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Background Stress radiographs have demonstrated superior efficacy in the evaluation of ankle instability. Aim To determine if there is a degree of instability evidenced by stress radiographs that is associated with pathology concomitant with ankle ligamentous instability. Methods A retrospective review of 87 consecutive patients aged 18-74 who had stress radiographs performed at a single institution between 2014 and 2020 was performed. These manual radiographic stress views were then correlated with magnetic resonance imaging and operative findings. Results A statistically significant association was determined for the mean and median stress radiographic values and the presence of peroneal pathology (P = 0.008 for tendonitis and P = 0.020 for peroneal tendon tears). A significant inverse relationship was found between the presence of an osteochondral defect and increasing degrees of instability (P = 0.043). Conclusion Although valuable in the clinical evaluation of ankle instability, stress radiographs are not an independent predictor of conditions associated with ankle instability.

Following closed reduction of distal radius fractures, formal radiographs are often obtained despite previous verification on fluoroscopy. A prospective collection of 60 consecutive distal radius fractures was obtained to compare the quality of the fluoroscopic images obtained from a mini C-arm versus formal radiographs. The images were reviewed by six orthopedic surgeons and one radiologist. The likelihood that further imaging was deemed necessary to guide treatment decisions was 1.9 times higher in the mini C-arm imaging cohort (95% CI: 1:34, 2.69). While mini C-arm remains a useful reduction aid, formal radiographs should still be obtained to document post-reduction alignment and to guide treatment decisions.

PurposeThe purpose of this research is to develop a dynamic conceptual framework depicting factors related to the adoption of a healthy diet, which will underpin the development of an agent-based model (ABM) to uncover the dynamic interplay between these factors.Design/methodology/approachThe conceptual framework was developed in three steps using available empirical data from a semi-structured in-depth interview qualitative study, comprehensive systematic literature searches, existing theories and models and expert opinions from across the world.FindingsThe conceptual framework explicitly presents intention as the key determinant of the tendency to adopt a healthy diet. Intention is determined by demographic, psychological and behavioural factors and individual dietary mindset factors and dynamically affected by social environment and the person's past behaviour. The relationship between intention and behaviour is dynamically moderated by perceived control factors (price and accessibility of healthy food and time).Originality/valueThe conceptual framework developed in this study is well supported by evidence and experts' opinions. This conceptual framework will be used to design the ABM of this study, and it can be used in future investigations on the tendency to adopt healthy diet and food choices.

Objective: Inconsistent results regarding the association between the Body Mass Index (BMI) and brain disorders have been reported. We performed this study to investigate the association between BM...

Background The relationship between body mass index (BMI) and risk of venous thromboembolism (VTE) and pulmonary embolism (PE) is a controversial issue. This dose-response meta-analysis was performed to investigate the association between BMI and risk of VTE and PE incidence based on cohort studies. Method A comprehensive systematic search was conducted up to August 2019 in MEDLINE/PubMed, SCOPUS, and Cochrane. DerSimonian and Laird random-effects models were run to estimate combined hazard ratios (HRs) with 95% confidence intervals (CIs). Dose-response analysis was also carried out based on BMI values. Results Eleven articles with 16 arms and 3,910,747 participants were eligible for inclusion in this systematic review and meta-analysis. Pooled results showed a positive association between BMI and risk of VTE in the obese participants compared to participants classified in the normal BMI category (HR: 1.62, 95% CI: 1.29–2.04, I2 = 95%). Furthermore, results showed a significant association between lower BMI (underweight versus normal BMI category) and reduced risk of PE (HR: 0.80, 95% CI: 0.70–0.92, I2 = 9%) and higher risk of PE in obese versus normal BMI participants (HR: 2.24, 95% CI: 1.93–2.60, I2 = 0%). There was a significant linear relationship between BMI and risk of VTE (p Conclusions This systematic review and dose-response meta-analysis with 3,910,747 participants highlights obesity as a significant risk factor related to the incidence of VTE and PE.

Coronavirus disease 2019 (COVID‐19), the worst pandemic in more than a century, has claimed >125,000 lives worldwide to date. Emerging predictors for poor outcomes include advanced age, male sex, preexisting cardiovascular disease, and risk factors including hypertension, diabetes, and, more recently, obesity. This article posits new obesity‐driven predictors of poor COVID‐19 outcomes, over and above the more obvious extant risks associated with obesity, including cardiometabolic disease and hypoventilation syndrome in intensive care patients. This article also outlines a theoretical mechanistic framework whereby adipose tissue in individuals with obesity may act as a reservoir for more extensive viral spread, with increased shedding, immune activation, and cytokine amplification. This paper proposes studies to test this reservoir concept with a focus on specific cytokine pathways that might be amplified in individuals with obesity and COVID‐19. Finally, this paper underscores emerging therapeutic strategies that might benefit subsets of patients in which cytokine amplification is excessive and potentially fatal.

Background: Patient-reported outcomes (PROs) measure progression and quality of care. While legacy PROs such as the International Knee Documentation Committee (IKDC) survey are well-validated, a lengthy PRO creates a time burden on patients, decreasing adherence. In recent years, PROs such as the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function and Pain Interference surveys were developed as computer adaptive tests, reducing time to completion. Previous studies have examined correlation between legacy PROs and PROMIS; however, no studies have developed effective prediction models utilizing PROMIS to create an IKDC index. While the IKDC is the standard knee PRO, computer adaptive PROs offer numerous practical advantages. Purpose: To develop a nonlinear predictive model utilizing PROMIS Physical Function and Pain Interference to estimate IKDC survey scores and examine algorithm sensitivity and validity. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: The MOTION (Military Orthopaedics Tracking Injuries and Outcomes Network) database is a prospectively collected repository of PROs and intraoperative variables. Patients undergoing knee surgery completed the IKDC and PROMIS surveys at varying time points. Nonlinear multivariable predictive models using Gaussian and beta distributions were created to establish an IKDC index score, which was then validated using leave-one-out techniques and minimal clinically important difference analysis. Results: A total of 1011 patients completed the IKDC and PROMIS Physical Function and Pain Interference, providing 1618 complete observations. The algorithms for the Gaussian and beta distribution were validated to predict the IKDC (Pearson = 0.84-0.86; R2 = 0.71-0.74; root mean square error = 9.3-10.0). Conclusion: The publicly available predictive models can approximate the IKDC score. The results can be used to compare PROMIS Physical Function and Pain Interference against historical IKDC scores by creating an IKDC index score. Serial use of the IKDC index allows for a lower minimal clinically important difference than the conventional IKDC. PROMIS can be substituted to reduce patient burden, increase completion rates, and produce orthopaedic-specific survey analogs.

