BACKGROUND: With population aging and advances in surgical and anesthetic procedures, the incidence of surgery in patients over the age of 65 years is increasing. One post-operative complication often encountered by older surgical patients is post-operative cognitive dysfunction (POCD). Preoperative exercise training can improve the overall physiological resilience of older surgical patients, yet its impact on post-operative cognition is less well-established. METHODS: Six databases (Medline (OVID); EMBASE (OVID); EMCARE (OVID); CINAHL (EBSCOHost), the Cochrane Library, and PubMed) were searched for studies reporting the effect of pre-operative physical training on post-operative cognition. The quality of evidence was assessed using the Mixed Methods Assessment Tool. RESULTS: A total of 3983 studies were initially identified, three of which met the inclusion criteria for this review. Two studies were pilot randomized trials, and one was a prospective randomized trial. Two of the studies were high-quality. Each study used a different type of physical exercise and cognition assessment tool. Across the studies, post-operative cognition (p = 0.005) and attention (p = 0.04) were found to be better in the intervention groups compared to control, with one study reporting no difference between the groups. CONCLUSION: Preoperative physical training may improve post-operative cognitive function, although more research with a consistent endpoint is required. Future studies should focus on patients at high risk of POCD, such as older adults, and explore the impact of different exercise regimes, including frequency, intensity, time, and type.

Background Sepsis is a potentially fatal condition that necessitates prompt identification and assessment of its severity for effective management. However, evaluating sepsis severity using the Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE II) scores can be complex and costly. This study aimed to assess the association between neutrophil-to-lymphocyte ratio (NLR) and sepsis severity, as well as the role of NLR as a predictive indicator of sepsis severity in ICU patients. Methods This cross-sectional study was conducted among 180 ICU-admitted patients at Benazir Bhutto Hospital (BBH) in Rawalpindi, Pakistan, from January 2022 to January 2023. Participants were enrolled using defined inclusion and exclusion criteria along with consecutive sampling. Following ethical approval and informed consent, data were collected using a self-structured form. The study population was divided into three groups based on sepsis severity, which was assessed via the SOFA score. Data analysis was performed using IBM SPSS Statistics for Windows, Version 25.0 (Released 2017; IBM Corp., Armonk, NY, USA) through chi-squared tests, one-way ANOVA, Pearson's correlation, and a simple linear regression model, with a significance threshold set at p < 0.05. Results In the study population of 180 patients, the frequencies of sepsis, severe sepsis, and septic shock were 69 (38.34%), 86 (47.78%), and 25 (13.88%), respectively. Significant variations were observed among the three study groups in the means of the PaO2/FiO2 ratio, mean arterial pressure, Glasgow Coma Scale score, total bilirubin level, serum creatinine level, platelet count, SOFA score, neutrophil count, lymphocyte count, and NLR (p < 0.05). Pearson's correlation analysis indicated a strong positive correlation between the NLR and SOFA score, with a correlation coefficient (r) of 0.80 and significance at p < 0.001. Furthermore, linear regression analysis identified NLR as a significant predictor of sepsis severity, with a beta coefficient (β) of 3.55 and a 95% CI of 1.92-5.60 (p < 0.001). Conclusions In the current study, a positive and significant correlation was found between the NLR and the severity of sepsis. Higher NLR values were associated with increased SOFA scores, indicating a greater severity of sepsis. This study supports the use of NLR as a complementary and cost-effective tool for the early detection of high-risk patients with sepsis, facilitating timely interventions and improving outcomes, particularly in under-resourced healthcare settings.

