An optimized ligation-mediated PCR method for chromosome walking and fusion gene chromosomal breakpoints identification.

Molecular techniques that recover unknown sequences next to a known sequence region have been widely applied in various molecular studies, such as chromosome walking, identification of the insertion site of transposon mutagenesis, fusion gene partner, and chromosomal breakpoints, as well as targeted sequencing library preparation. Although various techniques have been introduced for efficiency enhancement, searching for relevant single molecular event present in a large-sized genome remains challenging. Here, the optimized ligation-mediated polymerase chain reaction (PCR) method was developed and successfully identified chromosomal breakpoints far away from the exon of the new exon junction without the need for nested PCR. In addition to recovering unknown sequences next to a known sequence region, the high efficiency of the method could also improve the performance of targeted  next-generation sequencing (NGS).

Invasive pulmonary aspergillosis among patients with severe community-acquired pneumonia and influenza in ICUs: a retrospective cohort study.

RATIONALE: The prevalence, clinical characteristics, and outcomes of invasive pulmonary aspergillosis in patients with severe community-acquired pneumonia (CAP) in intensive care units remain underestimated because of the lack of a disease-recognition scheme and the inadequacy of diagnostic tests. OBJECTIVES: To identify the prevalence, risk factors, and outcomes of severe CAP complicated with invasive pulmonary aspergillosis (IPA) in intensive care units (ICUs). METHODS: We conducted a retrospective cohort study including recruited 311 ICU-hospitalized patients with severe CAP without influenza or with influenza. Bronchoalveolar lavage fluid (BALF) samples were from all patients and subjected to mycological testing. Patients were categorized as having proven or probable Aspergillus infection using a modified form of the AspICU algorithm comprising clinical, radiological, and mycological criteria. MEASUREMENTS AND MAIN RESULTS: Of the 252 patients with severe CAP and 59 influenza patients evaluated, 24 met the diagnostic criteria for proven or probable Aspergillus infection in the CAP group and 9 patients in the influenza group, giving estimated prevalence values of 9.5% and 15.3%, respectively. COPD and the use of inhaled corticosteroids were independent risk factors for IPA. IPA in patients with severe CAP was significantly associated with the duration of mechanical support, the length of ICU stay, and the 28-day mortality. CONCLUSIONS: An aggressive diagnostic approach for IPA patients with severe CAP and not only influenza or COVID-19 should be pursued. Further randomized controlled trials need to evaluate the timing, safety, and efficacy of antifungal therapy in reducing IPA incidence and improving clinical outcomes.

Risks of carpal tunnel syndrome and carpal tunnel release surgery in users of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists: A target trial emulation study.

AIM: Preclinical studies have shown that sodium-glucose cotransporter 2 inhibitors (SGLT2is) have a neuroprotective effect. This study compared the risks of carpal tunnel syndrome and carpal tunnel release surgery between new users of SGLT2is and new users of glucagon-like peptide-1 receptor agonists (GLP-1RAs). METHODS: A retrospective new-user active comparator cohort study with a target trial design was conducted by using the TriNetX platform. Patients with type 2 diabetes mellitus prescribed SGLT2is or GLP-1RAs were identified. Covariates were balanced using propensity score matching to form 2 homogenous treatment groups. Outcomes were the risk of carpal tunnel syndrome and the risk of carpal tunnel release surgery. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated using the TriNetX platform. RESULTS: The crude cohort included 86,188 and 100,244 patients in the SGLT2is group and GLP-1RAs group, respectively. After matching, each group included 65,464 patients. The SGLT2is group had an average age of 59.6 years, and 46 % were women. The GLP-1RAs group had an average age of 59.5 years, and 45.9 % were women. The incidences of carpal tunnel syndrome (HR: 0.928; 95 % CI: 0.869 to 0.991) and carpal tunnel release surgery (HR: 0.840; 95 % CI: 0.726 to 0.971) were significantly lower in the SGLT2is group than in the GLP-1RAs group. CONCLUSION: In patients with type 2 diabetes mellitus, SGLT2is seem to decrease the risk of carpal tunnel syndrome and the need for carpal tunnel release surgery. Prospective studies are required to confirm our results.

Relationship Between Serum 25-Hydroxyvitamin D and Bone Mineral Density, Fracture Risk, and Bone Metabolism in Adults With Osteoporosis/Fractures.

