Myocarditis occurrence with cancer immunotherapy across indications in clinical trial and post-marketing data.

Antibodies targeting the PD-1, PD-L1, and CTLA-4 immune checkpoint axis have been used in a variety of tumor types. They achieve anti-tumor activity through activating the patient's own immune system to target immune response evading cancer cells. However, this unique mechanism of action may cause immune-related adverse events, irAEs. One of these irAEs is myocarditis which is associated with an alarming mortality rate. In this study we presented clinical cases of myocarditis from safety trial datasets submitted to the U.S. Food and Drug Administration, FDA. Additionally, we analyzed over fourteen million FDA Adverse Event Reporting System, FAERS, submissions. The statistical analysis of the FAERS data provided evidence of significantly increased reporting of myocarditis in patients administered immune checkpoint inhibitors alone, in combination with another immune checkpoint inhibitor, the kinase inhibitor axitinib, or chemotherapy, for all cancer types, when compared to patients administered chemotherapy. All combination therapies led to further increased reporting odds ratios of myocarditis. We further analyzed the occurrence of myocarditis by stratifying the reports into sub-cohorts based on specific cancer types and treatment/control groups in major cancer immunotherapy efficacy trials and confirmed the observed trend for each cohort.

Cardiac adverse events associated with chloroquine and hydroxychloroquine exposure in 20 years of drug safety surveillance reports.

Chloroquine (CQ) and hydroxychloroquine (HCQ) are on the World Health Organization's List of Essential Medications for treating non-resistant malaria, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, both drugs are currently used off-label in hospitals worldwide and in numerous clinical trials for the treatment of SARS-CoV-2 infection. However, CQ and HCQ use has been associated with cardiac side effects, which is of concern due to the higher risk of COVID-19 complications in patients with heart related disorders, and increased mortality associated with COVID-19 cardiac complications. In this study we analyzed over thirteen million adverse event reports form the United States Food and Drug Administration Adverse Event Reporting System to confirm and quantify the association of cardiac side effects of CQ and HCQ. Additionally, we identified several confounding factors, including male sex, NSAID coadministration, advanced age, and prior diagnoses contributing to drug related cardiotoxicity. These findings may help guide therapeutic decision making and ethical trial design for COVID-19 treatment.

Female pattern hair loss: A clinical, pathophysiologic, and therapeutic review.

Female pattern hair loss (FPHL) is the most common form of alopecia in women. Affected women may experience psychological distress and impaired social functioning. Early diagnosis and initiation of treatment are desirable because treatments are more effective to avoid the progression of hair loss than stimulating regrowth. Typically, a diagnosis of FPHL can be confirmed by review of a patient's medical history and a physical examination alone. Testing a scalp biopsy is diagnostic but usually not required. In women with signs of hyperandrogenism, an investigation for ovarian or adrenal disorders should be performed. Treatment for FPHL is obscured by myths. The aim of FPHL treatment could be two-fold: Reverse or stabilize the process of hair follicle miniaturization. Mild-to-moderate FPHL in women can be treated with oral antiandrogen therapies (cyproterone acetate and spironolactone) and/or topical minoxidil with good results in many cases. If used correctly, available medical treatments arrest the progression of the disease and reverse miniaturization in most patients with mild-to-moderate FPHL. Hair systems and surgery may be considered for selected cases of severe FPHL.

Malignant melanoma in Ferrara, Northern Italy: epidemiologic survey focusing on tumor thickness.

AIM: Estimates of malignant melanoma (MM) incidence and prognosis vary widely. The present study was performed to analyze epidemiologic and prognostic aspects of primary MM mainly in relation to tumor thickness. METHODS: We conducted a retrospective study on a cohort of 435 patients with diagnosis of primary MM between 1997 and 2011. RESULTS: In the period 2009-2011, among the MM diagnosed 50.00% were thin, 32.43% in situ and 17.57% thicker while in 1997-1999 MM>1 mm accounted for 51.61% of diagnoses. Mean age of patients affected with thin MM was significantly lower than that of patients with MM>1 mm, and mean thickness resulted significantly lower in female patients than in males. Mean thickness of MM located on easily self-evaluable body areas was significantly lower than in those not accessible for skin self-examination. The commonest histogenetic type was superficially spreading melanoma. Mitotic rate, ulceration and vertical growth phase all resulted related to MM thickness. Out of 61 patients with thin MM who underwent SLNB, 3 resulted positive (4.92%): neither thickness >0.75 mm, nor ulceration, mitotic rate or Clark level were found to be associated with SLNB positivity. Five-year survival rate was 98.3% for thin MM patients and 76.4% for thick MM patients. CONCLUSION: Our trend analysis evidences a continuing increase of thinner primary MM throughout the study period, potentially enhancing patient prognosis. Regular skin self-examination could contribute to earlier recognition of MM. Identification of more powerful predictors of thin MM prognosis is necessary.