Metformin in elderly type 2 diabetes mellitus: dose-dependent dementia risk reduction.

This study aimed to investigate the controversial association between metformin use and diabetes-associated dementia in elderly patients with type 2 diabetes mellitus (T2DM) and evaluate the potential protective effects of metformin, as well as its intensity of use and dose-dependency, against dementia in this population. The study used a time-dependent Cox hazards model to evaluate the effect of metformin use on the incidence of dementia. The case group included elderly patients with T2DM (≥60 years old) who received metformin, while the control group consisted of elderly patients with T2DM who did not receive metformin during the follow-up period. Our analysis revealed a significant reduction in the risk of dementia among elderly individuals using metformin, with an adjusted hazard ratio of 0.34 (95% confidence interval: 0.33 to 0.36). Notably, metformin users with a daily intensity of 1 defined daily dose (DDD) or higher had a lower risk of dementia, with an adjusted hazard ratio (95% confidence interval) of 0.46 (0.22 to 0.6), compared to those with a daily intensity of <1 DDD. Additionally, the analysis of cumulative DDDs of metformin showed a dose-response relationship, with progressively lower adjusted hazard ratio across quartiles (0.15, 0.21, 0.28, and 0.53 for quartiles 4, 3, 2 and 1, respectively), compared to never metformin users (P for trend < 0.0001). Metformin use in elderly patients with T2DM is significantly associated with a substantial reduction in the risk of dementia. Notably, the protective effect of metformin demonstrates a dose-dependent relationship, with higher daily and cumulative dosages of metformin showing a greater risk reduction.

Prognostic factors for survival in unresectable stage III EGFR mutation-positive lung adenocarcinoma: impact of pre-CCRT PET-CT.

PURPOSE: To assess the survival impact of pre-concurrent chemoradiotherapy (CCRT) staging with positron emission tomography-CT (PET-CT) in patients with unresectable epidermal growth factor receptor (EGFR) mutation-positive adenocarcinoma. METHODS: Patients with unresectable stage IIIA-IIIC EGFR mutation-positive adenocarcinoma undergoing definitive CCRT were divided into two groups: those who received PET-CT staging prior to CCRT and those with other staging methods. Survival outcomes were compared after propensity score matching. RESULTS: Analysis of 11 856 patients (5928 in each group) showed that PET-CT staging was associated with improved survival (adjusted HR of all-cause mortality: 0.74, 95% CI 0.71 to 0.79). Other prognostic factors included male sex, age group, clinical stage, adjuvant treatment, smoking status, Charlson Comorbidity Index score and treatment setting. CONCLUSION: Pre-CCRT staging with PET-CT in patients with unresectable EGFR mutation-positive adenocarcinoma of clinical stage IIIA-IIIC was associated with enhanced survival. Independent prognostic factors were also identified.

Early childhood general anesthesia and risk of Attention Deficit Hyperactivity Disorder.

BACKGROUND: The relationship between early childhood exposure to general anesthesia (GA) and the risk of developing Attention Deficit Hyperactivity Disorder (ADHD) is still uncertain and previous studies have presented conflicting results. This population-based cohort study aimed to investigate the potential relationship between GA exposure and ADHD risk using propensity score matching (PSM) in a large sample size. METHODS: The study included 15,072 children aged 0-3 years who received GA and were hospitalized for more than 1 day in Taiwan from 2004 to 2014. The nonexposed group was randomly selected through 1:1 PSM from the Taiwan Maternal and Child Health Database (TMCHD). The primary objectives of this study were to determine the incidence rates (IR) and incidence rate ratios (IRR) of ADHD in the two cohorts, employing Poisson regression models. RESULTS: The GA group and non-GA group each comprised 7,536 patients. The IR of ADHD was higher in the GA group (122.45 per 10,000 person-years) than in the non-GA group (64.15 per 10,000 person-years), and the IRR of ADHD in the GA group was 1.39 (95% CI: 1.26, 1.55). The study found that the number of times of exposure to GA, duration of exposure, male gender, and central nervous system surgery were significant risk factors for ADHD in the future. CONCLUSIONS: This study's findings suggest that there is a significant correlation between early childhood exposure to GA and the risk of developing ADHD, and GA may be an important risk factor for ADHD in children undergoing surgery. The study also identified several risk factors for ADHD, including the number of times of exposure to GA, duration of exposure, male gender, and central nervous system surgery.

