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.

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.

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.

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.

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.

Performance of the Fecal Immunochemical Test in Detecting Advanced Colorectal Neoplasms and Colorectal Cancers in People Aged 40-49 Years: A Systematic Review and Meta-Analysis.

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.

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.

Human SCARB2 Acts as a Cellular Associator for Helping Coxsackieviruses A10 Infection.

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.

Serum vascular endothelial growth factor affects tissue fluid accumulation and is associated with deteriorating tissue perfusion and oxygenation in severe sepsis: a prospective observational study.

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 ([HbO2]), deoxy-Hb ([HbR]), total Hb ([HbT]), and H2O ([H2O]) 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 < 0.001) and had more positive daily net intake and output (mean [SD], 1,235.06 [1303.14] mL/day vs. 313.17 [744.75] mL/day, p = 0.012), lower [HbO2] and [HbT] over the three-day measurement (analyzed by GEE p = 0.01 and 0.043, respectively) and significantly higher [H2O] on the third day than on the first two days (analyzed by GEE p = 0.034 and 0.018, respectively). Overall, serum VEGF levels were significantly negatively correlated with [HbO2] and [HbT] (rho = - 0.246 and - 0.266, p = 0.042 and 0.027, respectively) but positively correlated with [H2O] (rho = 0.449, p < 0.001). Subgroup analysis revealed a significant correlation between serum VEGF and [H2O] in oliguric patients (rho = 0.532, p = 0.003). Multiple regression analysis determined the independent effect of serum VEGF on [H2O] (standardized coefficient = 0.281, p = 0.038). CONCLUSIONS: In severe sepsis, oliguria relates to higher positive fluid balance, lower tissue perfusion and oxygenation, and progressive tissue fluid accumulation. Elevated serum VEGF is associated with worsening tissue perfusion and oxygenation and independently affects tissue fluid accumulation.

Recurrent spinal meningeal melanocytoma at lumbar spine level: a case report.

INTRODUCTION: Spinal meningeal melanocytoma is an extremely rare tumour with an estimated annual incidence of 1 per 10 million people. It usually arises from the intradural extramedullary compartment at the cervical levels. Although these tumours are histologically benign, they may behave aggressively. Local recurrence could occur even after total tumour excision. CASE REPORT: We report a case of a 33-year-old Asian male who developed progressive weakness and numbness of the bilateral lower extremities as well as urinary retention five years after complete tumour resection of lumbar spinal meningeal melanocytoma. Magnetic resonance imaging of the lumbar spine revealed a mass with thecal sac compression which was hypointense on T2-weighted images and hyperintense on T1-weighted images. The patient underwent total tumour removal. Histologic examination was compatible with recurrent meningeal melanocytoma. After a 4-week inpatient rehabilitation programme, he was able to ambulate without assistance and to do clean intermittent catheterisation for micturition on a regular basis. DISCUSSION: This is the first reported case of intradural extramedullary meningeal melanocytoma located at the lumbar region. Clinicians should consider the possibility of these rare tumours at any level of the spine, and be aware of sphincter dysfunction in addition to motor and sensory deficits of extremities.

The Impact of Exercise on Improving Body Composition and PSA in High-Risk Prostate Cancer Patients on Androgen-Deprivation Therapy.

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.

Changes of Health Outcomes, Healthy Behaviors, Generalized Trust, and Accessibility to Health Promotion Resources in Taiwan Before and During COVID-19 Pandemic: Comparing 2011 and 2021 Taiwan Social Change Survey (TSCS) Cohorts.

Purpose: The present study compared two nationally representative cohort datasets concerning Taiwan residents' healthy behaviors, subjective health outcomes, generalized trust, and accessibility to health promotion resources. Patients and Methods: The Taiwan Social Change Survey (TSCS) was conducted in two waves ten years apart: 2011 cohort (n = 1021; 48.4% males) and 2021 cohort (n = 1425; 47.4%) cohorts. Descriptive statistics were calculated to compare the two TSCS datasets. Then, multiple regression models were constructed with health outcome as the dependent variable, and demographics and other key components as independent variables. Results: The 2011 TSCS cohort showed higher prevalence for cigarette smoking (30.8% vs 25.2%; p=0.002), alcohol drinking (52.5% vs 24.3%; p<0.001), exercise habits (52.7% vs 48.0%; p=0.02), and better fruit and vegetable accessibility (Mean=3.91 vs 3.82; p=0.04). The 2021 TSCS cohort reported higher body mass index (Mean=24.20 vs 23.63; p<0.001), less residency in urban areas (22.4% vs 31.1%; p<0.001), better jogging accessibility (4.14 vs 4.05; p=0.006), higher generalized trust (2.26 vs 2.17; p=0.001), and greater internet usage (3.43 vs 2.89; p<0.001). The regression model showed that exercise habits (standardized coefficient=0.20 and 0.10; p<0.001) and generalized trust (standardized coefficient=0.11 and 0.11; p=0.004 and <0.001) were consistently associated with health outcomes in both cohorts. Additionally, internet use (standardized coefficient=-0.07; p=0.026) and alcohol drinking behaviors (standardized coefficient=-0.07; p=0.0022) were negatively associated with health outcomes in the 2021 cohort. Conclusion: The present study demonstrated the trends and changes over 10 years regarding multiple health-related components among Taiwan residents. The study's findings provide insight into education promotion programs to reduce unhealthy behaviors as well as enhancing generalized trust building and developing healthy behaviors for Taiwan residents.

