Effect of age and gender in rates of achieving minimal clinically important difference and patient-acceptable symptom state 2 years after arthroscopic superior capsular reconstruction.

PURPOSE: This study aimed to evaluate patient-reported outcome measures (PROMs) and the effects of gender and age on achieving clinically significant outcomes in patients undergoing arthroscopic superior capsular reconstruction (ASCR) with a minimum 2-year follow-up. METHODS: Patients undergoing ASCR for irreparable rotator cuff tear between 2013 and 2020 were reviewed. Preoperative and minimum 2-year postoperative PROMs were collected, including American Shoulder and Elbow Surgeons (ASES), Constant, single assessment numeric evaluation (SANE), and visual analog scale (VAS) scores. Minimal clinically important difference (MCID) and patient-acceptable symptomatic state (PASS) were calculated for each functional score and analyzed according to age and gender. The percentages of patients achieving MCID and PASS were recorded. RESULTS: The study included 83 patients, with a mean follow-up of 3.5 ± 1.4 years. Significant improvements were found in ASES, Constant, SANE, and VAS for all groups based on gender and age. Based on receiver-operating characteristic curves, all scores had acceptable areas under the curve for PASS. Values for PASS and MCID were 81.5 and 10.3 for ASES; 61.5 and 6.2 for Constant; 82.5 and 11.5 for SANE and 1.5 and 1.1 for VAS, respectively. Analysis of achieving MCID and PASS showed no difference between the groups in the majority of outcome measures. However, female patients achieved the SANE thresholds for PASS at significantly higher rates than male patients. Patients ≥65 years old achieved ASES and Constant thresholds for MCID at significantly higher rates than patients ˂65 years old. CONCLUSION: Most patients achieved MCID and PASS at a 2-year follow-up. Patients showed comparable rates of MCID and PASS achievement on most outcome tools based on age and gender. Female patients achieved PASS on SANE at significantly higher rates than male patients and older patients achieved MCID on ASES and Constant at higher rates than young patients. Thus, age is a stronger factor for achieving MCID than gender. LEVEL OF EVIDENCE: Level II.

Preoperative magnetic resonance imaging rotator cuff tendon stump classification correlates with the surgical outcomes following superior capsular reconstruction.

HYPOTHESIS: This study aimed to investigate the correlation between rotator cuff stump classification and postoperative outcomes after superior capsular reconstruction (SCR). METHODS: A total of 75 patients who underwent SCR between June 2013 and May 2021 were included in this study. Based on stump classification using the signal intensity ratio of the tendon rupture site to the deltoid muscle in the coronal view of preoperative T2-weighted, fat-suppressed magnetic resonance imaging scans, the patients were classified into types 1, 2, and 3 with ratios of <0.8, 0.8-1.3, and >1.3 (44, 17, and 14 patients, respectively). The American Shoulder and Elbow Surgeons (ASES), Constant, and visual analog scale (VAS) scores for pain and range of motion were evaluated at a minimum of 1 year of follow-up postoperatively. The acromiohumeral distance and rotator cuff arthropathy according to the Hamada classification were assessed on plain radiography. The graft integrity was evaluated by magnetic resonance imaging at 3 and 12 months postoperatively and annually thereafter. RESULTS: Clinical and radiological outcomes were significantly improved after SCR. In comparison with type 2 and 3 patients, type 1 patients had significantly higher ASES scores (type 1, 2, and 3 = 84 ± 10, 75 ± 15, and 76 ± 14; all P = .014), Constant scores (type 1, 2, and 3 = 65 ± 5, 61 ± 9, and 56 ± 13; all P = .005), and forward flexion (type 1, 2, and 3 = 155 ± 10, 154 ± 15, and 145 ± 13; all P = .013). However, these statistical differences between groups were below the established minimum clinically important difference values for the ASES and Constant scores after rotator cuff repair. The graft failure rate after surgery was lower in the type 1 group than that in the other 2 groups; however, the difference was not statistically significant (P = .749). CONCLUSION: Patients with stump classification type 1 showed significantly better functional scores (ASES and VAS scores) and forward flexion; however, the clinical importance of these differences may be limited. Stump classification may be useful for predicting postoperative clinical outcomes.

Anterior radial head subluxation in primary elbow osteoarthritis.

PURPOSE: To investigate elbows with primary osteoarthritis (OA) for the presence of anterior radial head subluxation. METHODS: A total of 71 patients with elbow osteoarthritis and 45 with lateral epicondylitis were initially identified. The baseline characteristics and preoperative elbow X-rays of consecutive patients that had been clinically confirmed with elbow OA or lateral epicondylitis between March 2011 and January 2020 were then retrospectively reviewed. The radiocapitellar ratio (RCR; the ratio of the displacement of the radial head about the diameter of the capitulum) was calculated using lateral views. These RCR values were compared between the OA and lateral epicondylitis cases. RESULT: A significant increase was detected in RCR values between patients in elbow OA and the control group (13.2% (± 10.6) vs -1.2% (± 6.8), P<0.001). Based on receiver operating characteristic curves, RCR values had an excellent area under the curve (0.89) for the detection of elbow OA (Youden index, 0.69; sensitivity, 89%; specificity, 80%). Based on the ROC curve, the cutoff value of RCR was 0.04. Patients with RCR ≥ 0.04 had a significantly higher proportion of cases with elbow OA (risk ratio, 31.50 [95% CI, 11.17-88.82]) than those with RCR ˂ 0.04 (P ˂ 0.001). CONCLUSION: Radial head subluxation is a radiographic finding associated with elbow OA and RCR ≥ 0.04 could be used as an aetiological factor for elbow OA diagnosis.