OBJECTIVE: To evaluate the association of serum 25-hydroxyvitamin D (25(OH) D) levels with bone mineral density (BMD), fracture risk, and bone metabolism. METHODS: This multicenter cross-sectional study recruited menopausal females and males greater than or equal to 50 year old with osteoporosis/fractures between September 2016 and September 2021. Assessment included clinical data, 25(OH)D, intact parathyroid hormone (iPTH), procollagen type 1 amino-terminal propeptide (P1NP), carboxy-terminal collagen crosslinks (CTX), lateral thoracolumbar spine x-rays, and BMD. RESULTS: A total of 3003 individuals were stratified by 25(OH) D levels: 720 individuals (24%) <20 ng/mL, 1338 individuals (44.5%) 20 to 29 ng/mL, and 945 individuals (31.5%) ≥30 ng/mL. In unadjusted and multivariable models, BMD T-score, except spine, was significantly and positively associated with 25(OH)D levels. 25(OH) D levels were inversely associated with Fracture Risk Assessment Tool scores. Patients with 25(OH)D <20 ng/mL had significantly higher iPTH and bone turnover markers (P1NP and CTX) than patients with 25(OH)D â‰§20 ng/mL in all models. When analyzing bone-related markers and BMD, total hip and femoral neck BMD T-scores were positively correlated with 25(OH)D concentrations and BMI but negatively correlated with iPTH, P1NP, CTX, and age. In multivariate models with all bone-related markers, only 25(OH)D levels were significantly associated with total hip and femoral neck BMD. CONCLUSION: Vitamin D deficiency is significantly associated with decreased total hip and femoral neck BMD and increased fracture risk as assessed by Fracture Risk Assessment Tool. In those with osteoporosis/fractures, vitamin D is implicated in the causal relationship between bone remodeling and BMD. Assessing vitamin D status is imperative for those at risk for osteoporosis/fractures.

A Clinical Analysis of Anti-Programmed Death-Ligand 1 (PD-L1) Immune Checkpoint Inhibitor Treatments Combined with Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer.

Real-world clinical experience of using anti-programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer (SCLC) patients has rarely been reported. In this study, we aimed to perform a retrospective multicenter clinical analysis of extensive-stage SCLC patients receiving first-line therapy with anti-PD-L1 ICIs combined with chemotherapy. Between November 2018 and March 2022, 72 extensive-stage SCLC patients receiving first-line atezolizumab or durvalumab in combination with chemotherapy, according to the cancer center databases of Linkou, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals, were retrospectively included in the analysis. Twenty-one patients (29.2%) received atezolizumab and fifty-one (70.8%) received durvalumab. Objective response (OR) and disease control (DC) rates of 59.7% and 73.6%, respectively, were observed with first-line ICI plus chemotherapy. The median progression-free survival (PFS) was 6.63 months (95% confidence interval (CI), 5.25-8.02), and the median overall survival (OS) was 16.07 months (95% CI, 15.12-17.0) in all study patients. A high neutrophil-to-lymphocyte ratio (NLR; >4) and a high serum lactate dehydrogenase (LDH) concentration (>260 UL) were identified as independent unfavorable factors associated with shorter OS in the multivariate analysis. Regarding safety, neutropenia was the most common grade 3 treatment-related adverse event (AE), but no treatment-related deaths occurred in the study patients. First-line anti-PD-L1 ICIs combined with chemotherapy are effective and safe for male extensive-stage SCLC patients. Further therapeutic strategies may need to be developed for patients with unfavorable outcomes (e.g., baseline high NLR and serum LDH level).

Risk of rotator cuff tear and rotator cuff repair surgery comparison between sodium-glucose cotransporter 2 inhibitors and glucagon like peptide-1 receptor agonists: A real-world study.

AIM: Theoretically, sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce the risk of rotator cuff tear through an anti-inflammatory mechanism. To clarify this association, in this study, we compared SGLT2is users and glucagon-like peptide-1 receptor agonists (GLP-1RAs) users in terms of the risk of rotator cuff tear and the risk of receiving rotator cuff repair surgery. METHODS: A retrospective cohort analysis was conducted using data from the TriNetX platform. A target trial design was adopted to identify patients with type 2 diabetes mellitus who started receiving SGLT2is or GLP-1RAs. Propensity score matching was used to form two homogeneous groups. The study outcomes were the risk of rotator cuff tear and the risk of receiving rotator cuff repair surgery. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated within the TriNetX platform. RESULTS: Initially, 351,800 SGLT2is users and 387,616 GLP-1RAs users were identified. After propensity score matching, each group comprised 274,026 patients. The mean age was 59.5 years in both groups; the proportions of women in the SGLT2is and GLP-1RAs groups were 46.9 % and 46.7 %, respectively. Compared with the GLP-1RAs group, the SGLT2is group had significantly reduced risks of rotator cuff tear (HR 0.812 [0.761;0.867]) and rotator cuff repair surgery (HR 0.900 [0.815;0.994]). CONCLUSION: SGLT2is appear to reduce the risk of rotator cuff tear and the risk of receiving rotator cuff repair surgery in patients with type 2 diabetes mellitus. Further prospective studies are needed to validate our findings.

