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Abstract 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.

Abstract 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

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).

Abstract Background Positive fluid balance and tissue fluid accumulation are associated with adverse outcomes in sepsis. Vascular endothelial growth factor (VEGF) increases in sepsis, promotes vascular permeability, and may affect tissue fluid accumulation and oxygenation. We used near-infrared spectroscopy (NIRS) to estimate tissue hemoglobin (Hb) oxygenation and water (H2O) levels to investigate their relationship with serum VEGF levels. Material and methods New-onset severe sepsis patients admitted to the intensive care unit were enrolled. Relative tissue concentrations of oxy-Hb ([HbO 2 ]), deoxy-Hb ([HbR]), total Hb ([HbT]), and H2O ([H 2 O]) were estimated by near-infrared spectroscopy (NIRS) for three consecutive days and serum VEGF levels were measured. Comparisons between oliguric and non-oliguric patients were conducted and the correlations between variables were analyzed. Results Among 75 eligible patients, compared with non-oliguric patients, oliguric patients were administrated more intravascular fluids (median [IQR], 1926.00 [1348.50–3092.00] mL/day vs. 1069.00 [722.00–1486.75] mL/day, p

Abstract 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.

IntroductionThe 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

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.

Background: To determine a reliable method to predict prevalent vertebral fractures (VF) by assessing the association between dysmobility syndrome (DS) and VF in a community-dwelling population. Methods: This cross-sectional study enrolled 518 participants from fracture-prevention educational activities held in multiple communities in Taiwan. Assessments included questionnaires, fracture risk assessment tool (FRAX), bone mineral density (BMD) and body composition using dual-energy x-ray absorptiometry (DXA), lateral thoracolumbar spine x-rays (specifically T8-S1), grip strength (GS), walking speed, and fall history. Results: DS was noted in 257 participants (49.6%) and VF was identified in 196 participants (37.8%). A higher prevalence of VF was noted in those with DS. The prevalence of VF was significantly associated with age, gender, FRAX both with and without BMD, osteoporosis, low GS, and DS. In multivariate models accounting for age and sex, the c-index was greater in those with low GS plus osteoporosis as compared to DS alone. Low GS, osteoporosis, and pre-BMD FRAX all had similar c-indexes. Pre-BMD FRAX plus low GS and osteoporosis was superior in predicting VF compared to pre-BMD FRAX plus low GS or osteoporosis alone. Besides the inclusion of age and gender, the nomogram with pre-BMD FRAX major osteoporosis fracture probability (MOF) plus low GS had improved correlation between the estimated and actual VF probability than those with pre-BMD FRAX MOF plus osteoporosis. Conclusions: The constructed nomogram containing pre-BMD FRAX MOF plus low GS may be considered as a first-line prevalent VF screening method. Those with high-risk scores should subsequently undergo vertebral radiography and/or BMD.

We explore the effect of complete oral motor intervention (OMI) and nonnutritive sucking (NNS) alone on oral feeding in preterm infants through a meta-analysis. We searched the Embased, Medline, Cochrane Library, and Web of Science databases for randomized controlled trials up to 8 August 2023, based on established selection criteria. Quality evaluations of the studies were carried out by applying both the Cochrane risk of bias assessment tool and the Jadad scale. The outcome measures of three clinical indicators included transition time to oral feeding, weight gain, and hospitalization duration. We conducted a meta-analysis using a random-effects model to determine the pooled effect sizes, expressed as standardized mean differences (SMDs) and their corresponding confidence intervals (CIs). Additionally, we undertook a subgroup analysis and meta-regression to investigate any potential moderating factors. Eight randomized controlled trials with 419 participants were selected. Meta-analysis revealed that receiving a complete OMI had significantly reduced transition time compared with those receiving NNS alone in preterm newborns (SMD, −1.186; 95% CI, −2.160 to −0.212, p = 0.017). However, complete OMI had no significant effect on shortened hospitalization duration (SMD, −0.394; 95% CI, −0.979 to 0.192, p = 0.188) and increased weight gain (SMD, 0.346; 95% CI, −0.147 to 0.838, p = 0.169) compared with NNS alone. In brief, a complete OMI should not be replaced by NNS alone. However, we were unable to draw decisive conclusions because of the limitations of our meta-analysis. Future well-designed randomized controlled trials are necessary to confirm our conclusion.

IntroductionBody 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).MethodsPatients 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.ResultsA 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.DiscussionBody 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.

Abstract Background To explore the efficacy and safety of botulinum toxin in patients who received distraction osteogenesis of the lower extremities. Methods We searched the PubMed, Medline, Cochrane Library, and Web of Science databases for randomized controlled trials that administered botulinum toxin to individuals who underwent distraction osteogenesis of the lower limbs. The final search was conducted on July 6, 2021. Quality assessments were conducted using the Cochrane risk of bias tool and the Jadad scale. We performed random-effects meta-analysis to calculate the standardized mean differences (SMDs) and confidence intervals (CIs) of the pooled effect sizes, and subgroup analysis and meta-regression were performed for potential moderators. Results Our analysis of four randomized controlled trials, which enrolled a total of 257 participants, revealed that the difference in pain during the distraction phase was not statistically significant between groups (SMD, − 0.165; 95% CI, − 0.379 to 0.050, p = 0.133, I2 = 0.0%). The meta-regression analyses did not find any influence on the effect size, considering age (β = − 0.0092; p = 0.61) and the amount of lengthening (β = 0.0023; p = 0.99). Subgroup analysis did not reveal difference between different doses of botulinum toxin and single or multi-site study design. An analysis of two randomized controlled trials enrolling a total of 177 individuals demonstrated a limited effect of botulinum toxin in reducing postoperative pain (SMD, − 0.239; 95% CI, − 0.641 to 0.162, p = 0.24, I2 = 37.6%), total adverse events (SMD, − 0.207; 95% CI, − 0.505 to 0.090, p = 0.17, I2 = 0.0%), and infection of pin site (SMD, − 0.131; 95% CI, − 0.428 to 0.165, p = 0.39, I2 = 0.0%). No botulinum toxin–related adverse events were reported. Conclusions The current evidence does not support the administration of botulinum toxin in patients who receive distraction osteogenesis of the lower limbs. However, we were unable to draw decisive conclusions because of the limitations of our meta-analysis. Future well-designed, large-scale randomized controlled trials are necessary to confirm our conclusions.

Abstract A non-framework surgery could change the postoperative components of breathing disturbances and increase the frequency or duration of hypopnea in patients with very severe obstructive sleep apnea (OSA). Either an increase of hypopnea index, which increases apnea–hypopnea index (AHI), or an increase of its duration raises the concern of worsening the oxygen desaturation and so morbidity and mortality associated with OSA. It is unclear how the oxygen saturation would change in those having increased frequency or duration of hypopneas after the surgery. Here in 17 patients with AHI ≥ 60 events/h, having increased frequency or duration of hypopneas after the non-framework surgery, the results show that the surgery improved oxygen saturation by reducing obstructive-apnea index (36.1 events/h) and duration (8.6 s/event), despite it increased hypopnea index (16.8 events/h) and duration (9.8 s/event). The surgery improved the average of the mean oxyhemoglobin saturation of pulse oximetry (SpO2) by 2.8% (toward a ceiling mean of 94.3%), mean minimal SpO2 by 7.5%, and mean desaturation by 5%. The results suggest sufficient apnea reduction and shift from apnea to hypopnea may mask the negative impact of the increase of hypopnea index or duration and improve postoperative mean SpO2, minimal SpO2, and mean desaturation.

