The multinomial mixed-effect regression model for predicting PCOC phases in hospice patients.

PURPOSE: The Palliative Care Outcomes Collaboration (PCOC) aims to enhance patient outcomes systematically. However, identifying crucial items and accurately determining PCOC phases remain challenging. This study aims to identify essential PCOC data items and construct a prediction model to accurately classify PCOC phases in terminal patients. METHODS: A retrospective cohort study assessed PCOC data items across four PCOC phases: stable, unstable, deteriorating, and terminal. From July 2020 to March 2023, terminal patients were enrolled. A multinomial mixed-effect regression model was used for the analysis of multivariate PCOC repeated measurement data. RESULTS: The dataset comprised 1933 terminally ill patients from 4 different hospice service settings. A total of 13,219 phases of care were analyzed. There were significant differences in the symptom assessment scale, palliative care problem severity score, Australia-modified Karnofsky performance status, and resource utilization groups-activities of daily living among the four PCOC phases of care. Clinical needs, including pain and other symptoms, declined from unstable to terminal phases, while psychological/spiritual and functional status for bed mobility, eating, and transfers increased. A robust prediction model achieved areas under the curves (AUCs) of 0.94, 0.94, 0.920, and 0.96 for stable, unstable, deteriorating, and terminal phases, respectively. CONCLUSIONS: Critical PCOC items distinguishing between PCOC phases were identified, enabling the development of an accurate prediction model. This model enhances hospice care quality by facilitating timely interventions and adjustments based on patients' PCOC phases.

A computed tomography radiomics-based model for predicting osteoporosis after breast cancer treatment.

Many treatments against breast cancer decrease the level of estrogen in blood, resulting in bone loss, osteoporosis and fragility fractures in breast cancer patients. This retrospective study aimed to evaluate a novel opportunistic screening for cancer treatment-induced bone loss (CTIBL) in breast cancer patients using CT radiomics. Between 2011 and 2021, a total of 412 female breast cancer patients who received treatment and were followed up in our institution, had post-treatment dual-energy X-ray absorptiometry (DXA) examination of the lumbar vertebrae and had post-treatment chest CT scan that encompassed the L1 vertebra, were included in this study. Results indicated that the T-score of L1 vertebra had a strongly positive correlation with the average T-score of L1-L4 vertebrae derived from DXA (r = 0.91, p < 0.05). On multivariable analysis, four clinical variables (age, body weight, menopause status, aromatase inhibitor exposure duration) and three radiomic features extracted from the region of interest of L1 vertebra (original_firstorder_RootMeanSquared, wavelet.HH_glcm_InverseVariance, and wavelet.LL_glcm_MCC) were selected for building predictive models of L1 T-score and bone health. The predictive model combining clinical and radiomic features showed the greatest adjusted R2 value (0.557), sensitivity (83.6%), specificity (74.2%) and total accuracy (79.4%) compared to models that relied solely on clinical data, radiomic features, or Hounsfield units. In conclusion, the clinical-radiomic predictive model may be used as an opportunistic screening tool for early identification of breast cancer survivors at high risk of CTIBL based on non-contrast CT images of the L1 vertebra, thereby facilitating early intervention for osteoporosis.

Pendelluft in patients with acute respiratory distress syndrome during trigger and reverse triggering breaths.

Pendelluft, the shift of air from non-dependent to dependent lung regions, is known to occur during active breathing in ventilated patients. However, information about pendelluft in ARDS patients under assisted mechanical ventilation is limited. In this prospectively collected and retrospectively analyzed study, we combined electrical impedance tomography and respiratory mechanics monitoring to quantitatively examine pendelluft in trigger and reverse triggering breaths in 20 mechanically ventilated patients with ARDS during the transition from controlled to active breaths under volume-cycled ventilation. Besides the 10 resting breaths in each patient, 20% of the counted active breaths were selected based on three levels of esophageal pressure swing (∆Pes): low (< 5 cm H2O, breaths = 471), moderate (≥ 5, < 10 cm H2O, breaths = 906), and high effort (≥ 10 cm H2O, breaths = 565). The pendelluft response to breathing efforts was significantly greater in trigger breaths than in reverse triggering breaths (p < 0.0001). Based on the pendelluft-∆Pes slope (ml/cmH2O), there were two distinct patterns of effort-related pendelluft (high vs. low pendelluft group). For trigger breaths, the high pendelluft group (n = 9, slope 0.7-2.4 ml/cmH2O) was significantly associated with lower peak airway/plateau pressure and lower respiratory system/lung elastance than the low pendelluft group (n = 11, slope - 0.1 to 0.3 ml/cmH2O). However, there was no difference in respiratory mechanics between high and low pendelluft groups for reverse triggering breathes. The use of ∆Pes to predict pendelluft was found to have a low positive predictive value.