Purpose: Tenofovir (TDF) and entecavir (ETV) are both equally recommended as first-line treatments for patients with chronic hepatitis B (CHB). They have comparable efficacy in virologic response, but their effect on the development of hepatocellular carcinoma (HCC) in CHB is controversial. Therefore, we aimed to compare TDF and ETV evaluating the risk of HCC development in CHB patients. Methods: A systematic literature search was conducted up to November 2019 in MEDLINE/PubMed, SCOPUS, and Web of Science databases without language and time restrictions. DerSimonian and Laird random-effects models were used to estimate combined hazard ratios (HRs) and 95% CIs. Results: Seven studies containing 35,785 participants were included in this systematic review and meta-analysis. The pooled HR (95% CI) of HCC in the patients who used TDF versus patients who used ETV was 0.75 (0.56–0.96). There was no significant heterogeneity detected among the included studies results (I2 = 47.5%). There was no significant publication bias detected among the included studies (Begg’s p = 0.88 and Egger’s regression test p = 0.96). Conclusions: Evidence to date suggests that TDF treatment is associated with significantly fewer cases of HCC when compared to ETV.

Relationship between liver enzymes such as gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate transaminase (AST) and alkaline phosphatase and risk of gestational diabetes mellitus (GDM) is a controversial issue. The aim of this systematic review and dose–response meta-analysis was to investigate the association between liver enzymes and risk of GDM in observational studies. A comprehensive systematic literature search was conducted in MEDLINE/PubMed, SCOPUS and Web of Science databases up to September 2019. Combined odds ratios (ORs) with 95% confidence intervals (CIs) were evaluated by DerSimonian and Laird random-effects models. Dose–response analyses of these relationships were also carried out. Eight studies with 25,451 participants containing 2549 cases were included in this study. Pooled results showed a significant association between GGT levels and risk of GDM (OR 2.10, 95% CI 1.14–3.86, I2 84%). In addition, random-effects model indicated a dramatic and direct significant association between GGT and risk of GDM in nonlinear (p

Objective There is compelling clinical evidence implicating certain dietary components in the development and clinical course of progression in ulcerative colitis (UC). This study aimed to assess whether any association exists between ulcerative colitis and scores on a healthy eating index. Methods In this case-control study patients with UC were recruited and assessed together with healthy controls. The participants completed a validated 168-item food frequency questionnaire, the results of which were subsequently used to generate individual healthy eating index (HEI-2015) scores. Results Altogether 58 patients with UC and 123 healthy controls were recruited. After controlling for confounding factors, participants who were in the highest quartile of the HEI-2015 had a 66% lower odds ratio (OR) of UC than the lowest quartile (OR = 0.34, 95% confidence interval 0.12-0.96). Conclusion HEI-2015 was associated with UC in this cohort. Further elucidation of the role of key dietary elements is now warranted.

Adequate reduction of posterior malleolar fractures leads to better outcomes. Arthroscopic reduction and internal fixation presents an opportunity for excellent reduction with a minimally invasive approach. Herein, we present a technique with some discussion on outcomes.

Osteochondral lesions of the talus (OLTs) continue to be a challenge for the treating surgeon, especially when lesions are refractory to marrow stimulation techniques. The purpose of this study is to evaluate the outcomes of lesions treated with osteochondral allograft transplantation. A review was performed of 30 athletes with 31 OLTs that were refractory to marrow stimulation or predicted to be refractory based on size and location of the lesion. Results were evaluated in terms of occupational outcomes and numeric pain scales. Lesions treated had a mean area of 1.37 (range 0.36 to 3.3) cm2. Overall excellent outcomes were achieved in 11 (35%) ankles. Nineteen (61%) ankles achieved good or excellent occupational outcomes, and 12 (39%) ankles demonstrated poor occupational outcomes and the patients were unable to continue their previous active occupations. Patients were found to have a mean pain scale score of 3 (range 0 to 7) of 10 at a mean of 21 (range 10 to 24) months after operative management. Osteochondral allograft transplantation is an option for the treatment of selected athletes with large OLTs, as well as lesions that are refractory to marrow stimulation techniques. The results of this study may help active young patients and their surgeons to better understand outcomes and options in their shared decision-making process.

Due to its innately intriguing nature and recent genomic technological advances, gut microbiome research has been at the epicentre of medical research for over a decade now. Despite the degree of publicisation, a comprehensive understanding and, therefore, acceptance of the area as a whole may be somewhat lacking within the broader medical community. This paper summarises the main analytical techniques and tools currently applied to compositional microbiome research. In addition, we outline five major lessons learnt from a decade of infant microbiome research, along with the current research gaps. Finally, we aim to provide an introduction and general guidelines relating to infant gut microbiome research for the practising paediatrician.

A 41-year-old woman presented by ambulance with a 1-day history of new-onset paralysis and nausea and vomiting ongoing for 48 hours. She had no history of any similar episodes. Biochemical analysis showed profound hypokalaemia with a non-anion gap metabolic acidosis. Her initial serum chloride was within the normal range. She had significant electrocardiographic changes on admission with ST depression, U waves and a prolonged QT interval. Urinary anion gap supported the diagnosis of a distal renal tubular acidosis. Subsequent connective tissue disease serology confirmed previously undiagnosed Sjogren’s syndrome. Successful recovery for this patient required multidisciplinary input from the intensive care, nephrology and neurology teams.