Does body mass index affect outcomes following arthroscopic superior capsular reconstruction using fascia lata autograft for massive irreparable rotator cuff tear?

PURPOSE: This study aimed to evaluate the effect of increased body mass index (BMI) on patient-reported outcomes (PROs) and clinically significant outcomes (CSOs) obtained > two years postoperatively following arthroscopic superior capsular reconstruction (ASCR). METHODS: A retrospective study was conducted on patients who underwent ASCR with a minimum two year follow-up. All patients were divided into normal (BMI < 25.0), overweight (BMI 25-30.0), and obese (BMI ≥ 30) according to preoperative BMI. Patients were assessed using the PROs preoperatively and at six months, one year, and two years postoperatively, including the visual analog scale (VAS), American Shoulder and Elbow Surgeons (ASES), and Constant-Murley scores. The time required to achieve each CSO was analyzed and compared. Multivariate analyses evaluated the predictor variables and time required to achieve CSOs. RESULTS: This study included 63 patients with a mean age of 64.8 ± 8.6 years, including 31 normal BMI, 25 overweight, and seven obese patients. Significant improvements in VAS and ASES scores after ASCR were observed in all three groups. Normal and overweight patients had significant improvements in the Constant score; however, no difference was observed in obese patients. No significant difference was observed in the probability distributions of CSOs between the BMI groups. Similarly, no significant differences were observed in the probability distributions of the CSOs, ASES, and Constant scores at each time point, among the BMI groups. CONCLUSION: Patients in the normal and overweight groups had significant improvements in the VAS, ASES, and Constant scores after ASCR. Patients in the obese group had a significant improvement in VAS score; however, there is no difference for the ASES and Constant scores in the obese group. However, no differences were observed in all PROMs and the likelihood of achieving CSOs among the different BMI groups.

Molecular subtypes of breast cancer predicting clinical benefits of radiotherapy after breast-conserving surgery: a propensity-score-matched cohort study.

BACKGROUND: Based on the molecular expression of cancer cells, molecular subtypes of breast cancer have been applied to classify patients for predicting clinical outcomes and prognosis. However, further evidence is needed regarding the influence of molecular subtypes on the efficacy of radiotherapy (RT) after breast-conserving surgery (BCS), particularly in a population-based context. Hence, the present study employed a propensity-score-matched cohort design to investigate the potential role of molecular subtypes in stratifying patient outcomes for post-BCS RT and to identify the specific clinical benefits that may emerge. METHODS: From 2006 to 2019, the present study included 59,502 breast cancer patients who underwent BCS from the Taiwan National Health Insurance Research Database. Propensity scores were utilized to match confounding variables between patients with and without RT within each subtype of breast cancer, namely luminal A, luminal B/HER2-negative, luminal B/HER2-positive, basal-like, and HER2-enriched ones. Several clinical outcomes were assessed, in terms of local recurrence (LR), regional recurrence (RR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS). RESULTS: After post-BCS RT, patients with luminal A and luminal B/HER2-positive breast cancers exhibited a decrease in LR (adjusted hazard ratio [aHR] = 0.18, p < 0.0001; and, 0.24, p = 0.0049, respectively). Furthermore, reduced RR and improved DFS were observed in patients with luminal A (aHR = 0.15, p = 0.0004; and 0.29, p < 0.0001), luminal B/HER2-negative (aHR = 0.06, p = 0.0093; and, 0.46, p = 0.028), and luminal B/HER2-positive (aHR = 0.14, p = 0.01; and, 0.38, p < 0.0001) breast cancers. Notably, OS benefits were found in patients with luminal A (aHR = 0.62, p = 0.002), luminal B/HER2-negative (aHR = 0.30, p < 0.0001), basal-like (aHR = 0.40, p < 0.0001), and HER2-enriched (aHR = 0.50, p = 0.03), but not luminal B/HER2-positive diseases. Remarkably, when considering DM, luminal A patients who received RT demonstrated a lower cumulative incidence of DM than those without RT (p = 0.02). CONCLUSION: In patients with luminal A breast cancer who undergo BCS, RT could decrease the likelihood of tumor metastasis. After RT, the tumor's hormone receptor status may predict tumor control regarding LR, RR, and DFS. Besides, the HER2 status of luminal breast cancer patients may serve as an additional predictor of OS after post-BCS RT. However, further prospective studies are required to validate these findings.

Cancellous bone should not be exposed during medialized rotator cuff repair based on bone-to-tendon healing in a rat mode.

