Sex Differences in Cardiovascular Mortality in Diabetics and Nondiabetic Subjects: A Population-Based Study (Italy)

The objective of this study is to assess the impact of diabetes on cardiovascular mortality, focusing on sex differences. The inhabitants of Reggio Emilia province on December 31, 2009, aged 20–84 were followed up for three years for mortality. The exposure was determined using Reggio Emilia diabetes register. The age-adjusted death rates were estimated as well as the incidence rate ratios using Poisson regression model. Interaction terms for diabetes and sex were tested by the Wald test. People with diabetes had an excess of mortality, compared with nondiabetic subjects (all cause: IRR = 1.68; 95%CI 1.60–1.78; CVD: IRR = 1.61; 95%CI 1.47–1.76; AMI: IRR = 1.59; 95%CI 1.27–1.99; renal causes: IRR = 1.71; 95%CI 1.22–2.38). The impact of diabetes is greater in females than males for all causes (P=0.0321) and for CVD, IMA, and renal causes. Further studies are needed to investigate whether the difference in cardiovascular risk profile or in the quality of care delivered justifies the higher excess of mortality in females with diabetes compared to males

Nutrient withdrawal rescues growth factor-deprived cells from mTOR-dependent damage

Deregulated nutrient signaling plays pivotal roles in body ageing and in diabetic complications; biochemical cascades linking energy dysmetabolism to cell damage and loss are still incompletely clarified, and novel molecular paradigms and pharmacological targets critically needed. We provide evidence that in the retrovirus-packaging cell line HEK293-T Phoenix, massive cell death in serum-free medium is remarkably prevented or attenuated by either glucose or aminoacid withdrawal, and by the glycolysis inhibitor 2-deoxy-glucose. A similar protection was also elicited by interference with mitochondrial function, clearly suggesting involvement of energy metabolism in increased cell survival. Oxidative stress did not account for nutrient toxicity on serum-starved cells. Instead, nutrient restriction was associated with reduced activity of the mTOR/S6 Kinase cascade. Moreover, pharmacological and genetic manipulation of the mTOR pathway modulated in an opposite fashion signaling to S6K/S6 and cell viability in nutrient-repleted medium. Additionally, stimulation of the AMP-activated Protein Kinase concomitantly inhibited mTOR signaling and cell death, while neither event was affected by overexpression of the NAD+ dependent deacetylase Sirt-1, another cellular sensor of nutrient scarcity. Finally, blockade of the mTOR cascade reduced hyperglycemic damage also in a more pathophysiologically relevant model, i.e. in human umbilical vein endothelial cells (HUVEC) exposed to hyperglycemia. Taken together these findings point to a key role of the mTOR/S6K cascade in cell damage by excess nutrients and scarcity of growth-factors, a condition shared by diabetes and other ageing-related pathologies

Multi-approach methods to predict cryptic carbapenem resistance mechanisms in Klebsiella pneumoniae detected in Central Italy

The rapid emergence of carbapenem-resistant Klebsiella pneumoniae (Kp) strains in diverse environmental niches, even outside of the clinical setting, poses a challenge for the detection and the real-time monitoring of novel antimicrobial resistance trends using molecular and whole genome sequencing-based methods. The aim of our study was to understand cryptic resistance determinants responsible for the phenotypic carbapenem resistance observed in strains circulating in Italy by using a combined approach involving whole genome sequencing (WGS) and genome-wide association study (GWAS). In this study, we collected 303 Kp strains from inside and outside clinical settings between 2018–2022 in the Abruzzo region of Italy. The antimicrobial resistance profile of all isolates was assessed using both phenotypic and bioinformatic methods. We identified 11 strains resistant to carbapenems, which did not carry any known genetic determinants explaining their phenotype. The GWAS results showed that incongruent carbapenem-resistant phenotype was associated specifically with strains with two capsular types, KL13 and KL116 including genes involved in the capsule synthesis, encoding proteins involved in the assembly of the capsule biosynthesis apparatus, capsule-specific sugar synthesis, processing and export, polysaccharide pyruvyl transferase, and lipopolysaccharide biosynthesis protein. These preliminary results confirmed the potential of GWAS in identifying genetic variants present in KL13 and KL116 that could be associated with carbapenem resistance traits in Kp. The implementation of advanced methods, such as GWAS with increased antimicrobial resistance surveillance will potentially improve Kp infection treatment and patient outcomes