Effects of an assist-as-needed equipped Tenodesis-Induced-Grip Exoskeleton Robot (TIGER) on upper limb function in patients with chronic stroke.

BACKGROUND: The original version of the Tenodesis-Induced-Grip Exoskeleton Robot (TIGER) significantly improved the motor and functional performance of the affected upper extremity of chronic stroke patients. The assist-as-needed (AAN) technique in robot-involved therapy is widely favored for promoting patient active involvement, thereby fostering motor recovery. However, the TIGER lacked an AAN control strategy, which limited its use in different clinical applications. The present study aimed to develop and analyze the training effects of an AAN control mode to be integrated into the TIGER, to analyze the impact of baseline patient characteristics and training paradigms on outcomes for individuals with chronic stroke and to compare training effects on the upper limb function between using the AAN-equipped TIGER and using the original prototype. METHODS: This was a single-arm prospective interventional study which was conducted at a university hospital. In addition to 20 min of regular task-specific motor training, each participant completed a 20-min robotic training program consisting of 10 min in the AAN control mode and 10 min in the functional mode. The training sessions took place twice a week for 9 weeks. The primary outcome was the change score of the Fugl-Meyer Assessment of the Upper Extremity (FMA-UE), and the secondary outcomes were the change score of the Box and Blocks Test (BBT), the amount of use (AOU) and quality of movement (QOM) scales of the Motor Activity Log (MAL), the Semmes-Weinstein Monofilament (SWM) test, and the Modified Ashworth Scale (MAS) for fingers and wrist joints. The Generalized Estimating Equations (GEE) and stepwise regression model were used as the statistical analysis methods. RESULTS: Sixteen chronic stroke patients completed all steps of the study. The time from stroke onset to entry into the trial was 21.7 ± 18.9 months. After completing the training with the AAN-equipped TIGER, they exhibited significant improvements in movement reflected in their total score (pre/post values were 34.6 ± 11.5/38.5 ± 13.4) and all their sub-scores (pre/post values were 21.5 ± 6.0/23.3 ± 6.5, 9.5 ± 6.2/11.3 ± 7.2, and 3.6 ± 1.0/3.9 ± 1.0 for the shoulder, elbow, and forearm sub-category, the wrist and hand sub-category, and the coordination sub-category, respectively) on the FMA-UE (GEE, p < 0.05), as well as their scores on the BBT (pre/post values were 5.9 ± 6.5/9.5 ± 10.1; GEE, p = 0.004) and the AOU (pre/post values were 0.35 ± 0.50/0.48 ± 0.65; GEE, p = 0.02). However, the original TIGER exhibited greater improvements in their performance on the FMA-UE than the participants training with the AAN-equipped TIGER (GEE, p = 0.008). The baseline score for the wrist and hand sub-category of the FMA-UE was clearly the best predictor of TIGER-mediated improvements in hand function during the post-treatment assessment (adjusted R2 = 0.282, p = 0.001). CONCLUSIONS: This study developed an AAN-equipped TIGER system and demonstrated its potential effects on improving both the function and activity level of the affected upper extremity of patients with stroke. Nevertheless, its training effects were not found to be advantageous to the original prototype. The baseline score for the FMA-UE sub-category of wrist and hand was the best predictor of improvements in hand function after TIGER rehabilitation. Clinical trial registration ClinicalTrials.gov, identifier NCT03713476; date of registration: October19, 2018. https://clinicaltrials.gov/ct2/show/NCT03713476.

A path analysis investigation into menopausal osteoporosis, sarcopenia risk, and their impact on sleep quality, depressive symptoms and quality of life.

PURPOSE: The objective was to investigate the relationships among disease characteristics, sarcopenia risk, bone function, sleep quality, depressive symptoms, and health-related quality of life in menopausal women. Additionally, we also examined the potential mediating role of coping in the relationship between these factors and health outcomes for individuals with osteoporosis. METHODS: In a cross-sectional approach, 201 participants were referred by a physician from the Family Medicine Department during their outpatient visits at a general hospital in Southern Taiwan. Data collection involved structured one-on-one interviews, and the analysis included descriptive and inferential statistics, along with a structural equation modeling. RESULTS: The participants' bone function was strongly positively related to coping, physical and mental quality of life (QOL), and negatively related to sleep quality and depressive symptoms. The duration of osteoporosis was positively related to pain, sarcopenia risk, sleep quality, but negatively related to bone function, physical and mental QOL. This structural framework explains 36% of the variance in depressive symptoms, 25% in sleep disturbances, 54% in mental QOL, and 72% in physical QOL. The best-fit structural equation modeling showed that physical function, exercise, sarcopenia, pain, and coping were significant predictors of depressive symptoms, with coping acting as a mediator in these relationships. CONCLUSION: Individuals who employed more active coping strategies exhibited fewer depressive symptoms, better sleep quality, and superior physical and mental QOL. Further, individuals with osteoporosis had lower pain levels, less sarcopenia risk, and higher engaged in exercise presentation improved physical and mental QOL. Future longitudinal research holds the promise of providing deeper insights into these complex relationships.