Abstract Background The coexistence of sarcopenia and dementia in aging populations is not uncommon, and they may share common risk factors and pathophysiological pathways. This study aimed to evaluate the relationship between brain atrophy and low lean mass in the elderly with impaired cognitive function. Methods This cross-sectional study included 168 elderly patients who visited the multi-disciplinary dementia outpatient clinic at Kaohsiung Chang Gung Memorial Hospital for memory issues, between 2017 and 2019. The body composition was assessed by dual energy X-ray absorptiometry (DEXA) and CT based skeletal muscle index including L3 skeletal muscle index (L3SMI) and masseter muscle mass index (MSMI). The brain atrophy assessment was measured by CT based visual rating scale. Possible predictors of low lean mass in the elderly with cognitive impairement were identified by binary logistic regression. ROC curves were generated from binary logistic regression. Results Among the 81 participants, 43 (53%) remained at a normal appendicular skeletal muscle index (ASMI), whereas 38 (47%) showed low ASMI. Compared with the normal ASMI group, subjects with low ASMI exhibited significantly lower BMI, L3SMI, and MSMI (all p

Abstract Osteoporosis is a critical problem during aging. Ultrasound signals backscattered from bone contain information associated with microstructures. This study proposed using entropy imaging to collect the information in bone microstructures as a possible solution for ultrasound bone tissue characterization. Bone phantoms with different pounds per cubic foot (PCF) were used for ultrasound scanning by using single-element transducers of 1 (nonfocused) and 3.5 MHz (nonfocused and focused). Clinical measurements were also performed on lumbar vertebrae (L3 spinal segment) in participants with different ages (n = 34) and postmenopausal women with low or moderate-to-high risk of osteoporosis (n = 50; identified using the Osteoporosis Self-Assessment Tool for Taiwan). The signals backscattered from the bone phantoms and subjects were acquired for ultrasound entropy imaging by using sliding window processing. The independent t-test, one-way analysis of variance, Spearman correlation coefficient r s, and the receiver operating characteristic (ROC) curve were used for statistical analysis. The results indicated that ultrasound entropy imaging revealed changes in bone microstructures. Using the 3.5-MHz focused ultrasound, small-window entropy imaging (side length: one pulse length of the transducer) was found to have high performance and sensitivity in detecting variation among the PCFs (r s = − 0.83; p

Objective: To evaluate the association between P1NP and bone strength in postmenopausal women treated with teriparatide. Materials and Methods: This prospective study enrolled 248 postmenopausal women with severe osteoporosis treated with teriparatide. Procollagen type 1 N-terminal propeptide (P1NP) were assessed at baseline, 3, 6, and 12 months. Lumbar spine (LS), femoral neck (FN), and total hip (TH) bone mineral density (BMD) and LS trabecular bone score (TBS) were measured by Dual-energy x-ray absorptiometry at baseline and 12 months. Results: With teriparatide use, P1NP levels increase and peaked at 6 months. Significant increase in LS and hip BMD and LS TBS were also noted. The percentage change or absolute change >10 μg/L in PINP at 3 months was only related to changes in LS BMD at 12 months. With a median baseline P1NP level was 65.5 ng/mL, we found no correlation between P1NP and LS and hip BMD nor LS TBS. There was no association between LS TBS and axial BMD. After treatment, there was also no significance between the changes in TBS and axial BMD. Over the study period, 83.9% of the 248 participants were persistent with teriparatide at 3 months, 77.8% at 6 months, and 67.3% women at 12 months. Conclusion: P1NP levels may provide a signal of osteoporosis risk but is not related to bone strength. Early changes in P1NP may offer information regarding subsequent BMD response so standardized monitoring of P1NP levels at baseline and at 3 months should be considered during osteoporosis therapy. As an additional benefit, serum level monitoring during treatment may also improve medication persistence.

(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.

Abstract Background Music-based interventions (MBI), using music as a therapeutic medium, has been utilized as a promising strategy for motor relearning and shaping. However, currently, MBI with active performance training is restricted to being extensively applied for patients with various levels of defects in fine motor skills and cognitive functions. Therefore, the integration of vibrotactile stimulation with MBI has been adopted as a motor training strategy intended to enhance motor learning through use of vibration stimuli. The current study was designed to investigate differences in the sensorimotor performance of older adults’ hands under baseline, a single session of active MBI, and vibrotactile-enriched MBI conditions. Methods Thirty healthy older adults were recruited and randomized to receive either the single session of 30-min of vibrotactile-enriched MBI or 30-min of active MBI at the beginning of the experiment. After a one-week washout period, they switched their treatment programs and then were assessed to study the training effects of both approaches through measuring precision pinch performance, hand function, and sensory status. Results The results of the Pinch-Holding-Up Activity test revealed a statistically significant difference in the FRpeak parameter (F = 14.37, p

Abstract Background Studies have indicated that individuals taking aspirin have a reduced risk of cancers and have also established chemo-preventive benefit of aspirin in colorectal cancer. However, research on the association between aspirin use and the survival in patients with lung cancer has revealed inconsistent results. In this study, we investigated the effect of aspirin use on the survival of inoperable non-small cell lung cancer (NSCLC) patients. Methods We identified a cohort of 38,842 patients diagnosed with NSCLC between 2000 and 2012 using the Taiwan’s National Health Insurance Research Database and used propensity score matching to reduce possible confounding factors. In total, 9864 patients (4932 matched pairs) were included in the matched cohort. Aspirin exposure was analyzed to identify a possible association with mortality in patients with inoperable NSCLC. Time-dependent Cox regression models were used to calculate the hazard ratios (HRs) and the 95% confidence intervals (95% CIs) that corresponded with aspirin exposure. Results A total of 4979 patients used aspirin at the time of diagnosis of NSCLC. The median overall survival (OS) of the aspirin users was 1.73 (interquartile range, 0.94–3.53) years compared with the 1.30 (interquartile range, 0.69–2.62) years of the non-aspirin users. The Cox proportional hazard model with the time-dependent covariate revealed that aspirin use was associated with a significantly longer OS (HR: 0.83, 95.0% CI: 0.80–0.86). After controlling the sociodemographic characteristics (age, sex, income, and level of urbanization) and lung cancer treatments by propensity score matching, the aspirin users still had a significantly longer OS than the non-aspirin users (HR: 0.79, 95.0% CI: 0.75–0.83). Conclusion Aspirin use is associated with a longer OS in patients with inoperable NSCLC, suggesting that aspirin has a potential anticancer effect. These results warrant further randomized clinical trials to evaluate the actual role of aspirin in the treatment of NSCLC patients.

