Rationale and design of the HIP fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) Trial: a protocol for an international randomised controlled trial evaluating early surgery for hip fracture patients

Accelerated surgery; Hip fracture; Randomised control trialCirurgia accelerada; Fractura de maluc; Prova controlada aleatòriaCirugía acelerada; Fractura de cadera; Prueba controlada aleatorizadaINTRODUCTION: Annually, millions of adults suffer hip fractures. The mortality rate post a hip fracture is 7%-10% at 30 days and 10%-20% at 90 days. Observational data suggest that early surgery can improve these outcomes in hip fracture patients. We designed a clinical trial-HIP fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) to determine the effect of accelerated surgery compared with standard care on the 90-day risk of all-cause mortality and major perioperative complications. METHODS AND ANALYSIS: HIP ATTACK is a multicentre, international, parallel group randomised controlled trial (RCT) that will include patients ≥45 years of age and diagnosed with a hip fracture from a low-energy mechanism requiring surgery. Patients are randomised to accelerated medical assessment and surgical repair (goal within 6 h) or standard care. The co-primary outcomes are (1) all-cause mortality and (2) a composite of major perioperative complications (ie, mortality and non-fatal myocardial infarction, pulmonary embolism, pneumonia, sepsis, stroke, and life-threatening and major bleeding) at 90 days after randomisation. All patients will be followed up for a period of 1 year. We will enrol 3000 patients. ETHICS AND DISSEMINATION: All centres had ethics approval before randomising patients. Written informed consent is required for all patients before randomisation. HIP ATTACK is the first large international trial designed to examine whether accelerated surgery can improve outcomes in patients with a hip fracture. The dissemination plan includes publishing the results in a policy-influencing journal, conference presentations, engagement of influential medical organisations, and providing public awareness through multimedia resources. TRIAL REGISTRATION NUMBER: NCT02027896; Pre-results

Effects of accelerated versus standard care surgery on the risk of acute kidney injury in patients with a hip fracture: A substudy protocol of the hip fracture accelerated surgical treatment and care track (hip attack) international randomised controlled trial

Introduction: Inflammation, dehydration, hypotension and bleeding may all contribute to the development of acute kidney injury (AKI). Accelerated surgery after a hip fracture can decrease the exposure time to such contributors and may reduce the risk of AKI.Methods and analysis: Hip fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) is a multicentre, international, parallel-group randomised controlled trial (RCT). Patients who suffer a hip fracture are randomly allocated to either accelerated medical assessment and surgical repair with a goal of surgery within 6 hours of diagnosis or standard care where a repair typically occurs 24 to 48 hours after diagnosis. The primary outcome of this substudy is the development of AKI within 7 days of randomisation. We anticipate at least 1998 patients will participate in this substudy.Ethics and dissemination: We obtained ethics approval for additional serum creatinine recordings in consecutive patients enrolled at 70 participating centres. All patients provide consent before randomisation. We anticipate reporting substudy results by 2021.Trial registration number: NCT02027896; Pre-results

Accelerated surgery versus standard care in hip fracture (HIP ATTACK): an international, randomised, controlled trial

© 2020 Elsevier Ltd Background: Observational studies have suggested that accelerated surgery is associated with improved outcomes in patients with a hip fracture. The HIP ATTACK trial assessed whether accelerated surgery could reduce mortality and major complications. Methods: HIP ATTACK was an international, randomised, controlled trial done at 69 hospitals in 17 countries. Patients with a hip fracture that required surgery and were aged 45 years or older were eligible. Research personnel randomly assigned patients (1:1) through a central computerised randomisation system using randomly varying block sizes to either accelerated surgery (goal of surgery within 6 h of diagnosis) or standard care. The coprimary outcomes were mortality and a composite of major complications (ie, mortality and non-fatal myocardial infarction, stroke, venous thromboembolism, sepsis, pneumonia, life-threatening bleeding, and major bleeding) at 90 days after randomisation. Patients, health-care providers, and study staff were aware of treatment assignment, but outcome adjudicators were masked to treatment allocation. Patients were analysed according to the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT02027896). Findings: Between March 14, 2014, and May 24, 2019, 27 701 patients were screened, of whom 7780 were eligible. 2970 of these were enrolled and randomly assigned to receive accelerated surgery (n=1487) or standard care (n=1483). The median time from hip fracture diagnosis to surgery was 6 h (IQR 4–9) in the accelerated-surgery group and 24 h (10–42) in the standard-care group (p\u3c0·0001). 140 (9%) patients assigned to accelerated surgery and 154 (10%) assigned to standard care died, with a hazard ratio (HR) of 0·91 (95% CI 0·72 to 1·14) and absolute risk reduction (ARR) of 1% (−1 to 3; p=0·40). Major complications occurred in 321 (22%) patients assigned to accelerated surgery and 331 (22%) assigned to standard care, with an HR of 0·97 (0·83 to 1·13) and an ARR of 1% (−2 to 4; p=0·71). Interpretation: Among patients with a hip fracture, accelerated surgery did not significantly lower the risk of mortality or a composite of major complications compared with standard care. Funding: Canadian Institutes of Health Research

Rationale and design of the HIP fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) Trial : a protocol for an international randomised controlled trial evaluating early surgery for hip fracture patients

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Peer reviewedPublisher PD

Perioperative vascular events and myocardial injury after noncardiac surgery in vascular surgery: An overview of the current emerging evidence and guidelines