Metformin monotherapy versus predominantly older non-metformin antidiabetic medications for cerebrovascular risk in early type 2 diabetes management.

AIM: Choosing the initial treatment for type 2 diabetes (T2D) is pivotal, requiring consideration of solid clinical evidence and patient characteristics. Despite metformin's historical preference, its efficacy in preventing cerebrovascular events lacked empirical validation. This study aimed to evaluate the associations between first-line monotherapy (metformin or non-metformin antidiabetic medications) and cerebrovascular complications in patients with T2D without diabetic complications. METHODS: We analysed 9090 patients with T2D without complications who were prescribed either metformin or non-metformin medications as initial therapy. Propensity score matching ensured group comparability. Cox regression analyses, stratified by initial metformin use, assessed cerebrovascular disease risk, adjusting for multiple covariates and using competing risk analysis. Metformin exposure was measured using cumulative defined daily doses. RESULTS: Metformin users had a significantly lower crude incidence of cerebrovascular diseases compared with non-users (p < .0001). Adjusted hazard ratios (aHRs) consistently showed an association between metformin use and a lower risk of overall cerebrovascular diseases (aHRs: 0.67-0.69) and severe events (aHRs: 0.67-0.69). The association with reduced risk of mild cerebrovascular diseases was significant across all models (aHRs: 0.73-0.74). Higher cumulative defined daily doses of metformin correlated with reduced cerebrovascular risk (incidence rate ratio: 0.62-0.94, p < .0001), indicating a dose-dependent effect. CONCLUSION: Metformin monotherapy is associated with a reduced risk of cerebrovascular diseases in early-stage T2D, highlighting its dose-dependent efficacy. However, the observed benefits might also be influenced by baseline differences and the increased risks associated with other medications, such as sulphonylureas. These findings emphasize the need for personalized diabetes management, particularly in mitigating cerebrovascular risk in early T2D stages.

Improved postoperative outcomes in pediatric major surgery: evidence from hospital volume analysis.

This study aimed to examine the association between hospital volume and postoperative outcomes in pediatric major surgery using a nationwide database. The study included pediatric patients who underwent first major elective inpatient surgery and hospitalization for more than 1 day. The results showed no significant difference in the risk of 30-day postoperative mortality based on hospital volume. However, patients in the middle- and high-volume groups had significantly lower rates of 30-day major complications, particularly deep wound infection. In terms of 90-day postoperative outcomes, patients in the high-volume group had a significantly lower risk of mortality and lower rates of major complications, particularly deep wound infection, pneumonia, and septicemia.  Conclusions: The study suggests that pediatric patients undergoing major surgery in high and middle-volume groups have better outcomes in terms of major complications compared to the low-volume group. What is Known: • Limited evidence exists on the connection between hospital volume and pediatric surgery outcomes. What is New: • A Taiwan-based study, using national data, found that high and middle hospital-volume groups experienced significantly lower rates of major complications within 30 and 90 days after surgery. • High-volume hospitals demonstrated a substantial decrease in the risk of 90-day postoperative mortality. • The study underscores the importance of specialized pediatric surgical centers and advocates for clear guidelines for hospital selection, potentially improving outcomes and informing future health policies.

Adverse postoperative outcomes in elderly patients with sarcopenia.