IntroductionUncommon epidermal growth factor receptor (EGFR) mutations include single and complex mutations. However, the association of the smoking status of patients with uncommon and complex EGFR mutations remains unclear.MethodsThis retrospective study evaluates the spectrum of uncommon EGFR mutations and investigates the influence of smoking status on the frequency of various uncommon EGFR mutations using a multi-institutional medical database.ResultsBetween 2010 and 2019, 5,608 non-small cell lung cancer (NSCLC) patients were analyzed. EGFR mutations were detected in 3,155 (56.3%) patients. Among the 399 (12.6%) patients with uncommon mutations, 198 had single uncommon and 201 complex mutations, including 87 exon 20 insertions, 79 de novo T790M, 70 complex common, and 52 complex uncommon mutations. For comparison, we also included 402 patients with common EGFR mutations. The percentage of ever-smokers was significantly higher in patients with uncommon EGFR mutations than in patients with common EGFR mutations (25.8% vs. 17.4%, p = 0.005). Furthermore, the percentage of ever-smokers was higher in those with a complex mutation than in those with a single uncommon mutation (30.3% vs. 21.2%, p = 0.040). Among patients carrying uncommon EGFR mutations, ever-smokers had significantly more complex uncommon EGFR mutations than never-smokers (22.3% vs. 9.8%, p = 0.002). Among patients carrying G719X, L861Q, and S768I, ever-smokers tended to have complex EGFR mutations more frequently than never-smokers (64.7% vs. 28.7%, 50.0% vs. 18.7%, 88.9% vs. 81.2%, respectively).ConclusionsOur study demonstrates not only a comprehensive spectrum of uncommon EGFR mutations, but also a positive relationship between smoking status and uncommon EGFR mutation frequency, especially complex uncommon EGFR mutations. The results suggest that smoking contributes to the development of complex EGFR mutations.

Background: Although bevacizumab in combination with afatinib or erlotinib is an effective and safe first-line therapy for advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC), there are very few clinical data comparing afatinib and erlotinib combined with bevacizumab. We performed a retrospective multicenter analysis for the comparison of two combination therapies. Methods: Between May 2015 and October 2020, data of 135 stage IIIB/IV EGFR-mutated NSCLC patients receiving first-line afatinib or erlotinib combined with bevacizumab combination therapy in Linkou, Keelung, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals were retrieved and retrospectively analyzed. Results: In all, 67 patients received afatinib plus bevacizumab, and 68 patients received erlotinib plus bevacizumab. Afatinib combined with bevacizumab had an objective response rate (ORR) of 82.1% and a disease control rate (DCR) of 97.0%, and the ORR and DCR were 83.8 and 95.6%, respectively, in the erlotinib combined with bevacizumab group ( p = 0.798 and p = 1.000). The median progression-free survival was 20.7 and 20.3 months for the afatinib plus bevacizumab group and the erlotinib plus bevacizumab group, respectively [hazard ratio (HR) = 1.02; 95% confidence interval (CI), 0.891–1.953; p = 0.167). The overall survival was 41.9 and 51.0 months for the afatinib plus bevacizumab group and erlotinib plus bevacizumab group, respectively (HR = 1.42; 95% CI, 0.829–2.436; p = 0.201). The secondary EGFR-T790M mutation rates after disease progression were 44% in the afatinib plus bevacizumab group and 58.8% in the erlotinib plus bevacizumab group ( p = 0.165). Skin toxicity was the most frequent treatment-related adverse event (AE) in both treatment groups. Diarrhea, an AE, occurred significantly more frequently in the afatinib plus bevacizumab group than in the erlotinib plus bevacizumab group ( p

Background: The incidence of early-onset colorectal cancer (CRC) is increasing. Many guidelines recommend initiating screening at 45 years. This study investigated the detection rate of advanced colorectal neoplasm (ACRN) by using fecal immunochemical tests (FITs) in individuals aged 40–49 years. Methods: PubMed, Embase, and Cochrane Library databases were searched from inception to May 2022. The primary outcomes were the detection rates and positive predictive values of FITs for ACRN and CRC in people aged 40–49 (younger age group) and ≥50 years (average risk group). Results: Ten studies with 664,159 FITs were included. The FIT positivity rate was 4.9% and 7.3% for the younger age and average risk groups, respectively. Younger individuals with positive FIT results had significantly higher risks of ACRN (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.79–3.73) or CRC (OR 2.86, 95% CI 1.59–5.13) than did individuals in the average-risk group, regardless of FIT results. Individuals aged 45–49 years with positive FIT results had a similar risk of ACRN (OR 0.80, 95% CI 0.49–1.29) to that of people aged 50–59 years with positive FIT results, although significant heterogeneity was observed. The positive predictive values of the FIT were 10–28.1% for ACRN and 2.7–6.8% for CRC in the younger age group. Conclusion: The detection rate of ACRN and CRC based on FITs in individuals aged 40–49 years is acceptable, and the yield of ACRN might be similar between individuals aged 45–49 and 50–59 years. Further prospective cohort and cost-effective analysis are warranted.

Coxsackievirus A10 (CVA10) causes hand, foot, and mouth disease (HFMD) and herpangina, which can result in severe neurological symptoms in children. CVA10 does not use the common enterovirus 71 (EV71) receptor, human SCARB2 (hSCARB2, scavenger receptor class B, member 2), for infection but instead uses another receptor, such as KREMEN1. Our research has shown that CVA10 can infect and replicate in mouse cells expressing human SCARB2 (3T3-SCARB2) but not in the parental NIH3T3 cells, which do not express hSCARB2 for CVA10 entry. Knocking down endogenous hSCARB2 and KREMEN1 with specific siRNAs inhibited CVA10 infection in human cells. Co-immunoprecipitation confirmed that VP1, a main capsid protein where virus receptors for attaching to the host cells, could physically interact with hSCARB2 and KREMEN1 during CVA10 infection. It is the efficient virus replication following virus attachment to its cellular receptor. It resulted in severe limb paralysis and a high mortality rate in 12-day-old transgenic mice challenged with CVA10 but not in wild-type mice of the same age. Massive amounts of CVA10 accumulated in the muscles, spinal cords, and brains of the transgenic mice. Formalin inactivated CVA10 vaccine-induced protective immunity against lethal CVA10 challenge and reduced the severity of disease and tissue viral loads. This is the first report to show that hSCARB2 serves as an associate to aid CVA10 infection. hSCARB2-transgenic mice could be useful in evaluating anti-CVA10 medications and studying the pathogenesis induced by CVA10.

Abstract Very severe obstructive sleep apnea (OSA) with apnea–hypopnea index (AHI) ≥ 60 events/h differs in several areas from OSA with other severities, including having a low-level daytime partial pressure of oxygen and residual on-CPAP (continuous positive airway pressure) AHIs greater than 20/h. Patients with very severe OSA show narrow retroglossal space and confined framework, which is difficult to be enlarged via conventional Uvulopalatopharyngoplasty (UPPP) surgery, resulting in poor response to non-framework surgeries. Our latest report showed efficacy and efficiency for subjects undergoing modified Z-palatoplasty (ZPP) with one-layer closure in a one-stage multilevel surgery. It is unclear whether and how this procedure could help patients with very severe OSA characterized with confined framework. From Mar. 2015 to May 2018, we enrolled 12 patients with very severe OSA receiving one-stage multi-level surgery with modified ZPP with one-layer closure, CO2 laser partial tongue-base glossectomy, and bilateral septomeatoplasty. Our results show that the surgery reduced AHI from 73.8 ± 10.7 to 30.8 ± 23.2 events/h and achieved a mean AHI reduction of 58.3% (p

Abstract Few studies have demonstrated an association of sarcopenia-associated body measurements with chronic diseases through a comprehensive methodology. This study aims to examine the relationship between sarcopenia-associated body measurements and chronic diseases. This is a cohort study. We recruited 316 community dwellers, including 76 patients with sarcopenia and 240 controls, and obtained their body measurements associated with sarcopenia. We collected three-dimensional anthropometric body-surface measurements from 11,158 participants during 2000–2008 and followed up this cohort for 15 years to examine the association of these measurements with the risk of chronic diseases such as hypertension, type 2 diabetes mellitus (T2DM), heart disease, and nephrotic syndrome. Univariate analysis, canonical correlation, and Cox regression analysis were performed to explore the associations. Decreased waist width, upper left arm circumference, and left thigh circumference were significantly associated with sarcopenia. The adverse body measure score (ABMS) was derived by combining significant measurements, namely left upper arm circumference, waist width, and left thigh circumference, and used to predict the risk of hypertension, T2DM, heart diseases, and nephrotic syndrome. A positive association was observed between the ABMS and chronic diseases. Considering the first quartile of the ABMS as a reference, we determined hazard ratios of 2.259, 2.495, 1.332, and 1.595 for hypertension, T2DM, heart disease, and nephrotic syndrome, respectively, in the fourth quartile. Chronic diseases were more strongly associated with the ABMS than with sarcopenia-related body measurements alone. A high ABMS, which includes higher upper arm circumference, higher waist width, and lower thigh circumference, can significantly predict chronic diseases.