Vascular surgery is considered a high-risk noncardiac surgery. It is associated with an increased risk of cardiovascular events in the perioperative period. Preoperative assessment of risk using validated scales such as Revised Cardiac Risk Index, helps informing patients, surgeons, and anesthetists on the potential risk of cardiovascular events. Cardiac biomarkers, such as NT pro-brain natriuretic peptide (pro-BNP)/BNP, improve the sensitivity of these scales, in predicting potential serious perioperative cardiovascular outcomes. It is cost effective and quicker than other invasive or noninvasive procedures, usually done before any vascular surgery. Several interventions have been tested in trials for potentially preventing an event, but none have given good quality evidence for benefit, except the use of statins. Postoperatively, use of drugs to prevent a cardiovascular event has not been as effective as in the nonsurgical setting (aspirin, β-blockers, α2agonists, and angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers). Monitoring of highly sensitive troponins better predicts 30-day mortality in patients undergoing any noncardiac surgery. This event is called myocardial injury after noncardiac surgery (MINS) or in short MINS. Currently, MINS is not detected in over 75% of vascular surgery patients as it is not routinely performed. As per the evidence reviewed in this article and as recommended by the Canadian Cardiovascular Society Guidelines, it is imperative we monitor all patients aged above 45 years undergoing vascular surgery. Even though there is no evidence for an effective intervention of MINS, detections help in better monitoring of the patient and initiating effective secondary prevention treatment, as indicated

A systematic review on normative values of trimester-specific thyroid function tests in Indian women

Background: Small cross-sectional studies are published on the trimester-specific normal ranges of thyrotropin and thyroxine levels in Indian women from various parts of the country. Objective: We sought to review the published literature on thyroid function tests in normal pregnant Indian women to see if the pooled data from various studies can define normative data and hypothyroidism in pregnancy. Methods: We retrieved 56 studies from online databases with detailed search using multiple search terms. Unanimously eight studies were finalized. Results: Data of 2703 pregnant women (age 16–45 years; 966 were in the first trimester, 1072 in their second trimester, and 1037 women in their third trimester) were analyzed. All eight studies included singleton pregnancies from the northern and eastern part of India with seven studies being cross-sectional in nature. The exclusion criteria in all studies included those with historical/clinical evidence of thyroid dysfunction, those with family history of thyroid dysfunction, infertility and those with history of recurrent miscarriages (usually >3). Ultrasound evidence of thyroid disease, urinary iodine assessment, and thyroid antibodies were included as additional exclusion criteria in two, three, and four studies, respectively. None of the studies included the outcome of pregnancy as part of follow-up. As part of the pooled data analysis, the 5th–95th centile values of normal TSH extended from 0.09 to 6.65 IU/mL in the first trimester, 0.39–6.61 IU/mL in the second trimester, and 0.70–5.18 IU/mL in the third trimester. The FT4 levels (5th–95th centile values) extended from 8.24 to 25.74 pmol/L in the first trimester, 6.82–26.0 pmol/L, and 5.18–25.61 pmol/L in the third trimester. Conclusions: With due limitations imposed by the quality of the available studies, the current review suggests that upper normal limit of TSH values can extend up to 5–6 IU/mL in pregnancy

Inflammatory bowel disease-related colorectal cancer: Past, present and future perspectives.

Inflammatory bowel disease-related colorectal cancer (IBD-CRC) is one of the most serious complications of IBD contributing to significant mortality in this cohort of patients. IBD is often associated with diet and lifestyle-related gut microbial dysbiosis, the interaction of genetic and environmental factors, leading to chronic gut inflammation. According to the "common ground hypothesis", microbial dysbiosis and intestinal barrier impairment are at the core of the chronic inflammatory process associated with IBD-CRC. Among the many underlying factors known to increase the risk of IBD-CRC, perhaps the most important factor is chronic persistent inflammation. The persistent inflammation in the colon results in increased proliferation of cells necessary for repair but this also increases the risk of dysplastic changes due to chromosomal and microsatellite instability. Multiple pathways have been identified, regulated by many positive and negative factors involved in the development of cancer, which in this case follows the 'inflammation-dysplasia-carcinoma' sequence. Strategies to lower this risk are extremely important to reduce morbidity and mortality due to IBD-CRC, among which colonoscopic surveillance is the most widely accepted and implemented modality, forming part of many national and international guidelines. However, the effectiveness of surveillance in IBD has been a topic of much debate in recent years for multiple reasons - cost-benefit to health systems, resource requirements, and also because of studies showing conflicting long-term data. Our review provides a comprehensive overview of past, present, and future perspectives of IBD-CRC. We explore and analyse evidence from studies over decades and current best practices followed globally. In the future directions section, we cover emerging novel endoscopic techniques and artificial intelligence that could play an important role in managing the risk of IBD-CRC

Carbohydrate prolectin-M, a galectin-3 antagonist, blocks SARS-CoV-2 activity

The SARS-COV-2 (severe acute respiratory syndrome coronavirus 2) virus binds to human lectins to gain entry into cells to replicate. Blocking the virus’s entry using a complex polysaccharide component of [a (1-6)- D-mannopyranose termed “ProLectin M” has an effect on viral replication as a therapeutic tool and a safe alternative to existing antiviral therapies. Little is known about how galectin-3 inhibits viral entry into cells and its impact on the course of viral infection. Here, we investigated the effect of these non-cytotoxic polysaccharides on Vero cells infected with SARS-CoV-2 and demonstrated a dose-dependent reduction in viral load over a 48-hour viral incubation period. A pilot clinical study in five patients with laboratory-confirmed COVID-19 disease was treated with an oral formulation of ProLectin M, and all patients achieved complete disease remission with zero hospitalization or need for oxygen support. Moreover, the viral load was significantly lowered within 2 days of drug administration. On the viral envelope, glycans often play a crucial role in enabling pathogen transmission and/or entry into susceptible target cells. On the molecular level, our NMR spectroscopic studies show that ProLectin M binds relatively strongly to galectin-3, supporting the idea of an antagonist effect on the lectin.&nbsp