PURPOSE: No study has compared 30-day and 90-day adverse postoperative outcomes between old-age patients with and those without sarcopenia. PATIENTS AND METHODS: We categorize elderly patients receiving major surgery into two groups according to the presence or absence of preoperative sarcopenia that were matched at a 1:4 ratio through propensity score matching (PSM). We analyzed 30-day or 90-day adverse postoperative outcomes and mortality in patients with and without sarcopenia receiving major surgery. RESULTS: Multivariate logistic regression analyses revealed that the patients with preoperative sarcopenia were at significantly higher risk of 30-day postoperative mortality (adjusted odds ratio [aOR]. = 1.25; 95% confidence interval [CI]. = 1.03-1.52) and 30-day major complications such as postoperative pneumonia (aOR = 1.15; 95% CI = 1.00-1.40), postoperative bleeding (aOR = 2.18; 95% CI = 1.04-4.57), septicemia (aOR = 1.31; 95% CI = 1.03-1.66), and overall complications (aOR = 1.13; 95% CI = 1.00-1.46). In addition, surgical patients with sarcopenia were at significantly higher risk of 90-day postoperative mortality (aOR = 1.50; 95% CI = 1.29-1.74) and 90-day major complications such as pneumonia (aOR = 1.27; 95% CI = 1.10-1.47), postoperative bleeding (aOR = 1.90; 95% CI = 1.04-3.48), septicemia (aOR = 1.52; 95% CI = 1.28-1.82), and overall complications (aOR = 1.24; 95% CI = 1.08-1.42). CONCLUSIONS: Sarcopenia is an independent risk factor for 30-day and 90-day adverse postoperative outcomes such as pneumonia, postoperative bleeding, and septicemia and increases 30-day and 90-day postoperative mortality among patients receiving major surgery. No study has compared 30-day and 90-day adverse postoperative outcomes between patients with and those without sarcopenia. We conducted a propensity score?matched (PSM) population-based cohort study to investigate the adverse postoperative outcomes and mortality in patients undergoing major elective surgery with preoperative sarcopenia versus those without preoperative sarcopenia. We demonstrated that sarcopenia is an independent risk factor for 30-day and 90-day adverse postoperative outcomes, such as postoperative pneumonia, bleeding, septicemia, and mortality after major surgery. Therefore, surgeons and anesthesiologists should attempt to correct preoperative sarcopenia, swallowing function, and respiratory muscle training before elective surgery to reduce postoperative complications that contribute to the decrease in surgical mortality.

Salvage therapy for refractory sudden sensorineural hearing loss (RSSNHL): a systematic review and network meta-analysis.

OBJECTIVE: Approximately 30-50% of sudden sensorineural hearing loss (SSNHL) patients show poor response to systemic steroid therapy. Additionally, the most appropriate treatment for patients with refractory sudden sensorineural hearing loss (RSSNHL) is unknown. This study aimed to explore the best treatment for RSSNHL. DESIGN: Using a frequentist contrast-based model and PRISMA guidelines, this study compared five salvage regimes: intratympanic injection of steroids (ITS), hyperbaric oxygen (HBO) therapy, post auricle steroid injection (PSI), ITS combined with HBO therapy, and continued systemic steroids. STUDY SAMPLE: We searched the PubMed, EMBASE, Web of Science, and Cochrane Library databases for randomised controlled trials and cohort studies comparing treatment regimens for RSSNHL. RESULTS: Compared with the control group (no additional treatment), PSI and ITS demonstrated significant improvements. The mean hearing gain was greater after PSI (11.1 dB [95% CI, 4.4-17.9]) than after ITS (7.7 dB [95% CI, 4.8-10.7]). When a restricted definition of RSSNHL was used, the ITS + HBO therapy showed the largest difference in improvement for pure tone average compared with the control group (14.5 dB [95% CI, 4.2-25.0]). CONCLUSIONS: The administration of either PSI or ITS leads to the greatest therapeutic effect in patients with RSSNHL. However, a consensus on the definition of RSSNHL is needed.

Protective Effects of Different Classes, Intensity, Cumulative Dose-Dependent of Statins Against Primary Ischemic Stroke in Patients with Type 2 Diabetes Mellitus.