Mirror therapy (MT) has been proposed as an essential component of upper limb neurorehabilitation, using mirror illusion of the unaffected hand movement and superimposing it on the affected hand to improve neuroplasticity for improving motor recovery in stroke patients. In this paper, we developed a virtual reality mirror therapy (VRMT) system, and examined the performance of the proposed VRMT system. The VRMT system consists of a motion-tracking device, a VR goggle, and a VRMT software. Young, healthy participants, and stroke patients with mild-to-severe hemiparesis were recruited in this study, to validate the effectiveness of the proposed VRMT system. Experimental results based on the pinch-holding-up activity (PHUA) test revealed a significant effect on the precision pinch performance of young-healthy participants receiving VRMT, whereas traditional MT could not improve the precision pinch performance in young-healthy participants (Wilcoxon signed-rank test, Z = -2.693, p = 0.007). For patients having suffered a stroke and being treated with VRMT, significant beneficial effects examined by mixed effect model were found on the total score of FMA (p = 0.033) and hand part of FMA (p = 0.008). The findings in this study indicate that the VRMT system has a potentially positive effects on the sensorimotor performance of hands in healthy participants. In addition, add-on effect of VR to MT provides beneficial effects on motor function of the upper extremity in chronic stroke patients.

Complex regional pain syndrome (CRPS) is characterized by pain, limited range of motion, swelling, skin changes, vasomotor instability, and patchy bone demineralization. Conservative management strategies for CRPS include physical and occupational therapy, psychosocial and behavioral therapy, and pharmacotherapy. However, some patients still experience CRPS symptoms after receiving conventional treatments. Therefore, botulinum toxin (BoNT) has been applied to patients with CRPS in several trials considering its analgesic effect in musculoskeletal and neuropathic pain; however, the results were controversial. We conducted the study to explore the effectiveness and safety of BoNT in patients with complex regional pain syndrome (CRPS). A search was performed using the following electronic databases up to 19 October 2022: PubMed, Embase, and Cochrane Library. We included both randomized controlled trials and nonrandomized controlled studies involving patients with complex regional pain syndrome managed with botulinum toxin. Cochrane risk-of-bias tool and Joanna Briggs Institute Critical Appraisal Checklist were used for quality assessment for randomized controlled trials and quasi-experimental studies. Only randomized controlled trials entered the meta-analysis. The primary outcome was the visual analogue scale of pain presented as a weighted mean difference (WMD) and 95% confidence interval (CI). The secondary outcome was the risk of adverse events presented as an odds ratio (OR) with 95% CI. We analyzed eight articles with 176 patients, including three randomized controlled trials with 62 participants. The age of the patients ranged from 23.8 to 51 years old. The duration of the disease ranged from 2.2 to 11.8 years. The proportion of females ranged from 16.6% to 100%. The route of administration of BoNT included: (1) lumbar sympathetic block (LSB), (2) intramuscular injection, (3) subcutaneous or intradermal injection (SC/ID). Improvement in pain was revealed in six studies, and adverse events were all self-limited and temporary. Meta-analysis revealed a significant reduction in pain at the first follow-up between 3 weeks to 1 month after intervention (WMD, −1.036, 95% CI, −1.673 to −0.400) but not at the second follow-up between 2 to 3 months after treatment (WMD, −0.895, 95% CI, −2.249 to 0.458). Subgroup analyses between LSB and SC/ID were nonsignificant at both follow-up periods (p = 0.422, 0.139). The risk of adverse events was similar between the BoNT and control group (OR, 0.698, 95% CI, 0.136 to 3.581). In conclusion, BoNT may be effective and safe for alleviating pain in patients with CRPS. However, we could not draw definite conclusions due to small sample size and high between-study heterogeneity. The limited number of participants may conceal the possibility of serious adverse events. Further large-scale randomized controlled trials are warranted to delineate the role of BoNT in CRPS.

Abstract Background This study proposes a prediction model for the automatic assessment of lung cancer risk based on an artificial neural network (ANN) with a data-driven approach to the low-dose computed tomography (LDCT) standardized structure report. Methods This comparative validation study analysed a prospective cohort from Chiayi Chang Gung Memorial Hospital, Taiwan. In total, 836 asymptomatic patients who had undergone LDCT scans between February 2017 and August 2018 were included, comprising 27 lung cancer cases and 809 controls. A derivation cohort of 602 participants (19 lung cancer cases and 583 controls) was collected to construct the ANN prediction model. A comparative validation of the ANN and Lung-RADS was conducted with a prospective cohort of 234 participants (8 lung cancer cases and 226 controls). The areas under the curves (AUCs) of the receiver operating characteristic (ROC) curves were used to compare the prediction models. Results At the cut-off of category 3, the Lung-RADS had a sensitivity of 12.5%, specificity of 96.0%, positive predictive value of 10.0%, and negative predictive value of 96.9%. At its optimal cut-off value, the ANN had a sensitivity of 75.0%, specificity of 85.0%, positive predictive value of 15.0%, and negative predictive value of 99.0%. The area under the ROC curve was 0.764 for the Lung-RADS and 0.873 for the ANN (P = 0.01). The two most important predictors used by the ANN for predicting lung cancer were the documented sizes of partially solid nodules and ground-glass nodules. Conclusions Compared to the Lung-RADS, the ANN provided better sensitivity for the detection of lung cancer in an Asian population. In addition, the ANN provided a more refined discriminative ability than the Lung-RADS for lung cancer risk stratification with population-specific demographic characteristics. When lung nodules are detected and documented in a standardized structured report, ANNs may better provide important insights for lung cancer prediction than conventional rule-based criteria.

Background Whether the prevalence of frailty and its clinical significance are relevant to treatment outcomes in younger (aged < 65 years) cancer patients remains uncertain. This study aimed to evaluate the impact of frailty on treatment outcomes in younger cancer patients with head and neck and esophageal malignancy. Material and methods This multicenter prospective study recruited 502 patients with locally advanced head and neck and esophageal cancer during 2016–2017 in Taiwan, aged 20–64 years who received curative-intent concurrent chemoradiotherapy (CCRT) as first-line antitumor treatment. Baseline frailty assessment using geriatric assessment (GA) was performed for each patient within 7 days before CCRT initiation. Results Frailty was observed in 169 (33.7%) of 502 middle-aged patients. Frail patients had significantly higher incidences of chemotherapy incompletion (16.6% versus 3.3%, P < .001) and radiotherapy incompletion (16.6% versus 3.6%, P < .001) than fit patients. During CCRT, frail patients had a significantly higher percentage of hospitalizations (42.0% versus 24.6%, P < .001) and a trend toward a higher percentage of emergency room visits (37.9% versus 30.0%, P = .08) than fit patients. Frail patients more likely had a significantly higher incidence of grade ≥ 3 adverse events than fit patients during CCRT. The 1-year survival rate was 68.7% and 85.2% (hazard ratio 2.56, 95% confidence interval 1.80–3.63, P < .001) for frail and fit patients, respectively. Conclusions This study demonstrated the significance of pretreatment frailty on treatment tolerance, treatment-related toxicity, and survival outcome in younger patients with head and neck and esophageal cancer undergoing CCRT. While GA is commonly targeted toward the older population, frailty assessment by GA may also be utilized in younger patients for decision-making guidance and prognosis prediction.