Trainability for cardiopulmonary fitness is low in patients with peripheral artery disease.

AIMS: In patients with peripheral arterial disease (PAD), exercise therapy is recommended to relieve leg symptoms, as noted in the 2016 AHA/ACC and 2017 ESC/ESVS guidelines. We assessed the trainability for cardiopulmonary fitness (CPF) and quality of life (QOL); three distinct patient types, namely, PAD, heart failure (HF), and stroke, were compared. METHODS AND RESULTS: This is a multicentre, retrospective analysis of prospectively collected data from three clinical studies. Data collected from 123 patients who completed 36 sessions of supervised aerobic training of moderate intensity were analysed, with 28 PAD, 55 HF, and 40 stroke patients totalling 123. Before and after training, cardiopulmonary exercise testing with non-invasive cardiac output monitoring and QOL evaluation using a 36-Item Short Form Survey (SF-36) were performed. Non-response was defined as a negative change in the post-training value compared with that in the pre-training value. The result showed an improvement in CPF in all three groups. However, cardiorespiratory fitness (CRF) increased by a lesser extent in the PAD group than in the HF and stroke groups; the physical and mental component scores (MCS) of SF-36 exhibited a similar pattern. Non-response rates of peak V˙O2, oxygen uptake efficiency slope, and MCS were higher in the PAD group. In the PAD group, non-responders regarding peak V˙O2 had a higher pulse wave velocity than responders. CONCLUSION: In patients with PAD following exercise therapy, CRF and QOL improved to a lesser extent on average; their non-response rate was also higher compared with that of HF or stroke patients. Therefore, a higher dose of exercise might be needed to elicit adaptation in PAD patients, especially those with high pulse wave velocity.

Low-dose CT screening among never-smokers with or without a family history of lung cancer in Taiwan: a prospective cohort study.

BACKGROUND: In Taiwan, lung cancers occur predominantly in never-smokers, of whom nearly 60% have stage IV disease at diagnosis. We aimed to assess the efficacy of low-dose CT (LDCT) screening among never-smokers, who had other risk factors for lung cancer. METHODS: The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) was a nationwide, multicentre, prospective cohort study done at 17 tertiary medical centres in Taiwan. Eligible individuals had negative chest radiography, were aged 55-75 years, had never smoked or had smoked fewer than 10 pack-years and stopped smoking for more than 15 years (self-report), and had one of the following risk factors: a family history of lung cancer; passive smoke exposure; a history of pulmonary tuberculosis or chronic obstructive pulmonary disorders; a cooking index of 110 or higher; or cooking without using ventilation. Eligible participants underwent LDCT at baseline, then annually for 2 years, and then every 2 years up to 6 years thereafter, with follow-up assessments at each LDCT scan (ie, total follow-up of 8 years). A positive scan was defined as a solid or part-solid nodule larger than 6 mm in mean diameter or a pure ground-glass nodule larger than 5 mm in mean diameter. Lung cancer was diagnosed through invasive procedures, such as image-guided aspiration or biopsy or surgery. Here, we report the results of 1-year follow-up after LDCT screening at baseline. The primary outcome was lung cancer detection rate. The p value for detection rates was estimated by the χ2 test. Univariate and multivariable logistic regression analyses were used to assess the association between lung cancer incidence and each risk factor. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of LDCT screening were also assessed. This study is registered with ClinicalTrials.gov, NCT02611570, and is ongoing. FINDINGS: Between Dec 1, 2015, and July 31, 2019, 12 011 participants (8868 females) were enrolled, of whom 6009 had a family history of lung cancer. Among 12 011 LDCT scans done at baseline, 2094 (17·4%) were positive. Lung cancer was diagnosed in 318 (2·6%) of 12 011 participants (257 [2·1%] participants had invasive lung cancer and 61 [0·5%] had adenocarcinomas in situ). 317 of 318 participants had adenocarcinoma and 246 (77·4%) of 318 had stage I disease. The prevalence of invasive lung cancer was higher among participants with a family history of lung cancer (161 [2·7%] of 6009 participants) than in those without (96 [1·6%] of 6002 participants). In participants with a family history of lung cancer, the detection rate of invasive lung cancer increased significantly with age, whereas the detection rate of adenocarcinoma in situ remained stable. In multivariable analysis, female sex, a family history of lung cancer, and age older than 60 years were associated with an increased risk of lung cancer and invasive lung cancer; passive smoke exposure, cumulative exposure to cooking, cooking without ventilation, and a previous history of chronic lung diseases were not associated with lung cancer, even after stratification by family history of lung cancer. In participants with a family history of lung cancer, the higher the number of first-degree relatives affected, the higher the risk of lung cancer; participants whose mother or sibling had lung cancer were also at an increased risk. A positive LDCT scan had 92·1% sensitivity, 84·6% specificity, a PPV of 14·0%, and a NPV of 99·7% for lung cancer diagnosis. INTERPRETATION: TALENT had a high invasive lung cancer detection rate at 1 year after baseline LDCT scan. Overdiagnosis could have occurred, especially in participants diagnosed with adenocarcinoma in situ. In individuals who do not smoke, our findings suggest that a family history of lung cancer among first-degree relatives significantly increases the risk of lung cancer as well as the rate of invasive lung cancer with increasing age. Further research on risk factors for lung cancer in this population is needed, particularly for those without a family history of lung cancer. FUNDING: Ministry of Health and Welfare of Taiwan.