PURPOSE: To compare the biological bone-to-tendon healing using three different medialized bone bed preparation techniques (i.e. cortical bone exposure, cancellous bone exposure, and no cartilage removal) in a rat model of medialized rotator cuff repair. METHODS: Twenty-one male Sprague-Dawley rats with 42 shoulders were subjected to bilateral supraspinatus tenotomy from the greater tuberosity. The rotator cuff was repaired using medialized anchoring with the cortical bone exposed, the cancellous bone exposed, or no cartilage removed. Four and three rats in each group were killed for biomechanical testing and histological evaluation, respectively, at postoperative 6 weeks. RESULTS: All rats survived until the end of the study, but one infected shoulder in the cancellous bone exposure group was excluded from further analysis. Compared with the cortical bone exposure and no cartilage removal groups, the rotator cuff healing of the cancellous bone exposure group showed significantly lower maximum load (cancellous bone exposure group: 26.2 ± 2.3 N, cortical bone exposure group: 37.6 ± 7.9 N, no cartilage removal group: 34.6 ± 7.2 N, P = 0.005 and 0.029) and less stiffness (cancellous bone exposure group: 10.5 ± 2.4 N/mm, cortical bone exposure group: 17.4 ± 6.7 N, no cartilage removal group: 16.0 ± 3.9 N, P = 0.015 and 0.050) at postoperative 6 weeks. In all three groups, the repaired supraspinatus tendon healed towards the original insertion rather than the medialized insertion. The cancellous bone exposure group showed inferior fibrocartilage formation and insertion healing. CONCLUSIONS: The medialized bone-to-tendon repair strategy does not guarantee complete histological healing, and the removal of excessive bony structure impairs bone-to-tendon healing. This study concludes that surgeons should not expose the cancellous bone during the medialized rotator cuff repair.

Absorbable suture knots on the supraspinatus tendon prevent adverse effects of nonabsorbable suture knots in a rat model.

PURPOSE: To compare the absorbable and nonabsorbable suture knots on the tendon on bone-to-tendon healing during the early phase in a rat rotator cuff tear (RCT) model. METHODS: Fifty-two male Sprague-Dawley rats (10 weeks old; mean weight, 380 g) were used in this study, and 51 of them were randomly assigned into three groups: absorbable suture group (ASG, n = 22), nonabsorbable suture group (NSG, n = 22), and sham surgery group (SSG, n = 7), and the remaining rat was used to take surgical pictures. Bilateral supraspinatus tendon tears were created and repaired immediately in ASG and NSG. Three rats from ASG and NSG were killed for Western blot and histological evaluation at 3 days, 1 week, and 4 weeks after surgery. At 4 weeks, four rats from each group were killed for biomechanical test, and three rats from SSG were used for histological evaluation. RESULTS: Absorbable suture knots on the tendon completely degraded at 4 weeks. However, nonabsorbable suture knots remained intact between the tendon and articular side. ASG showed a stronger inflammatory reaction at 3 days and 1 week, but a weaker reaction at 4 weeks as confirmed by gross observation and Western blot. Besides, ASG showed superior biomechanical properties in terms of maximum load to failure and stiffness at 4 weeks. Modified Bonar score revealed superior maturity for tissue healing in ASG to that in NSG at 4 weeks. Furthermore, inferior bone-to-tendon interface and weakest link formation were observed in NSG on histologic images. CONCLUSION: Absorbable suture knots on the tendon contributed to better mechanical properties compared with the nonabsorbable one after rotator cuff repair.

Postoperative MRI signal intensity correlates functional outcomes after superior capsular reconstruction.

PURPOSE: Superior capsular reconstruction (SCR) using fascia lata autograft has been performed for irreparable rotator cuff tear recently. The signal-to-noise quotient (SNQ) of the graft on magnetic resonance imaging (MRI) may reflect the degree of graft maturity and healing. However, how SNQ changes with graft remodelling and time and whether this change correlates with postoperative clinical outcomes after SCR remain unknown. This study aimed to explore the correlation between SNQ of the fascia lata autograft and clinical functional outcomes after SCR. METHODS: Patients with irreparable posterosuperior rotator cuff tear undergoing SCR using fascia lata autograft between 2013 and 2017 were retrospectively analysed. For clinical outcomes, the American Shoulder and Elbow Surgeons (ASES) score, Constant-Murley score, Single Assessment Numeric Evaluation (SANE), and Visual Analogue Scale (VAS) for pain and range of motion (ROM; forward flexion and external rotation) were evaluated at postoperative 6 and 12 months. Signal intensity of the humeral, mid-substance, and glenoid sites and background were measured to calculate the SNQ values on follow-up MRI at 3 and 12 months. The correlations between clinical outcomes and SNQ at different time points were then analysed. RESULTS: A total of 15 patients were enrolled in the study. The mean postoperative VAS score significantly increased at postoperative 6 months and significantly decreased at postoperative 12 months. Except for forward flexion, all other functional outcomes were improved at postoperative 6 months. Analysis of MRI showed SNQ at the humeral (SNQh), mid-substance, and glenoid sites decreased from postoperative 3 to 12 months with a statistical significance detected in SNQh (P < 0.01). Correlation analyses showed that the SNQh values negatively correlated with VAS, ASES, Constant-Murley score, SANE, ROM (forward flexion), and ROM (external rotation) (all P < 0.05). CONCLUSION: SNQ of the fascia lata autograft decreased with time in patients receiving SCR. SNQ at the humeral site was negatively correlated with clinical outcomes. LEVEL OF EVIDENCE: III.