PURPOSE OF REVIEW: The aim of this study is to investigate the protective effects of different statin classes, intensity, and cumulative dose-dependent against primary ischemic stroke in patients with T2DM. RECENT FINDINGS: The Cox hazards model was used to evaluate statin use on primary ischemic stroke. Case group: T2DM patients who received statins; control group: T2DM patients who received no statins during the follow-up. Adjusted hazard ratio (aHR) for primary ischemic stroke was 0.45 (95% CI: 0.44 to 0.46). Cox regression analysis showed significant reductions in primary ischemic stroke incidence in users of different statin classes. Corresponding aHRs (95% CI) were 0.09 to 0.79 for pitavastatin, rosuvastatin, atorvastatin, pravastatin, simvastatin, fluvastatin, and lovastatin. Multivariate analyses indicated significant reductions in primary ischemic stroke incidence for patients who received different cumulative defined daily doses (cDDDs) per year (cDDD-year). Corresponding aHRs (95% CI) were 0.17 to 0.77 for quartiles 4 to 1 of cDDD-years, respectively (P for trend < .0001). Optimal intensity daily dose of statin use was 0.89 DDD with the lowest aHR of primary ischemic stroke compared with other DDDs. Persistent statin use reduces the risk of primary ischemic stroke in T2DM patients. Higher cDDD-year values are associated with higher reductions in primary ischemic stroke risk in T2DM patients.

Protective effects of statins on the incidence of NAFLD-related decompensated cirrhosis in T2DM.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome and poses a significant threat to patients with type 2 diabetes mellitus (T2DM) and metabolic dysregulation. Statins exert anti-inflammatory, antioxidative and antithrombotic effects that target mechanisms underlying NAFLD. However, the protective effects of the different doses, intensities and types of statins on the incidence of NAFLD-related decompensated liver cirrhosis (DLC) in patients with T2DM remain unclear. METHODS: This study used the data of patients with T2DM who were non-HBV and non-HCV carriers from a national population database to examine the protective effects of statin use on DLC incidence through propensity score matching. The incidence rate (IR) and incidence rate ratios (IRRs) of DLC in patients with T2DM with or without statin use were calculated. RESULTS: A higher cumulative dose and specific types of statins, namely rosuvastatin, pravastatin, atorvastatin, simvastatin and fluvastatin, reduced the risk of DLC in patients with T2DM. Statin use was associated with a significant reduction in the risk of DLC (HR: .65, 95% CI: .61-.70). The optimal daily intensity of statin use with the lowest risk of DLC was .88 defined daily dose (DDD). CONCLUSIONS: The results revealed the protective effects of specific types of statins on DLC risk in patients with T2DM and indicated a dose-response relationship. Additional studies are warranted to understand the specific mechanisms of action of different types of statins and their effect on DLC risk in patients with T2DM.

Long-term outcomes of statin dose, class, and use intensity on primary prevention of cardiovascular mortality: a national T2DM cohort study.

PURPOSE: To investigate how statins reduce cardiovascular mortality in patients with type 2 diabetes (T2DM) in a dose-, class-, and use intensity-dependent manner. METHODS: We used an inverse probability of treatment-weighted Cox hazards model, with statin use status as a time-dependent variable, to estimate the effects of statin use on cardiovascular mortality. RESULTS: Adjusted hazard ratio [aHR; 95% confidence interval (CI)] for cardiovascular mortality was 0.41 (0.39-0.42). Compared with nonusers, pitavastatin, pravastatin, simvastatin, rosuvastatin, atorvastatin, fluvastatin, and lovastatin users demonstrated significant reductions in cardiovascular mortality [aHRs (95% CIs) = 0.11 (0.06, 0.22), 0.35 (0.32, 0.39), 0.36 (0.34, 0.38), 0.39 (0.36, 0.41), 0.42 (0.40, 0.44), 0.46 (0.43, 0.49), and 0.52 (0.48, 0.56), respectively]. In Q1, Q2, Q3, and Q4 of cDDD-year, our multivariate analysis demonstrated significant reductions in cardiovascular mortality [aHRs (95% CIs) = 0.63 (0.6, 0.65), 0.44 (0.42, 0.46), 0.33 (0.31, 0.35), and 0.17 (0.16, 0.19), respectively; P for trend < 0.0001]. The optimal statin dose daily was 0.86 DDD, with the lowest aHR for cardiovascular mortality of 0.43. CONCLUSIONS: Persistent statin use can reduce cardiovascular mortality in patients with T2DM; in particular, the higher is the cDDD-year of statin, the lower is the cardiovascular mortality. The optimal statin dose daily was 0.86 DDD. The priority of protective effects on mortality are pitavastatin, rosuvastatin, pravastatin, simvastatin, atorvastatin, fluvastatin, and lovastatin for the statin users compared with non-statin users.

