Fear-avoidant beliefs and behaviours after upper limb fracture in older people: a systematic review and meta-ethnography.

PURPOSE: This systematic review aimed to understand older people's perspectives of associated fear-avoidant beliefs following upper limb fracture. METHODS: Published and unpublished literature databases were systematically searched from inception to 1st April 2023. Qualitative studies reporting the perspectives of fear-avoidant beliefs or behaviours in people who had sustained an upper limb fracture were eligible. Data extracted included characteristics of people interviewed, experiences and perceptions of fear, fear of falling, and fear-avoidant beliefs and behaviours. Data were synthesised using a meta-ethnography approach and the GRADE-CERQUAL tool. RESULTS: Eight studies were eligible (n = 150 participants; 109 distal radial/41 humeral fracture). Three overarching themes were identified: (1) type of fear-avoidant experiences, (2) drivers of fear-avoidant beliefs and behaviours, and (3) consequences of fear-avoidant beliefs and behaviours. The themes generated were based on moderate confidence evidence. In summary, whilst some patients initially consider upper limb fractures to be relatively minor injuries, over time, the realisation occurs that they have wide-ranging consequences with longer-term perspectives on recovery. This often occurs following an initial period of reduced fear. Providing education and support immediately post-fracture to prevent or challenge initial health beliefs around fear of falls and fear of movement is imperative to recovery. CONCLUSIONS: Fear-avoidant beliefs can impact heavily on certain older people's recovery, as well as their longer-term health and wellbeing. Consideration of fear avoidance and taking steps to mitigate against this in the acute upper limb trauma setting will better serve these patients in their ongoing recovery from injury.

Management of septic and aseptic prepatellar bursitis: a systematic review.

BACKGROUND: Despite contributing to significant morbidity in working-age adults, there is no consensus on the optimal treatment for prepatellar bursitis. Much of the existing literature combines prepatellar and olecranon bursitis. This systematic review aims to determine the optimal management of prepatellar bursitis. STUDY DESIGN AND METHODS: A primary search of electronic published and unpublished literature databases from inception to November 2019 was completed. Articles over 25 years old, case reports with less than four patients, paediatric studies, and non-English language papers were excluded. Our primary outcome was recurrence after 1 year. Comparisons included endoscopic vs open bursectomy, duration of antibiotics. Methodological quality was assessed using the Institute of Health Economics and Revised Cochrane Risk of Bias scoring systems. Meta-analyses were conducted where appropriate. RESULTS: In total 10 studies were included (N = 702). Endoscopic and open bursectomy showed no difference in recurrence after 1 year (OR 0.41, 95% CI 0.05-3.53, p = 0.67), and surgical complications (OR 1.44, 95% CI 0.34-6.08, p = 0.44). 80% endoscopically-treated patients were pain free after 1 year. Patients treated with antibiotics for less than 8 days were not significantly more prone to recurrence (2/17 vs 10/114, OR 0.66, 95% CI 0.13-3.29, p = 0.64) compared to 8 days plus at minimum 1 year post injury. CONCLUSIONS: Our study represents the largest cohort of patients evaluating management strategies for prepatellar bursitis, and includes data not previously published. Endoscopic bursectomy is non-inferior to open bursectomy, enabling a shorter hospital stay. It also offers a relatively low risk of post-operative pain. Endoscopic bursectomy is a viable option to treat both septic and aseptic prepatellar bursitis. Our small cohort suggests recurrence and hospital stay are not improved with antibiotic treatment exceeding 7 days for septic prepatellar bursitis.

Increased proportion of alcohol-related trauma in a South London major trauma centre during lockdown: A cohort study.