Effect of atosiban on in vitro fertilization pregnancy outcome among women with endometriosis in presence or absence of adenomyosis.

OBJECTIVE: This study aimed to assess the effect of atosiban on in vitro fertilization (IVF) pregnancy outcome among women with both endometriosis and adenomyosis, and compared it to that of patients with endometriosis but without adenomyosis and that of patients with tubal factor only. MATERIALS AND METHODS: 106 infertile women (176 embryo transfers) from a medical center in Taiwan were included in the analysis, where 34 (54), 34 (66), and 38 (56) cases (embryo transfers) were endometriosis without adenomyosis, endometriosis with adenomyosis, and tubal infertility factor only, respectively. Adenomyosis morphologies were classified using an ultrasound-based classification system. The logistic generalized estimating equation model was used to analyze the association between atosiban use and pregnancy outcomes. RESULTS: The crude pregnancy rates for the endometriosis-only group were significantly higher than those for the endometriosis + adenomyosis group (i.e., biochemical pregnancy: 50.0% versus 29.7%, p = 0.041; ongoing pregnancy: 35.2% versus 16.9%, p = 0.038). Significantly higher chances of biochemical pregnancy and ongoing pregnancy among endometriosis patients without adenomyosis versus those with both endometriosis and adenomyosis were found (odds ratios [95% confidence intervals]: 2.981 [1.307, 6.803]; p = 0.009, 2.694 [1.151, 6.304]; p = 0.022). A significant positive association between atosiban use and biochemical pregnancy existed among endometriosis cases without adenomyosis (a 2.43-fold [1.01, 5.89] increase in successful pregnancy; p<0.05), but not for the other groups. CONCLUSIONS: Poor pregnancy outcomes among adenomyosis-affected women were confirmed. The use of atosiban significantly enhanced IVF pregnancy among endometriosis patients without adenomyosis.

Feasibility of simultaneous development of laparoscopic and robotic pancreaticoduodenectomy.

Laparoscopic (LPD) and robotic pancreaticoduodenectomy (RPD) are both challenging procedures. The feasibility and safety of simultaneously developing LPD and RPD remain unreported. We retrospectively reviewed the data of patients undergoing LPD or RPD between 2014 and 2021. A total of 114 patients underwent minimally invasive pancreaticoduodenectomy (MIPD): 39 LPDs and 75 RPDs. The learning process of LPD and RPD were similar. The cutoff points of the learning curve were LPD, 13th patient (the 27th patient of MIPD), and RPD, 18th patient (the 31st patient of MIPD) according the cumulative sum analysis of operative time. A decrease in the operative time was associated with the case sequence (p < 0.001) but not with the surgical approach (p = 0.36). The overall surgical outcomes were comparable between both the LPD and RPD groups. When evaluating the learning curve impact on MIPD, LPD had higher major complication (≧ Clavien-Dindo grade III), bile leak and wound infection rates in the pre-learning curve phase than those in the after-learning curve phase, while RPD had similar surgical outcomes between two phases. Simultaneous development of LPD and RPD is feasible and safe for experienced surgeons, with similar learning process and comparable surgical outcomes.

Management of Restenosis after Stenting in Left Main Coronary Artery Disease.

Background: The optimal alternative treatment strategy to coronary artery bypass graft surgery (CABG) for in-stent restenosis (ISR) in left main (LM) coronary artery disease remains uncertain. Methods: We retrospectively screened all intervention reports from an intervention database and extracted those mentioning an LM stent. We then manually confirmed reports involving LM ISR and divided them into two groups, those in which the patient received a new drug-eluting stent (new-DES) strategy, and those in which the patient received a drug-coated balloon (DCB) only. A composite endpoint of major adverse cardiovascular events (MACEs) and each individual endpoint were compared. We also performed a brief analysis of similar designed studies. Results: Between the new-DES (n = 40) and DCB-only (n = 22) groups, during median respective follow-up times of 581.5 and 642.5 days, no significant statistical differences were detected in MACEs (50.0% vs. 50.0%, p = 0.974), cardiovascular death (27.5% vs. 13.6%, p = 0.214), nonfatal myocardial infarction (30.0% vs. 31.8%, p = 0.835), or target lesion revascularization (35.0% vs. 45.5%, p = 0.542). We analyzed four similar studies and found comparable MACE findings (odds ratio: 0.85, 95% CI: 0.44-1.67). Conclusions: Our findings support both DCB angioplasty and repeat DES implantation for LMISR lesions in patients who were clinically judged to be unsuitable for CABG; the treatments achieved comparable clinical results in terms of MACEs in the medium term.

Lidocaine transdermal patches reduced pain intensity in neuropathic cancer patients already receiving opioid treatment.