BACKGROUND: Thumb carpometacarpal osteoarthritis (CMC-1 OA) is a common and debilitating condition, particularly among older adults and women. With the aging population, the prevalence of CMC-1 OA is expected to rise, emphasizing the need to find effective nonoperative strategies. So far, for determining the most effective nonoperative interventions in CMC-1 OA, two network meta-analyses (NMAs) have been published. However, these NMAs were limited to specific intervention types: one comparing multiple splints and the other comparing different intraarticular injections. Therefore, an NMA that compared all nonoperative intervention types is urgently needed. QUESTIONS/PURPOSES: This study aimed to assess and compare the effectiveness of available nonoperative interventions (both nonpharmacologic and pharmacologic) for CMC-1 OA to establish which nonoperative options are more effective than control in terms of (1) pain, (2) function, and (3) grip strength. METHODS: We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) NMA guidelines (PROSPERO: CRD2021272247) and conducted a comprehensive search across Medline, Embase, CENTRAL, and CINAHL up to March 2023. We included randomized controlled trials (RCTs) and quasi-RCTs evaluating nonoperative interventions for symptomatic CMC-1 OA, excluding inflammatory or posttraumatic arthritis. Studies comparing ≥ 2 interventions or against a control, focusing on pain reduction, functional improvement, and grip strength, were selected. We assessed methodologic quality using the modified Coleman Methodology Score, including only studies scoring > 70. Risk of bias was evaluated with the Risk of Bias 2.0 tool, and evidence quality with Confidence in Network Meta-Analysis (CINeMA). Of 29 screened studies, 22 (21 RCTs and one quasi-RCT) were included, involving 1631 women and 331 men. We analyzed eight different nonoperative interventions, including splints, hand exercises, injections, and multimodal treatment (≥ 2 nonpharmacologic interventions or nonpharmacologic with a pharmacologic intervention). Six studies had a low risk of bias, eight had a high risk, and the remainder were moderate. We extracted mean and SD scores, and NMA and pairwise analyses were performed at short- (≤ 3 months) and medium-term (> 3 to ≤ 12 months) time points. Standardized mean differences were re-expressed into common units for interpretation, which were the VAS (range 0 to 10) for pain, the DASH test (range to 100) for function, and pounds for grip strength. Clinical recommendations were considered strong if the mean differences exceeded the minimum clinically important difference-1.4 points for VAS, 10 points for DASH, and 14 pounds for grip strength-and were supported by moderate or high confidence in the evidence, as assessed using CINeMA methodology. RESULTS: Our NMA (based on moderate or high confidence) showed a clinically important reduction in pain at the short-term time point for multimodal treatment and hand exercises versus control (mean difference VAS score -5.3 [95% confidence interval (CI) -7.6 to -3.0] and -5.0 [95% CI -8.5 to -1.5]). At the medium-term time point, only the rigid carpometacarpal-metacarpophalangeal (CMC-MCP) splint was superior to control (mean difference VAS score -1.9 [95% CI -3.1 to -0.6]) and demonstrated clinical importance. For function, only the rigid CMC-MCP splint demonstrated a clinically important improvement at the medium-term time point versus control (mean difference DASH score -11 [95% CI -21 to -1]). Hand exercises resulted in a clinically important improvement in short-term grip strength versus control (mean difference 21 pounds [95% CI 11 to 31]). CONCLUSION: This systematic review and NMA show that multimodal treatment and hand exercises reduce short-term pain and improve grip strength, while a rigid CMC-MCP splint enhances medium-term function. Future research should evaluate long-term efficacy. LEVEL OF EVIDENCE: Level I, therapeutic study.

BACKGROUND: Surgeons are sometimes reluctant to manage uncomplicated appendicitis non-operatively. Reasons cited include the risk of recurrent appendicitis and the risk of missed appendiceal malignancy. The aim of this study was to address these uncertainties and determine the long-term efficacy of antibiotic versus operative management of appendicitis. METHOD: One-year follow-up of patients enrolled in the multicentre, COVID:HAREM cohort study during March-June 2020 was performed. Initial operative or non-operative management was determined on a case-by-case basis by the responsible surgeon. Outcomes were appendicectomy rate at 1-year, histology of removed appendix and predictors of unsuccessful antibiotic treatment. RESULTS: A total of 625 patients who had non-operative management were included. Emergency appendicectomy had been performed by 1-year in 24% (149/625), with a median time to appendicectomy of 12 days [IQR 1-77] from presentation. Thirty-one patients had elective appendicectomy. Normal histology was reported in 6% of emergency procedures and 58% of elective ones. There were 7 malignancies and 3 neuroendocrine tumors identified at histology. All patients with malignant histology had ≥1 risk factors for malignancy at initial presentation. Faecolithiasis (hazard ratios (HR) 2.3, 95% confidence intervals (CI) 1.51-3.49) and a high Adult Appendicitis Score (AAS >16; HR 2.44, 95% CI 1.52-3.92) were independent risk factors for unsuccessful non-operative management. CONCLUSION: At 1 year, 71% of patients managed non-operatively did not undergo an appendicectomy. Recurrence of appendicitis was associated with faecolithiasis and a high AAS. Patients at higher risk for appendiceal malignancy should have targeted follow-up. These factors should be considered when counseling patients on non-operative management.