PURPOSE: Alcohol has been associated with 10%-35% trauma admissions and 40% trauma-related deaths globally. In response to the COVID-19 pandemic, the United Kingdom entered a state of "lockdown" on March 23, 2020. Restrictions were most significantly eased on June 1, 2020, when shops and schools re-opened. The purpose of this study was to quantify the effect of lockdown on alcohol-related trauma admissions. METHODS: All adult patients admitted as "trauma calls" to a London major trauma centre during April 2018 and April 2019 (pre-lockdown, n = 316), and 1st April-31st May 2020 (lockdown, n = 191) had electronic patient records analysed retrospectively. Patients' blood alcohol level and records of intoxication were used to identify alcohol-related trauma. Trauma admissions from pre-lockdown and lockdown cohorts were compared using multiple regression analyses. RESULTS: Alcohol-related trauma was present in a significantly higher proportion of adult trauma calls during lockdown (lockdown 60/191 (31.4%), vs. pre-lockdown 62/316 (19.6%); (odds ratio (OR): 0.83, 95% CI: 0.38-1.28, p < 0.001). Lockdown was also associated with increased weekend admissions of trauma (lockdown 125/191 weekend (65.5%) vs. pre-lockdown 179/316 (56.7%); OR: 0.40, 95% CI: 0.79 to -0.02, p = 0.041). No significant difference existed in the age, gender, or mechanism between pre-lockdown and lockdown cohorts (p > 0.05). CONCLUSIONS: The United Kingdom lockdown was independently associated with an increased proportion of alcohol-related trauma. Trauma admissions were increased during the weekend when staffing levels are reduced. With the possibility of further global "waves" of COVID-19, the long-term repercussions of dangerous alcohol-related behaviour to public health must be addressed.

Systematic review of randomised controlled trials for interventions to treat injuries to the medial ligaments of the knee.

BACKGROUND: Optimal management of severe and complex injuries to the medial knee ligaments remains uncertain. This systematic review evaluates outcomes from randomised controlled trials investigating interventions for treating injuries of medial ligaments of the knee. METHODS: Randomised controlled clinical trials evaluating interventions for treating injuries of the medial knee ligaments were identified through searching EMBASE, Medline, Cochrane, WHO, and clinicaltrials.org. Comparisons were made between different non-operative interventions, surgical versus non-operative interventions, different surgical interventions, and different postoperative interventions. Primary outcome measures included patient reported outcome measures (PROM) of knee function, pain, and treatment failure. RESULTS: 412 trial records were identified; 259 were non-redundant and distinct studies, of which eight were included for analysis. No differences between operative and non-operative management strategies were found for either primary outcome: Lysholm and IKDC scores. Compared to non-operative interventions, operative interventions resulted in reduced quadriceps strength at eight weeks (mean difference (MD) 29 (% knee extension strength deficit compared with unaffected knee); 95%CI 3.89-54.11) and were associated with greater incidence of minor complications (relative risk (RR) 25; 95%CI: 1.51-421, and RR 25; 95%CI: 1.50-416.58, respectively). Quadriceps strength between 16 and 52 weeks was similar in non-operative and operative groups (MD 20; 95%CI -1.92-41.92). Functional rehabilitation was associated with reduced valgus laxity at six weeks compared to bracing ((MD) -1.40; 95%CI: -2.21-0.59). CONCLUSIONS: Non-operative interventions provided similar functional results to operative interventions for grade I-III injuries of the medial collateral ligaments. Non-operative intervention was associated with improved quadriceps strength during rehabilitation, and fewer complications, compared to operative interventions.

The effects of kinesiophobia on outcome following total knee replacement: a systematic review.

INTRODUCTION: Kinesiophobia, the fear of physical movement and activity related to injury vulnerability, has been linked to sub-optimal outcomes following total knee replacement (TKR). This systematic review has two aims: to define the relationship between kinesiophobia and functional outcomes, pain and range of motion following TKR, and to evaluate published treatments for kinesiophobia following TKR. MATERIALS AND METHODS: A primary search of electronic databases, grey literature, and trial registries was performed in March 2020. English-language studies recruiting adult primary TKR patients, using the Tampa Scale of Kinesiophobia (TSK) were included. Outcome measures were grouped into short (< 6 months), medium (6-12 months), and long term (> 12 months). Study quality was assessed using the Newcastle Ottawa Scale for cohort or case control studies, and the Cochrane Collaboration Risk of Bias tool for randomised controlled trials. RESULTS: All thirteen included papers (82 identified) showed adequately low risk of methodological bias. TSK1 (activity avoidance) correlated with WOMAC functional score at 12 months in three studies (r = 0.20 p < 0.05, R = 0.317 p = 0.001, and correlation coefficient 0.197 p = 0.005). TSK score significantly correlated with mean active range of motion (ROM) at 2 weeks [65.98 (SD = 14.51) versus 47.35 (SD = 14.48) p = 0.000], 4 weeks [88.20 (SD = 15.11) versus 57.65 (SD = 14.80) p = 0.000], and 6 months [105.33 (SD = 12.34) versus 85.53 (SD = 14.77) p = 0.000] post-operation. Three post-operative interventions improved TSK score vs control following TKR: a home-based functional exercise programme [TSK - 14.30 (SD = 0.80) versus - 2.10 (SD = 0.80) p < 0.001], an outpatient cognitive behavioural therapy (CBT) programme [TSK 27.76 (SD = 4.56) versus 36.54 (SD = 3.58)], and video-based psychological treatment [TSK 24 (SD = 5) versus 29 (SD = 5) p < 0.01]. CONCLUSIONS: Kinesiophobia negatively affects functional outcomes up until 1 year post-operatively, while active ROM is reduced up to 6 months post-procedure. Post-operative functional and psychological interventions can improve kinesiophobia following TKR.