Effectiveness and safety of botulinum neurotoxin for treating dyssynergic defecation: A systematic review and meta-analysis.

Dyssynergic defecation (DD) is a common cause of chronic constipation. Owing to the lack of a comprehensive synthesis of available data on the effectiveness of botulinum neurotoxin (BoNT) for treating DD, we performed a systematic review and meta-analysis. We searched the PubMed, Embase, and Cochrane databases from inception to May 9, 2023. The outcomes comprise short-term and long-term symptom improvement, various anorectal function measurements, complications of fecal incontinence, and symptom improvement after repeated BoNT injections. A meta-analysis comparing BoNT injection with either surgery or biofeedback (BFB) therapy in treating DD was also conducted. Subgroup analysis and meta-regression were performed to identify possible moderator effects. We included five randomized controlled trials, seven prospective studies, and two retrospective observational studies. Short-term potential improvement in symptoms (event rate [ER], 66.4%; 95% CI, 0.513 to 0.783) was identified, but in the long-term (>12 months), this effect was decreased (ER, 38.2%; 95% CI, 0.267 to 0.511). Short-term improvements in objective anorectal physiologic parameters were also observed. Repeated BoNT injection was effective for patients with symptom recurrence. Subgroup analysis revealed enhanced long-term symptom improvement with high-dose BoNT, but this treatment also increased the risk of complications and recurrence compared with low doses. The effectiveness, complications, and recurrence of symptoms associated with BoNT injection and surgery did not differ significantly. BoNT injection significantly provided short-term symptom improvement but also heightened the risk of incontinence compared with BFB therapy. Our systematic review and meta-analysis indicated that BoNT could be beneficial for short-term symptom improvement in patients with DD, but this effect tended to decline 12 months after injection. Standardized BoNT intervention protocols remain warranted. Among the several treatments for DD, we concluded that BoNT injection is not inferior to other options considering its effectiveness in relieving symptoms, the associated complication development, and the risk of symptom recurrence.

Sequential treatment in advanced epidermal growth factor receptor-mutated lung adenocarcinoma patients receiving first-line bevacizumab combined with 1st/2nd-generation EGFR-tyrosine kinase inhibitors.

Introduction: The clinical outcomes of sequential treatment of advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients with first-line bevacizumab combined with 1st/2nd-generation EGFR-TKIs are unclear. Thus, we aimed to analyze the outcomes of these patients. Methods: Between January 2015 and December 2020, data for 102 advanced EGFR-mutated lung adenocarcinoma patients receiving first-line bevacizumab combined with erlotinib or afatinib followed by treatments at multiple institutions were retrospectively analyzed. All patients with progressive disease (PD) after first-line therapy underwent secondary T790M mutation detection. Results: The secondary T790M mutation positive rate of all study patients was 57.9%. First-line erlotinib use and progression-free survival (PFS) after first-line therapy > 12 months were positively associated with the T790M mutation (P <0.05). The response rates (RRs) to second-line treatments were 51.7% and 22.7% for the osimertinib and nonosimertinib groups, respectively (P = 0.001). The median PFS associated with second-line osimertinib and nonosimertinib therapy was 13.7 and 7.1 months, respectively (hazard ratio (HR) = 0.38; 95% confidence interval (CI), 0.23-0.63; P< 0.001). Patients with a secondary T790M mutation receiving second-line osimertinib treatment had a median overall survival (OS) of 54.3 months, and the median OS was 31.9 months for non-T790M-mutated patients receiving second-line nonosimertinib treatments (HR = 0.36; CI: 0.21-0.62, P < 0.001). Conclusion: The majority of acquired resistance to first-line bevacizumab combined with 1st/2nd-generation EGFR-TKIs is associated with the T790M mutation. Sequential osimertinib treatment in patients with positive secondary T790M mutation is associated with better outcomes among these patients.