BACKGROUND: Limited efficacy has been observed when using opioids to treat neuropathic pain. Lidocaine patches reduce neuropathic pain in postherpetic neuralgia, but their benefits for cancer-related neuropathic pain remain unclear. This study aimed to investigate a treatment for cancer-related neuropathic pain. METHODS: We conducted a prospective, open-label, single-arm study to assess the efficacy and safety of lidocaine transdermal patches in patients experiencing localized, superficial, neuropathic cancer pain. Terminal cancer patients already receiving opioid treatment participated in the 3-day study. The primary endpoint was pain intensity evaluated by the numerical rating scale (NRS). The secondary endpoints were the pain relief score and the quality of analgesic treatment. RESULTS: The results showed a significant difference in the median NRS over 3 days (Kruskal-Wallis test, p < 0.0001). The median NRS pain intensity from Day 1 to Day 3 was 4.0 with 95% C.I. (3.3, 5.0), 3.0 (2.5, 3.5), and 2.6 (2.0, 3.0), respectively. The difference between the median NRS pain intensities of any 2 days was significant (Wilcoxon signed-rank test, p < 0.0001). The generalized estimating equation (GEE) estimation model showed significant differences between the NRS pain intensities on any 2 days. There was no significant difference in the pain relief score or the quality of analgesic treatment. CONCLUSIONS: In this study, the 5% lidocaine transdermal patch reduced the NRS pain intensity in neuropathic cancer patients already receiving opioid treatment. Treatment of localized and superficial neuropathic pain caused by cancer was well tolerated and effective.

Repurposing nitric oxide donating drugs in cancer therapy through immune modulation.

BACKGROUND: Nitric oxide-releasing drugs are used for cardiovascular diseases; however, their effects on the tumor immune microenvironment are less clear. Therefore, this study explored the impact of nitric oxide donors on tumor progression in immune-competent mice. METHODS: The effects of three different nitric oxide-releasing compounds (SNAP, SNP, and ISMN) on tumor growth were studied in tumor-bearing mouse models. Three mouse tumor models were used: B16F1 melanoma and LL2 lung carcinoma in C57BL/6 mice, CT26 colon cancer in BALB/c mice, and LL2 lung carcinoma in NOD/SCID mice. After nitric oxide treatment, splenic cytokines and lymphocytes were analyzed by cytokine array and flow cytometry, and tumor-infiltrating lymphocytes in the TME were analyzed using flow cytometry and single-cell RNA sequencing. RESULTS: Low doses of three exogenous nitric oxide donors inhibited tumor growth in two immunocompetent mouse models but not in NOD/SCID immunodeficient mice. Low-dose nitric oxide donors increase the levels of splenic cytokines IFN-γ and TNF-α but decrease the levels of cytokines IL-6 and IL-10, suggesting an alteration in Th2 cells. Nitric oxide donors increased the number of CD8+ T cells with activation gene signatures, as indicated by single-cell RNA sequencing. Flow cytometry analysis confirmed an increase in infiltrating CD8+ T cells and dendritic cells. The antitumor effect of nitric oxide donors was abolished by depletion of CD8+ T cells, indicating the requirement for CD8+ T cells. Tumor inhibition correlated with a decrease in a subtype of protumor macrophages and an increase in a subset of Arg1-positive macrophages expressing antitumor gene signatures. The increase in this subset of macrophages was confirmed by flow cytometry analysis. Finally, the combination of low-dose nitric oxide donor and cisplatin induced an additive cancer therapeutic effect in two immunocompetent animal models. The enhanced therapeutic effect was accompanied by an increase in the cells expressing the gene signature of NK cell. CONCLUSIONS: Low concentrations of exogenous nitric oxide donors inhibit tumor growth in vivo by regulating T cells and macrophages. CD8+ T cells are essential for antitumor effects. In addition, low-dose nitric oxide donors may be combined with chemotherapeutic drugs in cancer therapy in the future.

HER2 amplification in colorectal cancer with brain metastasis: A propensity score matching study.

BACKGROUND: The association between human epidermal growth factor receptor-2 (HER2) amplification and brain metastasis (BM) in patients having colorectal cancer (CRC) has been suggested but not yet established. This study investigated the expression patterns of HER2, its association with BM, and its prognostic value in patients having CRC. METHODS: We retrospectively identified 99 patients having metastatic CRC (mCRC) and BM (the BM cohort) and compared them with a cohort of 249 patients having mCRC and without BM (the stage IV cohort) by propensity score matching. Immunohistochemical studies of HER2 on all available paraffin-embedded tumour samples, either from the primary tumour, the metastasis (brain and/or extracranial sites) or both, were performed and analysed. HER2 fluorescent in situ hybridisation was applied when necessary. The expression of HER2 was compared and correlated with survival. RESULTS: HER2 amplifications were detected in 16 (18.4%) of 87 and 9 (3.6%) of 249 patients who had specimens available in the BM and stage IV cohorts, respectively (P < .001). After propensity score matching, HER2 amplification was significantly associated with BM (odds ratio: 5.38, P = .003). HER2 heterogeneity was frequently observed not only at the single tumour level but also in paired tumour samples. A marginally significant longer survival since BM was found in patients having HER2-amplified mCRC than in those without (P = .07). CONCLUSIONS: HER2 amplification was significantly associated with BM in patients having mCRC and might have prognostic value for survival since BM. Given the heterogeneity of HER2 expression, the testing of HER2 status on available tissues from both primary and metastatic tumours should be encouraged.