Background: The overlapping clinical presentations of limb-girdle muscular dystrophy (LGMD) and idiopathic inflammatory myopathy (IIM) make clinical diagnosis challenging. This study provides a comprehensive evaluation of the distributions and characteristics of muscle fat substitution and edema and aims to differentiate those two diseases.Methods: This retrospective study reviewed magnetic resonance imaging (MRI) of seventeen patients with pathologically proved diagnosis, comprising 11 with LGMD and 6 with IIM. The fat-only and water-only images from a Dixon sequence were used to evaluate muscle fat substitution and edema, respectively. The degrees of muscle fat substitution and edema were graded and compared using the appropriate statistical methods.Results: In LGMD, more than 50% of patients had high-grade fat substitution in the majority of muscle groups in the thigh and calf. However,

Background: Psoriasis is a chronic inflammatory skin disease that has been associated with various inflammatory comorbidities such as cardiovascular disease and uveitis. Asthma involves inflammation of the airway. The two diseases share cytokine-mediated inflammatory mechanisms. Objectives: The main objective of the study was to examine the association of psoriasis with asthma. Methods: We conducted a systematic review and meta-analysis of observational studies that examined the association of psoriasis with asthma. We searched MEDLINE, Embase, and CENTRAL from inception to May 2, 2019 for relevant case–control, cross-sectional, or cohort studies. The risk of bias of included studies was assessed by using the Newcastle–Ottawa Scale. The random-effects model meta-analysis was used to calculate the odds ratio (OR) for case–control/cross-sectional studies and hazard ratio (HR) for cohort studies. Results: We included six case–control/cross-sectional (one case–control and five cross-sectional studies) and one cohort studies. Three studies were rated with a high risk of bias in case definition, representativeness of the cases, selection of controls, definition of controls, and ascertainment of exposure. Psoriasis was associated with significantly increased odds (OR 1.29; 95% confidence interval [CI] 1.20-'1.37) and risk (HR 1.38; 95% CI 1.23-'1.54) for asthma. A subgroup analysis revealed increased odds for asthma in both pediatric and adult patients with psoriasis (pooled OR being 1.24 [95% CI 1.10-'1.41] and OR 1.38 [95% CI 1.27-'1.50], respectively). Conclusion: The current evidence indicates a significant association of psoriasis with asthma. When psoriasis patients present with respiratory symptoms for shortness of breath, wheezing, and chest tightness, referral to pulmonologist may be considered.

Background: The number of elderly diabetic patients has been increasing recently, and these patients have a higher morbidity of dementia than those without diabetes. Diabetes is associated with an increased risk for the development of dementia in elderly individuals, which is a serious health problem. Objectives: The primary aim was to examine whether diabetes is a risk factor for dementia among elderly individuals. The secondary aim was to apply grey theory to integrate the results and how they relate to cognitive impairments in elderly diabetic patients and to predict which participants are at high risk of developing dementia. Methods: Two hundred and twenty patients aged 50 years or older who were diagnosed with diabetes mellitus were recruited. Information on demographics, disease characteristics, activities of daily living, Mini Mental State Examination, sleep quality, depressive symptoms, and health-related quality of life was collected via questionnaires. The grey relational analysis approach was applied to evaluate the relationship between the results and health outcomes. Results: A total of 13.6% of participants had cognitive disturbances, of whom 1.4% had severe cognitive dysfunction. However, with regard to sleep disorders, 56.4% had sleep disturbances of varying degrees from light to severe. Further investigation is needed to address this problem. A higher prevalence of sleep disturbances among diabetic patients translates to a higher degree of depressive symptoms and a worse physical and mental health-related quality of life. Furthermore, based on the grey relational analysis, the grey relation coefficient varies from 0.6217~0.7540. Among the subjects, Participant 101 had the highest value, suggesting a need for immediate medical care. In this study, we observed that 20% of the total participants, for whom the grey relation coefficient was 0.6730, needed further and immediate medical care.

Obstetric brachial plexus injury, also known as neonatal brachial plexus injury, is not unusual in newborns. Given the lack of a comprehensive synthesis of the available data on the effectiveness of botulinum neurotoxin (BoNT) in treating children with obstetric brachial plexus injury, we conducted a systematic review and meta-analysis. We searched PubMed, Embase, Web of Science, and Cochrane databases from inception to 25 November 2022. Outcomes were function of the shoulder and elbow joints, muscle power of the deltoid, biceps brachii and triceps brachii, and the recurrence rate of subluxation or dislocation after reduction of the shoulder joint after BoNT application. Meta-regression was conducted to assess the moderator effect of age. We included 11 case series and 2 cohort studies. Passive range of motion of shoulder external rotation (standardized mean difference [SMD], 0.678; 95% confidence interval [95%CI], 0.423 to 0.934), Active Movement Scale for shoulder external rotation (SMD, 0.47; 95%CI, 0.131 to 0.808), and active range of motion of elbow extension (SMD, 2.445; 95%CI, 1.556 to 3.334) increased significantly after BoNT. However, the modified Gilbert scale for shoulder abduction (SMD, 1.239; 95% CI, −0.2 to 2.678), the Toronto score for active elbow flexion (SMD, 1.099; 95% CI, −0.053 to 2.252), muscle power of deltoid (SMD, 0.675; 95% CI, −0.599 to 1.949), biceps brachii (SMD, 0.225; 95% CI, −0.633 to 1.083), and triceps brachii (SMD, 1.354; 95% CI, −1.493 to 4.202) did not reach statistical significance. The moderator effect of age was not significant (p = 0.88). Meta-analysis was not done for recurrence rate of subluxation or dislocation due to insufficient data. In conclusion, our data support BoNT use in patients with obstetric brachial plexus injury. However, definite conclusions cannot be drawn due to small sample size and the lack of randomized controlled trials. More research is warranted to clarify the effectiveness of BoNT in patients with obstetric brachial plexus injury by using standardized injection protocols and outcome measurements.

This prospective study investigated how exercise impacted chronological changes in anthropometrics, body composition, prostate-specific antigen (PSA) level and prognostic nutrition index (PNI) in high-risk prostate cancer (PCa) patients on androgen deprivation therapy (ADT). The patients were divided into either the usual care or exercise group. All patients received measurements a week before ADT initiation, six- and twelve months after treatment. The exercise group received both aerobic and resistance training. The analysis was conducted using appropriate statistical methods. There were 45 males enrolled (age 67.4 ± 8 years and BMI 25.5 ± 3.6 kg/m2). Profound changes were observed at six months follow-up. The exercise group showed a significant increase in the trunk and leg lean mass, and a lesser loss of total and arm lean mass. A significant decrease in PSA was also observed among the exercise group. PNI and PSA were significantly associated with regional lean mass. Exercise can prevent loss or even increase lean mass in high-risk PCa, especially in the early stage of ADT treatment. Moreover, a strong bond between lean mass and PNI and PSA further underscores the importance of early and continuous exercise interventions.