Background The prevalence and severity of COVID-19 are greatly reduced in children, yet some pediatric patients develop a syndrome resembling Kawasaki Disease (KD), termed Multisystem Inflammatory Syndrome in Children (MIS-C). With an estimated incidence of 2/100,000 children, MIS-C is relatively rare but can be fatal. Clinical features can include fever, hyperinflammatory state, gastrointestinal symptoms, myocardial dysfunction, and shock. The pathogenesis of MIS-C, although yet to be completely elucidated, appears to be distinct from KD in terms of epidemiology, severity, and biochemical signature. Aim of Review Although efficacy of treatments for MIS-C have largely not yet been investigated, we aim to conduct a comprehensive literature search of numerous medical databases (AMED, EBM Reviews, Embase, Healthstar, MEDLINE, ERIC, and Cochrane) to highlight treatments used around the world, their rationale, and outcomes to better inform guidelines in the future. Using the findings, an approach to MIS-C management will be outlined. Key Scientific Concepts of Review • MIS-C appears to be a SARS-CoV-2 related post-infection phenomenon that is distinct from Kawasaki disease. • Although outcomes are largely favorable, there is significant variation in MIS-C treatment. Most management regimens reported to date mirror that of KD; however, targeted therapy based on specific MIS-C phenotypes may have the potential to improve outcomes. • We recommend close monitoring by a multidisciplinary team, symptomatic treatment (e.g., intravenous immunoglobulin for KD-like symptoms, steroids/immunotherapy for multisystem inflammation), and long-term follow-up. • Further research is required to evaluate the effectiveness of current MIS-C treatments and to determine more refined therapies.

BackgroundCOVID-19 has resulted in the death of over 1 million people to date. Following government-implemented regulations, there has been concern over the apparent decline in emergency department (ED) attendances and the resultant health legacy. Therefore, we aimed to characterise the attendances to an Irish tertiary hospital ED following the implementation of these regulations during the COVID-19 pandemic.MethodsThis retrospective observational study investigated all attendances to the Cork University Hospital ED from 15 February to 11 April in 2020 and 2017–2019. Attendances were stratified into four periods: Before COVID (BC) (15 February to 5 March), After COVID (AC) (6 March to 12 March), Educational Closure (EC) (13 March to 27 March) and Stay Home (SH) (28 March to 11 April), as per government regulations. Triage presentations of abdominal pain, shortness of breath, chest pain, headache and trauma were examined. Data were analysed by independent t-tests and χ2analysis.ResultsThere were 8261 attendances to the ED in the 2020 time period compared with a mean of 10 389 attendances during the corresponding periods in 2017–2019. There was a significant decrease in daily attendances in 2020 compared with 2017–2019 in the AC (142 vs 188, p=0.02), EC (122 vs 184, p).ConclusionOur findings suggest that the combination of government-imposed restrictions and perceived risk of attending an ED during a pandemic may contribute to reduced attendances. Public confidence in EDs is necessary to reduce collateral damage caused by failure to seek medical attention during a pandemic; adequate infrastructure to allow social distancing and isolation capacity in EDs is a necessity.

Objective This study was aimed to establish a reference interval for high-sensitivity cardiac troponin I (hs-cTnI) in umbilical cord blood of infants and to assess its association with the risk of predetermined early neonatal outcomes in a high-acuity tertiary care hospital. Study Design Umbilical cord-blood samples were collected and hs-cTnI was measured in all infants born between August 2015 and September 2015 at McMaster Children's Hospital (n = 256). Gestational age, birth weight, Apgar's scores, age in days at which feeding was established, neonatal intensive care unit (NICU) admission, and discharge in days after birth were recorded. Results The 90th, 95th, and 99th percentiles for the term infant subcohort were 19.75, 41.45, and 166.30 ng/L, respectively. We observed decreased mean gestational ages and birth weights in both the 90th (37.7 weeks; 2,961.4 g) and 95th percentiles (37.1 weeks; 2,709.9 g) when compared with the remaining infants. Moreover, levels of hs-cTnI were significantly higher in infants with respiratory distress requiring intervention (p Conclusion This study establishes the reference values for cord-blood hs-cTnI in infants at a tertiary care center. Premature and sick infants requiring NICU admission had significantly higher levels of hs-cTnI. Key Points

Background: The preferred patient-reported outcome measure for the assessment of shoulder conditions continues to evolve. Previous studies correlating the Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive tests (CATs) to the American Shoulder and Elbow Surgeons (ASES) score have focused on a singular domain (pain or physical function) but have not evaluated the combined domains of pain and physical function that compose the ASES score. Additionally, previous studies have not provided a multivariable prediction tool to convert PROMIS scores to more familiar legacy scores. Purpose: To establish a valid predictive model of ASES scores using a nonlinear combination of PROMIS domains for physical function and pain. Study Design: Cohort study (Diagnosis); Level of evidence, 3. Methods: The Military Orthopaedics Tracking Injuries and Outcomes Network (MOTION) database is a prospectively collected repository of patient-reported outcomes and intraoperative variables. Patients in MOTION research who underwent shoulder surgery and completed the ASES, PROMIS Physical Function, and PROMIS Pain Interference at varying time points were included in the present analysis. Nonlinear multivariable predictive models were created to establish an ASES index score and then validated using “leave 1 out” techniques and minimal clinically important difference /substantial clinical benefit (MCID/SCB) analysis. Results: A total of 909 patients completed the ASES, PROMIS Physical Function, and PROMIS Pain Interference at presurgery, 6 weeks, 6 months, and 1 year after surgery, providing 1502 complete observations. The PROMIS CAT predictive model was strongly validated to predict the ASES (Pearson coefficient = 0.76-0.78; R2 = 0.57-0.62; root mean square error = 13.3-14.1). The MCID/SCB for the ASES was 21.7, and the best ASES index MCID/SCB was 19.4, suggesting that the derived ASES index is effective and can reliably re-create ASES scores. Conclusion: The PROMIS CAT predictive models are able to approximate the ASES score within 13 to 14 points, which is 7 points more accurate than the ASES MCID/SCB derived from the sample. Our ASES index algorithm, which is freely available online ( https://osf.io/ctmnd/ ), has a lower MCID/SCB than the ASES itself. This algorithm can be used to decrease patient survey burden by 11 questions and provide a reliable ASES analog to clinicians.