Health, burnout and well-being of UK cardiology trainees: insights from the British Junior Cardiologists' Association Survey.

BACKGROUND: Cardiology training is demanding and associated with high workloads. Poor lifestyle and health among clinicians may stretch workforces and impact patient care. It has not been established what impact training in cardiology has on the doctors undertaking it. We aimed to establish the prevalence of physical and mental illness, burnout and the ability to maintain a healthy lifestyle among cardiology trainees in the United Kingdom (UK). METHODS: The 2023 British Junior Cardiologists' Association training survey included questions on ill health, burnout, healthy living and invited responders to complete screening questionnaires for depression (Patient Health Questionnaire 9; PHQ-9) and anxiety (Generalised Anxiety Disorder 7; GAD-7). Significant anxiety and depression were defined as scoring within the moderate or severe range (PHQ-9≥10; GAD-7≥10). Burnout was a self-reported outcome. Poisson regression was used to determine prevalence ratios (PR) between univariate predictors of anxiety, depression and burnout. RESULTS: Of 398 responders, 212 consented to answer health and well-being questions. Prior physical and mental health conditions were reported by 9% and 7% of trainees, respectively. Significant depression and anxiety symptoms were reported by 25% and 18% of trainees, respectively. Burnout was reported by 76% of trainees. Less than full-time trainees reported greater anxiety (PR 2.92, 95% CI 1.39 to 6.16, p<0.01) and depression (PR 3.66, 95% CI 2.24 to 5.98, p<0.01), while trainees with dependents reported less burnout (PR 0.77, 95% CI 0.65 to 0.92, p<0.01). Exercise, good sleep quality and maintaining a healthy diet were associated with less burnout and depressive symptoms (p<0.05). Half of trainees reported training having a negative impact on well-being, driven by the amount of service provision, curriculum requirements and lack of training opportunities. CONCLUSIONS: The prevalence of anxiety, depression and burnout is high among UK cardiology trainees. Further work should establish the impact of cardiology trainee health on the quality of patient care. Training bodies should consider how occupational factors may contribute to health.

Hospital admissions in the last year of life of patients with heart failure.

AIM: To explore the frequency, causes, and pattern of hospitalisation for patients with chronic heart failure (HF) in the 12 months preceding death. We also investigated cause of death. METHODS: Patients referred to a secondary care HF clinic were routinely consented for follow-up between 2001 and 2020 and classified into three phenotypes: (i) HF with reduced ejection fraction (HFrEF), (ii) HF with preserved ejection fraction (HFpEF) with plasma N-terminal pro B-type natriuretic peptide (NT-proBNP) 125-399 ng L-1, and (iii) HFpEF with NT-proBNP ≥400 ng L-1. Hospital admissions in the last year of life were classified as: HF, other cardiovascular (CV), or non-cardiovascular (non-CV). The cause of death was systematically adjudicated. RESULTS: A total of 4925 patients (38% women; median age at death 81 [75-87] years) had 9127 hospitalisations in the last year of life. The median number of hospitalisations was 2 (1-3) and total days spent in hospital was 12 (2-25). Out of the total, 83% of patients had ≥1 hospitalisation but only 20% had ≥1 HF hospitalisation; 24% had ≥1 CV hospitalisation; 70% had ≥1 non-CV hospitalisation. Heart failure hospitalisations were most common in patients with HFrEF, but in all groups, at least two thirds of admissions were for non-CV causes. There were 788 (16%) deaths due to progressive HF, of which 74% occurred in hospital. CONCLUSION: For patients with chronic HF in the last year of life, most hospitalisations were for non-CV causes regardless of HF phenotype. Most patients had no HF hospitalisations in their last year of life. Most deaths were from causes other than progressive HF.

Medicines optimization prior to discharge in patients admitted to hospital with heart failure.