Scoliosis refers to a three-dimensional deviation in the axis of the spine. Muscle imbalance is believed to play a role in scoliosis. Botulinum neurotoxin (BoNT) can reduce muscle overactivity and may have the potential to ameliorate spinal scoliosis. This study investigated the effectiveness of intramuscular BoNT injection in vertebral curve correction and reviewed the possible influencing factors. PubMed, Medline, Cochrane Central Register of Controlled Trials, Web of Science, Airiti Library, and Index of the Taiwan Periodical Literature System databases were searched from inception until 7 September 2022 for eligible studies. The main outcome was the change in Cobb angle after BoNT application. Subgroup analysis was conducted according to differences in study designs, etiology of scoliosis, and methods used for target muscle selection. We enrolled three studies including 31 participants aged between 2 and 18 years. The meta-analysis revealed no significant reduction in the Cobb angle after BoNT injection (standardized mean difference, −0.783, 95% CI, −2.142 to 0.576). Study designs (p = 0.011) and methods used for target muscle selection (p = 0.017) but not etiology of scoliosis (p = 0.997) reached statistical significance between subgroups. In conclusion, the current meta-analysis does not support the application of BoNT in children and adolescents with scoliosis. However, a decisive conclusion could not be made due to high between-study heterogeneity and small sample size. More randomized controlled trials with appropriate target muscle selection and standard outcome measurement should be conducted to examine the efficacy of botulinum neurotoxin in treating scoliosis. INPLASY ID: INPLASY202290031.

For rapid and unlimited cell growth and proliferation, cancer cells require large quantities of nutrients. Many metabolic pathways and nutrient uptake systems are frequently reprogrammed and upregulated to meet the demand from cancer cells, including the demand for lipids. The lipids for most adult normal cells are mainly acquired from the circulatory system. Whether different cancer cells adopt identical mechanisms to ensure sufficient lipid supply, and whether the lipid demand and supply meet each other, remains unclear, and was investigated in lung cancer cells. Results showed that, despite frequent upregulation in de novo lipogenesis and the lipid transporter system, different lung cancer cells adopt different proteins to acquire sufficient lipids, and the lipid supply frequently exceeds the demand, as significant amounts of lipids stored in the lipid droplets could be found within lung cancer cells. Lipid droplet surface protein, PLIN3, was found frequently overexpressed since the early stage in lung cancer tissues. Although the expression is not significantly associated with a specific gender, age, histology type, disease stage, and smoking habit, the frequently elevated expression of PLIN3 protein indicates the importance of lipid droplets for lung cancer. These lipid droplets are not only for nutrient storage, but are also crucial for tumor growth and proliferation, as well as survival in starvation. These results suggest that manipulation of lipid droplet formation or TG storage in lung cancer cells could potentially decrease the progression of lung cancer. Further exploration of lipid biology in lung cancer could help design novel treatment strategies.

The effects of lacosamide (LCS, Vimpat®), an anti-convulsant and analgesic, on voltage-gated Na+ current (INa) were investigated. LCS suppressed both the peak (transient, INa(T)) and sustained (late, INa(L)) components of INa with the IC50 values of 78 and 34 μM found in GH3 cells and of 112 and 26 μM in Neuro-2a cells, respectively. In GH3 cells, the voltage-dependent hysteresis of persistent INa (INa(P)) during the triangular ramp pulse was strikingly attenuated, and the decaying time constant (τ) of INa(T) or INa(L) during a train of depolarizing pulses was further shortened by LCS. The recovery time course from the INa block elicited by the preceding conditioning train can be fitted by two exponential processes, while the single exponential increase in current recovery without a conditioning train was adequately fitted. The fast and slow τ’s of recovery from the INa block by the same conditioning protocol arose in the presence of LCS. In Neuro-2a cells, the strength of the instantaneous window INa (INa(W)) during the rapid ramp pulse was reduced by LCS. This reduction could be reversed by tefluthrin. Moreover, LCS accelerated the inactivation time course of INa activated by pulse train stimulation, and veratridine reversed its decrease in the decaying τ value in current inactivation. The docking results predicted the capability of LCS binding to some amino-acid residues in sodium channels owing to the occurrence of hydrophobic contact. Overall, our findings unveiled that LCS can interact with the sodium channels to alter the magnitude, gating, voltage-dependent hysteresis behavior, and use dependence of INa in excitable cells.

We investigated risk factors for treatment interruption (TI) in patients with locally advanced head and neck squamous-cell carcinoma (LAHNSCC) following concurrent chemoradiotherapy (CCRT), under the provision of recommended calorie and protein intake; we also evaluated the associations between clinicopathological variables, calorie and protein supply, nutrition–inflammation biomarkers (NIBs), total body composition change (TBC), and a four-serum-amino-acid metabolite panel (histidine, leucine, ornithine, and phenylalanine) among these patients. Patients with LAHNSCC who completed the entire planned CCRT course and received at least 25 kcal/kg/day and 1 g of protein/kg/day during CCRT were prospectively recruited. Clinicopathological variables, anthropometric data, blood NIBs, CCRT-related factors, TBC data, and metabolite panels before and after treatment were collected; 44 patients with LAHNSCC were enrolled. Nine patients (20.4%) experienced TIs. Patients with TIs experienced greater reductions in hemoglobin, serum levels of albumin, uric acid, histidine, and appendicular skeletal mass, and suffered from more grade 3/4 toxicities than those with no TI. Neither increased daily calorie supply (≥30 kcal/kg/day) nor feeding tube placement was correlated with TI. Multivariate analysis showed that treatment-interval changes in serum albumin and histidine levels, but not treatment toxicity, were independently associated with TI. Thus, changes in serum levels of albumin and histidine over the treatment course could cause TI in patients with LAHNSCC following CCRT.

Background Concurrent chemoradiotherapy (CCRT) is an optimal recommended treatment for stage III non‐small cell lung cancer (NSCLC). Herein, we aimed to investigate the efficacy and safety of oral vinorelbine plus cisplatin with concomitant radiotherapy for stage III NSCLC. Methods This prospective, open‐label, single‐arm, observational cohort study was performed between January 2010 and September 2016. Patients were treated with two cycles of chemotherapy with 60 mg/m2 intravenous cisplatin on day 1 and 50 mg/m2 oral vinorelbine on days 1, 8, and 15; radiotherapy was administered concurrently from day 1 when chemotherapy was initiated. A total dose of 66–70 Gy radiotherapy was delivered in daily fractions of 2 Gy for 6.5–7 consecutive weeks. The tumor response was assessed after completing concomitant treatment. Results A total of 58 patients were enrolled and analyzed; 31 patients had stage IIIA NSCLC and 27 had stage IIIB NSCLC. After induction CCRT, 31 patients achieved an objective response (complete response in one and partial response in 30; the response rate was 53.4%). The median progression‐free survival was 6.73 months (95% confidence interval [CI], 5.42–7.91), duration of response was 12.30 months (95% CI, 5.59–19.01), and overall survival was 24.83 months (95% CI, 19.26–30.21). No treatment‐related mortality was observed, and neutropenia was the most common grade 3 and 4 treatment‐related toxicity (11 patients; 18.9%). Conclusions CCRT with the weekly regimen of oral vinorelbine plus triweekly cisplatin was effective and safe for stage III NSCLC.