Association of smoking status with non-small cell lung cancer patients harboring uncommon epidermal growth factor receptor mutation.

Introduction: Uncommon 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. Methods: This 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. Results: Between 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). Conclusions: Our 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.

Potential Utility of the Mallampati Score for Prediction of Treatment Compliance and Safety Profiles of Patients With Head and Neck Cancer Undergoing Definitive Concurrent Chemoradiotherapy.

BACKGROUND/AIM: Restriction of mouth opening (RMO) is a common manifestation of head and neck cancer (HNC) and a poor prognostic factor following concurrent chemoradiotherapy (CCRT) of patients. This study aimed to explore whether the Mallampati score, a visual assessment of the distance from the tongue base to the roof of the mouth, can be used as a surrogate for RMO in predicting treatment outcomes in patients with HNC undergoing CCRT. PATIENTS AND METHODS: A total of 461 consecutive patients who received definitive CCRT for the treatment of locally advanced HNC between August 2016 and December 2017 at Chang Gung Memorial Hospital in Taiwan (Linkou, Keelung, and Kaohsiung branches) were enrolled in this prospective study. Patients were allocated by the pre-treatment Mallampati score of 1 or 2 (n=24) vs. 3 or 4 (n=207) to compare treatment compliance and treatment-related complications. RESULTS: Patients in the Mallampati score of 3 or 4 group had a higher prevalence of betel quid chewing, oral cavity and oropharynx cancers, advanced tumor stage, poorer performance status, and were more likely to receive platinum monotherapy during CCRT. Patients in the Mallampati score of 3 or 4 group had a 2.08-fold (p=0.002) hazard ratio (HR) for overall survival compared to those in the score of 1 or 2 group in the univariate analysis, the difference remained significant in multivariate analysis (adjusted HR=1.61; 95% CI=1.02-2.61; p=0.047). Patients in the Mallampati score 3 or 4 group had a 2.36-fold (95% CI=1.07-5.19; p=0.033) increased likelihood of incomplete chemotherapy, 2.44-fold (95% CI=1.17-5.06; p=0.017) increased likelihood of incomplete radiotherapy, and 1.84-fold (95% CI=1.18-2.87; p=0.007) risk of unexpected hospitalization compared to those with a Mallampati score of 1 or 2 in multivariate analysis. CONCLUSION: Patients with HNC with higher pre-treatment Mallampati scores had poorer survival outcomes and were at a higher risk of treatment incompletion and treatment-related toxicities when undergoing CCRT. Our results support the utility of Mallampati score as a surrogate for measuring RMO to predict survival outcomes, treatment compliance, and safety profiles in patients with HNC undergoing CCRT.

Lipid Droplets in Lung Cancers Are Crucial for the Cell Growth and Starvation Survival.

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.

Increased tissue water in patients with severe sepsis affects tissue oxygenation measured by near-infrared spectroscopy: a prospective, observational case-control study.

Background: Tissue oedema affects tissue perfusion and interferes with the monitoring of tissue oxygenation in patients with severe sepsis. However, the underlying mechanisms remain unclear. We used a wireless near-infrared spectroscopy (NIRS) device that transmits tri-wavelength light to quantify tissue haemoglobin (Hb) and water (H2O) content. We estimated tissue H2O in severe sepsis patients and healthy controls, compared their difference, and investigated the correlation of tissue H2O with systemic haemodynamics and its impact on tissue oxygenation. Methods: Seventy-seven adult patients with new-onset severe sepsis admitted to the intensive care unit within 72 h and 30 healthy volunteers (controls) were enrolled. The NIRS device was placed on the participant's leg to estimate the relative tissue concentrations of oxy-Hb ([HbO2]), deoxy-Hb ([HbR]), total Hb ([HbT]), and H2O ([H2O]) at rest for three consecutive days. Two-sample t-test or Mann-Whitney U test, chi-square test, and generalised estimating equations (GEEs) were used for comparisons. Results: In severe sepsis patients, the [H2O] in the anterior tibia was higher [mean (standard deviation, 95% confidence interval), 10.57 (3.37, 9.81-11.34) vs. 7.40 (1.89, 6.70-8.11)] and the [HbO2], [HbT], and tissue Hb oxygen saturation (StO2) were lower [0.20 (0.01, 0.20-0.20) vs. 0.22 (0.01, 0.22-0.23), 0.42 (0.02, 0.42-0.43) vs. 0.44 (0.02, 0.44-0.45), and 47.25% (1.97%, 46.80-47.70%) vs. 49.88% (1.26%, 49.41-50.35%), respectively] than in healthy controls in first-day measurements. GEE analysis revealed significant differences in [H2O], [HbO2], [HbT], and StO2 between groups over three consecutive days (all P≤0.001). In addition, [HbO2] and StO2 levels gradually decreased over time in the patient group. A negative correlation was observed between [H2O] and [HbO2] and StO2, which became more obvious over time (day 1: r=-0.51 and r=-0.42, respectively; both P<0.01; day 3: r=-0.67 and r=-0.63, respectively, both P<0.01). Systolic arterial pressure was positively related to [H2O] (r=0.51, P<0.05, on day 1) but was not associated with tissue oxygenation parameters. Conclusions: NIRS can be used to quantify tissue H2O. Severe sepsis patients have increased tissue H2O, which responds to changes in arterial blood pressure and affects tissue oxygenation.