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The impact of overlapping risk factors on coronavirus disease (COVID-19) severity is unclear. To evaluate the impact of type 2 diabetes (T2D) and obesity on COVID-19 severity, we conducted a cohort study with 28,095 anonymized COVID-19 patients using data from the COVID-19 Research Database from January 1, 2020 to November 30, 2020. The mean age was 50.8 ± 17.5 years, and 11,802 (42%) patients were male. Data on age, race, sex, T2D complications, antidiabetic medication prescription, and body mass index ≥ 30 kg/m 2 (obesity) were analysed using Cox proportional hazard models, with hospitalization risk and critical care within 30 days of COVID-19 diagnosis as the main outcomes. The risk scores were 0–4 for age ≥ 65 years, male sex, T2D, and obesity. Among the participants, 11,294 (61.9%) had obesity, and 4445 (15.8%) had T2D. T2D, obesity, and male sex were significantly associated with COVID-19 hospitalization risk. Regarding hospitalization risk scores, compared with those for hospitalization risk score 0 and critical care risk score 0, hazard ratios [95% confidence intervals] were 19.034 [10.470–34.600] and 55.803 [12.761–244.015] ( P  < 0.001) ( P  < 0.001), respectively, for risk score 4. Complications from diabetes and obesity increased hospitalization and critical care risks for COVID-19 patients.

Purpose We investigated the accuracy of the acetabular cup position and orientation in robotic-assisted total hip arthroplasty (rTHA) compared to navigated THA (nTHA) using computed tomography (CT) for patients with osteoarthritis secondary to developmental dysplasia of the hip (DDH). Methods We studied 31 hips of 28 patients who underwent rTHA and 119 hips of 112 patients who underwent nTHA with the same target cup orientation. After propensity score matching, each group comprised 29 hips. Post-operative cup position and orientation were measured from the postoperative CT data. Errors from the target cup position and orientation were compared between the two groups. Results Post-operatively, the absolute error of the anteroposterior and superoinferior cup positions from the target position was significantly lower in the rTHA group than in the nTHA group. The change in the post-operative radiographic inclination from the target orientation was lower in the rTHA group than in the nTHA group. Screw fixation for cup implantation was required for three hips in the nTHA group but not in the rTHA group. Conclusion rTHA achieved more precise cup implantation with reduced variation from the target orientation compared to nTHA in patients with osteoarthritis secondary to DDH.

The aim of this study was to investigate the effect of bisphosphonates on preventing osteoporotic hip fracture in patients with or without prior major osteoporotic fracture. Randomized controlled trials (RCTs) and observational studies (OSs) based on electronic health records were used to assess bisphosphonate efficacy and were searched using PubMed, Scopus, and the Cochrane Library databases. Eight RCT studies and 14 OSs were extracted from the studies and quantitatively combined by random-effects meta-analysis. The odds ratio (OR) for all hip fractures in RCTs of 0.66, with a 95% confidence interval (CI) of 0.55–0.79, was lower than that in the OSs (OR 0.83; CI 0.74–0.94). The OR in patients with prior fracture was significantly reduced by bisphosphonates in both RCTs and OSs. Conversely, significant fracture reduction was not apparent in patients without prior fracture. A moderate relationship between prior major fracture rates and OR in hip fractures was defined. In patients with an average age of over 80 years, similar results were confirmed. In this meta-analysis, the efficacy of bisphosphonates was significant in patients with prior major fracture, recommending to prescribe for such patients. Their effect in patients without prior fracture, in contrast, remains unclear.

ObjectiveNon-alcoholic steatohepatitis (NASH) can progress to fibrosis, cirrhosis and end-stage liver disease. Glucagon-like peptide 1 receptor (GLP-1R) mediates β cell function. Its receptor agonists, currently used to treat type 2 diabetes mellitus, might be effective against NASH. GLP-1R, a G protein-coupled receptor family member, preferentially localises to caveolae. Therefore, we ascertained the cellular localisation of GLP-1R and caveolin (CAV)-1 in NASH liver.MethodsLiver biopsies were obtained from three patients with NASH and were compared with those of four normal patients. Immunohistochemistry (IHC) and immunoelectron microscopy (IEM) were used to compare GLP-1R and CAV-1 expression in the livers of patients with metastatic liver cancer and normal patients.ResultsIHC showed that GLP-1R localised to basolateral membranes of hepatocytes with macrovesicular steatosis and was expressed in monocytes infiltrating hepatic sinusoids. CAV-1 was minimally associated with low-electron density lipid droplets (LDs) in hepatocytes. IEM showed small clusters of GLP-1R molecules on the peripheral rims of LDs and on cytoplasmic leaflets of endoplasmic reticulum membranes and vesicles, whereas CAV-1 molecules were found in LD caveolae.ConclusionsGLP-1R is present in the lipid microdomains of hepatocytes with macrovesicular steatosis. These results may help inform future studies about the liver-specific mechanisms of GLP-1 modulation in NASH therapy.