Synovectomy refers to the removal of all or part of the hypertrophied soft tissue membrane on the inside of the joint capsule or around tendons. Historically, this was typically performed for rheumatoid arthritis and other inflammatory conditions of the hand, but following the development of more advanced medical treatments, the role of synovectomy has come into question. In this article, the authors outline the biologic basis for synovectomy and then consider its present and future role in the management of joint and tendon disease, followed by what further research is needed.

Purpose and aims Hip hemiarthroplasty (HHA) is a common procedure undertaken to manage intracapsular neck of femur fractures. Dislocation of HHA is one of the most dreadful complications. There is a paucity of clinical evidence to guide decision-making for managing these patients. The aim of this study was to describe the operative management and outcomes of patients with dislocated hemiarthroplasties of the hip and outline a treatment strategy for their management. Methods We conducted a retrospective analysis of all the patients presenting to University Hospitals of Derby and Burton, UK with hip fractures between 2016-2022. We included all the patients who underwent a hemiarthroplasty for their fracture. We excluded patients who had malignancy and if clinical data was missing. Each operative intervention and subsequent dislocations were recorded. We recorded the following outcome measures: dislocation, surgical interventions, mortality, revision surgery, cognition status, residential status, and mobility. We also compare these outcomes with the patients who had HHA and did not sustain any dislocation. Results Of the 1134 patients treated with HHA during this period, 33 patients sustained dislocation. Of the 33 patients, 29 were female and 4 were male with mean ages of 87.4±7.4 and 89.25 ± 9.54, respectively. Following the first dislocation, 25 patients were treated with closed reduction, six patients had excision arthroplasty (EA), and two patients were treated non-operatively. About 21 patients went on to have second and third dislocations, none of these had EA and others had conversion to total hip replacement (THR). Nearly 80% of dislocations occurred within two months of the initial procedure. The mean mental test score was 7.91±2.01 (p=0.001) and was significantly higher in patients who underwent conversion to THR. The average ASA grade was significantly higher in patients who had closed reduction (2.93±0.25, p=0.001) and EA (3.28±0.46, p=0.002) compared to the patients who had no dislocation. Patients who underwent EA had significantly higher acute length of hospital stay 23.5±13.5 (p=0.02) and mortality (p=0.001) compared to other groups. We found no significant difference in dislocation rates where the initial procedure was carried out by registrars or consultants (p=0.567). Conclusion We concluded that the dislocation risk is higher in females and within the first two months of the index procedure. More than 80% of patients had a second dislocation following a successful closed reduction. In our cohort, 45% of patients had EA (Girdlestone procedure) and 36% had a conversion to THR. EA was associated with increased mortality rates, acute length of hospital stays, and significant change to premorbid mobility status. A multidisciplinary team (MDT) approach is necessary following the second dislocation to prevent further morbidity associated with recurrent dislocations.

