Exenatide is a subcutaneous injectable glucagon-like peptide 1 receptor agonist that has been approved by the Federal Drug Administration for the treatment of type 2 diabetes mellitus. While side effects such as nausea, vomiting and local hypersensitivity reactions are more commonly described, angio-oedema has never been previously reported in the literature. We present the case of a 67-year-old woman who presented to the emergency department with acute-onset tongue swelling, difficulty breathing, dizziness and diffuse itching which began shortly after receiving her first dose of intramuscular extended release (ER) exenatide. This case aims to raise awareness of the potential adverse effect of angio-oedema secondary to exenatide ER and serves as a reminder to clinicians to discuss possible adverse effects of medications and early recognition of symptoms which would prompt further medical attention.
Rubinstein-Taybi syndrome (RSTS) is a congenital syndrome most associated with mutations on chromosome 16p13.3 that can result in both benign and malignant neurologic and hematologic neoplasms of various primary origins. We present the case of a 39-year old female with RSTS who presented with severe abdominal and pelvic pain. Abdominal and pelvic imaging revealed multiple masses involving the uterus, liver and spleen concerning for malignancy. Biopsies from the endometrium and cervix confirmed this as a poorly differentiated, widely invasive squamous cell carcinoma. This represents the first case of primary squamous cell carcinoma of gynecologic origin in a patient with Rubinstein-Taybi syndrome. This case aims to raise awareness of the gynecological malignancy in patients with RSTS as well as serves as a reminder to clinicians to have a broad differential diagnosis in all patients which may help lead to early recognition of pathology.
The use of glycosylated hemoglobin as a diabetic glycemic control and cardiovascular risk marker is well documented. It has also been suggested as a marker for early diastolic hemodynamic changes leading to clinical heart failure, but is less well characterized. This study explored the association between elevated glycosylated hemoglobin and liver Fibrosis-4 values and worsening measures of diastolic cardiac function in order to assess their potential as early serologic markers in cardiovascular disease prevention.A retrospective cohort analysis was conducted in 102 patients presenting to the Parkview Medical Center health system who had received a full resting echo characterized by normal systolic ejection fraction and clinical risk factors associated with stage A heart failure in conjunction with glycosylated hemoglobin and Fibrosis-4 scores within a 3-month time window. Using regression analysis, measures of diastolic cardiac function were assessed in conjunction with rising glycosylated hemoglobin levels characterized as <6.5 and > 6.5 and Fibrosis-4 scores after controlling for the presence of hypertension, coronary artery disease and valvular heart disease. Glycosylated hemoglobin levels > 6.5 were significantly associated with a higher E/e’ ratio and closely associated with an elevated left atrial volume index both indicative of elevated left atrial pressure as a sensitive marker for diastolic cardiac dysfunction. Fibrosis-4 scores did not appear to be clinically associated with progression of diastolic dysfunction.Thus, glycosylated hemoglobin may act as an early marker for identifying patients at increased risk for the progression of stage A heart failure. Fibrosis-4 scores do not appear to be related.
Introduction: Intracellular molecular inhibitors act by inducing apoptosis due to inhibition of intracellular proteins like 20S proteasome subunit, histone deacetylases (HDAC's), exportin 1 (XPO1), cyclin-dependent kinases (CDKs) and kinesin spindle protein (KSP). These proteins are involved in the regulation of cell cycle. The aim of our analysis is to report published literature on the clinical efficacy of intracellular molecular inhibitors in relapsed and refractory multiple myeloma (RRMM) patients. Methods: Following Prisma guidelines, we performed a comprehensive literature search on articles published after 2011. Four hundred eighty-nine articles were identified using the following five databases (Pubmed, Embase Cochrane, Web of Science and Clinical Trials.gov). After a detailed screening, we finalized 13 studies involving 902 RRMM patients. We included phase I/II, II and III studies. The studies involving drugs approved by the US Food and Drug Administration were excluded. Results:Selective inhibitor of nuclear export (SINE) compounds: Selinexor A total of 112 RRMM patients were included. Thirty-three patients were in phase I/II while 79 patients were in phase II. All patients received selinexor (60-100 mg) in different combination regimens. Forty-eight patients were quad-refractory (refractory to bortezomib, carfilzomib, lenalidomide, and pomalidomide) while 31 patients were penta-refractory (including isatuximab/daratumumab). In 110 evaluable patients, the pooled overall response rate (ORR) was 35.45%. The ORR in the subset of quad-refractory and penta-refractory patients was 21% and 20% respectively. The best response was seen when selinexor was used in combination with bortezomib (V) and dexamethasone (d) i.e. 77%.HDAC inhibitors: Vorinostat and Ricolinostat A total of 562 RRMM patients were included. Seventy-seven patients were in phase I/II, 168 patients in phase II, and 317 patients were in phase III. Five hundred and eighteen patients received vorinostat (100-400 mg) in different combination regimens while 44 patients received ricolinostat (160-240mg) in combination with Vd. The median follow-up period was 13.2-30.8 months. In 560 evaluable patients, the pooled ORR was 42.83% and 31.81% in patients who received vorinostat and ricolinostat, respectively. The best response was seen when vorinostat was used in combination with V, doxorubicin (DX) and d i.e. 67%.Proteasome inhibitors: Oprozomib and Marizomib A total of 117 RRMM patients were included. Hundred and two patients were in phase I/II while 15 patients were in phase II. Twenty-seven, 34 and 41 patients received single-agent oprozomib in the dose of 240 mg, 150-180 mg, and 240-300 mg respectively while 15 patients received single-agent marizomib (0.5 mg/m2). Out of 107 evaluable patients, the pooled ORR was 27.65% in patients who received oprozomib while no response was seen in patients who received marizomib however stable disease was seen in 31% of patients.KSP inhibitor: Filanesib A total of 50 RRMM patients were included. All patients were in phase II. Thirty-two patients received single-agent filanesib (1.5mg/m2) while 18 patients received filanesib (1.5mg/m2) in combination with d. The pooled ORR was 22%. The ORR was 19% when filanesib was used as a single agent while it was 28% when filanesib was used in combination with d.CDK inhibitors: Dinaciclib and Palbociclib A total of 61 RRMM patients were included. All patients were in phase I/II. Twenty-nine patients received single-agent dinaciclib (30-50 mg/m2) while 32 patients received palbociclib (100mg) in combination with Vd. In 52 evaluable patients, the ORR in patients who received dinaciclib was 11% while the ORR in patients who received palbociclib was 20%. Conclusion: In RRMM patients, vorinostat and selinexor when used in combination regimens demonstrated a weak efficacy with a pooled ORR of 43% and 36% respectively. The best response was seen in combination with Vd i.e. 67% and 77% respectively. The data on other intracellular molecular inhibitors (ricolinostat, oprozomib, marizomib, filanesib, dinaciclib, and palbociclib) when used either as single agents or in combination regimens, suggested a poor efficacy with an ORR of < 35%. However, future randomized well designed prospective clinical trials involving a larger population are required to further explore the efficacy of these agents in RRMM patients. Disclosures No relevant conflicts of interest to declare.
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