Dementia risk amongst older adults with hip fracture receiving general anaesthesia or regional anaesthesia: a propensity-score-matched population-based cohort study.

BACKGROUND: Preclinical studies have indicated that anaesthesia is an independent risk factor for dementia, but the clinical associations between dementia and different types of general anaesthesia or regional anaesthesia remain unclear. We conducted a population-based cohort study using propensity-score matching to compare dementia incidence in patients included in the Taiwanese National Health Insurance Research Database who received various anaesthetic types for hip fracture surgery. METHODS: Patients aged ≥65 yr who received elective hip fracture surgery from 2002 to 2019 were divided into three groups receiving either inhalational anaesthesia (GA), total intravenous anaesthesia-general anaesthesia (TIVA-GA), or regional anaesthesia (RA), and matched in a 1:1 ratio. The incidence rates of dementia were then determined. RESULTS: Propensity-score matching yielded 89 338 patients in each group (N=268 014). Dementia incidence rates in the inhalational GA, TIVA-GA, and RA groups were 4821, 3400, and 2692 per 100 000 person-years, respectively. The dementia incidence rate ratio (95% confidence interval [CI]) for inhalational GA to TIVA-GA was 1.19 (1.14-1.25), for inhalational GA to RA was 1.51 (1.15-1.66), and for TIVA-GA to RA was 1.28 (1.09-1.51). CONCLUSIONS: The incidence rate ratios of dementia amongst older adults undergoing hip fracture surgery were higher for those receiving general anaesthesia than for those receiving regional anaesthesia, with inhalational anaesthesia associated with a higher incidence rate ratio for dementia than total intravenous anaesthesia (TIVA).

Survival effect of pretreatment FDG-PET-CT on nasopharyngeal cancer.

BACKGROUND/PURPOSE: Accurate staging is the first step for optimal treatment selection in patients with nasopharyngeal carcinoma (NPC). In this propensity-score-matched, population-based cohort study, we investigated the survival effects of pretreatment 8-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) on patients with NPC. METHODS: We included patients with stage I-IVA NPC receiving radiotherapy or concurrent chemoradiotherapy and categorized them into two 1:1 propensity score-matched groups according to whether or not they underwent pretreatment 18FDG-PET-CT and compared their outcomes. RESULTS: Of the 10,756 patients, propensity score matching yielded 4366 patients in each group. According to multivariable Cox regression analyses, the most prominent correlation between pretreatment 18FDG-PET-CT and all-cause death was observed in patients with stage II NPC (adjusted hazard ratio [aHR], 0.77; 95% confidence interval [CI], 0.60-0.90; P = .0433), followed by patients with stage III NPC (aHR, 0.81; 95% CI, 0.69-0.94; P = .0071) and patients with stage IVA NPC (aHR, 0.88; 95% CI, 0.79-0.97; P = .0091). This association was not significant in patients with stage I NPC (aHR, 1.20; 95% CI, 0.75-1.93; P = .4426). CONCLUSION: Pretreatment 18FDG-PET-CT is associated with longer survival in patients with clinical stage II-IVA NPC but not in stage I NPC.

Chronic pain following elective surgery under general anesthesia in older adults.