Time required to achieve clinically significant outcomes after arthroscopic superior capsular reconstruction.

PURPOSE: To investigate the time-dependent nature of clinically significant outcomes, including the minimal clinically important difference (MCID), substantial clinical benefit, and Patient Acceptable Symptomatic State (PASS) after arthroscopic superior capsular reconstruction, and the factors contributing to the achievement of early clinically significant outcomes. METHODS: Patients who underwent ASCR between March 2015 and September 2020 with complete preoperative and postoperative 6-month, 1-year, and 2-year patient-reported outcome measures (PROMs) were retrospectively analysed. Threshold values for MCID, substantial clinical benefit, and PASS were obtained from the previous literature for the PROMs. The time required to achieve clinically significant outcomes was calculated using Kaplan-Meier analysis. Multivariate Cox regression was performed to evaluate the variables predictive of an earlier or delayed achievement of MCID. RESULTS: Fifty-nine patients with a mean age of 64.5 ± 8.7 years old were included. The time of mean achievement of MCID, substantial clinical benefit, and PASS for VAS was 11.2 ± 0.9, 16.3 ± 1.1, and 16.6 ± 0.9 months, respectively. The time of mean achievement of MCID, substantial clinical benefit, and PASS for ASES was 13.2 ± 1.0, 16.8 ± 1.0, and 18.3 ± 0.9 months, respectively. The time of mean achievement of MCID, substantial clinical benefit, and PASS for the Constant score was 11.6 ± 0.9, 15.1 ± 1.0, and 14.7 ± 0.9 months, respectively. The time of mean achievement of MCID, substantial clinical benefit, and PASS for SANE was 14.4 ± 1.0, 16.1 ± 1.0, and 15.5 ± 0.8 months, respectively. Patients with a higher preoperative VAS score achieved an earlier MCID for VAS (P = 0.014). However, patients with a higher preoperative ASES and SANE scores achieved delayed MCID for ASES and SANE (P = 0.026, and P < 0.001, respectively). CONCLUSION: Most patients achieved MCIDs around 1 year after arthroscopic superior capsular reconstruction. A higher preoperative VAS score favours faster MCID achievement, while higher preoperative ASES and SANE scores contribute to delayed MCID achievement. STUDY DESIGN: Cohort study LEVEL OF EVIDENCE: Level IV.

Radiologically severe osteoarthritis is related to worse clinical outcomes after arthroscopic osteocapsular arthroplasty in primary elbow osteoarthritis at medium-term follow-up: a retrospective cohort study.

HYPOTHESIS: This study aimed to compare the clinical outcomes after arthroscopic osteocapsular arthroplasty (OCA) at medium-term follow-up according to the radiologic severity of primary elbow osteoarthritis (OA) and assess serial changes in clinical outcomes in each group. METHODS: Patients treated from January 2010 to April 2019 with arthroscopic OCA for primary elbow OA with a minimum of 3 years' follow-up were retrospectively assessed regarding range of motion (ROM), visual analog scale (VAS) pain score, and Mayo Elbow Performance Score (MEPS) preoperatively, at short-term follow-up (3-12 months postoperatively), and at medium-term follow-up (≥3 years after surgery). Preoperative computed tomography was performed to evaluate the radiologic severity of OA using the Kwak classification. Clinical outcomes were compared according to the radiologic severity of OA by their absolute values and the number of patients achieving the patient acceptable symptomatic state (PASS). Serial changes in the clinical outcomes in each subgroup were also assessed. RESULTS: Of the 43 patients, 14, 18, and 11 were classified as the stage I, II, and III groups, respectively; the mean follow-up duration was 71.3 ± 28.9 months, and the mean age was 56.5 ± 7.2 years. At medium-term follow-up, the stage I group had a better ROM arc (stage I, 114° ± 14°; stage II, 100° ± 23°; and stage III, 97° ± 20°; P = .067) and VAS pain score (stage I, 0.9 ± 1.3; stage II, 1.8 ± 2.1; and stage III, 2.4 ± 2.1; P = .168) than the stage II and III groups without reaching statistical significance, whereas the stage I group had a significantly better MEPS (stage I, 93.2 ± 7.5; stage II, 84.7 ± 11.9; and stage III, 78.6 ± 15.2; P = .017) than the stage III group. The percentages of patients achieving the PASS for the ROM arc (P = .684) and VAS pain score (P = .398) were comparable between the 3 groups; however, the percentage achieving the PASS for the MEPS was significantly higher in the stage I group than in the stage III group (100.0% vs. 54.5%, P = .016). During serial assessment, all clinical outcomes tended to improve at the short-term follow-up. Compared with the short-term period, the ROM arc tended to decrease at the medium-term follow-up whereas the VAS pain score and MEPS overall did not show significant changes. CONCLUSION: After arthroscopic OCA, the stage I group showed an overall better ROM arc and pain score than the stage II and III groups at medium-term follow-up, whereas the stage I group showed a significantly better MEPS and higher percentage of patients achieving the PASS for the MEPS than the stage III group.