AIMS: Approximately half of patients with heart failure and a reduced ejection fraction (HeFREF) are discharged from hospital on triple therapy [angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs), beta-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs)]. We investigated what proportion of patients are on optimal doses prior to discharge and how many might be eligible for initiation of sacubitril-valsartan or sodium-glucose co-transporter-2 inhibitors (SGLT2Is). METHODS AND RESULTS: Between 2012 and 2017, 1277 patients admitted with suspected heart failure were enrolled at a single hospital serving a local community around Kingston upon Hull, UK. Eligibility for sacubitril-valsartan or SGLT2I was based on entry criteria for the PIONEER-HF, DAPA-HF, and EMPEROR-Reduced trials. Four hundred fifty-five patients had HeFREF with complete data on renal function, heart rate, and systolic blood pressure (SBP) prior to discharge. Eighty-three per cent of patients were taking an ACE-I or ARB, 85% a BB, and 63% an MRA at discharge. More than 60% of patients were eligible for sacubitril-valsartan and >70% for SGLT2I. Among those not already receiving a prescription, 37%, 28%, and 49% were eligible to start ACE-I or ARB, BB, and MRA, respectively. Low SBP (≤105 mmHg) was the most frequent explanation for failure to initiate or up-titrate therapy. CONCLUSIONS: Most patients admitted for heart failure are eligible for initiation of life-prolonging medications prior to discharge. A hospital admission may be a common missed opportunity to improve treatment for patients with HeFREF.

Plasma MERTK is causally associated with infection mortality.

BACKGROUND: Infectious diseases are a major cause of mortality in spite of existing public health, anti-microbial and vaccine interventions. We aimed to define plasma proteomic associates of infection mortality and then apply Mendelian randomisation (MR) to yield biomarkers that may be causally associated. METHODS: We used UK Biobank plasma proteomic data to associate 2923 plasma proteins with infection mortality before 31st December 2019 (240 events in 52,520 participants). Since many plasma proteins also predict non-infection mortality, we focussed on those associated with >1.5-fold risk of infection mortality in an analysis excluding survivors. Protein quantitative trait scores (pQTS) were then used to identify whether genetically predicted protein levels also associated with infection mortality. To conduct Two Sample MR, we performed a genome-wide association study (GWAS) of infection mortality using UK Biobank participants without plasma proteomic data (n = 363,953 including 984 infection deaths). FINDINGS: After adjusting for clinical risk factors, 1142 plasma proteins were associated with risk of infection mortality (false discovery rate <0.05). 259 proteins were associated with >1.5-fold increased risk of infection versus non-infection mortality. Of these, we identified genetically predicted increasing MERTK concentration was associated with increased risk of infection mortality. MR supported a causal association between increasing plasma MERTK protein and infection mortality (odds ratio 1.46 per unit; 95% CI 1.15- 1.85; p = 0.002). CONCLUSION: Plasma MERTK is causally associated with infection mortality and warrants exploration as a potential therapeutic target.

Studying Adipose Endothelial Cell/Adipocyte Cross-Talk in Human Subcutaneous Adipose Tissue.

Microvascular endothelial cells (MVECs) have many critical roles, including control of vascular tone, regulation of thrombosis, and angiogenesis. Significant heterogeneity in endothelial cell (EC) genotype and phenotype depends on their vascular bed and host disease state. The ability to isolate MVECs from tissue-specific vascular beds and individual patient groups offers the opportunity to directly compare MVEC function in different disease states. Here, using subcutaneous adipose tissue (SAT) taken at the time of insertion of cardiac implantable electronic devices (CIED), we describe a method for the isolation of a pure population of functional human subcutaneous adipose tissue MVEC (hSATMVEC) and an experimental model of hSATMVEC-adipocyte cross-talk. hSATMVEC were isolated following enzymatic digestion of SAT by incubation with anti-CD31 antibody-coated magnetic beads and passage through magnetic columns. hSATMVEC were grown and passaged on gelatin-coated plates. Experiments used cells at passages 2-4. Cells maintained classic features of EC morphology until at least passage 5. Flow cytometric assessment showed 99.5% purity of isolated hSATMVEC, defined as CD31+/CD144+/CD45-. Isolated hSATMVEC from controls had a population doubling time of approximately 57 h, and active proliferation was confirmed using a cell proliferation imaging kit. Isolated hSATMVEC function was assessed using their response to insulin stimulation and angiogenic tube-forming potential. We then established an hSATMVEC-subcutaneous adipocyte co-culture model to study cellular cross-talk and demonstrated a downstream effect of hSATMVEC on adipocyte function. hSATMVEC can be isolated from SAT taken at the time of CIED insertion and are of sufficient purity to both experimentally phenotype and study hSATMVEC-adipocyte cross-talk.

