Pregnancy Protects Hyperandrogenemic Female Rats from Postmenopausal Hypertension

Polycystic ovary syndrome, the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenemia, obesity, insulin resistance, and elevated blood pressure. However, few studies have focused on the consequences of pregnancy on postmenopausal cardiovascular disease and hypertension in polycystic ovary syndrome women. In hyperandrogenemic female (HAF) rats, the hypothesis was tested that previous pregnancy protects against age-related hypertension. Rats were implanted with dihydrotestosterone (7.5 mg/90 days, beginning at 4 weeks and continued throughout life) or placebo pellets (controls), became pregnant at 10 to 15 weeks, and pups were weaned at postnatal day 21. Dams and virgins were then aged to 10 months (still estrous cycling) or 16 months (postcycling). Although numbers of offspring per litter were similar for HAF and control dams, birth weights were lower in HAF offspring. At 10 months of age, there were no differences in blood pressure, proteinuria, nitrate/nitrite excretion, or body composition in previously pregnant HAF versus virgin HAF. However, by 16 months of age, despite no differences in dihydrotestosterone, fat mass/or lean mass/body weight, previously pregnant HAF had significantly lower blood pressure and proteinuria, higher nitrate/nitrite excretion, with increased intrarenal mRNA expression of endothelin B receptor and eNOS (endothelial nitric oxide synthase), and decreased ACE (angiotensin-converting enzyme), AT1aR (angiotensin 1a receptor), and endothelin A receptor than virgin HAF. Thus, pregnancy protects HAF rats against age-related hypertension, and the mechanism(s) may be due to differential regulation of the nitric oxide, endothelin, and renin-angiotensin systems. These data suggest that polycystic ovary syndrome women who have experienced uncomplicated pregnancy may be protected from postmenopausal hypertension.Fil: Shawky, Noha M.. University Of Mississippi Medical Center; Estados UnidosFil: Patil, Chetan N.. Medical College Of Wisconsin; Estados UnidosFil: Dalmasso, Carolina. University of Kentucky; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa | Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa | Instituto de Investigación Médica Mercedes y Martín Ferreyra. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa; ArgentinaFil: Marañón, Rodrigo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; Argentina. Universidad Nacional de Tucumán. Facultad de Medicina; ArgentinaFil: Romero, Damián Gastón. University Of Mississippi Medical Center; Estados UnidosFil: Drummond, Heather. University Of Mississippi Medical Center; Estados UnidosFil: Reckelhoff, Jane F.. University Of Mississippi Medical Center; Estados Unido

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

A study of clinical pattern and seasonal variation of dermatoses in children: Contemplating findings for family physicians

Introduction: Pediatric skin disorders are different from the adult type in their presentations, types, treatment and prognosis. Their presentation varies from place to place. Aim: To study the different clinical pattern and seasonal variation of dermatoses in children attending a multispecialty hospital in Uttar Pradesh. Materials and Methods: This study was conducted among 640 children who attended the OPD of multispecialty hospital over a period of one year. All children up to 10 years of age with cutaneous presentations were included in the study. Results: Study showed that there was a male preponderance among the study participants. According to the age group, school-aged children (6-10 years) constituted the highest percentage (53%) followed by toddlers or pre-school children (41%). The most common skin conditions were infections (47%) followed by eczematous group (31%) of disorders. Among the infections, the most common infections were fungal - 35.64% (107) followed by parasitic infection (31%), viral infections (20%) and then bacterial infections (12.5%). Out of total eczematous dermatoses, Atopic dermatosis was maximum in number (61; 30%). This was followed by pityriasis Alba (47; 23.15%), and acute eczemas (32; 15.76%). Third most common dermatosis was Appendageal disorder (33; 5.15%). It included 15 cases of miliaria i.e. approximately 45.45%. Seventeen (2.65%) children reported for treatment of different kind of nevi. Pigmentary disorders were seen in 16 cases (2.5%). Three nutritional disorders were also seen. Season wise, most of the cases were seen in monsoons (June to October). Conclusions: Dermatoses is very common in children in the western region of Uttar Pradesh. The largest group was formed by infections followed by eczemas. Few cases increased in number depending upon the weather like fungal and bacterial infections, acne, miliaria in summers and xerosis, scabies in winters. This variation strongly suggests that weather has a very important role. Thus various measures including health education programs to be initiated to control and prevent the sudden spread of the diseases. Thus, Primary care providers and family physicians being the first responders should always keep in mind the seasonal variations while dealing with dermatosis in children