Deciphering gp120 sequence variation and structural dynamics in HIV neutralization phenotype by molecular dynamics simulations and graph machine learning.

Human immunodeficiency virus (HIV) exploits the sequence variation and structural dynamics of the envelope glycoprotein gp120 to evade the immune attack of neutralization antibodies, contributing to various HIV neutralization phenotypes. Although the HIV neutralization phenotype has been experimentally characterized, the roles of rapid sequence variability and significant structural dynamics of gp120 are not well understood. Here, 45 prefusion gp120 from different HIV strains belong to three tiers of sensitive, moderate, and resistant neutralization phenotype are structurally modeled by homology modeling and then investigated by molecular dynamics (MD) simulations and graph machine learning (ML). Our results show that the structural deviations, population distribution, and conformational flexibility of gp120 are related to the HIV neutralization phenotype. Per-residue dynamics indicate the local regions especially in the second structural elements with high-flexibility, may be responsible for the HIV neutralization phenotype. Moreover, a graph ML model with the attention mechanism was trained to explore inherent representation related to the classification of the HIV neutralization phenotype, further distinguishing the strong related gp120 sequence variation together with structural dynamics in the HIV neutralization phenotype. Our study not only deciphers gp120 sequence variation and structural dynamics in the HIV neutralization phenotype but also explores complex relationships between the sequence, structure, and dynamics of protein by combining MD simulations and ML.

Impact of Hypertensive Disorders of Pregnancy on the Risk of Stroke Stratified by Subtypes and Follow-Up Time.

BACKGROUND AND PURPOSE: Hypertensive disorders of pregnancy (HDP) comprise 4 subtypes. Previous studies have not investigated the relationship between stroke risk, different HDP subtypes, and follow-up time, which was the purpose of this study. METHODS: Data of 17 588 women aged 18 to 45 years who had a history of HDP in Taiwan from 2000 to 2017 was retrospectively reviewed. After matching with confounders, 13 617 HDP women and 54 468 non-HDP women were recruited. RESULTS: HDP women had an adjusted hazard ratio (aHR) of 1.71 (95% CI, 1.46-2.00) for stroke, and 1.60 (1.35-1.89) and 2.98 (2.13-4.18) for ischemic and hemorrhagic stroke, respectively (P<0.001 for all). The overall stroke risk in the HDP group was still 2.04 times 10 to 15 years after childbirth (1.47-2.83, P<0.001). Although the risks of both ischemic and hemorrhagic stroke persisted, their risk time trends were different. The risk of ischemic stroke reached peak during 1 to 3 years after childbirth with an aHR of 2.14 (1.36-3.38), while hemorrhagic stroke risk gradually increased and had an aHR of 4.64 (2.47-8.73) after 10 to 15 years of childbirth (both P<0.001). Among the 4 HDP subtypes, chronic hypertension with superimposed preeclampsia had the highest stroke risk (aHR=3.86, 1.91-7.82, P<0.001), followed by preeclampsia-eclampsia (aHR=2.00, 1.63-2.45, P<0.001), and gestational hypertension (aHR=1.68, 1.13-2.52, P<0.05); chronic preexisting hypertension had the lowest stroke risk (aHR=1.27, 0.97-1.68, P>0.05). Furthermore, multiple HDP combined with preeclampsia had aHR of 5.48 (1.14-26.42, P<0.05). CONCLUSIONS: The effect of HDP on the risk of future stroke persisted for up to 17 years, both for ischemic and hemorrhagic strokes. The presence of multiple HDP and preeclampsia further increase the stroke risk.

A nationwide cohort study suggests clarithromycin-based therapy for Helicobacter pylori eradication is safe in patients with stable coronary heart disease and subsequent peptic ulcer disease.