The diabetic myocardial transcriptome reveals Erbb3 and Hspa2 as a novel biomarkers of incident heart failure.

AIMS: Diabetes mellitus (DM) increases heart failure incidence and worsens prognosis, but its molecular basis is poorly defined in humans. We aimed to define the diabetic myocardial transcriptome and validate hits in their circulating protein form to define disease mechanisms and biomarkers. METHODS AND RESULTS: RNA-sequencing data from the Genotype-Tissue Expression (GTEx) project was used to define differentially expressed genes (DEGs) in right atrial (RA) and left ventricular (LV) myocardium from people with versus without DM (type 1 or 2). DEGs were validated as plasma proteins in the UK Biobank cohort, searching for directionally concordant differential expression. Validated plasma proteins were characterized in UK Biobank participants, irrespective of diabetes status, using cardiac magnetic resonance imaging, incident heart failure and cardiovascular mortality.We found 32 and 32 DEGs associated with DM in the RA and LV, respectively, with no overlap between these. Plasma proteomic data was available for 12, with ERBB3, NRXN3 and HSPA2 (all LV hits) exhibiting directional concordance. Irrespective of DM status, lower circulating ERBB3 and higher HSPA2 were associated with impaired left ventricular contractility and higher LV mass. Participants in the lowest quartile of circulating ERBB3 or highest quartile of circulating HSPA2 had increased incident heart failure and cardiovascular death vs. all other quartiles. CONCLUSIONS: DM is characterized by lower Erbb3 and higher Hspa2 expression in the myocardium, with directionally concordant differences in their plasma protein concentration. These are associated with left ventricular dysfunction, incident heart failure and cardiovascular mortality.

Distinct, common and synergistic effects of insulin and IGF-1 receptors on healthy murine ageing.

Objective: Reduced IGF-1 signalling is an evolutionarily conserved mediator of longevity, yet the magnitude of this effect is substantially larger in organisms retaining a common insulin and IGF-1 receptor. Whether this reflects the failure to simultaneously reduce IGF-1 and insulin signalling in mammalian model systems remains unexplored, as is the associated impact on markers of healthy ageing. We set out to address these uncertainties. Methods: We compared the duration of healthy life (healthspan) in male mice with haploinsufficiency of the insulin receptor (IRKO), IGF-1 receptor (IGF-1RKO), or both (DKO), versus wildtype (WT) littermates. Cognitive performance was defined using nesting studies at 3- and 24-months of age. Brain transcriptome was characterised at 3- and 18-months of age using RNA-seq. Results: Healthspan was longer in DKO versus WT, with IRKO and IGF-1RKO being intermediate. At 2 years of age, DKO also exhibited preserved nesting behaviour in contrast with all other genotypes. Differential insulin sensitivity or weight gain during ageing did not explain the preserved healthspan of DKO, since these were comparable to IRKO littermates. Brain transcriptomics at 18 months of age revealed lower expression of canonical ageing-associated genes in DKO versus WT, although many of these findings were replicated in IRKO versus WT or IGF-1RKO vs WT. Conclusions: Reduced insulin and IGF-1 receptor expression have both common and synergistic effects upon elements of healthy mammalian ageing, suggesting future ageing studies should consider targeting both insulin and IGF-1 signalling.

Angioleiomyoma - A Case Report.

Angioleiomyoma is a rare benign soft tissue tumour arising from smooth muscle, representing <1% of upper limb soft tissue tumours. We report a 54-year-old male presenting with a progressively enlarging atraumatic lesion along the palmar side of the base of the ring and little finger. A biopsy was done to determine the diagnosis. Intraoperatively, the lump was found to be intimately related to the radial digital artery, it could not be excised en-bloc without transecting the radial digital artery of the little finger. Following excision, the ends of the digital artery were anastomosed. At 10-months follow-up, the hand was fully functional without any evidence of cold-intolerance or neurological deficit along the distribution of the digital nerve. We review the literature on angioleiomyoma and report careful resection of the tumour with digital artery transection and repair as a treatment option for angioleiomyoma of the digital artery. Level of Evidence: Level V (Therapeutic).