Senior individuals can suffer from immunosenescence and novel strategies to bolster the immune response could contribute to healthy ageing. In this double-blind, randomised, controlled pilot trial, we investigated the ability of non-digestible polysaccharide (NPS) preparations to enhance the immune response in a human vaccination model. In total, 239 subjects (aged 50–79 years) were randomised to consume one of five different NPS (yeast β-glucan (YBG), shiitake β-glucan (SBG), oat β-glucan (OBG), arabinoxylan (AX), bacterial exopolysaccharide (EPS)) or control (CTRL) product daily for five weeks. After two weeks of intervention, subjects were vaccinated with seasonal influenza vaccine. The post-vaccination increases in haemagglutination inhibition antibody titres and seroprotection rate against the influenza strains were non-significantly enhanced in the NPS intervention groups compared to CTRL. Specifically, a trend towards a higher mean log2 fold increase was observed in the AX group (uncorrected p = 0.074) combined with a trend for an increased seroprotection rate, AX group (48.7%) compared to CTRL (25.6%) (uncorrected p = 0.057), for the influenza A H1N1 strain. Subjects consuming AX also had a reduced incidence of common colds compared to CTRL (1 vs. 8, p = 0.029 in Fisher exact test). No adverse effects of NPS consumption were reported. The findings of this pilot study warrant further research to study AX as an oral adjuvant to support vaccine efficacy.

Category: Ankle; Trauma Introduction/Purpose: Syndesmotic screw fixation is frequently required in rotational ankle injuries. Fibular malreduction after syndesmotic screw fixation occurs in as many as 52% of cases, which has been shown to detrimentally affect subjective outcomes and increase the probability of developing arthritis. The glidepath technique has been proposed as a useful technique to prevent malreduction. We hypothesize that the glidepath technique reduces the occurrence of fibular malreduction and results in improved outcomes compared to clamping. Methods: A retrospective cohort study comparing 25 patients reduced with a clamp compared to 18 patient using the glidepath technique. The glidepath technique, described by Needleman, the fibula is manually reduced and a Kirschner wire is placed through the fibula and tibia along the transmalleolar axis, parallel to the superior border of the ankle mortise. CT scans of the injured and contralateral ankles were obtained postoperatively to assess reduction. Malreduction is defined as >2mm difference between the anterior or posterior incisura-fibular distance of the injured ankle compared to the contralateral side. Prospective outcomes were assessed using the AOFAS and VR-12 scores at preoperative, 3 month, 6 month and 1 year followup of the glidepath cohort only. Results: We found a statistically significant reduction in malreduced syndesmoses using the glidepath technique when compared with the clamping technique. In our study, 17% (3/18) were malreduced using the glidepath technique, compared with 48% (12/25 patients) with clamping (p=0.005). The three malreductions seen in our study were anterior, we had no posterior malreductions. Compared with the clamping cohort that had 10/25 posterior malreductions and 2/25 anterior malreductions. Mean outcomes at 3,6 and 1 year scores were AOFAS 76, 86,86; VR-12 46,53,50/ 42,44,47 (physical/mental) respectively. Conclusion: Historically, malreduction for syndesmotic fixation is as high as 52%. The glidepath technique is a viable reduction maneuver that has lower rates of malreduction compared to clamping in our study. This is the first ever CT confirmed study measuring syndesmosis reduction utilizing manual reduction. The value of this technique is that is does not require an open reduction, arthroscopic visualization/reduction or CT guidance to achieve syndesmotic reduction.

Implication Statement In order to best treat a patient, the carer must be able to clearly see their point of view. In the case of the complexities of insulin pump therapy, physicians may not fully understand the common challenges that drive patients to non-adherence. The author undertook a three-day simulation using wearable technology to explore this experience. This form of simulation represents a simple yet effective means by which to foster cognitive empathy in undergraduate and postgraduate medical education settings alike.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus first identified in an outbreak of pneumonia in Wuhan, Hubei Province, China in December 2019. Despite mitigation of the initial epidemic, the viral syndrome now named coronavirus disease (COVID)-19 has since spread rapidly throughout the world, representing a pandemic with profound implications for human morbidity and mortality. In turn, the capacity of diverse healthcare and economic systems to cope with rising infections and associated intensive care requirements is strained. The most extensive clinical experience of this virus to date comes from the more than 80 000 positive cases identified in Hubei Province.1–4 These early clinical reports clearly indicated that although most clinical manifestations of COVID-19 requiring hospitalisation are respiratory, there is a substantial minority of patients who undergo progressive and severe cardiovascular compromise.1 2 4 Subjects at highest risk of death appear to be more elderly patients with pre-existing cardiovascular disease and/or classical risk factors that accompany advanced cardiovascular illness.3 The goal of this viewpoint article is to examine whether the nature of SARS-CoV2 infection and the homeostatic status of high-risk cardiovascular patients can be linked in a mechanistic framework that provides insights into corrective therapy over and above current and emergent antiviral approaches to COVID-19. There are a number of reasons why COVID-19 may be associated with cardiovascular complications that include inter alia-specific aspects of SARS-CoV-2 structure and receptor targeting, and target cell location and its relationship with cardiovascular disease homeostasis. In addition, there are potential risk amplifiers including hitherto unanticipated interactions between viral targets within the host and established homeostatic pathways that may already be perturbed in patients with advanced cardiovascular disease. In this viewpoint, we underscored specific alterations in renin angiotensin system-ACE 2 (RAS-ACE2) homeostasis that may contribute to more adverse COVID-19 outcomes in …