BACKGROUND: Clarithromycin-based therapy is important for Helicobacter pylori eradication treatment. However, clarithromycin may increase cardiovascular risk. Hence, we investigated the association between clarithromycin use and outcomes in adults with stable coronary heart disease (CHD) and subsequent peptic ulcer disease (PUD). METHODS: This nationwide cohort study used a national health insurance database to screen 298,417 Taiwanese residents who were diagnosed with coronary heart disease from 2001 to 2015 for eligibility in the study and to evaluate select eligible patients with CHD-PUD from 2004 to 2015. Data were obtained from new users of clarithromycin (n = 4183) and nonusers of clarithromycin (n = 24,752) during follow-up. A total of 4070 eligible clarithromycin users and 4070 nonusers were subject to final analysis by 1:1 propensity score matching. Participants were followed up after receiving clarithromycin or at the corresponding date until the occurrence of cardiovascular morbidity in the presence of competing mortality, overall mortality and cardiovascular mortality, or through the end of 2015. The incidence rates and risks of overall mortality and cardiovascular outcomes were evaluated. The associations between clarithromycin and arrhythmia risk, as well as its dose and duration and overall mortality and cardiovascular outcomes were also addressed. RESULTS: Clarithromycin users were associated with adjusted hazard ratios of 1.08 (95% confidence interval, 0.93-1.24; 21.5 compared with 21.2 per 1000 patient-years) for overall mortality, 0.95 (0.57-1.59; 1.5 compared with 1.8 per 1000 patient-years) for cardiovascular mortality, and 0.94 (0.89-1.09; 19.6 compared with 20.2 per 1000 patient-years) for cardiovascular morbidity in the presence of competing mortality, as compared with nonusers. We found no relationship between dose and duration of clarithromycin and overall mortality and cardiovascular outcomes and no increased risk of arrhythmia during follow-up period. After inclusion of arrhythmia events to re-estimate the risks of all study outcomes, the results remained insignificant. CONCLUSION: Concerning overall mortality, cardiovascular mortality, and cardiovascular morbidity, our results suggest clarithromycin-based therapy for Helicobacter pylori eradication may be safe in patients with stable CHD and subsequent PUD.

Impact of 23-valent pneumococcal polysaccharide vaccination on the frequency of pneumonia-related hospitalization and survival in elderly patients with prostate cancer: A seven-year nationwide matched cohort study.

BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is indicated for adults who have a high risk of pneumonia; however, its effectiveness in patients with prostate cancer who are at a risk of pneumonia because of age and cancer treatments, including androgen-deprivation therapy, is unknown. METHODS: Between 2000 and 2010, 38,735 patients with prostate cancer were diagnosed in Taiwan. After exclusions and exact matching for age, previous pneumonia, and influenza vaccination, 2188 vaccinated patients and 2188 unvaccinated patients were recruited. The incidence density of all-cause bacterial pneumonia hospitalizations was analyzed. RESULTS: Over 7 years of follow-up, patients who received the PPSV23 had a significantly lower incidence density, with 142.8 per 1000 person-years versus 162.0 per 1000 person-years for unvaccinated patients. More patients in the vaccinated cohort were never hospitalized for pneumonia compared with those in the unvaccinated cohort (64.2% vs 62.2%, respectively). After adjusting for the Charlson comorbidity index, cancer treatment modalities, and socioeconomic levels, the risk of pneumonia-related hospitalization in the PPSV23 vaccination cohort was 0.48 times lower than that in the unvaccinated cohort (adjusted incidence rate ratio, 0.48; P = .046). For patients who received the influenza vaccination, subgroup analysis demonstrated that PPSV23 vaccination significantly decreased the risk (adjusted incidence rate ratio, 0.45; P < .001). Compared with unvaccinated controls, PPSV23-vaccinated patients had a lower cumulative incidence for the first occurrence of pneumonia-related hospitalization (34.49% vs 36.36%; P = .178) and higher overall survival (47.5% and 42.3%, respectively; P < .001). CONCLUSIONS: Vaccination of elderly patients who have prostate cancer with the relatively common and inexpensive PPSV23 can decrease the risk of pneumonia and prolong survival.

Risk Factors for Postoperative Retention After Hemorrhoidectomy: A Cohort Study.

The objective of this study was to identify the risk factors for urinary retention after hemorrhoidectomy. With the approval of West China Hospital of Sichuan University Ethics Board, data were abstracted from 961 charts of patients who underwent hemorrhoidectomy from January 1, 2009, to June 30, 2011. The outcome was urinary retention in the first 24 hours after surgery. Risk factors were identified using multivariable logistic regression, and they were expressed as odds ratios or 95% confidence intervals. The overall urinary retention rate was 14.8% (n = 142). Significant risk factors associated with postoperative urinary retention included female gender, anesthesia methods, severity of hemorrhoid, a large amount of intravenous fluid administered perioperatively, and length of hospital stay. Logistic regression analysis revealed that female gender (odds ratio, 2.607; p < .01), sacral anesthesia (odds ratio, 2.481; p = .02), more than 3 hemorrhoids resected (odds ratio, 2.658; p < .01), hemorrhoids having 4 degrees of severity (odds ratio, 3.101; p < .01), intravenous fluids > 700 ml (odds ratio, 1.597; p = .02), and length of stay more than 7 days (odds ratio, 1.852; p < .01) were significant predictors of urinary retention post-hemorrhoidectomy.

Transcutaneous vagus nerve stimulation for refractory epilepsy: a randomized controlled trial.