BACKGROUND: The purpose of this study was to investigate the association between age and chronic postsurgical pain (CPSP) in patients who underwent elective surgery under general anesthesia, with a focus on long-term postsurgical analgesic use. To our knowledge, no previous study has examined this relationship in detail between older and younger patients. METHODS: We conducted a propensity score-matched (PSM) study to compare the rates of long-term (3 or 6 months) postoperative analgesic use between older adult (≥ 65 years) and younger (< 65 years) patients. Multivariate logistic regression was used to assess the use of analgesics as a surrogate indicator of CPSP. RESULTS: The PSM analysis included 62,784 surgical patients (31,392 in each group). Three months after surgery, the rates of analgesic use were significantly higher in the older age group (adjusted odds ratio [aOR], 1.45; 95% confidence interval [CI], 1.41-1.49) as well as for opioid use specifically (aOR, 1.34; 95% CI, 1.29-1.39). Six months after surgery, the rates of analgesic use remained higher in the older age group (aOR, 1.52; 95% CI, 1.47-1.58), and similarly for opioid use specifically (aOR, 1.42; 95% CI, 1.36-1.48). CONCLUSIONS: Our findings suggest that older adults have higher rates of long-term analgesic use for CPSP after elective surgery under general anesthesia. This study highlights the importance of addressing CPSP in older adult patients and considering age-related factors when managing postoperative pain.

Use of Preoperative FDG PET/CT and Survival of Patients with Resectable Non-Small Cell Lung Cancer.

Background The added value of preoperative PET/CT for the overall survival of patients with resectable non-small cell lung cancer (NSCLC) is unknown. Purpose To investigate the association of the use of preoperative PET/CT on survival of patients with resectable stage I-IIIB NSCLC. Materials and Methods In this retrospective study, patients with resectable stage I-IIIB NSCLC who underwent thoracic surgery from January 1, 2009, to December 31, 2018, from the Taiwan Cancer Registry were included. The last follow-up date was December 31, 2019. Patients were categorized into two groups according to whether they underwent preoperative metabolic imaging with fluorine 18 fluorodeoxyglucose PET/CT. Patients who did not undergo preoperative imaging were used as the control group. The primary outcome of interest was all-cause mortality. Patients in both groups were propensity score matched at a ratio of 1:1. Matching variables used were sex, age, histologic findings, American Joint Committee on Cancer clinical stage, cT stage, cN stage, current and past smoker history, adjuvant chemotherapy, adjuvant chemoradiation, Charlson comorbidity index, and hospital type. Survival curves were generated using the Kaplan-Meier method and compared using the log-rank test. Results In the matched cohort, 6754 patients (3349 men, mean age ± SD: 64 years ± 11) underwent PET/CT and 6754 did not (3362 men, mean age: 64 years ± 11). In adjusted analysis, patients with stage IIIA or IIIB NSCLC and preoperative PET/CT had a lower risk of death versus those without PET/CT (for stage IIIA: hazard ratio [HR] = 0.90 [95% CI: 0.79, 0.94], P = .02; for stage IIIB: HR = 0.80 [95% CI: 0.71, 0.90], P < .01). There was no improvement in a lower risk of death for patients with stage I-II NSCLC (after multivariable adjustment, the HR was 1.19 [95% CI: 0.89, 1.30], P = .65). Conclusion Use of preoperative PET/CT was associated with lower risk of death in patients with stage IIIA-IIIB non-small cell lung cancer compared with those without preoperative PET/CT. © RSNA, 2022 Online supplemental material is available for this article.

Effect of Preexisting Sarcopenia on Acute and Late Postoperative Pneumonia Among Patients With Oral Cavity Squamous Cell Carcinoma.

BACKGROUND: Whether preexisting sarcopenia is an independent risk factor for postoperative pneumonia (POP) for patients with oral cavity squamous cell carcinoma (OCSCC) remains unclear. Therefore, we conducted a propensity score-matched population-based cohort study to compare the risk of acute and late POP for patients with sarcopenic and nonsarcopenic OCSCC who underwent curative surgery. PATIENTS AND METHODS: We included patients with OCSCC who underwent curative surgery and categorized them into 2 groups depending on whether they had preexisting sarcopenia. The patients in the sarcopenic and nonsarcopenic groups were matched at a ratio of 2:1. RESULTS: The matching process yielded 16,257 patients (10,822 without sarcopenia and 5,435 with sarcopenia). In multivariate Cox regression analyses, the adjusted hazard ratio of POP for the group with OCSCC with preexisting sarcopenia was 1.20 (95% CI, 1.14-1.26; P<.0001) compared with the nonsarcopenic group. Among the patients with OCSCC who received curative surgery, those in the sarcopenic group exhibited a higher POP risk than those in the nonsarcopenic group for the following postoperative time periods: 31st to 90th day, 91st day to first year, first to second year, second to third year, third to fourth year, and fourth to fifth year. CONCLUSIONS: The high incidence of pneumonia persists for a long time in patients with OCSCC who receive curative surgery; this high incidence may even persist for 5 years after surgery, especially in patients with sarcopenia. For susceptible patients who are at risk for OCSCC, sarcopenia prevention measures (eg, exercise and early nutrition intervention) should be implemented.

