Bilateral breast carcinoma – a study of patients admitted in a university emergency hospital

Introduction. Breast carcinoma represents the leading cause of oncologic mortality among women worldwide. Bilateral breast carcinoma is a distinct pathologic entity, with particular prognostic and therapeutic implications. Objective. The objective of the study was to determine the histologic and immunohistochemical characteristics of patients with bilateral breast carcinoma admitted in a university emergency hospital from Bucharest, Romania. Materials and methods. We analyzed breast carcinoma specimens registered as bilateral in the Department of Pathology of the University Emergency Hospital, Bucharest, Romania, between 2015‑2017, and studied their histologic and molecular features in the clinical context obtained from our hospital database. Results. All the analyzed patients were postmenopausal women. The extent of time between the diagnosis of the first and second tumor varied in metachronous cases from 8 months to 7 years. In the majority of cases, the bilateral breast lesions shared histologic, grading and hormone expression similarities. Conclusions. Bilateral breast carcinoma is a rare entity that needs more histologic parameters to be defined as primary or metastatic

Clinico‑morphological aspects and new immunohistochemistry characteristics of ovarian high‑grade serous carcinoma

Introduction. High‑grade serous carcinoma of the ovary is an aggressive form of cancer, with unknown precursor lesions and often delayed diagnosis because of non‑specific, mild symptoms. Objective. We performed a clinical‑pathological study of ovarian high‑grade serous carcinomas, in order to evaluate morphological and new immunohistochemistry characteristics of this malignancy. Methods. This is a retrospective study of 10 cases of ovarian high‑grade serous carcinoma. We evaluated patients’ age, symptoms at presentation, macroscopic aspects, bilateral involvement, microscopic features: papillary/solid areas, mitotic index, psammoma bodies, tumoral extension, lymph node metastasis, immunohistochemistry markers: CD44, ER, AR, Ki67 index. Results. Mean age was 56.9 years old. Tumors were bilateral in 50% of cases. Only 30% were limited to the ovary. Maximum tumor diameter was 16 cm. Solid component in a proportion of 50‑95% was more characteristic. Most tumors had a mitotic index of 30‑50 mitosis/10HPF (70% of cases). 20% of cases contained psammoma bodies. 2 cases out of 7 had lymph node metastasis. We noticed one case with pleural metastasis (M1). We observed AR80% was noticed in 30% of cases. CD44 was positive in 50% of cases and one case had diffuse positivity of CD44 in corpus luteum cells near the tumoral bed. Conclusions. The majority of patients with ovarian high‑grade serous carcinomas presented with extraovarian extension and were characterized by high mitotic index, rare presence of psammoma bodies, AR expression <10%, novel marker CD44 positive in 50% of cases and curious positivity in corpus luteum cells associated with the tumor

Risk factors for infections caused by carbapenem-resistant Enterobacterales: an international matched case-control-control study (EURECA)

Cases were patients with complicated urinary tract infection (cUTI), complicated intraabdominal (cIAI), pneumonia or bacteraemia from other sources (BSI-OS) due to CRE; control groups were patients with infection caused by carbapenem-susceptible Enterobacterales (CSE), and by non-infected patients, respectively. Matching criteria included type of infection for CSE group, ward and duration of hospital admission. Conditional logistic regression was used to identify risk factors. Findings Overall, 235 CRE case patients, 235 CSE controls and 705 non-infected controls were included. The CRE infections were cUTI (133, 56.7%), pneumonia (44, 18.7%), cIAI and BSI-OS (29, 12.3% each). Carbapenemase genes were found in 228 isolates: OXA-48/like, 112 (47.6%), KPC, 84 (35.7%), and metallo-beta-lactamases, 44 (18.7%); 13 produced two. The risk factors for CRE infection in both type of controls were (adjusted OR for CSE controls; 95% CI; p value) previous colonisation/infection by CRE (6.94; 2.74-15.53; <0.001), urinary catheter (1.78; 1.03-3.07; 0.038) and exposure to broad spectrum antibiotics, as categorical (2.20; 1.25-3.88; 0.006) and time-dependent (1.04 per day; 1.00-1.07; 0.014); chronic renal failure (2.81; 1.40-5.64; 0.004) and admission from home (0.44; 0.23-0.85; 0.014) were significant only for CSE controls. Subgroup analyses provided similar results. Interpretation The main risk factors for CRE infections in hospitals with high incidence included previous coloni-zation, urinary catheter and exposure to broad spectrum antibiotics

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Conformational Analysis of Seven Membered Nitrogen Heterocycles Employing Molecular Modeling. Part II: 1-(ONitrophenyl)-2-Phenyl-1h-4,5,6,7-Tetrahydro-1,3-Diazepine

Geometry optimization of 1-(o-nitrophenyl)-2-phenyl-1H-4,5,6,7-tetrahydro-1,3-diazepine is performed by means of molecular modeling. Results are correlated with theoretical and experimental UV spectra

Assessment of the worldwide burden of critical illness: The Intensive Care Over Nations (ICON) audit

Background Global epidemiological data regarding outcomes for patients in intensive care units (ICUs) are scarce, but are important in understanding the worldwide burden of critical illness. We, therefore, did an international audit of ICU patients worldwide and assessed variations between hospitals and countries in terms of ICU mortality.Methods 730 participating centres in 84 countries prospectively collected data on all adult (&gt;16 years) patients admitted to their ICU between May 8 and May 18, 2012, except those admitted for fewer than 24 h for routine postoperative monitoring. Participation was voluntary. Data were collected daily for a maximum of 28 days in the ICU and patients were followed up for outcome data until death or hospital discharge. In-hospital death was analysed using multilevel logistic regression with three levels: patient, hospital, and country.Findings 10 069 patients were included from ICUs in Europe (5445 patients; 54.1%), Asia (1928; 19.2%), the Americas (1723; 17.1%), Oceania (439; 4.4%), the Middle East (393; 3.9%), and Africa (141; 1.4%). Overall, 2973 patients (29.5%) had sepsis on admission or during the ICU stay. ICU mortality rates were 16.2% (95% CI 15.5-16.9) across the whole population and 25.8% (24.2-27.4) in patients with sepsis. Hospital mortality rates were 22.4% (21.6-23.2) in the whole population and 35.3% (33.5-37.1) in patients with sepsis. Using a multilevel analysis, the unconditional model suggested significant between-country variations (var=0.19, p=0.002) and between-hospital variations (var=0.43, p&lt;0.0001) in the individual risk of in-hospital death. There was a stepwise increase in the adjusted risk of in-hospital death according to decrease in global national income.Interpretation This large database highlights that sepsis remains a major health problem worldwide, associated with high mortality rates in all countries. Our findings also show a significant association between the risk of death and the global national income and suggest that ICU organisation has an important effect on risk of death

Correction to collaborators in acknowledgments in: Decision-making on withholding or withdrawing life support in the ICU: A worldwide perspective

The authors have reported to CHEST that the collaborators from the ICON Investigators were omitted from the Acknowledgments in “Decision-Making on Withholding or Withdrawing Life Support in the ICU: A Worldwide Perspective” (Chest. 2017;152(2):321-329). https://doi.org/10.1016/j.chest.2017.04.17