Fibroblast growth factor-19 (FGF-19) is a gut hormone which interacts with metabolism and is depleted in obesity. There is some indication that the hormone undergoes a resurgence following bariatric surgery (BS), an effect which may contribute to the beneficial outcomes of such procedures. This systematic review and meta-analysis aims to synthesize the available literature on FGF-19 levels before and after BS. MEDLINE, Scopus and Web of Science databases were searched, and the effect of different surgical procedures and degrees of body mass index (BMI) reduction on FGF-19 levels was assessed by DerSimonian and Laird random-effects model in meta-analysis and dose-response analyses. This meta-analysis, which included 474 patients from 25 arms undergoing one of five BS procedures, revealed a significant increase in the levels of circulating FGF-19 following all-type BS. Vertical sleeve gastrectomy, duodenal-jejunal bypass liner and Roux-en-Y gastric bypass all significantly increased circulating FGF-19 levels from baseline. However, gastric banding failed to achieve the same, and in fact, biliopancreatic diversion was associated with decreased circulating FGF-19. Finally, an inverse association between FGF-19 and the degree of BMI-reduction post-operatively was noted. FGF-19 is increased by BS and may represent a pharmaceutical target in efforts to reproduce the beneficial effects of BS in a medical setting.

Background: It is not known how peroneal tendon exploration influences results after modified Broström for lateral ankle instability. We propose peroneal exploration at the time of modified Broström will have similar outcomes as no peroneal exploration. Methods: A retrospective analysis was performed of patients undergoing modified Broström with and without peroneal exploration. Foot and Ankle Outcome scores and data regarding military retention were gathered and compared. Results: Seventeen patients were identified in the modified Broström only cohort and 24 in the peroneal exploration cohort. Patients had mean follow-up of 5 years in both cohorts. The mean FAOS in the modified Broström only cohort was 68 and 72 in the cohort with peroneal exploration (P = .541). When each FAOS subcategory was analyzed, no difference was identified in any subcategory. Eight of 17 patients (47%) in the modified Broström only cohort remained active duty compared with 8 of 24 patients (33%) in the modified Broström with peroneal exploration cohort (P = .518). One patient medically discharged in the modified Broström only cohort versus 6 in peroneal exploration cohort (P = .109). Overall satisfaction with the procedure was 12 of 17 (71%) in the modified Broström only cohort and 19 of 24 (79%) in the peroneal exploration cohort (P = .529). Conclusions: No significant difference was identified between patients undergoing modified Broström alone or modified Broström with peroneal exploration. There was no significant difference in return to duty, medical discharge or patient satisfaction. Levels of Evidence: Level III: retrospective case-control study with prospectively collected data

A retrospective review of consecutive patients diagnosed with insertional Achilles tendinopathy (IAT) was performed. Outcomes included Visual Analog Scale (VAS) pain scores, return to run rates, and return to military duty rates. Our data analysis included 113 patients; 58 (55%) patients required surgery. Mean duration of follow-up was 42 months (range, 12-143). Mean age at the time of surgery was 37.2 years (range, 21-54). VAS scores significantly improved from 5.4 at the preoperative visit to 2.9 at 24 months. There was no significant improvement in VAS scores after the 3-month postoperative visit. Mean return to run time was 9 months (range, 4.5-16). At 1 year, 80% (46/58) of patients returned to military duty. Complications requiring return to the operating room were observed in 6 patients (9%). The high rate of return to duty and significant improvement in pain scores demonstrate that the surgical management of IAT is a viable treatment option for patients who could not otherwise remain on active duty. With that said, the complication rate of 27% is high. Patients and providers should consider the risks, benefits, and duration of therapy during their shared decision-making process. Level of Evidence: Level IV

The Achilles tendon is a common site of anatomical injury among athletes and those participating in recreational sporting activities. Acute Achilles tendon ruptures are often misdiagnosed as a sprained ankle and are more common in the male population. Mechanism of injury is often a noncontact injury, resulting from sudden forced plantar flexion or violent dorsiflexion in a plantar flexed foot. Delays in diagnosis and treatment may complicate the clinical outcome. Because findings may be subtle on history and physical examination, the use of readily available adjunctive studies is important for practitioners. One method is the analysis of Kager's triangle on lateral ankle radiographs. Obscuration of Kager's triangle has been described as a radiographic indicator of Achilles tendon rupture, but the sensitivity and specificity of this finding have been poorly reported. [ Orthopedics . 2020; 43(2): e91–e94.]

Metabolic syndrome (MetS) is a composite of cardiometabolic risk factors, including obesity, dyslipidemia, hypertension, and insulin resistance, with a range of secondary sequelae such as nonalcoholic fatty liver disease and diastolic heart failure. This syndrome has been identified as one of the greatest global health challenges of the 21st century. Herein, we examine whether a porcine model of diet- and mineralocorticoid-induced MetS closely mimics the cardiovascular, metabolic, gut microbiota, and functional metataxonomic phenotype observed in human studies. Landrace pigs with deoxycorticosterone acetate-induced hypertension fed a diet high in fat, salt, and sugar over 12 wk were assessed for hyperlipidemia, hyperinsulinemia, and immunohistologic, echocardiographic, and hemodynamic parameters, as well as assessed for microbiome phenotype and function through 16S rRNA metataxonomic and metabolomic analysis, respectively. All MetS animals developed obesity, hyperlipidemia, insulin resistance, hypertension, fatty liver, structural cardiovascular changes including left ventricular hypertrophy and left atrial enlargement, and increased circulating saturated fatty acid levels, all in keeping with the human phenotype. A reduction in α-diversity and specific microbiota changes at phylum, family, and genus levels were also observed in this model. Specifically, this porcine model of MetS displayed increased abundances of proinflammatory bacteria coupled with increased circulating tumor necrosis factor-α and increased secondary bile acid-producing bacteria, which substantially impacted fibroblast growth factor-19 expression. Finally, a significant decrease in enteroprotective bacteria and a reduction in short-chain fatty acid-producing bacteria were also noted. Together, these data suggest that diet and mineralocorticoid-mediated development of biochemical and cardiovascular stigmata of metabolic syndrome in pigs leads to temporal gut microbiome changes that mimic key gut microbial population signatures in human cardiometabolic disease. NEW & NOTEWORTHY This study extends a prior porcine model of cardiometabolic syndrome to include systemic inflammation, fatty liver, and insulin sensitivity. Gut microbiome changes during evolution of porcine cardiometabolic disease recapitulate those in human subjects with alterations in gut taxa associated with proinflammatory bacteria, bile acid, and fatty acid pathways. This clinical scale model may facilitate design of future interventional trials to test causal relationships between gut dysbiosis and cardiometabolic syndrome at a systemic and organ level.