The study aimed to present a case of ocular syphilis mimicking Vogt–Koyanagi–Harada (VKH) disease. This is an observational case report. A 59-year-old female with Sicca syndrome and rheumatoid arthritis presented to the ophthalmologic department with blurred vision of the right eye for 5 days accompanied by color sensation loss in both eyes. Bilateral disc hyperemia and serous retinal detachment at the posterior pole were noted in her both eyes by fundus examination. Fluorescein angiography revealed bilateral late dye leakage from the disc and posterior choroid. Optical coherence tomography showed bilateral subretinal fluid and choroidal thickening. The impression of her condition was VKH disease initially. However, she was later diagnosed with bilateral ocular syphilis with optic neuritis which was proved by laboratory data. After appropriate antimicrobial agent treatment, her best-corrected visual acuity, serous retinal detachment, and disc hyperemia improved. There was no recurrent intraocular inflammation even without systemic steroid or immunosuppressive therapy control during the following 1 year. Ocular syphilis can mimic many other ocular inflammatory diseases including VKH disease. It is necessary to differentiate infectious causes from inflammatory origins due to the substantially different treatment and prognosis.

Respiratory arousal is the change from a state of sleep to a state of wakefulness following an apnea or hypopnea. In patients with obstructive sleep apnea (OSA), it could have a helpful role to activate upper airway muscles and the resumption of airflow and an opposing role to contribute to greater ventilatory instability, continue cycling, and likely exacerbate OSA. Patients with very severe OSA (apnea-hypopnea index (AHI) ≥ 60 events/h) may have specific chemical (e.g., possible awake hypercapnic hypoxemia) and mechanical (e.g., restricted dilator muscles) stimuli to initiate a respiratory arousal. Little was reported about how respiratory arousal presents in this distinct subgroup, how it relates to AHI, Epworth Sleepiness Scale (ESS), body mass index (BMI), and oxygen saturation, and how a non-framework surgery may change it. Here, in 27 patients with very severe OSA, we show respiratory arousal index was correlated with each of AHI, mean oxyhemoglobin saturation of pulse oximetry (SpO2), mean desaturation, and desaturation index, but not in BMI or ESS. The mean (53.5 events/h) was higher than other reports with less severe OSAs in the literature. The respiratory arousal index can be reduced by about half (45.3%) after a non-framework multilevel surgery in these patients.

Background: The study was designed to compare the efficacy and tolerability of a fixed combination of extra-fine beclomethasone and formoterol, with the fixed combination fluticasone and salmeterol in Taiwanese asthmatic patients. Methods: This was a phase III, multicentre, randomized, two-arm parallel groups, controlled study. Patients with moderate to severe asthma were randomized to a 12-week treatment with either beclomethasone 100 mcg plus formoterol 6 mcg (BDP/F) or fluticasone 125 mcg plus salmeterol 25 mcg (FP/S), both delivered 2 inhalations twice daily. The efficacy and tolerability of these two combinations were compared. Results: Among the 253 randomized subjects, 244 patients were evaluable (119 in the BDP/F group and 125 in the FP/S group). A significant improvement from baseline to the end of treatment period was observed in both BDP/F and FP/S groups in forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), morning and evening peak expiratory flow (PEF), Asthma Control Test (ACT) score and the use of rescue medication. FVC increase from pre-dose was significant after 5 min post inhalation in the BDP/F group only, while statistically significant within group improvement was not achieved until 30 min post inhalation in the FP/S group. Conclusion: The BDP/F combination is comparable in efficacy and tolerability to FP/S combination in Taiwanese asthmatic patients, with the advantage of rapid onset of improvement of FVC, consistent with the faster improvement of pulmonary hyperinflation with BDP/F. Keywords: Asthma, Combination therapy, Inhaled corticosteroid, Long acting beta2-agonist, Pulmonary hyperinflation

Purpose: To present the clinical and imaging findings and results of treatment in patients with intra-articular long head of the biceps tendon (LHBT) adhesion to the undersurface of the rotator cuff found incidentally during shoulder arthroscopy. Methods: Patients with intra-articular LHBT adhesion to the undersurface of the rotator cuff found incidentally during arthroscopy were included with a minimal 2-year follow-up. Demographic data, images, and physical examinations were recorded. LHBT release, tenotomy, or tenodesis were performed according to the patient’s age and surgeon’s preference. Results: Twelve patients were included in the study. All of them presented with chronic anterior shoulder pain and positive Speed and O’Brien tests. The average age was 46.8 ± 17 years (range 20-79 years) and the pain sustained from 6 to 96 (average 25.5 ± 28.6) months. Before the operation, 6 patients had a positive Jobe’s test, 1 had a positive lift-off test, and all had positive O’Brien and Speed tests and tenderness over the LHBT. Three release, 4 tenotomy, and 5 LHBT tenodesis were done in addition to other procedures if needed. All range of motion except external rotation, pain visual analog score, and functional outcome scores showed significant improvement at 6 months after surgery. There were no significant differences in range of motion and functional scores between 6 months and 12 months postoperatively. No difference was found in LHBT scores at 6 and 12 months after the operation. Magnetic resonance imaging revealed thickened coracohumeral ligament overlying the LHBT. Conclusions: Patients who had intra-articular LHBT adhesion to the undersurface of the rotator cuff and underwent release of the adhesion around LHBT, tenotomy, or tenodesis all had good clinical outcomes. The lesion was observed in 2.2% of all shoulder arthroscopies. Although difficult to diagnose before surgery, surgeons should be aware of this unusual condition in patients with chronic and insidious anterior shoulder pain. Level of Evidence: Level IV, Therapeutic case series.

Only few prospective cohort trials have evaluated the risk factors for the 2-year mortality rate between two patient subgroups with locally advanced head and neck squamous cell carcinoma (LAHNSCC): oral cavity cancer with adjuvant concurrent chemoradiotherapy (CCRT) (OCC) and non-oral cavity cancer with primary CCRT (NOCC), under the recommended calorie intake and investigated the interplay among calorie supply, nutrition–inflammation biomarkers (NIBs), and total body composition change (TBC), as assessed using dual-energy X-ray absorptiometry (DXA). Patients with LAHNSCC who consumed at least 25 kcal/kg/day during CCRT were prospectively recruited. Clinicopathological variables, blood NIBs, CCRT-related factors, and TBC data before and after treatment were collected. Factor analysis was performed to reduce the number of anthropometric and DXA-derived measurements. Cox proportional hazards models were used for analysis. We enrolled 123 patients with LAHNSCC (69 with OCC and 54 with NOCC). The mean daily calorie intake correlated with the treatment interval changes in total body muscle and fat. Patients consuming ≥30 kcal/kg/day had lower pretreatment levels but exhibited fewer treatment interval changes in anthropometric and DXA measurements than patients consuming

An increased risk of cardiovascular events was identified in patients with peripheral artery disease (PAD). Clopidogrel is one of the most widely used antiplatelet medications. However, there are heterogeneous outcomes when clopidogrel is used to prevent cardiovascular events in PAD patients. Here, we use an artificial intelligence (AI)-assisted methodology to identify genetic factors potentially involved in the clopidogrel-resistant mechanism, which is currently unclear. Several discoveries can be pinpointed. Firstly, a high proportion (>50%) of clopidogrel resistance was found among diabetic PAD patients in Taiwan. Interestingly, our result suggests that platelet function test-guided antiplatelet therapy appears to reduce the post-interventional occurrence of major adverse cerebrovascular and cardiac events in diabetic PAD patients. Secondly, AI-assisted genome-wide association study of a single-nucleotide polymorphism (SNP) database identified a SNP signature composed of 20 SNPs, which are mapped into 9 protein-coding genes (SLC37A2, IQSEC1, WASHC3, PSD3, BTBD7, GLIS3, PRDM11, LRBA1, and CNR1). Finally, analysis of the protein connectivity map revealed that LRBA, GLIS3, BTBD7, IQSEC1, and PSD3 appear to form a protein interaction network. Intriguingly, the genetic factors seem to pinpoint a pathway related to endocytosis and recycling of P2Y12 receptor, which is the drug target of clopidogrel. Our findings reveal that a combination of AI-assisted discovery of SNP signatures and clinical parameters has the potential to develop an ethnic-specific precision medicine for antiplatelet therapy in diabetic PAD patients.

