Many reports indicate a hypercoagulative state in diabetes mellitus as result of endothelial damage. Experimental evidence suggests that a metabolic derangement triggers a cascade of biochemical events that lead to vascular dysfunction. The net effect is to convert the endothelium from thromboresistant to thrombogenic surface. In literature, a strong association between type 1 diabetes mellitus (DM1) and celiac disease (CD) has been reported. We do not have information about the hemostatic system in these associated conditions. Our study aims at evaluating whether the presence of CD in a group of DM1 patients is associated with a different expression of some hemostatic factors and with a different manifestation and/or progression of microvascular complications of DM1 in comparison with patients with only diabetes. Ninety-four adult DM1 patients were enrolled in the study and subsequently screened for CD. Anti-endomysial antibodies (EMA) were positive in 13 of 94 DM1 patients (13.8%). CD diagnosis was confirmed by histology and organ culture. The mean age and duration of DM1 of patients also affected by CD were similar to those of only diabetic patients, but the metabolic control and the hemocoagulative parameters were significantly different between the two groups: DM1 patients also affected by CD presented significantly lower concentrations of glycosylated hemoglobin (HbA1c) (P < 0.05), cholesterol (P < 0.001), triglycerides (P < 0.001), factor VII antigen (FVII:ag) (P < 0.005), factor VII coagulant activity (FVII:c) (P < 0.05), and prothrombin degradation fragments (F1+2) (P < 0.001), as well as higher values of activated C protein (APC) (<0.001). No retinal abnormalities and no signs of renal damage were observed in DM1 patients also affected by CD. Our results suggest a potential protective role of CD in the prothrombotic state of DM1.

In the observational study cited above, we evaluated whether the presence of undiagnosed CD in a group of adult DM1 patients is associated with a different expression of some hemostatic factors, as well as with a different manifestation and/or progression of microvascular complications in comparison with patients suffering from DM1 only. The Ventura group has carefully examined and commented on this study, but we are only partially in agreement with their observations. First, the including criterion HbA1c B 7.5% or 58 mmol/mol was chosen to ensure the selection of DM1 patients with a satisfactory long-standing metabolic control. This is to prevent that, during the disease progression, an inadequate metabolic control may have affected adversely on the study parameters. The evaluation of hemostatic factors and microvascular complications in DM1 patients also suffering from CD and presenting an unsatisfactory metabolic control could become the object of a future study.Second, we have chosen to assess the metabolic control by means of HbA1c in order to obtain long-standing information reflecting the chronic state that may culminate in microvascular complications. On the other hand, the metabolic control of adult patients with a long-standing DM1 is generally better than that found in diabetic children, to whom the Ventura group refers. This is because children have a shorter disease duration and they are more exposed to factors that can alter their metabolic control. In relation to the other parameters able to evaluate the metabolic control, the diabetologists have obviously considered the presence of frequent hypoglycemic events, the extreme glycemia variability, and the increment in daily insulin needs as an implicit exclusion criterion.Third, in most of the patients evaluated in our study, the presence of other autoimmune diseases has been investigated by means of a wide autoantibody serum panel (data not shown), and the results are not relevant. Finally, since our study was performed on a group of adult DM1 patients, we have obviously not considered anthropometric parameters because the patients enrolled in our study were all already adult, eventually affected by CD, and presenting negative malabsorption clinical picture. It would however be interesting to assess, in the future, the role of CD on hemostatic factors and microvascular complications also in diabetic children.In conclusion, we observed a better metabolic control and a thromboresistant condition in adult patients with both DM1 and undiagnosed CD, even if our opinion is that gluten-free diet is mandatory in all patients suffering from CD.Rome. 22 July 2011.

Awareness of the influence of sex ands gender on the natural history of several diseases is increasing. Community-acquired pneumonia (CAP) is the most common acute respiratory disease, and it is associated with both morbidity and mortality across all age groups. Although a role for sex- and gender-based differences in the development and associated complications of CAP has been postulated, there is currently high uncertainty on the actual contribution of these factors in the epidemiology and clinical course of CAP. More evidence has been produced on the topic during the last decades, and sex- and gender-based differences have also been extensively studied in COVID-19 patients since the beginning of the SARS-CoV-2 pandemic. This review aims to provide an extensive outlook of the role of sex and gender in the epidemiology, pathogenesis, treatment, and outcomes of patients with CAP, and on the future research scenarios, with also a specific focus on COVID-19.

Rational: The growing population of young cancer survivors and a trend toward postponing pregnancy until later years in life are leading to a deeper attention towards understanding treatment-induced sequelae, and, in particular, the effects of cancer and/or treatment on fertility. Nowadays, the infertility risks potentially associated with molecular targeted therapies are not established, and clinical reports are sparse. Moreover, the increasing use of molecular targeted drugs in the adjuvant setting and in diseases with better prognosis makes preservation of fertility a major topic in current research. Patient's concerns: Here, we report the case of an 18-year-old woman, with a 3-cm superficial lump of the right breast, who had no remarkable family or medical history. Menarche had occurred at the age of 14 years, with normal regular periods. Diagnosis: High-grade angiosarcoma, with metastatic progression and multiple relapse, was diagnosed. Interventions: After diagnosis, right radical mastectomy was carried out with no evidence of residual disease. No adjuvant treatment was delivered. Lymph node metastasis were found later and chemotherapy with doxorubicin 25 mg/m2/day and ifosfamide 1 g/m2/day (both on days 1–3) every 21 days was administered. During treatment, the patient reported menstrual irregularities but no amenorrhea. Due to further local relapse a few years later, the patient was treated for progressive metastatic disease with gemcitabine 1000 mg/m2 on days 1 and 8 every 21 days for 6 cycles, and underwent surgery, followed by pegylated liposomal doxorubicin, 50 mg/m2 on day 1 every 28 days. After further disease progression 5 years after first diagnosis, pazopanib was administered at a dose of 800 mg daily for 10 months. Outcomes: The patient experienced a transient ovarian insufficiency possibly due to pazopanib. Since amenorrhea developed within 2 months from the initiation of pazopanib treatment and menses returned regularly only after discontinuation of the treatment itself. Lessons: This is the first case report that strongly suggests a correlation between pazopanib exposure and development of ovarian insufficiency. Our case tantalizes to inspire additional preclinical and clinical research on the true incidence, possible dose dependence, and reversibility of pazopanib (and other TKIs) -induced ovarian failure.

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