Serum and tissue miR-21 expression in patients with breast cancer (BC) is a useful biomarker for cancer diagnosis, progression, and treatment. Matrix metalloproteinase-1 (MMP-1) is also important in breast cancer carcinogenesis. However, miR-21 and MMP-1/CD63 in urine exosomes in these patients have not been examined. Urine samples were collected from patients with BC and 26 healthy females. Urinary exosomes were isolated and confirmed by western blotting with anti-CD63 antibody and electron microscopy observation. MiR-21 and MMP-1/CD63 expression was examined by quantitative RT-PCR and western blotting, respectively. Patients with very early stage breast cancer were evaluated. MiR-21 expression in the patients was 0.26 [95% CI: 0.20–0.78], which was significant lower than in the 26 controls (1.00 [95% CI: 1.01–3.37], p = 0.0947). MMP-1/CD63 expression in patients was significantly higher than in controls (1.74 [95% CI: 0.86–5.08] vs 0.535 [95% CI: −0.01–2.81], p = 0.0001). Sensitivity and specificity were 0.708 and 0.783 for miR-21 and 0.792 and 0.840 for MMP-1/CD63, respectively. Sensitivity and specificity of combined expression were 95% and 79%, respectively. The sensitivity of MMP-1/CD63 expression in urinary exosomes was better than that of miR-21 expression. Thus, miR-21 and MMP/CD63 may be useful markers for BC screening.

Background This study aimed to identify the current risk factors for coronavirus disease 2019 severity and examine its association with medication use. Methods We used data from a large United States electronic health record database to conduct an anonymized cohort study of 171,491 patients with coronavirus disease 2019. The study was conducted from January 1, 2020, to August 27, 2021. Data on age, race, sex, history of diseases, and history of medication prescriptions were analyzed using the Cox proportional hazards model analysis to calculate hazard ratios for hospitalization and severe risk. Results Factors that increased the risk of hospitalization and critical care were age ≥ 65 years, male sex, type 2 diabetes, hypertension, interstitial pneumonia, and cardiovascular disease. In particular, age ≥ 65 years significantly increased the risk of hospitalization (hazard ratio, 2.81 [95% confidence interval, 2.58–3.07]; P  < 0.001) and critical care (hazard ratio, 3.45 [2.88–4.14]; P  < 0.001). In contrast, patients with hyperlipidemia had a reduced risk. However, patients with hyperlipidemia who were not taking statins had a significantly increased risk of hospitalization (hazard ratio, 1.24 [1.16–1.34]; P  < 0.001). Sodium-glucose cotransporter-2 inhibitors, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, glucocorticoids, and statins significantly reduced the risk of hospitalization and critical care. The risk of hospitalization and critical care increased in patients of all ethnicities with type 2 diabetes. The factors that significantly increased the risk of hospitalization in all regions were older age, hypertension, chronic obstructive pulmonary disease, and cardiovascular disease. Conclusion This study identified factors that increase or reduce the risk of severe coronavirus disease. The provision of appropriate drug treatment and modification of lifestyle-related risk factors may reduce coronavirus disease severity.

A nationwide multicenter follow-up cohort study of hip-replacement arthroplasties performed for nontraumatic osteonecrosis of the femoral head (ONFH) was conducted to clarify factors associated with need for reoperation. We analyzed 7393 arthroplasties including 6284 total hip arthroplasties (THAs), 886 bipolar hemiarthroplasties (BPs), 188 total resurfacing arthroplasties, and 35 hemi-resurfacing arthroplasties (hRSs). The identified risk factors were combined systemic steroid use and excessive alcohol consumption (both ONFH-associated factors), a lateral approach, alumina BPs (aBPs), and hRSs, which were reported previously. The present study performed further analyses separately for THAs and BPs to clarify risk factors in each surgical group. A Cox proportional-hazard model identified the following risk factors: the acetabular-articulating materials of conventional polyethylene (cPE) and metal in the THAs and both ONFH-associated factors, minimum-incision surgery (MIS), and aBPs in the BPs. The risk factors were specific to each surgical group. In the ONFH patients, when performing THA, cPE and metal are not recommended as the acetabular-articulating material. When performing BP, patients with both ONFH-associated factors should be treated carefully, and the employment of MIS and use of aBP are not good strategies.