Diagnostic values of glycated haemoglobin and diagnosis of diabetes: Results of a cross-sectional survey among general practitioners in the province of Reggio Emilia, Italy

AbstractAimsThe aim of this study was to investigate whether subjects included in the diabetes register solely because their HbA1c was over the diagnostic threshold received a diagnosis of diabetes from their general practitioner (GP).MethodsThe study included all registered cases in 2009–2010 aged 18 or over that were identified only by the laboratory database because they had one or more HbA1c over the 6.5% threshold and for whom we did not find any information in the search of full electronic clinical records. Multilevel logistic regression was used to examine the influence of GP and patient characteristics.ResultsThere were 228 participating GPs (76.3% of those invited) and 832 assessed subjects (68.8% of study population). There was a strong clustering among the GPs (residual intraclass correlation = 0.52, 95% CI 0.40–0.64). About one in two (55.5%) subjects with two or more HbA1c > =6.5% has been diagnosed as diabetic and the percentage declined – unless zeroing – in case the abnormal value was only one (28.3%). The likelihood of being labelled ‘no diabetes’ was greater in subjects aged less than 65 or over 74 with respect to the reference age group (OR 1.89, 95% CI 1.13–3.15; OR 1.55 95% CI 0.94–2.53). The same likelihood consistently decreased when HbA1c test was accompanied by abnormal fasting plasma glucose (FPG) assay (OR 0.20, 95% CI 0.12–0.32).ConclusionsA permanent exchange of information between the diabetes register and GPs should be maintained to improve the care of patients and the awareness of criteria for diabetes diagnosis among GPs

Sex Differences in Cardiovascular Mortality in Diabetics and Nondiabetic Subjects: A Population-Based Study (Italy)

The objective of this study is to assess the impact of diabetes on cardiovascular mortality, focusing on sex differences. The inhabitants of Reggio Emilia province on December 31, 2009, aged 20-84 were followed up for three years for mortality. The exposure was determined using Reggio Emilia diabetes register. The age-adjusted death rates were estimated as well as the incidence rate ratios using Poisson regression model. Interaction terms for diabetes and sex were tested by the Wald test. People with diabetes had an excess of mortality, compared with nondiabetic subjects (all cause: IRR = 1.68; 95%CI 1.60-1.78; CVD: IRR = 1.61; 95%CI 1.47-1.76; AMI: IRR = 1.59; 95%CI 1.27-1.99; renal causes: IRR = 1.71; 95%CI 1.22-2.38). The impact of diabetes is greater in females than males for all causes ( = 0.0321) and for CVD, IMA, and renal causes. Further studies are needed to investigate whether the difference in cardiovascular risk profile or in the quality of care delivered justifies the higher excess of mortality in females with diabetes compared to males

Is There a Role for Bone Marrow Biopsy In The Diagnosis of Masked Polycythemia Vera with Splanchnic Vein Thrombosis?

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Ten-year outcome of chronic-phase chronic myeloid leukemia patients treated with imatinib in real life