Does Botulinum Toxin Injection Exacerbate Sarcopenia and Bone Mass in Individuals With Cerebral Palsy?

BACKGROUND: Botulinum toxin (BoNT) causes sarcopenia and low bone mass in animal studies. Whether such effect exists in children and adolescents with spastic cerebral palsy (CP) is not clear yet. To investigate the influences of BoNT on grip strength (GS), skeletal muscle mass, and bone mineral density (BMD) in children and adolescents with spastic CP, we conducted this uncontrolled longitudinal study. METHODS: The body composition of individuals with spastic CP were measured by dual-energy X-ray absorptiometry at preinjection and at 12 and 24 weeks after BoNT intervention. Sarcopenia was defined as meeting both decreased GS and low muscle mass. Twenty-five participants were enrolled (mean age 8.5 years). RESULTS: Before BoNT intervention, four adolescents had sarcopenia and low bone mass. When the body composition was analyzed as four limbs, trunk, and head, the skeletal muscle mass of the injected limbs, appendicular skeletal muscle mass, and total body less head BMD increased significantly over 24-week follow-up period (P = 0.0117, 0.0032, 0.0229), whereas the GS remained unchanged. When the body composition was analyzed as segments derived from bilateral arms, forearms, hands, thighs, and lower legs, the skeletal muscle mass (P = 0.0113) but not BMD of the injected segments increased significantly over the 24 weeks. The prevalence of low muscle mass, decreased GS, sarcopenia, and low bone mass did not change over 24 weeks. CONCLUSIONS: The present study showed that BoNT does not exacerbate sarcopenia and low bone mass in individuals with spastic CP.

Clinical outcome analysis of non-small cell lung cancer patients with brain metastasis receiving metastatic brain tumor resection surgery: a multicenter observational study.

Brain metastasis is most common in primary non-small cell lung cancer (NSCLC), and some patients require neurosurgical resection for intracranial disease control. Because advances in systemic therapies for metastatic NSCLC have been developed in the past decade, we aimed to analyze and determine clinical factors associated with the postresection survival of NSCLC patients with brain metastasis who underwent neurosurgery followed by systemic therapy. Between January 2017 and December 2021, data for 93 NSCLC patients with brain metastasis treated with neurosurgery followed by systemic therapy at Linkou, Kaohsiung and Chiayi Chang Gung Memorial Hospitals were retrospectively retrieved for analysis. For all study patients, median postresection survival was 34.36 months (95% confidence interval (CI), 28.97-39.76), median brain metastasis (BM)-free survival was 26.90 months (95% CI, 22.71-31.09), and overall survival (OS) was 41.13 months (95% CI, 34.47-47.52). In multivariate analysis, poor performance status (Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2) and concurrent liver metastasis were identified as independent unfavorable factors associated with significantly shortened postresection survival (P<0.001). The histological type adenocarcinoma was associated with significantly longer postresection survival (P = 0.001). The median postresection survival for adenocarcinoma and nonadenocarcinoma patients was 36.23 and 10.30 months, respectively (hazard ratio (HR) = 0.122; 95% CI, 0.035-0.418; P<0.001); that for patients with and without concurrent liver metastasis was 11.43 and 36.23 months, respectively (HR = 22.18; 95% CI, 5.827-84.459; P<0.001). Patients with preserved ECOG PS, adenocarcinoma histology type and no concurrent liver metastasis appeared to have better postresection survival than nonadenocarcinoma patients. Our results provide counseling and decision-making references for neurosurgery feasibility in NSCLC patients with brain metastasis.

Body composition as a predictor of oncological outcome in patients with non-muscle-invasive bladder cancer receiving intravesical instillation after transurethral resection of bladder tumor.