(1) Background: Continuing to observe the grafted bone mineral density (BMD) is essential to ensure the success of alveolar bone grafting (ABG) in patients with cleft lip and palate. This study elaborates on three methods that can be used to evaluate the progressive BMD. (2) Methods: Forty patients with unilateral or bilateral clefts receiving ABG were enrolled. Cone beam computed tomography (CBCT) scans were taken at 6 months (T1) and 2 years (T2) postoperatively. In CBCT, measurements were obtained on three different planes using the circle located 1 mm from the adjacent teeth (Method A), the largest circle within the defect (Method B), or the central circle with a diameter of 2 mm (Method C). The BMD was the average density of the three planes and was adjusted by pogonion density. Bland–Altman plots were used to evaluate the agreement of each method. Inter-rater reliability was confirmed by the intraclass correlation coefficient (ICC). (3) Results: For Method A, B, and C, the mean-adjusted BMD (BMD/pogonion density, BMDa) was 17.44%, 17.88%, and 17.69%, respectively, at T1 (p = 0.495), and 22.51%, 22.87%, and 22.74%, respectively, at T2 (p = 0.690); the density enhancement rates were 40.54%, 38.92%, and 43.15% (p = 0.382). Significant differences between the BMDa at T1 and T2 were observed (p < 0.001, a via CBCT can be applied in post-ABG evaluations.

Our study aimed to investigate the effectiveness and safety of botulinum toxin type A in patients with restless legs syndrome. We searched electronic databases, including PubMed, Cochrane Library, and Web of Science, up to 12 June 2021, for published articles. We enrolled randomized controlled clinical trials and non-randomized controlled studies involving patients with restless legs syndrome who were treated with botulinum toxin. Quality assessment was performed using the Cochrane risk of bias tool and Joanna Briggs Institute Critical Appraisal Checklist for Quasi-Experimental Studies. As for the results, we included four articles comprising 62 participants, two studies were randomized controlled trials. Improvement in International Restless Legs Syndrome Study Group (IRLSSG) rating scale was observed in three studies. Adverse events were temporary and self-limited. Meta-analyses were performed, including the two randomized controlled trials with 27 participants. Compared with placebo, botulinum toxin injection significantly reduced scores of IRLSSG rating scale (SMD, −0.819, 95% confidence interval [CI], −1.377 to −0.262). A total of 11.8% (95% CI, 0.7–72.4%) of patients reported at least one adverse event. In conclusion, botulinum toxin injection may relieve restless legs syndrome related symptoms. However, decisive conclusions cannot be drawn because of the small number of patients included in our meta-analysis. Large-scale, randomized controlled trials are warranted to discover the optimal dose, safety, and long-term effect of intervention with botulinum toxin type A for patients with restless legs syndrome.

Background: We aimed to review and analyse the effectiveness and safety of botulinum toxin type A (BoNT-A) injections for drooling in children with cerebral palsy. Data sources: We searched the EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) databases from inception to January 2020. Methods: We included randomized controlled trials and observational studies which (1) involved children with cerebral palsy, (2) used BoNT-A for control of drooling, and (3) provided quantitative evaluations of drooling before and after intervention with BoNT-A. Results: Twenty-one trials met the inclusion criteria. Most studies showed that BoNT-A injections are safe and efficacious as a treatment for drooling in children with cerebral palsy. Four trials had sufficient data to pool the results for the meta-analysis. Both the drooling quotient (p = 0.002) and drooling Ffrequency and severity scale (p = 0.004) supported this conclusion. Conclusion: BoNT-A injections are a safe, reversible, effective treatment for drooling control in children with cerebral palsy that can offer effectiveness for more than 3 months with few side effects. The dosage of BoNT-A should not exceed 4 units/kg. Further studies are required to determine the optimal dosage and target glands.

Background and Objectives: This article aimed to investigate the risk factors for poststroke complex regional pain syndrome (CRPS). Materials and Methods: We searched electronic databases including PubMed, Medline, Web of Science, Cochrane Library, and Embase up to 27 October 2021. We enrolled analytical epidemiological studies comprising cohort, case-control, and cross-sectional studies. A quality assessment was performed using the Newcastle–Ottawa Quality Assessment Scale for cohort and case-control studies and the Joanna Briggs Institute critical appraisal checklist for analytical cross-sectional studies. Binary outcomes were reported as odds ratios (ORs), and continuous outcomes were described as standardized mean differences (SMDs) with 95% confidence intervals. For the meta-regression, beta coefficient and p value were adopted. Results: We included 21 articles comprising 2225 participants. Individuals with shoulder subluxation and spasticity were found to have higher risks for poststroke CRPS. Spasticity with higher modified Ashworth scale score, lower Brunnstrom hand stage, and inferior Barthel index scores were observed in patients with poststroke CRPS. The pooled incidence proportion in nine articles was 31.7%, and a correlation was found between effect sizes and the ratio of women and the proportion of left hemiparesis. The summarized prevalence in nine cross-sectional studies was 33.1%, and a correlation was observed between prevalence and the subluxation ratio and Brunnstrom stage. Conclusions: Based on our meta-analysis, being female, left hemiparesis, shoulder subluxation, spasticity, a lower Brunnstrom stage of distal upper limb, and an inferior Barthel index are all features for poststroke CRPS. Larger studies with greater statistical power may confirm our findings and clarify some other unknown risk factors for poststroke CRPS.

This article aimed to investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in fibromyalgia. The PubMed, Medline, Cochrane Library, and Web of Science databases were searched for articles published through 14 August 2021. We enrolled only randomized controlled trials. The Cochrane Collaboration risk of bias tool was used for quality assessment. Outcomes were analyzed as standardized mean differences (SMDs) with 95% CIs. The beta coefficient and p value were adopted for meta-regression. We included 18 studies comprising 643 participants. A significant reduction in disease influence, as measured by the Fibromyalgia Impact Questionnaire, was observed (SMD, −0.700, 95% CI, −1.173 to −0.228), and the reduction was larger in older patients (β = −0.1327, p = 0.008). The effect persisted at least two weeks after the final treatment session (SMD, −0.784, 95% CI, −1.136 to −0.432). Reductions in pain, depression, and anxiety were discovered, which persisted for at least two weeks after the last intervention. The effects on pain and depression remained significant up to one and a half months after the final session. No serious adverse events were reported by the included articles. In conclusion, our systematic review and meta-analysis revealed that rTMS is safe and effective for managing multiple domains of fibromyalgia-related symptoms and older patients may have a stronger treatment effect. Larger randomized controlled trials with sufficient male populations are warranted to confirm our findings, detect rare adverse events, and determine the optimal stimulation parameters.