Imatinib, the first BCR/ABL kinase inhibitor approved for the treatment of chronic myeloid leukemia (CML), has changed the long-term outcome of patients affected by this disease. The aim of our analysis was to report, after a median follow-up of 10.2years (range 5.8-14.8), the long-term outcome, efficacy, and safety of imatinib treatment (frontline and after interferon failure) in a single institution cohort of 459 patients with CML in chronic phase treated outside of clinical trials. The 10-year overall survival of the whole cohort was 77.1\%, while the 10-year probability of dying due to CML and other causes was 7.8\% and 16\%, respectively. The prognostic value of the BCR-ABL1 ratio at 3months (10\%) and of complete cytogenetic response and major molecular response at 1year was confirmed also in the real-life practice. The EUTOS long-term survival score better stratified the baseline risk of dying of CML compared with other risk scores. Two hundred thirty-six (51.4\%) patients achieved a deep molecular response during imatinib treatment after a median time of 4.57years, and 95 (20.6\%) had a stable deep molecular response maintained for at least 2 consecutive years. Imatinib was associated with a low rate of serious cardiovascular events and second neoplasia. This 10-year real-life follow-up study shows that imatinib maintains efficacy over time and that long-term administration of imatinib is not associated with notable cumulative or late toxic effects

Additional file 1: of Diabetes and risk of cancer incidence: results from a population-based cohort study in northern Italy

No. of subjects with cancer by diabetes status, Incidence Rate Ratios (IRR) and 95% Confidence Interval (95%CI) for subjects with at least 2 years of diabetes duration vs subjects without diabetes. Cancer incidence risk analysis for subjects with at least 2 years of diabetes duration compared to subjects without diabetes. (DOC 52 kb

Aplastic Anemia and Good Syndrome in a Heavily Treated Stage IV Thymoma Patient: A Case Report and Review of the Literature

Tymoma is an uncommon slowly growing neoplasm. It usually presents with paraneoplastic syndromes including the immunodeficiency syndrome called Good syndrome and hematological disorders. Pure red cell aplasia is a well-recognized complication of thymoma, and aplastic anemia is very rare in association with GS. We report a case of GS in a heavily treated patient with stage IV thymoma associated with a pure red cell aplasia and an amegakaryocytic thrombocytopenia that evolved into an AA and provide an up-to-date review of the relevant literature. )is is the first case of the association of GS and AA with the coexistence of a heavily treated stage IV thymoma. )e fatal outcome was not related to the progression of the thymoma, but rather to the severe infectious complications. )e combination of lymphopenia and hypogammaglobulinemia typical of GS, coupled to the neutropenia, caused by bone marrow failure, was the main predisposing factor for the unfavourable outcome

3D CT-Inclusive Deep-Learning Model to Predict Mortality, ICU Admittance, and Intubation in COVID-19 Patients

Chest CT is a useful initial exam in patients with coronavirus disease 2019 (COVID-19) for assessing lung damage. AI-powered predictive models could be useful to better allocate resources in the midst of the pandemic. Our aim was to build a deep-learning (DL) model for COVID-19 outcome prediction inclusive of 3D chest CT images acquired at hospital admission. This retrospective multicentric study included 1051 patients (mean age 69, SD = 15) who presented to the emergency department of three different institutions between 20th March 2020 and 20th January 2021 with COVID-19 confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Chest CT at hospital admission were evaluated by a 3D residual neural network algorithm. Training, internal validation, and external validation groups included 608, 153, and 290 patients, respectively. Images, clinical, and laboratory data were fed into different customizations of a dense neural network to choose the best performing architecture for the prediction of mortality, intubation, and intensive care unit (ICU) admission. The AI model tested on CT and clinical features displayed accuracy, sensitivity, specificity, and ROC-AUC, respectively, of 91.7%, 90.5%, 92.4%, and 95% for the prediction of patient's mortality; 91.3%, 91.5%, 89.8%, and 95% for intubation; and 89.6%, 90.2%, 86.5%, and 94% for ICU admission (internal validation) in the testing cohort. The performance was lower in the validation cohort for mortality (71.7%, 55.6%, 74.8%, 72%), intubation (72.6%, 74.7%, 45.7%, 64%), and ICU admission (74.7%, 77%, 46%, 70%) prediction. The addition of the available laboratory data led to an increase in sensitivity for patient's mortality (66%) and specificity for intubation and ICU admission (50%, 52%, respectively), while the other metrics maintained similar performance results. We present a deep-learning model to predict mortality, ICU admittance, and intubation in COVID-19 patients