Introduction: Body status, categorized as sarcopenia or obesity and assessed using body mass index and body composition, affects the outcome of bladder cancer patients. However, studies comparing disease progression, recurrence, or overall survival in patients with non-muscle-invasive bladder cancer (NMIBC) with different body compositions are lacking. Therefore, we conducted a retrospective study to identify the impact of body composition, sarcopenia, and obesity on the oncological prognosis of patients with NMIBC who underwent transurethral resection of bladder tumor (TURBT) with Bacillus Calmette-Guerin (BCG) intravesical instillation (IVI). Methods: Patients with NMIBC who had undergone TURBT with adjuvant IVI with BCG from March 2005 to April 2021 were included. Body composition parameters were evaluated using computed tomography images of the third lumbar vertebrae and further categorized by sarcopenia and obesity. Oncological outcomes including recurrence-free survival (RFS), progression-free survival, and overall survival (OS) after treatment were analyzed. Results: A total of 269 patients were enrolled. Subcutaneous adipose tissue (SAT) density was a significant predictor of RFS, whereas psoas muscle density was a significant predictor of OS in the multivariate analysis. Patients with sarcopenia but without obesity tolerated significantly fewer BCG IVIs than patients without sarcopenia or obesity. Patients with sarcopenia had poorer RFS and OS than those without sarcopenia. In contrast, patients with obesity had better OS than those without obesity. Discussion: Body composition parameters, including SAT density and psoas muscle density, emerged as significant predictors of OS and RFS, respectively. Hence, our findings indicate that body composition is a helpful measurement to assess the oncological outcomes of patients with NMIBC.

The Intention of Inhaled Medication Adherence Scale (IMAS): The Development of a New Instrument for Assessing Inhaled Medication Adherence Among Patients with Chronic Obstructive Pulmonary Disease (COPD) Using Theory of Planned Behavior.

Purpose: Inhaled medication adherence is an important issue for patients with chronic obstructive pulmonary disease (COPD) because adhering to inhaled medications could substantially improve their health. However, patients with COPD may not be always adhere to the prescribed inhaled medications. Therefore, understanding the underlying reasons for patients with COPD adhering to inhaled medications is important. The present study used Theory of Planned Behavior (TPB) as a theoretical framework to develop the Intention of Inhaled Medication Adherence Scale (IMAS) and assess its psychometric properties. Patients and Methods: After reviewing papers using the TPB to design psychometric scales and the TPB scale development guidelines, 28 items were generated for expert evaluation. Eight experts reported that the 28 items all had good content validity (content validity index ranged from 0.88 to 1.00 at item-level; and from 0.981 to 0.987 at scale-level) comprising four factors. Following initial development, 235 patients with COPD (mean age 73.12 years; 93.6% males) completed the IMAS via interview with a respiratory therapist and a research assistant. The four-factor structure of the IMAS was evaluated using confirmatory factor analysis (CFA). Results: Nine IMAS items were removed because of low factor loadings or offending estimates. The 19-item IMAS was confirmed as having a four-factor structure supported by the CFA results (comparative fit index=1.00; Tucker-Lewis index=1.00; root mean square error of approximation=0.00; standardized root mean square residual=0.06). Conclusion: The 19-item IMAS had satisfactory psychometric properties in construct validity. The 19-item IMAS is an instrument that could help healthcare providers understand potential factors associated with adherence to inhaled medications among people with COPD.

Orbital floor fractures in Taiwan: A 10-year nationwide population-based study.

PURPOSE: To characterize the epidemiology, associated complications, and risk factors of orbital floor fractures in a nationwide longitudinal health insurance database. MATERIALS AND METHODS: Claims data from a million randomly selected registered residents from the Taiwan National Health Insurance Research Database were analyzed between 2001 and 2011 as part of a retrospective cohort review. Patients were identified using the International Classification of Disease-9 diagnosis codes for orbital floor fracture (closed: 802.6; open: 802.7). The cases were categorized as surgical or nonsurgical based on the procedure codes and compared statistically. RESULTS: From 2001 to 2011, 663 patients were diagnosed with orbital floor fractures out of a total population at risk of 9,836,431 person-years (average incidence: 6.78 persons/100,000/year) with overall increasing incidence. Surgical treatments were performed in 213 (32%) patients. Patients who received surgical treatment were younger than those who did not (mean age 25.3 ± 13.6 years vs. 34.2 ± 18.6 years, P < 0.001). The diagnosis with diplopia was a significantly associated factor for surgical treatment (2.2% in nonsurgery group vs. 6.6% in surgery group, P = 0.007). Male gender (adjusted hazard ratios [aHR] = 2.1, 95% confidence interval [CI]: 1.79-2.49) and low monthly income (aHR = 1.76, 95% CI: 1.16-2.67) were the risk factors for orbital floor fracture. CONCLUSION: The incidence of orbital floor fractures increased in the Taiwanese population between 2001 and 2011. Men and low income patients were at increased risk of orbital floor fracture. More research is necessary to clarify what factors are driving the escalating incidence of orbital fractures in this national population.

Botulinum Toxin for Drooling in Adults with Diseases of the Central Nervous System: A Meta-Analysis.