This trial was designed to test the safety and effectiveness of transcutaneous auricular vagus nerve stimulation (ta-VNS) for patients with refractory epilepsy.Pre-trial：144 patients were randomly assigned to ta-VNS group (n=98) or transcutaneous auricular non-vagus nerve stimulation (tn-VNS) control group (n=46). Treatment was conducted twice per day for 24 weeks. After 8, 16 and 24 weeks of treatment，the patients were evaluated according to the Modified Engel Scale (four classes). After 8 weeks，according to the medical ethic design, patients in tn-VNS group were switched into ta-VNS group uniquely. After 8 weeks' treatment 41.0% and 27.5% of patients from ta-VNS and tn-VNS groups, respectively, experienced reduction in seizure frequency that reached I, II and III levels according to the standards of the Modified Engel Scale compared with the baselines, indicating significant difference in seizure reduction between the two groups. After 24 weeks of treatment, ta-VNS patients had a 47.7% reduction, and tn-VNS, with an additional 16 weeks of treatment, reached 47.5% in reduction. After 8 weeks' treatment, the percentages of average seizure frequency in ta-VNS and tn-VNS were reduced by 42.6% and 11.5% respectively, providing a statistically significant difference in the results between the two groups (P<0.05). In addition, there were significant improvements in electroencephalograph (EEG) and the quality of daily life of the patients after treatment.The results show that this ta-VNS treatment can effectively reduce the frequency of seizures and improve the patient's quality of life. This may be an effective treatment for refractory epilepsy. At the same time，it is also safe，economic, and widely applicable.

Dose and Time Effects of Renin-Angiotensin Inhibitors on Patients With Advanced Stages 4 to 5 of Diabetic Kidney Disease.

Context: Limited evidence exists regarding the cumulative dosing and duration impact of renin-angiotensin system inhibitors (RASis) on cardiorenal and mortality outcomes in patients with advanced stages (predominantly in stage 5 and a minority in stage 4) of diabetic kidney disease (DKD). Objective: To retrospectively investigate whether there are dose- and time-dependent relationships between RASis and cardiorenal and mortality outcomes in this population. Methods: Using Taiwan's national health insurance data in 2000-2017, we analyzed 2196 RASi users and 2196 propensity-matched nonusers among 8738 patients living with diabetes and newly diagnosed with advanced chronic kidney disease (23% stage 4, 77% stage 5). Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHRs) and 95% CI. Results: RASi use was significantly associated with reduced risks of all-cause mortality (aHR, 0.53; 95% CI 0.47-0.60) and cardiovascular mortality (0.68; 0.56-0.83) with the degree of benefit depending on therapeutic dosage and duration, despite a nonsignificant increase in acute kidney injury risk (1.16; 0.98-1.38) and a significant increase in hyperkalemia risk (1.45; 1.19-1.77). Significant differences in proteinuria risk (1.32; 1.21-1.43) were observed, while there were no significant differences in end-stage renal disease risk (1.01; 0.88-1.15) and no dose- or time-response relationships for either end-stage renal disease or proteinuria risks. Sensitivity analyses confirmed cardiovascular and survival benefits, even in patients with stage 5 DKD. Conclusion: This real-world study suggests that RASi use in advanced stages 4 to 5 DKD may provide dose- and time-dependent cardioprotection and improved survival, without excess renal harms.

Alleviating sleep disturbances and modulating neuronal activity after ischemia: Evidence for the benefits of zolpidem in stroke recovery.

AIMS: Sleep disorders are prevalent among stroke survivors and impede stroke recovery, yet they are still insufficiently considered in the management of stroke patients, and the mechanisms by which they occur remain unclear. There is evidence that boosting phasic GABA signaling with zolpidem during the repair phase improves stroke recovery by enhancing neural plasticity; however, as a non-benzodiazepine hypnotic, the effects of zolpidem on post-stroke sleep disorders remain unclear. METHOD: Transient ischemic stroke in male rats was induced with a 30-minute middle cerebral artery occlusion. Zolpidem or vehicle was intraperitoneally delivered once daily from 2 to 7 days after the stroke, and the electroencephalogram and electromyogram were recorded simultaneously. At 24 h after ischemia, c-Fos immunostaining was used to assess the effect of transient ischemic stroke and acute zolpidem treatment on neuronal activity. RESULTS: In addition to the effects on reducing brain damage and mitigating behavioral deficits, repeated zolpidem treatment during the subacute phase of stroke quickly ameliorated circadian rhythm disruption, alleviated sleep fragmentation, and increased sleep depth in ischemic rats. Immunohistochemical staining showed that in contrast to robust activation in para-infarct and some remote areas by 24 h after the onset of focal ischemia, the activity of the ipsilateral suprachiasmatic nucleus, the biological rhythm center, was strongly suppressed. A single dose of zolpidem significantly upregulated c-Fos expression in the ipsilateral suprachiasmatic nucleus to levels comparable to the contralateral side. CONCLUSION: Stroke leads to suprachiasmatic nucleus dysfunction. Zolpidem restores suprachiasmatic nucleus activity and effectively alleviates post-stroke sleep disturbances, indicating its potential to promote stroke recovery.

Clinical Outcomes of Arthroscopic Superior Capsular Reconstruction Using Fascia Lata Autograft Versus Reverse Shoulder Arthroplasty in Patients 65 Years and Older With Irreparable Rotator Cuff Tears: A Retrospective Cohort Study.

