Role of Breast Cancer Risk Estimation Models to Identify Women Eligible for Genetic Testing and Risk-Reducing Surgery.

Hereditary breast and ovarian cancer (HBOC) syndrome is responsible for approximately 10% of breast cancers (BCs). The HBOC gene panel includes both high-risk genes, i.e., a four times higher risk of BC (BRCA1, BRCA2, PALB2, CDH1, PTEN, STK11 and TP53), and moderate-risk genes, i.e., a two to four times higher risk of BC (BARD1, CHEK2, RAD51C, RAD51D and ATM). Pathogenic germline variants (PGVs) in HBOC genes confer an absolute risk of BC that changes according to the gene considered. We illustrate and compare different BC risk estimation models, also describing their limitations. These models allow us to identify women eligible for genetic testing and possibly to offer surgical strategies for primary prevention, i.e., risk-reducing mastectomies and salpingo-oophorectomies.

Diagnostic performance of a point of care high-sensitivity cardiac troponin I assay and single measurement evaluation to rule out and rule in acute coronary syndrome.

OBJECTIVES: About 10 million individuals in USA presented annually in the emergency department (ED) with chest pain or with signs and symptoms of acute coronary syndrome (ACS). The advent of point of care (POC) devices, able to measure high sensitivity troponin, are a very interesting tool in the ED setting for its rapid turnaround time (<10 min). METHODS: The present study evaluates the diagnostic performance of the Atellica VTLi (Siemens) in real life setting using the clinical data derived from integrated diagnoses of emergency room staff and cardiologist and in comparison with standard laboratory hs-cTnT assay (Cobas 8000, Elecsys, Roche). 966 patients admitted to the emergency department of "G. Mazzini Hospital" in Teramo, Italy, from July 27, 2022, through June 09, 2023, were enrolled. RESULTS: The diagnostic performance of POC hs-cTnI was evaluated. An appropriate POC hs-cTnI threshold values <4 ng/L supplied a sensitivity and an NPV of 100 % (95 % CI: 99.5-100) in order to achieve rapid rule out for MI through a single measurement at patient presentation in the ED. Furthermore, a derivation POC hs-cTnI concentration >54 ng/L provided a specificity of 97.2 % (95 % CI: 95.9-98.1) and a PPV of 43.5 % (95 % CI: 40.3-46.7) for ruling in MI. CONCLUSIONS: This platform showed comparable diagnostic performance for myocardial infarction to the central laboratory. Our data suggest the possible use of the Atellica VTLi hs-cTnI POC assay either in emergency department of urban medical centre, either in rural hospital for triage and patient management.

Role of the Molecular Tumor Board for the Personalized Treatment of Patients with Metastatic Breast Cancer: A Focus on the State of the Art in Italy.

Molecular tumor boards (MTBs) are multidisciplinary groups that combine molecular and clinical data from cancer patients in order to formulate treatment recommendations for precision medicine. To date, there is insufficient data to support the use of singleplex or next-generation sequencing (NGS) technologies to select first-line therapy for patients with metastatic breast cancer (MBC), but considering the high number of level II alterations, according to the ESMO scale for clinical actionability of molecular targets (ESCAT), it is suggested to include patients in molecular screening programs in order to be able to offer targeted therapies for specific genomic alterations. This article aims at reviewing the most recent literature related to the most used methodologies/approaches for molecular diagnostics and variants' classification, summarizing the internationally published molecular screening studies in support of MTB activity and, in the end, discussing MTBs' current position and role in Italy, the number of which is increasing, also thanks to the thrust of institutions.

Pleural empyema associated with alveolar-pleural fistulas in severe acute respiratory syndrome coronavirus 2.

Surgery in COVID-19 disease complicated by APF represents the last life-saving treatment option. The choice of the therapeutic period to indicate this approach is fundamental. In fact, the clinical stability of patient is necessary in order to allow single-lung ventilation and to minimize postoperative sequelae.

Clinical and Prognostic Features of Essential Thrombocythemia: Comparison of 2001 WHO Versus 2008/2016 WHO Criteria in a Large Single-center Cohort.