(1) Background: The purpose of this study was to determine whether the drooling of adult patients with diverse central nervous system diseases can be treated with botulinum toxin type A. (2) Methods: The Cochrane Library, MEDLINE, and Embase were all searched for studies that fit the inclusion criteria. The patients in the studies had to be adults (>18 years old), and the studies had to be randomized placebo-controlled trials, controlled trials, or prospective studies. Each study had to have enough quantifiable data available for meta-analysis. The primary outcome measure was the Drooling Severity and Frequency Scale (DSFS). (3) Results: The meta-analysis comprised three studies. A statistically significant difference in DSFS score between the treatment and control groups was observed in the meta-analysis, with an overall standardized mean difference of -0.9377 (95% CI, -1.2919 to -0.5836; p < 0.0001). A total of seven studies were ineligible for inclusion in the meta-analysis and were only assessed as qualitative data. All qualitative studies showed a significant reduction in DSFS score a few weeks or months after the injection of botulinum toxin. (4) Conclusions: Botulinum toxin type A is safe and effective as a treatment for drooling in adult patients with central nervous system diseases.

Bedtime extended release cornstarch improves biochemical profile and sleep quality for patients with glycogen storage disease type Ia.

BACKGROUND: Patients with glycogen storage disease type Ia (GSDIa) are prone to hypoglycemia. Uncooked cornstarch (CS) is the treatment, but maintaining nighttime blood glucose levels is still difficult. METHODS: The study enrolled patients with GSDIa to investigate the benefits of bedtime extended release CS (ER-CS, Glycosade®) versus regular CS. The daytime CS schedule was not altered. A 7-day continuous glucose monitoring (CGM) was performed at the baseline and 12 weeks after using ER-CS. Biochemical profile, sleep quality (Pittsburgh Sleep Quality Index, PSQI), and quality of life (SF-36 questionnaire) were measured at the baseline and 24 weeks after using ER-CS. RESULTS: Nine patients (9 to 33 years of age) were enrolled. Compared with the baseline (80.0 ± 6.33 mg/dL), the 12-week evaluations revealed higher mean morning glucose levels (86.5 ± 8.26 mg/dL, p = 0.015). Twenty-four weeks after the use of bedtime ER-CS, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels both decreased (from 69.3 ± 77.8 to 41.1 ± 40.4 U/L and from 78.8 ± 99.6 to 37.8 ± 28.81 U/L, respectively, p = 0.013 for both analyses), and sleep and fasting time both elongated (from 7.8 ± 0.87 to 8.6 ± 1.02 h and from 6.5 ± 1.22 to 7.6 ± 1.02 h, respectively, p = 0.011 for both analyses). The mean PSQI score in the five adult patients decreased significantly (from 5.8 ± 1.29 to 3.0 ± 1.71, p = 0.042). CONCLUSION: This study provides evidence of clinically meaningful improvements by shifting only bedtime regular CS to ER-CS in patients with GSDIa. As ER-CS is considerably more expensive than regular CS, this approach presents a cost-effective alternative.

Effect of body mass index on progressive bone mineral density in patients with cleft after secondary alveolar bone grafting.

BACKGROUND: Although childhood obesity matters, the association between body mass index (BMI) and bone mineral density (BMD) progression in grafted tissue after secondary alveolar bone grafting (ABG) for children with cleft alveolus is scarcely studied. Accordingly, this study explored the influence of BMI on BMD progression after ABG. METHODS: In total, 39 patients with cleft alveolus receiving ABG at the mixed dentition stage were enrolled. Patients were classified as underweight, normal weight, or overweight or obese according to age- and sex-adjusted BMI. BMD was measured in Hounsfield units (HU) from cone-beam computed tomography scans obtained 6 months (T1) and 2 years (T2) postoperatively. Adjusted BMD (HUgrafted tissue/HUpogonion, BMDa) was used for further analysis. RESULTS: For underweight, normal-weight, and overweight or obese patients, BMDaT1 values were 72.87%, 91.85%, and 92.89%, respectively (p = 0.727); BMDaT2 values were 111.49%, 112.57%, and 113.10% (p = 0.828); and density enhancement rates were 29.24%, 24.61%, and 22.14% (p = 0.936). No significant correlation was observed between BMI and BMDaT1, BMDaT2, or density enhancement rates (p = 0.223, 0.156, and 0.972, respectively). For patients with BMI < 17 and ≥ 17 kg/m2, BMDaT1 values were 89.80% and 92.89%, respectively (p = 0.496); BMDaT2 values were 111.49% and 113.10% (p = 0.216); and density enhancement rates were 23.06% and 26.39% (p = 0.573). CONCLUSION: Patients with different BMI values had similar outcomes (BMDaT1, BMDaT2, or density enhancement rate) after our ABG procedure in the 2-year postoperative follow-up.