Background: Arthroscopic superior capsular reconstruction (ASCR) and reverse shoulder arthroplasty (RSA) have both shown favorable outcomes in patients with irreparable rotator cuff tears (IRCTs). Purpose: To (1) compare the clinical outcomes of ASCR versus RSA in patients aged ≥65 years with IRCTs and (2) compare serial changes in clinical outcomes between treatment groups. Study Design: Cohort study; Level of evidence, 3. Methods: This study included patients with IRCTs without glenohumeral osteoarthritis who underwent either ASCR or RSA between March 2013 and December 2020 and had at least 2 years of follow-up data. We assessed active range of motion, a visual analog scale (VAS) pain score, the American Shoulder and Elbow Surgeons (ASES) score, and the Single Assessment Numeric Evaluation (SANE) score at the preoperative, short-term (postoperative 6-12 months), and final follow-up times. Results: In total, 64 patients (ASCR, 31 patients; RSA, 33 patients) were included. The mean age of patients was 71.3 ± 4.4 and 72.9 ± 4.1 years, and the mean final follow-up duration was 42 ± 21.8 and 37.7 ± 21.7 months in the ASCR and RSA groups, respectively. At the short-term follow-up, RSA achieved significant improvements in all clinical outcomes, except for internal rotation (IR), while ASCR only showed significant improvements in VAS pain, ASES, and SANE scores. Compared with the preoperative period, both ASCR and RSA achieved significant improvements in all clinical outcomes, except for IR in the RSA group at the final follow-up. The ASCR group achieved better IR and ASES scores at the final follow-up, while the time taken to recover from pseudoparalysis was shorter after RSA. The ASCR group showed a 67.8% graft healing rate at the 1-year follow-up, while the RSA group showed 12.1% of scapular notching at the final follow-up. No other postoperative complications were observed in either group. Conclusion: ASCR and RSA achieved favorable clinical outcomes in the study cohort. At the short-term follow-up, RSA showed significant improvements in all clinical outcomes, except for IR, while ASCR only showed significant improvements in VAS pain, ASES, and SANE scores. At the final follow-up, however, ASCR had better IR and ASES scores compared with RSA.

Handelin alleviates cachexia- and aging-induced skeletal muscle atrophy by improving protein homeostasis and inhibiting inflammation.

BACKGROUND: Handelin is a bioactive compound from Chrysanthemum indicum L. that improves motor function and muscle integrity during aging in Caenorhabditis elegans. This study aimed to further evaluate the protective effects and molecular mechanisms of handelin in a mouse muscle atrophy model induced by cachexia and aging. METHODS: A tumour necrosis factor (TNF)-α-induced atrophy model was used to examine handelin activity in cultured C2C12 myotubes in vitro. Lipopolysaccharide (LPS)-treated 8-week-old model mice and 23-month-old (aged) mice were used to examine the therapeutic effects of handelin on cachexia- and aging-induced muscle atrophy, respectively, in vivo. Protein and mRNA expressions were analysed by Western blotting, ELISA and quantitative PCR, respectively. Skeletal muscle mass was measured by histological analysis. RESULTS: Handelin treatment resulted in an upregulation of protein levels of early (MyoD and myogenin) and late (myosin heavy chain, MyHC) differentiation markers in C2C12 myotubes (P < 0.05), and enhanced mitochondrial respiratory (P < 0.05). In TNF-α-induced myotube atrophy model, handelin maintained MyHC protein levels, increased insulin-like growth factor (Igf1) mRNA expression and phosphorylated protein kinase B protein levels (P < 0.05). Handelin also reduced atrogin-1 expression, inhibited nuclear factor-κB activation and reduced mRNA levels of interleukin (Il)6, Il1b and chemokine ligand 1 (Cxcl1) (P < 0.05). In LPS-treated mice, handelin increased body weight (P < 0.05), the weight (P < 0.01) and cross-sectional area (CSA) of the soleus muscle (P < 0.0001) and improved motor function (P < 0.05). In aged mice, handelin slightly increased the weight of the tibialis anterior muscle (P = 0.06) and CSA of the tibialis anterior and gastrocnemius muscles (P < 0.0001). In the tibialis anterior muscle of aged mice, handelin upregulated mRNA levels of Igf1 (P < 0.01), anti-inflammatory cytokine Il10 (P < 0.01), mitochondrial biogenesis genes (P < 0.05) and antioxidant-related enzymes (P < 0.05) and strengthened Sod and Cat enzyme activity (P < 0.05). Handelin also reduced lipid peroxidation and protein carbonylation, downregulated mRNA levels of Fbxo32, Mstn, Cxcl1, Il1b and Tnf (P < 0.05), and decreased IL-1ß levels in serum (P < 0.05). Knockdown of Hsp70 or using an Hsp70 inhibitor abolished the ameliorating effects of handelin on myotube atrophy. CONCLUSIONS: Handelin ameliorated cachexia- and aging-induced skeletal muscle atrophy in vitro and in vivo, by maintaining homeostasis of protein synthesis and degradation, possibly by inhibiting inflammation. Handelin is a potentially promising drug candidate for the treatment of muscle wasting.