Association between Patellofemoral Anatomy and Chondral Lesions of the Knee in Patellofemoral Instability.

Chondral injury is a serious consequence of patellar dislocation and patellofemoral instability (PFI). There is limited data on the relationship between radiological features such as sulcus angle and patellar height to the presence, location, and severity of chondral lesions. The purpose of this study was to determine the association of anatomical variants in patellofemoral instability with injuries sustained due to patellar dislocation. A cohort of 101 patients who had four or more episodes of dislocation or instability undergoing isolated arthroscopy or arthroscopies at the time of corrective realignment surgery were identified. The prevalence of chondral, ligamentous, and meniscal injuries was determined and correlated to the sulcus angle, tibial tubercle trochlear groove distance, and patellar height on magnetic resonance imaging (MRI) scans. A total of 101 patients was identified. At arthroscopy, the patella demonstrated the highest incidence of chondral injury (68%) followed by the trochlear groove (40%). Lateral meniscal injuries were noted in 6% of patients, medial meniscal injuries in 2%, and anterior cruciate ligament (ACL) injury in 3%. Chondral injuries were graded using the Outerbridge criteria and there was a correlation between more severe chondral injuries and a greater tilt angle (p = 0.05). The occurrence of injury to the lateral meniscus was associated with a higher Insall-Salvati ratio (p = 0.05). More severe chondral injuries are seen in patients with a greater tilt angle.

Relationship Among Diabetes, Obesity, and Cardiovascular Disease Phenotypes: A UK Biobank Cohort Study.

OBJECTIVE: Obesity and diabetes frequently coexist, yet their individual contributions to cardiovascular risk remain debated. We explored cardiovascular disease biomarkers, events, and mortality in the UK Biobank stratified by BMI and diabetes. RESEARCH DESIGN AND METHODS: A total of 451,355 participants were stratified by ethnicity-specific BMI categories (normal, overweight, obese) and diabetes status. We examined cardiovascular biomarkers including carotid intima-media thickness (CIMT), arterial stiffness, left ventricular ejection fraction (LVEF), and cardiac contractility index (CCI). Poisson regression models estimated adjusted incidence rate ratios (IRRs) for myocardial infarction, ischemic stroke, and cardiovascular death, with normal-weight nondiabetes as comparator. RESULTS: Five percent of participants had diabetes (10% normal weight, 34% overweight, and 55% obese vs. 34%, 43%, and 23%, respectively, without diabetes). In the nondiabetes group, overweight/obesity was associated with higher CIMT, arterial stiffness, and CCI and lower LVEF (P < 0.005); these relationships were diminished in the diabetes group. Within BMI classes, diabetes was associated with adverse cardiovascular biomarker phenotype (P < 0.005), particularly in the normal-weight group. After 5,323,190 person-years follow-up, incident myocardial infarction, ischemic stroke, and cardiovascular mortality rose across increasing BMI categories without diabetes (P < 0.005); this was comparable in the diabetes groups (P-interaction > 0.05). Normal-weight diabetes had comparable adjusted cardiovascular mortality to obese nondiabetes (IRR 1.22 [95% CI 0.96-1.56]; P = 0.1). CONCLUSIONS: Obesity and diabetes are additively associated with adverse cardiovascular biomarkers and mortality risk. While adiposity metrics are more strongly correlated with cardiovascular biomarkers than diabetes-oriented metrics, both correlate weakly, suggesting that other factors underpin the high cardiovascular risk of normal-weight diabetes.

Nicotinamide Adenine Dinucleotide Phosphate Oxidases in Glucose Homeostasis and Diabetes-Related Endothelial Cell Dysfunction.

Oxidative stress within the vascular endothelium, due to excess generation of reactive oxygen species (ROS), is thought to be fundamental to the initiation and progression of the cardiovascular complications of type 2 diabetes mellitus. The term ROS encompasses a variety of chemical species including superoxide anion (O2•-), hydroxyl radical (OH-) and hydrogen peroxide (H2O2). While constitutive generation of low concentrations of ROS are indispensable for normal cellular function, excess O2•- can result in irreversible tissue damage. Excess ROS generation is catalysed by xanthine oxidase, uncoupled nitric oxide synthases, the mitochondrial electron transport chain and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. Amongst enzymatic sources of O2•- the Nox2 isoform of NADPH oxidase is thought to be critical to the oxidative stress found in type 2 diabetes mellitus. In contrast, the transcriptionally regulated Nox4 isoform, which generates H2O2, may fulfil a protective role and contribute to normal glucose homeostasis. This review describes the key roles of Nox2 and Nox4, as well as Nox1 and Nox5, in glucose homeostasis, endothelial function and oxidative stress, with a key focus on how they are regulated in health, and dysregulated in type 2 diabetes mellitus.