BACKGROUND: Severe caloric restriction interventions (such as very-low-calorie diets) are effective for inducing significant weight loss and remission of type 2 diabetes (T2DM). However, suggestions of associated significant muscle mass (MM) loss create apprehension regarding their widespread use. We conducted a systematic review and meta-analysis to provide a quantitative assessment of their effect on measures of MM in individuals with, or without, T2DM. METHODS: EMBASE, Medline, Pubmed, CINAHL, CENTRAL and Google Scholar were systematically searched for studies involving caloric restriction interventions up to 900 kilocalories per day reporting any measure of MM, in addition to fat mass (FM) or body weight (BW). RESULTS: Forty-nine studies were eligible for inclusion, involving 4785 participants. Individuals with T2DM experienced significant reductions in MM (WMD -2.88 kg, 95% CI: -3.54, -2.22; p < 0.0001), although this was significantly less than the reduction in FM (WMD -7.62 kg, 95% CI: -10.87, -4.37; p < 0.0001). A similar pattern was observed across studies involving individuals without T2DM. MM constituted approximately 25.5% of overall weight loss in individuals with T2DM, and 27.5% in individuals without T2DM. Subgroup analysis paradoxically revealed greater BW and FM reductions with less restrictive interventions. CONCLUSIONS: Our review suggests that caloric restriction interventions up to 900 kilocalories per day are associated with a significant reduction in MM, albeit in the context of a significantly greater reduction in FM. Furthermore, MM constituted approximately a quarter of the total weight loss. Finally, our data support the use of less restrictive interventions, which appear to be more beneficial for BW and FM loss.

BACKGROUND: Evaluation of glenoid bone loss following recurrent anterior shoulder dislocations is normally performed using cross sectional imaging. OBJECTIVES: To assess how anteroposterior (AP) and Bernageau view radiographs compare to computed tomography (CT), magnetic resonance imaging (MRI) and arthroscopy for evaluating glenoid bone loss in patients with recurrent anterior shoulder dislocation. MATERIALS AND METHODS: A prospective observational study was performed on 32 patients over two years at a tertiary orthopedic center. The loss of sclerotic glenoid rim (LSGL) on AP radiograph and the percentage relative glenoid bone loss on the Bernageau radiograph were assessed. The percentage glenoid bone loss and anterior straight line (ASL) were calculated using a best fit en face circle method using CT and MRI. Percentage glenoid bone loss was also calculated during arthroscopy in multiples of 5%. RESULTS: In our study, 90.6% (29) patients were males, while only 9.4% (3) were females. This can be attributed to the involvement of the males in outdoor activities and sports. Also, the maximum number of patients were found to belong to 21-30 years of age, with the mean age being 28.66 years. Of the 32 patients, loss of sclerotic glenoid line (LSGL) on AP radiographs correlated with glenoid bone loss on cross-sectional imaging in 27 patients. Three patients had equivocal LSGL and 2 patients with glenoid bone loss on CT did not demonstrate LSGL. The difference between the two modalities was not statistically significant (p value = 0.002). The glenoid bone loss on Bernageau view correlated with glenoid bone loss on cross sectional imaging in all but one patient. The bone loss as evaluated by radiograph Bernageau view was found to have strong correlation (correlation coefficient r = 0.948, p value < 0.0001). CONCLUSION: AP and Bernageau radiographic views for anterior shoulder dislocations demonstrate good correlation with glenoid bone loss on cross-sectional imaging. They may also be used as an adjunct to predict overall bone loss on CT and at arthroscopy.

In recent years, diabetes technologies have revolutionized the care of people with type 1 diabetes (T1D). Emerging evidence suggests that people with type 2 diabetes (T2D) can experience similar benefits from these advances in technology. While glycaemic outcomes are often a primary focus, the lived experience of the person with diabetes is equally important. In this review, we describe the impact of diabetes technologies on patient-reported outcome measures (PROMs). We highlight that most of the published studies investigated PROMs as secondary outcomes. Continuous glucose monitoring systems may have an important role in improving PROMs in individuals with T1D, which may be driven by the prevention or proactive management of hypoglycaemia. In people with T2D, continuous glucose monitoring may also have an important role in improving PROMs, particularly in those treated with insulin therapy. The impact of insulin pumps on PROMs seems positive in T1D, while there is limited evidence in T2D. Studies of hybrid closed-loop therapies suggest increased treatment satisfaction, improved quality of life and decreased diabetes-related distress in T1D, but it is unclear whether these benefits are because of a 'class-effect' or individual systems. We conclude that PROMs deserve a more central role in trials and clinical practice, and we discuss directions for future research.