A CLINICO-MYCOLOGICAL EVALUATION OF DERMATOPHYTIC INFECTIONS – A SINGLE CENTRE PROSPECTIVE OBSERVATIONAL STUDY

Background: The epidemiology of dermatophytic infection is influenced by the changing patterns of migration, growth in tourism, immunocompetence of the host, pathogenicity of the infectious agents, availability of medical treatment, and changes in socioeconomic conditions. Objectives: The objectives of the study were to assess the epidemiological profile, clinical types, and association between the etiological agent isolated and the clinical type of dermatophytic infections. Methods: An observational prospective study was carried out at large tertiary care hospital in Southern Maharashtra, India. 110 Participants were selected based on Inclusion and exclusion criteria. Data collection was done with help of personal interview and detailed examination by investigator using predesigned, pre-tested, and structured questionnaire. All patients were followed up in dermatology department till complete investigation, treatment, and discharge. Results: Patients belonging to 21−40 year constituted 45% of the study population. Male to female ratio was 3:1. About 51.82% belonged to low socio-economic status and 56.36% were from rural areas. The most common isolate obtained was Trichophyton rubrum (25.45%) followed by Trichophyton mentagrophytes (7.27%). Out of the 110 samples collected, 66.36% (73 samples) were KOH positive and 35.45% (39 samples) were culture positive. The most common type of mixed dermatophytic infection was Tinea Corporis with Tinea Cruris (38.46%) followed by Tinea Manuum with Tinea Unguium (30.77%). Mixed type was seen more commonly in 21−40 years age group (30.77%). Association of isolate and the clinical type involved among study participants was assessed by applying Chi-square test which showed no statistical significance (p=0.94). Similarly, association of results of KOH mount and culture report to clinical types also showed no statistical significance (p=0.94). However, when association of age and sex with clinical types was assessed, age showed statistically significant association (p=0.004) while sex showed no statistical significance (p=0.32). Conclusions: Incidence of dermatophytosis was maximum in rural areas, low socioeconomic group and in summer. Thus, changing environmental and socio-economic conditions often led to changing epidemiology of dermatophytic infections. Tinea corporis was found to be the commonest clinical type followed by Tinea cruris. T. rubrum was the commonest isolate obtained (25.45%). Fungi were demonstrated by direct microscopy and/or by culture in 73 cases (66.36%) out of 110 cases. Hence, direct microscopy with or without culture is an important diagnostic tool in dermatophytosis. Authors recommend more in-depth study with larger sample size and multicentric based to have clearer picture of dermatophytosis

DERIVATION OF COMPATIBILITY CONDITIONS AND NONCONSTANT MATERIAL FUNCTION FOR ONE-DIMENSIONAL CONSTITUTIVE RELATIONS OF SHAPE MEMORY ALLOYS

The present work investigates the thermodynamic inconsistencies in the definition of the compatibility conditions on stress for constant and nonconstant material functions in one-dimensional modeling of shape memory alloys based on the first principles. In this work, simplifications are provided validating inconsistencies in the earlier proposed non-constant material functions used to satisfy compatibility conditions. It is presented that the inconsistencies originate due to an incorrect definition of the compatibility conditions on stress. In the first step, it is shown that, due to inconsistent definitions of the compatibility conditions, the material functions cannot be derived from the first principles. Consequently, it is presented that the material functions result in an incorrect form of the differential constitutive equation. Furthermore, it is also analyzed that these incorrect definitions on the compatibility conditions result in an inconsistent form of nonconstant material functions as well as the differential equation, which are proposed in earlier models. As a result, in the present work the consistent definition of the compatibility conditions for one-dimensional shape memory alloy models is derived. Next, the new and correct definition for the compatibility conditions is proposed, which is used to derive a new and consistent form of nonconstant material function. Finally, a consistent form of non-constant material function and differential equation are derived from first principles, which satisfy the new definition of compatibility conditions on stress