The gut hormone glucagon-like peptide (GLP)-1 and its analogues represent a new generation of anti-diabetic drugs, which have also demonstrated propensity to modulate host lipid metabolism. Despite this, drugs of this nature are currently limited to intramuscular administration routes due to intestinal degradation. The aim of this study was to design a recombinant microbial delivery vector for a GLP-1 analogue and assess the efficacy of the therapeutic in improving host glucose, lipid and cholesterol metabolism in diet induced obese rodents. Diet-induced obese animals received either Lactobacillus paracasei NFBC 338 transformed to express a long-acting analogue of GLP-1 or the isogenic control microbe which solely harbored the pNZ44 plasmid. Short-term GLP-1 microbe intervention in rats reduced serum low-density lipoprotein cholesterol, triglycerides and triglyceride-rich lipoprotein cholesterol substantially. Conversely, extended GLP-1 microbe intervention improved glucose-dependent insulin secretion, glucose metabolism and cholesterol metabolism, compared to the high-fat control group. Interestingly, the microbe significantly attenuated the adiposity associated with the model and altered the serum lipidome, independently of GLP-1 secretion. These data indicate that recombinant incretin-secreting microbes may offer a novel and safe means of managing cholesterol metabolism and diet induced dyslipidaemia, as well as insulin sensitivity in metabolic dysfunction.

Accumulating evidence suggests obesity and its complication are linked to gut microbiota and probiotics can affect the metabolic functions of humans. The goal of this study was to systematically review the effect of probiotic and synbiotic formulations on body mass index (BMI), total body fat, waist circumstance (WC), Waist–hip ratio (WHR), and adiponectin in overweight and obese Participants in randomized trials (RCTs). A comprehensive search performed in PubMed/MEDLINE, Cochrane and SCOPUS by two researchers, independently without language or release date restrictions up to 15th October 2019. PRISMA guidelines followed to perform this meta-analysis. The inclusion criteria were: 1) RCT design, 2) intervention by pro or synbiotic, 3) Anthropometrics and/or adiponectin levels as outcome. DerSimonian and Laird random effect model used to combine results of included studies. Thirty-two studies contained 2105 participants (n = 28–200) were analyzed in this meta-analysis. Average length of intervention in included studies was 10.18 weeks and ranged from 3 to 12 weeks. Combined results showed significant reduction in BMI (WMD: −0.25 kg/m2; 95% CI −0.33, −0.17; I2 = 96%), total body fat (WMD: −0.75%; 95% CI −0.90, −0.61; I2 = 63%), WC (WMD: −0.99 cm; 95% CI −1.33, −0.66; I2 = 92%), and WHR (WMD: −0.01; 95% CI −0.02, 0.01; I2 = 15%) in probiotic group compared to placebo. There was no significant effect on adiponectin levels by probiotic intervention (WMD: −0.01 μg/ml; 95% CI −0.33, 0.32; I2 = 90%). Furthermore, meta-regression showed significant relation between duration of intervention and reduction of BMI (coef = −0.1533, p

Hormone therapy continues to be a favourable option in the management of menopausal symptomatology, but the associated risk-benefit ratios with respect to neurodegenerative diseases remain controversial. The study aim was to determine the relation between menopausal hormone therapy and Alzheimer's disease, dementia, and Parkinson's disease in human subjects. A literature search was performed in PubMed/Medline, Cochrane collaboration, and Scopus databases from onset of the database to September 2019. Random-effects model was used to estimate pooled odd ratio (OR) and 95 % confidence intervals (CI). Subgroup analysis was performed based on the type and formulation of hormone. In addition, the time-response effect of this relationship was also assessed based on duration of hormone therapy. Associations between hormone therapy and Alzheimer's disease, dementia, and Parkinson's disease in menopausal women were reported in 28 studies. Pooled results with random effect model showed a significant association between hormone therapy and Alzheimer's disease (OR 1.08, 95 % CI 1.03–1.14, I2: 69 %). This relationship was more pronounced in patients receiving the combined estrogen-progestogen formulation. Moreover, a significant non-linear time-response association between hormone therapy and Alzheimer's disease was also identified (Coef1 = 0.0477, p1

Water-soluble dietary fibers have been shown to improve lipid profile and glucose metabolism in diabetes. The aim of this study was to review the effects of psyllium consumption on weight, body mass index, lipid profiles, and glucose metabolism in diabetic patients in randomized controlled trials. A comprehensive systematic search was performed in PubMed/MEDLINE, Web of Sciences, Cochrane, and Scopus by two independent researchers up to August 2019 without any time and language restrictions. The DerSimonian and Laird random-effects model method performed to calculate the pooled results. Inclusion criteria were randomized controlled trial design, adult subjects, and studies reporting the mean differences with the 95% confidence interval for outcome. Eight studies containing nine arms with 395 participants were identified and included in final analysis. Combined results found a significant reduction in triglycerides, low-density lipoprotein, fasting blood sugar, and hemoglobin A1c following psyllium consumption (weighted mean differences [WMD]: -19.18 mg/dl, 95% CI [-31.76, -6.60], I2 = 98%), (WMD: -8.96 mg/dl, 95% CI [-13.39, -4.52], I2 = 97%), (WMD: -31.71 ml/dl, 95% CI [-50.04, -13.38], I2 = 97%), and (WMD: -0.91%, 95% CI [-1.31, -0.51], I2 = 99%), respectively. There was no significant change in high-density lipoprotein, body mass index, cholesterol, and weight. In conclusion, the results demonstrated a significant reduction in triglycerides, low-density lipoprotein, fasting blood sugar, and hemoglobin A1c by psyllium intervention among diabetic patients.