BACKGROUND: According to 2008/2016 classification of the World Health Organization (WHO), a platelet (PLT) count ≥ 450 × 109/L, reduced from the previously published WHO 2001 indicated level ≥ 600 × 109/L, was considered the new PLT threshold for the diagnosis of essential thrombocythemia (ET). PATIENTS AND METHODS: To validate this important diagnostic change in a setting of current clinical practice, we retrospectively analyzed clinical and hematologic features at diagnosis and during follow-up of 162 patients with ET, diagnosed in our center from January 2008 to December 2017. We subdivided patients according to PLT value at baseline into Group A (PLT ≥ 600 × 109/L) (124 patients; 76.5%) and Group B (PLT ≥ 450 × 109/L < 600 × 109/L) (38 patients; 23.5%). RESULTS: Among clinical features, only the median value of leukocytes (P < .001) was significantly higher in Group A. Cytostatic treatment was administered in 103 patients, with a significantly higher rate in patients of group A (P < .001). After a median follow-up of 42.4 months (interquartile range, 22.1-70.6 months), 8 thrombotic events were recorded in the entire cohort, without differences between the 2 groups (P = .336). The 5-year overall survival (OS) of the entire cohort was 96.9% (95% confidence interval, 92.6%-100%), without differences between the 2 groups (P = .255). CONCLUSIONS: Our data indicate a substantial homogeneity among patients with ET regardless of the PLT count at diagnosis, thus confirming the usefulness of the 2008/2016 WHO diagnostic criteria.

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

Thymoma 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. This is the first case of the association of GS and AA with the coexistence of a heavily treated stage IV thymoma. The fatal outcome was not related to the progression of the thymoma, but rather to the severe infectious complications. The 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.

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 10.2 years (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 3 months (⩽ 10%) and of complete cytogenetic response and major molecular response at 1 year 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 4.57 years, 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.

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

BACKGROUND: Aim of this study was to compare cancer incidence in populations with and without diabetes by cancer site. Furthermore, we aimed at comparing excess risk of cancer according to diabetes type, diabetes duration and treatment, the latter as regards Type 2 diabetes. METHODS: By use of the Reggio Emilia diabetes registry we classified the resident population aged 20-84 at December 31st 2009 into two groups: with and without diabetes. By linking with the cancer registry we calculated the 2010-2013 cancer incidence in both groups. The incidence rate ratios (IRR) by cancer site, type of diabetes, diabetes duration, and as concerns Type 2 diabetes, by treatment regimen were computed using Poisson regression model and non-diabetic group as reference. RESULTS: The cohort included 383,799 subjects without diabetes and 23,358 with diabetes. During follow-up, we identified 1464 cancer cases in subjects with diabetes and 9858 in the remaining population. Overall cancer incidence was higher in subjects with diabetes than in those without diabetes (IRR = 1.22, 95%CI 1.15-1.29), with similar results focusing on subjects with at least 2-year diabetes duration. Cancer sites driving overall increased risk were liver, pancreas, Colon rectum, and bladder in both sexes, corpus uteri for females. There was also suggestion of an increased risk for kidney cancer in females and a decreased risk for prostate cancer. Excess risk was found in patients with Type 2 diabetes, more marked among insulin users, especially with combined therapy. We observed an increasing risk for diabetes duration up to 10 years from diagnosis (IRR = 1.44, 95%CI 1.29-1.61) and a subsequent decrease to moderate-higher risk (IRR = 1.15, 95%CI 1.04-1.30). CONCLUSIONS: Our study indicates that the strength of association depends on specific cancer site. Insulin, monotherapy or combined therapy, per se or as an indication of poor blood glucose control, in addition to diabetes duration, may play a role in the association of diabetes and cancer.

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.

AIMS: The 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). METHODS: The 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. RESULTS: There 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). CONCLUSIONS: A 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.

Building a population-based diabetes register: an Italian experience.

AIMS: To describe the methodology used to set up the Reggio Emilia (northern Italy) Diabetes Register. The prevalence estimates on December 31st, 2009 are also provided. METHODS: The Diabetes Register covers all residents in the Reggio Emilia province. The register was created by deterministic linkage of six routinely collected data sources through a definite algorithm able to ascertain cases and to distinguish type of diabetes and model of care: Hospital Discharge, Drug Dispensation, Biochemistry Laboratory, Disease-specific Exemption, Diabetes Outpatient Clinics, and Mortality databases. Using these data, we estimated crude prevalence on December 31st, 2009 by sex, age groups, and type of diabetes. RESULTS: There were 25,425 ascertained prevalent cases on December 31st, 2009. Drug Dispensation and Exemption databases made the greatest contribution to prevalence. Analyzing overlapping sources, more than 80% of cases were reported by at least two sources. Crude prevalence was 4.8% and 5.9% for the whole population and for people aged 18 years and over, respectively. Males accounted for 53.6%. Type 1 diabetes accounted for 3.8% of cases, while people with Type 2 diabetes were the overriding majority (91.2%), and Diabetes Outpatient Clinics treated 75.4% of people with Type 2 diabetes. CONCLUSION: The Register is able to quantify the burden of disease, the first step in planning, implementing, and monitoring appropriate interventions. All data sources contributed to completeness and/or accuracy of the Register. Although all cases are identified by deterministic record linkage, manual revision and General Practitioner involvement are still necessary when information is insufficient or conflicting.