Background: Procarbazine-containing chemotherapy regimens are associated with cytopenias and infertility, suggesting stem-cell toxicity. When treating Hodgkin lymphoma, procarbazine in escalated-dose bleomycin-etoposide-doxorubicin-cyclophosphamide-vincristine-procarbazine-prednisolone (eBEACOPP) is increasingly replaced with dacarbazine (eBEACOPDac) to reduce toxicity. We aimed to investigate the impact of this drug substitution on the mutation burden in stem cells, patient survival, and toxicity. Methods: In this two-part retrospective, observational study, we first compared mutational landscapes in haematopoietic stem and progenitor cells (HSPCs) from patients with advanced-stage Hodgkin lymphoma in remission for at least 6 months who had been treated with eBEACOPDac (eBEACOPDac cohort), eBEACOPP (real-world eBEACOPP cohort), or doxorubicin-bleomycin-vinblastine-dacarbazine (ABVD); in buccal DNA from five children of a female patient with classical Hodgkin lymphoma treated with eBEACOPP before conceiving the third child; in sperm DNA from a patient with mild oligospermia treated with eBEACOPP; and in caecal adenocarcinoma and healthy colon tissue from a survivor of Hodgkin lymphoma treated with chlorambucil-vinblastine-procarbazine-prednisolone. For the second part, we analysed efficacy and toxicity data from adult patients (aged >16 years) treated with first-line eBEACOPDac (eBEACOPDac cohort) at 25 centres across UK, Ireland, and France; efficacy was compared with the German HD18 eBEACOPP trial data and toxicity with a UK real-world dataset. Participants in the German HD18 and UK real-world datasets were adults (aged >16 years) with previously untreated Hodgkin lymphoma, treated with first-line eBEACOPP. We had two co-primary objectives: to define the comparative stem-cell mutation burden and mutational signatures after treatment with or without procarbazine-containing chemotherapy (first study part); and to determine progression-free survival of patients with Hodgkin lymphoma treated with eBEACOPP or eBEACOPDac (second study part). Secondary objectives included overall survival and explored differences in specific toxicity outcomes, including transfusion requirements and measures of reproductive health (second study part). Findings: In the first part of the study (mutational analysis), patients treated with eBEACOPP (n=5) exhibited a higher burden of point mutations in HSPCs compared with those treated with eBEACOPDac (n=4) or ABVD (n=3; excess mutations 1150 [95% CI 934-1366] vs 290 [241-339] vs 186 [116-254]). Two novel mutational signatures, SBSA (SBS25-like) and SBSB, were identified in HSPCs and in a single neoplastic and healthy colon sample from patients who received procarbazine-containing chemotherapy. SBSB was also identified in germline DNA of three children conceived after eBEACOPP and in sperm of a male patient treated with eBEACOPP. SBSC was detected in patients treated with either ABVD or eBEACOPDac. In the second part of the study (efficacy and toxicity analysis), dacarbazine substitution did not appear to compromise efficacy or safety. 312 patients treated with eBEACOPDac (eBEACOPDac cohort; treated 2017-22, 186 [60%] male, median follow-up 36·0 months [IQR 25·2-50·1]) had a 3-year progression-free survival of 93·3% (95% CI 90·3-96·4), which was similar to the 93·3% [95% CI 92·1-94·4]) progression-free survival seen in 1945 patients in the German HD18 eBEACOPP trial (treated 2008-14, 1183 [61%] male, median follow-up 57·0 months [35·4-64·7]). Patients treated with eBEACOPDac required fewer blood transfusions (mean 1·70 units [SD 2·77] vs 3·69 units [3·89]; p<0·0001), demonstrated higher post-chemotherapy sperm concentrations (median 23·4 million per mL [IQR 11·0-632·3] vs 0·0 million per mL [0·0-0·001]; p=0·0040), and had earlier resumption of menstrual periods (mean 5·04 months [SD 3·07] vs 8·77 months [5·57]; p=0·0036) compared with 73 patients treated with eBEACOPP in the UK real-world dataset. Interpretation: Procarbazine induces a higher mutation burden and novel mutational signatures in patients with Hodgkin lymphoma treated with eBEACOPP and their germline DNA, raising concerns for the genomic health of survivors of Hodgkin lymphoma and hereditary consequences for their offspring. However, replacing procarbazine with dacarbazine appears to mitigate gonadal and stem-cell toxicity while maintaining similar clinical efficacy. Funding: Addenbrooke's Charitable Trust and Wellcome Trust.