Background Three-dimensional (3D)-printed acetabular cups may enhance initial fixation and osseointegration; however, early radiographic findings warrant careful monitoring. This study evaluated short-term radiographic outcomes of an electron beam melting (EBM)–fabricated 3D-printed titanium acetabular component (GS cup) used in primary total hip arthroplasty (THA). Methods This multicenter retrospective cohort study included 236 consecutive primary THAs performed at seven hospitals. Postoperative radiographs at approximately 2 years were analyzed (mean follow-up, 24.6 months; range, 23–31 months). The primary endpoint was the presence of a radiolucent line (RLL) in DeLee and Charnley Zone 2 at 2 years. Secondary endpoints included initial polar gaps (≥ 1 mm), gap filling, RLLs in other zones, osseointegration assessed by Moore criteria, and survivorship with acetabular component revision for any reason as the endpoint. Results Initial polar gaps occurred in 19/236 hips (8.1%); 14/19 (73.7%) demonstrated gap filling at follow-up. RLLs were present in 48/236 hips (20.3%) (Zone 1, 13.6%; Zone 2, 9.7%; Zone 3, 11.4%). In exploratory univariate analyses, same-diameter reaming showed lower proportions of polar gaps and Zone 2 RLLs compared with 1-mm underreaming; however, no factors remained independently associated with Zone 2 RLLs after multivariable adjustment. At follow-up, 188 cups (79.7%) demonstrated ≥ 3 Moore signs, and no acetabular component revisions occurred by the standardized 2-year assessment. Conclusions In this multicenter retrospective cohort, the EBM-fabricated 3D-printed titanium acetabular component demonstrated generally favorable early radiographic findings and no acetabular component revisions at approximately 2 years. Given the retrospective design and the limited number of Zone 2 RLL events, the observed associations between surgical factors and radiographic findings should be interpreted cautiously and considered hypothesis-generating. Longer-term follow-up, ideally with comparative designs and clinical outcomes, is warranted.

This study aims to optimize indoor thermal environment assessment methods for primary school classrooms in regions with hot summers and cold winters, enhancing air-conditioning management efficiency and accuracy. Given the complexity of Predicted Mean Vote (PMV) calculations and its reduced accuracy under high temperature and humidity, this research explores the use of Thermal Sensation Vote (TSV) as a simpler alternative. Field measurements and subjective assessments were conducted to analyze the relationship between TSV and PMV, leading to a regression model linking predicted TSV (TSVp) with temperature and humidity. Results indicate that temperature and humidity significantly impact TSV, with regression coefficients of 0.499 and 0.055, respectively. Furthermore, when TSV is ≥1, the proportion of PMV of ≥0.5 remains stable, validating TSVp as a reliable indicator. Based on these findings, energy-efficient air-conditioning management strategies are proposed, recommending a temperature setting of 28 °C for thermal comfort. This study provides insights into climate control strategies in educational buildings, promoting sustainable development.

Purpose While a wide variety of platelet-rich plasma (PRP) solutions has been developed, innovation continues. In this case, the freeze-dried platelet factor concentrate (PFC-FD) represents another step in PRP refinement. The preparation of PFC-FD at a central laboratory with freeze drying for shelf stabilization should provide additional quality improvements if clinical effectiveness can be demonstrated. Therefore, this study was undertaken to assess the safety and effectiveness of PFC-FD in a prospective open-label trial of patients suffering from knee osteoarthritis (OA). Methods 312 consecutive knee OA patients (67% female, mean age 63 ± 10 years), were prospectively recruited in an outpatient knee clinic in Japan. Of these, 10 (3.2%) were lost to follow-up at < 12 months and 17 (5.5%) sought additional knee therapy during the follow-up period. The primary outcome of interest was achievement of the OMERACT-OARSI responder criteria with secondary outcomes of adverse events and PROMs scores 1, 3, 6, 12 months following a single PFC-FD injection. Results 285 patients (91%) completed 12 month PROMs. The 17 who sought additional therapy were considered failures leaving an effective sample size of 302 for our primary outcome in which 62% of patients achieved OMERACT-OARSI responder status by 12 months. This varied by OA class with Kellgren–Lawrence grade 4 patients 3.6 times less likely to be responders than grade 1–2 patients. 6% of patients experienced a non-serious adverse event, primarily pain or swelling at the injection site. Conclusions PFC-FD provides an observable clinical improvement in 62% of knee OA patients at 12 months post-injection with very little risk of any clinically relevant adverse event. Of course, nearly 40% of patients did not experience an observable clinical improvement, primarily among those with worse KL grades. Level of evidence Therapeutic, Level II.