Small intestinal bacterial overgrowth (SIBO) is a heterogenous and poorly understood entity characterised by an excessive growth of select microorganisms within the small intestine. This excessive bacterial biomass, in turn, disrupts host physiology in a myriad of ways, leading to gastrointestinal and non-gastrointestinal symptoms and complications. SIBO is a common cause of non-specific gastrointestinal symptoms in children, such as chronic abdominal pain, abdominal distention, diarrhoea, and flatulence, amongst others. In addition, it has recently been implicated in the pathophysiology of stunting, a disease that affects millions of children worldwide. Risk factors such as acid-suppressive therapies, alterations in gastrointestinal motility and anatomy, as well as impoverished conditions, have been shown to predispose children to SIBO. SIBO can be diagnosed via culture-dependant or culture-independent approaches. SIBO's epidemiology is limited due to the lack of uniformity and consensus of its diagnostic criteria, as well as the paucity of literature available. Antibiotics remain the first-line treatment option for SIBO, although emerging modalities such as probiotics and diet manipulation could also have a role. Herein, we present a state-of-the-art-review which aims to comprehensively outline the most current information on SIBO in children, with particular emphasis on the gut microbiota.

A male premature infant born at 26 weeks of gestation is now at 32 weeks corrected age. He has developed chronic lung disease and is currently on low-flow oxygen. His growth has been faltering, falling below the 10th centile despite 180 mL/kg/day of fortified mother’s own milk. Postprandial regurgitation of milk has been occurring, with suspected gastro-oesophageal reflux. Ultrasound of the abdomen reveals no evidence of pyloric stenosis. Despite a trial of Gaviscon, he continues to regurgitate milk and his growth rate remains inadequate, so a decision is made to commence domperidone. Prior to initiation of therapy, an ECG performed to exclude prolonged QT interval reveals a corrected QTc of 400msec and an electrolyte panel was found to be entirely within normal range. You are asked to consider whether the risk of harm in developing a prolonged QTc and sudden death from a cardiac arrhythmia while receiving domperidone is low enough to warrant the introduction of this medication and whether follow-up ECGs are indicated. In the case of inpatient infants with GORD ( population ), does domperidone administration ( intervention ) cause clinically relevant QTc prolongation and/or arrhythmia ( outcomes ) when compared with baseline ( control )? PubMed, MEDLINE ( via EBSCOhost) and Cochrane CENTRAL databases were searched from article inception to 01/09/2019 with the following strategy: ‘((infant) OR (neonate) OR (newborn)) AND (domperidone) AND ((QT) OR (QTc) OR (prolonged) OR (ECG) OR (EKG) OR (arrhythmia))’. In all, 37 abstracts were identified (Medline 21, Embase 16, Cochrane 0) with 21 unique studies, of which five were included (table 1). Of the articles excluded, three were concerned with the use of domperidone as a galactagogue agent in lactating …

Background In April 2018, the Irish cervical smear screening programme, “CervicalCheck”, came under intense scrutiny as the accuracy of hundreds of “negative” results were brought in question. Aim The goal of this brief report was to assess the impact of this real-life event on public information-seeking behaviour, using Google search anomalies as a proxy. Irish relative search volume data for several terms relating to cervical testing/cancer and human papillomavirus were extracted for a five-year period from February 2014 to January 2019 and analysed for the presence of anomalous spikes and shifts in the mean baseline. Results An unprecedented positive spike in searches relating to cervical testing/cancer was observed immediately after the CervicalCheck revelations, which remained anomalous for the month to follow (p < 0.05). This public interest preceded a mirroring increase in uptake of complimentary consultations offered by the Department of Health to the women concerned. Despite this service engagement and interest in cervical health, the relative search volumes for terms “human papillomavirus infection” and ”HPV vaccine” were just 78 and 51% of their maximum search volume for the five-year period. Conclusions Anomaly analysis revealed an unprecedented spike in information-seeking behaviour following the CervicalCheck revelations. However, this was not associated with a comparable elevation in HPV interest. This suggests that more public education and promotion of the HPV vaccine is warranted, in the context of vastly reduced uptake in recent years. Finally, Google Trends data represents a free an open source means by which to assess information-seeking behaviour of the public in relation to health and disease.

Purpose: Liver cancer is the sixth most common type of cancer worldwide, and waist circumference (WC) is associated with its risk beyond body mass index (BMI). This dose-response meta-analysis was performed to investigate the association between WC and the risk of incident liver cancer using prospective cohort studies. Methods: A comprehensive systematic search was conducted in MEDLINE/PubMed, Web of Science databases, Scopus, and Coch­rane from inception to May 2019. Studies with retrospective or prospective cohort design that reported hazard ratio (HR), risk ratio, or odds ratio, and the corresponding 95% confidence intervals (CI) for liver cancer based on WC categories were included in this meta-analysis. Combined HRs with 95% CIs was estimated by DerSimonian and Laird random-effects models. Results: Associations between WC and liver cancer were reported in 5 articles with 2,547,188 participants. All studies were published between 2013 and 2019. Pooled results showed a strong significant association with minimum heterogeneity between WC and risk of liver cancer (HR 1.59, 95% CI 1.38–1.83, pheterogeneity = 0.42: I2 = 0%). Moreover, a dose-response model indicated a significant positive association between WC and risk of liver cancer (exp(b) = 1.018, p < 0.001). Conclusions: This systematic review and dose-response meta-analysis highlights WC as a significant risk factor related to the incidence of liver cancer.