Association between long-term opioid use and cancer risk in patients with chronic pain: a propensity score-matched cohort study.

BACKGROUND: Whether long-term opioid use is an independent risk factor for cancer progression remains unclear. Therefore, we conducted a propensity score-matched population-based cohort study to compare cancer incidence between patients with chronic pain with and without opioid use. METHODS: Data from January 2008 to December 2019 were obtained from the Taiwan National Health Insurance Research Database. Patients were categorised into two groups according to the presence or absence of opioid use, and matched at a 4:1 ratio. The incidence rate ratios for specific cancers were determined. RESULTS: Propensity score-matching yielded 63 610 patients: 50 888 with opioid use (the opioid group) and 12 722 without (the non-opioid group). In a multivariate Cox regression analysis, the adjusted hazard ratio (95% confidence interval) for cancers in the opioid group compared with the non-opioid group was 2.66 (1.44-2.94; P<0.001). The incidence rate ratios (95% confidence interval) for lung, hepatocellular, colorectal, breast, prostate, head and neck, pancreatic, gastric, oesophageal, and ovarian cancers for the opioid group were 1.87 (1.41-2.43), 1.97 (1.56-2.50), 2.39 (1.87-3.03), 2.43 (1.75-3.33), 2.00 (1.35-3.03), 1.79 (1.14-2.86), 1.87 (1.13-2.12), 2.43 (1.52-3.85), 1.82 (0.92-3.70), and 2.33 (1.01-5.55), respectively. CONCLUSION: There was an association between long-term opioid use and development of cancer in patients with chronic pain, which should be confirmed in future studies.

Effect of opioids on cancer survival in patients with chronic pain: a propensity score-matched population-based cohort study.

BACKGROUND: The impact of opioid analgesic use before cancer diagnosis on survival in patients with chronic pain is unclear. Therefore, we designed a propensity score-matched population-based cohort study to compare overall and cancer-related survival of patients with chronic pain who received long-term opioid analgesic treatment with that of those who did not receive such treatment. METHODS: We included patients with chronic pain and categorised them into the following two groups according to their analgesic use: patients with cancer and chronic pain who were prescribed ≥180 defined daily doses of opioid analgesics per year >3 months before cancer diagnosis comprised the case group, and those who were prescribed <28 defined daily doses of opioid analgesics per year before cancer diagnosis comprised the control group. Patients in both groups were matched at a ratio of 1:5. The primary outcome was overall long-term survival. RESULTS: The matching process yielded a final cohort of 1716 patients (286 and 1430 in the case and control groups, respectively) who were eligible for further analysis. The adjusted hazard ratio for overall survival in patients receiving long-term opioids was 3.53 (95% confidence interval: 3.03-4.11; P<0.001). CONCLUSIONS: Long-term opioid analgesic use before cancer diagnosis might be associated with poor overall survival in patients with chronic pain compared with such patients who did not receive long-term opioid analgesics.

Long-term survival outcomes and prognostic factors related to ruptured intracranial aneurysms: A comparison of surgical and endovascular options in a propensity score-matched, nationwide population-based cohort study.

