary outcomes were the incidences of diabetic ketoacidosis and hyperosmolar hyperglycemic state during the same period.ResultsWe randomly assigned 687 participants to low-dosage therapy (n = 458) or regular-dosage therapy (n = 229) and included 678 (452 and 226, respectively) in the final analysis. The incidence of hypoglycemia was lower in the low-dosage group compared with the regular-dosage group (19 [4.2%] vs. 52 [23.0%], respectively; OR, 0.15 [95% CI, 0.08–0.26]; P < 0.001). The incidence of hyperglycemia did not differ between the low- and regular-dosage groups (319 [70.6%] vs. 154 [68.1%], respectively; OR, 1.12 [95% CI, 0.79–1.58]; P = 0.5). No participants experienced diabetic ketoacidosis or hyperosmolar hyperglycemic state. Each 1% decrease in the baseline HbA1c concentration was associated with a 19.9-fold (95% CI, 9.6–41.5; P < 0.001) increase in the odds of hypoglycemia, and each 1% increase in the baseline HbA1c concentration was associated with a 15.7-fold (95% CI, 10.0–24.6; P < 0.001) increase in the odds of hyperglycemia.ConclusionDosage reduction decreases the incidence of hypoglycemia without a concomitant increase in the incidences of hyperglycemia, diabetic ketoacidosis, and hyperosmolar hyperglycemic state in people with type 2 diabetes who fast during Ramaḍān.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT04237493.
The authors report the first case of stage 4 cytokine release syndrome (CRS) (graded by the National Cancer Institute Common Terminology Criteria for Adverse Effects scale) involving a patient with advanced metastatic melanoma who was treated with the combination of two monoclonal antibodies, nivolumab (anti-programmed cell death receptor 1 inhibitor [PD-1]) and ipilimumab (a cytotoxic T lymphocyte-associated antigen 4 inhibitor [CTLA-4]) after her first dose of both. The patient was treated initially with methylprednisolone and tocilizumab but was refractory to treatment. A trial of etanercept was initiated due to her elevated levels of TNF-α which elicited a satisfactory response. Monoclonal antibody therapy is a new tool for the treatment of many cancers, and therefore there may be a subsequent rise in the cases of CRS and this case exemplifies a treatment algorithm. Utilizing levels of cytokines assists in tailoring treatment such as in this case where etanercept, a TNF-α inhibitor, was utilized due to the patient’s elevated levels of TNF-α.
Tumor lysis syndrome (TLS) is an oncologic emergency characterized by the destruction of tumor cells leading to an influx of large amounts of uric acid, potassium, and phosphorus into systemic circulation. It most often occurs after the initiation of cytotoxic therapy in high-grade lymphomas and leukemias; however, rarely it may occur spontaneously. The authors report a case of spontaneous tumor lysis causing electrolyte abnormalities and acute kidney injury in a patient with subsequently diagnosed large chronic lymphocytic leukemia tumor burden. Spontaneous TLS can be the first presentation of underlying malignancy; therefore, physicians should be aware of the associated findings.
The role of cytoreductive nephrectomy has become unclear since the introduction of immunotherapy which is now the backbone of the treatment for metastatic renal cell carcinoma. Different combinations are used based on the prognosis. Achieving a complete response would be ideal and includes radiographic disappearance of lesions. However, there have been a few reported cases of pathological complete response with persistent radiographic evidence of cancer. The authors report a case of pathological complete response despite persistent radiographic evidence of residual disease in a patient with metastatic renal cell carcinoma treated with pembrolizumab and axitinib. The patient subsequently underwent cytoreductive nephrectomy after the 13th dose of pembrolizumab. The resected mass consisted of scar tissue with no viable tumor cells seen on pathology but only scar tissue. This case reveals that persistent radiographic evidence of the tumor may be explained by scar tissue, challenging the role of cytoreductive nephrectomy in the era of immunotherapy.
Hereditary platelet delta (δ)-storage pool deficiency is a rare condition in which there are fewer dense granules in platelets disrupting primary hemostasis. It can cause a mild–moderate bleeding tendency with normal coagulation studies; hence, it is an underdiagnosed diagnostic challenge. The authors present three patients with hereditary platelet delta (δ)-storage pool deficiency who had heavy menstrual bleeding, excessive bleeding following surgery, mucocutaneous bleeding, and a bleeding score greater than or equal to 6. These cases reveal the susceptibility of underdiagnosing platelet disorders and the significance of utilizing a bleeding assessment tool to help guide further workup with transmission electron microscopy to visualize the fewer dense granules in platelets. Although bleeding is typically moderate, it can be severe in certain scenarios, like after mucosal surgeries, and can lead to death, highlighting the importance of the condition’s recognition and prophylactic treatment.
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