OBJECTIVE Data on the association between the antioxidant capacity of a diet and the risk of ulcerative colitis (UC) are scarce. This study aimed to assess whether a relationship exists between dietary total antioxidant capacity (TAC) and the odds of UC in Iranian adults. METHODS In this case-control study, patients with UC and age-matched healthy controls were recruited from a hospital clinic. All participants completed a validated 168-item food frequency questionnaire, the results of which were subsequently used to generate dietary TAC. Ferric reducing-antioxidant power values were used to calculate dietary TAC. RESULTS Altogether 62 patients with UC and 124 healthy controls were enrolled. UC patients had a higher calorific intake (P

Background Fasting and energy restricting diets have a potential means of delaying or preventing the onset of a range of age-related metabolic and neoplastic diseases. Consistently at the centre of this effect appears to be a significant reduction in circulating IGF-1 levels. The aim of the current systematic review and meta-analysis was to determine the influence of fasting and energy restriction on IGF-1 levels in human subjects. Methods A comprehensive systematic search was conducted from onset of the database to February 2019 in Embase, MEDLINE/PubMed, and SCOPUS to identify randomized clinical trials that investigating the impact of fasting or energy restriction circulating IGF-1 levels. Effect size was reported as weighted mean difference (WMD) and 95% confidence intervals (CI) using a random-effects models. Subgroup analysis was performed to identify the probable source of heterogeneity among trials. Results Total pooling of fasting and energy restriction randomised controlled trials in WMD analysis revealed no significant effect on circulating IGF-1 levels (WMD: −16.41 ng/ml, 95% CI: −35.88, 3.07). Sub grouped analysis fasting regimens appeared to substantially reduce IGF-1 (WMD: -28.87 ng/ml, 95% CI: −43.69, −14.05, I2 = 00%), energy restricting regimens failed to do the same (WMD: -10.98 ng/ml, 95% CI: −33.08, 11.11, I2 = 90%). Within this final subgrouping, it was observed that only energy restriction regimens of 50% or greater of normal daily energy intake were capable of significantly reducing IGF-1 levels (WMD: -36.57 ng/ml, 95% CI: −59.19, −13.95, I2 = 00%). Finally, a meta regression were noted in which the percentage restriction of daily energy intake inversely correlated with plasma IGF-1 levels (p = 0.04). Conclusion This study uncovered that fasting significantly reduced levels of IGF-1, while energy restriction diets were successful only when intake was reduced by 50% or more.

Objectives To determine the weight, body mass index (BMI), cardiometabolic, and gastrointestinal effects of glucagon-like peptide-1 (GLP-1) receptor agonists in children with obesity. Study design Web of Science, PubMed/MEDLINE, and Scopus databases from 01/01/1994-01/01/2021 for randomized control trials examining the weight, BMI, cardiometabolic, or gastrointestinal effects of GLP-1 receptor agonists in children and adolescents with obesity. Data were extracted by 2 independent surveyors and a random effects model was applied to meta-analyze generic inverse variance outcomes. Primary outcomes were related to weight and cardiometabolic profile, and secondary outcomes of interest were gastrointestinal-related treatment-emergent adverse events. Results Nine studies involving 574 participants were identified, of which 3 involved exenatide and 6 involved liraglutide. GLP-1 receptor agonists use caused a modest reduction in body weight (mean difference [MD] -1.50 [-2.50,-0.50] kg, I2 64%), BMI (MD -1.24 [-1.71,-0.77] kg/m2, I2 0%), and BMI z score (MD -0.14 [-0.23,-0.06], I2 43%). Glycemic control was improved in children with proven insulin resistance (glycated hemoglobin A1c MD -1.05 [-1.93,-0.18] %, I2 76%). Although no lipid profile improvements were noted, a modest decrease in systolic blood pressure was detected (MD -2.30 [-4.11,-0.49] mm Hg; I2 0%). Finally, analysis of gastrointestinal-related treatment-emergent adverse events revealed an increased risk of nausea (risk ratio 2.11 [1.44, 3.09]; I2 0%), without significant increases in other gastrointestinal symptoms. Conclusions This meta-analysis indicates that GLP-1 receptor agonists are safe and effective in modestly reducing weight, BMI, glycated hemoglobin A1c, and systolic blood pressure in children and adolescents with obesity in a clinical setting, albeit with increased rates of nausea. PROSPERO ID CRD42020195869.

Introduction: Optimal glycaemic control is often a challenge in children and adolescents with type 1 diabetes (T1D). Implementation of patient, clinician or organisation-targeted quality improvement (QI) strategies has been proven to be beneficial in terms of improving glycaemic outcomes in adults living with diabetes. This review aims to assess the effectiveness of such QI interventions in improving glycaemic control, care delivery, and screening rates in children and adolescents with T1D. Methods and analysis: MEDLINE, EMBASE, CINAHL and Cochrane CENTRAL databases will be searched for relevant studies up to January 2021. Trial registries, ClinicalTrials.gov and ICTRP, will also be explored for any ongoing trials of relevance. We will include trials which examine QI strategies as defined by a modified version of the Cochrane Effective Practice and Organisation of Care 2015 Taxonomy in children ( Dissemination: The results of this review will be disseminated through peer-reviewed publication in order to inform invested partners (e.g., Paediatric Endocrinologists) on the potential of QI strategies to improve glycaemic management and other related health outcomes in children with T1D, thereby guiding best practices in the outpatient management of the disorder. PROSPERO registration number: CRD42021233974 (28/02/2021).