BACKGROUND AND PURPOSE: To determine the long-term survival outcomes of and prognostic factors for survival in patients with a ruptured intracranial aneurysm (RIA) who underwent endovascular coil embolization or surgical clipping. METHODS: We selected patients who had received a diagnosis of RIA between January 1, 2011 and December 31, 2017. Propensity score matching was performed, and Cox proportional hazards model curves were plotted to analyze all-cause mortality in patients undergoing different treatments. RESULTS: The matching process yielded a final cohort of 8102 patients (4051 and 4051 in endovascular coil embolization and surgical clipping groups, respectively) who were eligible for inclusion. In multivariate Cox regression analyses, the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for endovascular coil embolization compared with surgical clipping were 0.87 (95% CI, 0.79-0.97). The aHRs for the ages of 65 to 74, 75 to 84, and ≥85 years compared with the ages of 20 to 64 years were 1.82 (95% CI, 1.60-2.07), 3.35 (95% CI, 2.93-3.84), and 6.99 (95% CI, 5.51-8.86), respectively. Surgical clipping; old age; male sex; treatment during 2011 to 2013; presence of diabetes, congestive heart failure, hypertension, chronic kidney disease, or end-stage renal disease; history of stroke or transient ischemic attack; Charlson Comorbidity Index ≥2; attendance of nonacademic hospitals; and low income were significant independent prognostic factors for poor survival. CONCLUSIONS: Compared with surgical clipping, endovascular coil embolization led to more favorable survival outcomes in patients with RIAs.

Neoadjuvant concurrent chemoradiotherapy followed by transanal total mesorectal excision assisted by single-port laparoscopic surgery for low-lying rectal adenocarcinoma: a single center study.

PURPOSE: To assess the feasibility and short-term outcomes of neoadjuvant chemoradiotherapy (CCRT) followed by transanal total mesorectal excision assisted by single-port laparoscopic surgery (TaTME-SPLS) for low-lying rectal adenocarcinoma. METHODS AND MATERIALS: A total of 23 patients with clinical stage II-III low-lying (from anal verge 0-8 cm) rectal adenocarcinoma who underwent neoadjuvant CCRT followed by TaTME-SPLS consecutively from December 2015 to December 2018, were enrolled into our study. Chi-squared testing and Student's t testing were used to make parametric comparisons, and Fisher's exact test or the Mann-Whitney U test were used to make nonparametric comparisons. RESULTS: Conversion rate in patients who underwent neoadjuvant CCRT followed by TaTME-SPLS was only 4%. The mean operation time was 366 min and the inter-sphincter resection (ISR) was done for 14 patients (60%). The mean number of lymph nodes harvested was 15. There was no surgical mortality, but the 30-day morbidity rate was 21% (5 patients were Clavien-Dindo I-II). Pathological complete response was 21.74% with 100% organ preservation and 100% clear distal margin after neoadjuvant CCRT followed by TaTME-SPLS. CONCLUSION: TaTME-SPLS would be highly successful in lymph node negative and low T stage of low-lying rectal cancer patients who had pathological complete remission or high percentage of partial remission after neoadjuvant CCRT.

Protective Effect of Low-Molecular-Weight Fucoidan on Radiation-Induced Fibrosis Through TGF-ß1/Smad Pathway-Mediated Inhibition of Collagen I Accumulation.

Radiation-induced fibrosis (RIF) occurs after radiation therapy in normal tissues due to excessive production and deposition of extracellular matrix proteins and collagen, possibly resulting in organ function impairment. This study investigates the effects of low-molecular-weight fucoidan (LMF) on irradiated NIH3T3 cells. Specifically, we quantified cellular metabolic activity, fibrosis-related mRNA expression, transforming growth factor beta-1 (TGF-ß1), and collagen-1 protein expression, and fibroblast contractility in response to LMF. LMF pre + post-treatment could more effectively increase cellular metabolic activity compared with LMF post-treatment. LMF pre + post-treatment inhibited TGF-ß1 expression, which mediates negative activation of phosphorylated Smad3 (pSmad3) and Smad4 complex formation and suppresses downstream collagen I accumulation. In addition, LMF pre + post-treatment significantly reduced actin-stress fibers in irradiated NIH3T3 cells. LMF, a natural substance obtained from brown seaweed, may be a candidate agent for preventing or inhibiting RIF.