COVID-19 progression, frailty, and use of prolonged continuous positive airway pressure as a ward-based treatment: Lessons to be learnt from a case.

Coronavirus disease 19 (COVID-19) poses the greatest public health threat in 100 years, with cases rising rapidly in many countries around the world. We report a case of a 78-year-old female who exhibited a biphasic course of COVID-19; showing initial clinical improvement followed by deterioration before making a full recovery. The patient was managed with prolonged continuous positive airway pressure (CPAP) and supportive care. In total, 24 days of treatment with CPAP was administered. We emphasize the role of CPAP in the management of severely hypoxemic patients who are inappropriate for mechanical ventilation and describe the role of adequate nutrition and hydration for such patients.

Relation Between Thyroid Function and Mortality in Patients With Chronic Heart Failure.

Thyroid dysfunction is common in patients with chronic heart failure (CHF), but there is conflicting evidence regarding its prognostic significance. We investigated the relation between thyroid function and prognosis in a large, well characterized cohort of ambulatory patients with CHF. Heart failure was defined as signs and symptoms of the disease and either left ventricular systolic dysfunction (LVSD) mild or worse (heart failure with reduced ejection fraction [HFrEF]), or no LVSD and raised amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (>125 ng/L; heart failure with normal ejection fraction [HFnEF]). Euthyroid state was defined as a thyroid-stimulating hormone (TSH) level between 0.35 and 4.70 mIU/l, hypothyroidism as TSH >4.70 mIU/l, and hyperthyroidism as TSH <0.35 mIU/l. 2997 patients had HFrEF and 1995 patients had HFnEF. 4491 (90%) patients were euthyroid, 312 (6%) were hypothyroid, and 189 (4%) were hyperthyroid. In univariable analysis, both hypothyroid patients (hazard ratio [HR] 1.25, 95% confidence interval [CI] 1.08 to 1.45) and hyperthyroid patients (HR 1.21, 95% CI 1.01 to 1.46) had a greater risk of death compared with euthyroid patients. There was a U-shaped relation between TSH and outcome. Increasing TSH was a predictor of mortality in univariable analysis (HR 1.02, 95% CI 1.01 to 1.03), but the association disappeared in multivariable analysis. The three strongest predictors of adverse outcome were increasing age, increasing NT-proBNP, and higher NYHA class. In conclusion, although thyroid dysfunction is associated with worse survival in patients with CHF, it is not an independent predictor of mortality.

Outcomes and characteristics of COVID-19 patients treated with continuous positive airway pressure/high-flow nasal oxygen outside the intensive care setting.

BACKGROUND: Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been used to manage hypoxaemic respiratory failure secondary to coronavirus disease 2019 (COVID-19) pneumonia. Limited data are available for patients treated with noninvasive respiratory support outside of the intensive care setting. METHODS: In this single-centre observational study we observed the characteristics, physiological observations, laboratory tests and outcomes of all consecutive patients with COVID-19 pneumonia between April 2020 and March 2021 treated with noninvasive respiratory support outside of the intensive care setting. RESULTS: We report the outcomes of 140 patients (mean±sd age: 71.2±11.1, 65% male (n=91)) treated with CPAP/HFNO outside of the intensive care setting. Overall mortality was 59% and was higher in those deemed unsuitable for mechanical ventilation (72%). The mean age of survivors was significantly lower than those who died (66.1 versus 74.4 years, p<0.001). Those who survived their admission also had a significantly lower median Clinical Frailty Score than the non-survivor group (2 versus 4, p<0.001). We report no significant difference in mortality between those treated with CPAP (n=92, mortality: 60%) or HFNO (n=48, mortality: 56%). Treatment was well tolerated in 86% of patients receiving either CPAP or HFNO. CONCLUSIONS: CPAP and HFNO delivered outside of the intensive care setting are viable treatment options for patients with hypoxaemic respiratory failure secondary to COVID-19 pneumonia, including those considered unsuitable for invasive mechanical ventilation. This provides an opportunity to safeguard intensive care capacity for COVID-19 patients requiring invasive mechanical ventilation.