Minimally invasive approaches increase postoperative complications in obese patients undergoing pancreaticoduodenectomy during the initial development period: a propensity score matching study.

BACKGROUND: Obesity increases surgical risks in various abdominal surgeries and its impact on open pancreaticoduodenectomy (OPD) and minimally invasive pancreaticoduodenectomy (MIPD) remains unknown. This study aimed to compare the surgical outcomes of OPD and MIPD in obese and non-obese patients by propensity score matching (PSM) analysis during the implementation of MIPD. METHODS: We retrospectively reviewed all pancreaticoduodenectomies from December 2014 to May 2021. Obesity was defined as body mass index > 25 kg/m2 according to World Health Organization International Obesity Task Force. PSM was used to minimize the selection bias of MIPD. RESULTS: Among 462 pancreaticoduodenectomies (339 OPDs, 123 MIPDs), there were 313 patients in the non-obese group (MIPD: 78, OPD: 235) and 149 patients in the obese group (MIPD: 45, OPD: 104). After PSM, there were 70 MIPD/106 OPD patients in the non-obese group and 38 MIPD/54 OPD patients in the obese group. The obese MIPD patients had more fluid collection (36.8% vs 9.8%, p = 0.002), a higher Clavien-Dindo (CD) grade (p = 0.007), more major complications (42.1% vs 14.8%, p = 0.004), and longer operative times (306 min vs 264 min, p < 0.001) than the obese OPD patients. The non-obese MIPD patients had lower CD grades (p = 0.02), longer operative times (294 vs 264 min, p < 0.001), and less blood loss (100 mL vs 200 mL) than the non-obese OPD patients. MIPD was a strong predictor of major complication (CD ≥ 3) in obese patients (odds ratio 3.11, 95% CI: 1.40-6.95, p = 0.005). CONCLUSIONS: Minimally invasive approaches deteriorate the CD grade, fluid collection, and major complications in obese patients undergoing pancreaticoduodenectomy during the initial development period. Non-obese patients may benefit from MIPD over OPD in terms of less blood loss and lower CD grades. The impact of BMI on MIPD should be considered when assessing the surgical risks.

The Proper Use and Reporting of Survival Analysis and Cox Regression.

BACKGROUND: Survival analyses are heavily used to analyze data in which the time to event is of interest. The purpose of this paper is to introduce some fundamental concepts for survival analyses in medical studies. METHODS: We comprehensively review current survival methodologies, such as the nonparametric Kaplan-Meier method used to estimate survival probability, the log-rank test, one of the most popular tests for comparing survival curves, and the Cox proportional hazard model, which is used for building the relationship between survival time and specific risk factors. More advanced methods, such as time-dependent receiver operating characteristic, restricted mean survival time, and time-dependent covariates are also introduced. RESULTS: This tutorial is aimed toward covering the basics of survival analysis. We used a neurosurgical case series of surgically treated brain metastases from non-small cell lung cancer patients as an example. The survival time was defined from the date of craniotomy to the date of patient death. CONCLUSIONS: This work is an attempt to encourage more investigators/medical practitioners to use survival analyses appropriately in medical research. We highlight some statistical issues, make recommendations, and provide more advanced survival modeling in this aspect.

Predicting the Need for Desmopressin Treatment During Inpatient and After Discharge Following Endoscopic Sellar Surgery.

INTRODUCTION: Postoperative diabetes insipidus (DI) is a common complication following endoscopic sellar surgery. However, the requirement of desmopressin treatment for patients with DI are heterogenous. Although the predictors of postoperative DI have been reported, whether these patients required desmopressin treatment remained uninvestigated. Predicting the need of desmopressin can benefit clinical decision making more directly than predicting the occurence of postoperative DI. This study aimed to identify variables that predict the need for desmopressin treatment following sellar surgery. METHODS: Patients undergoing endoscopic sellar surgery between 2016 and 2019 were retrospectively reviewed. Twenty-three variables, characterized as potential predictors for requiring desmopressin treatment, were analyzed. To assess the capability to generalize the identified predictors, external validation with receiver operating characteristic (ROC) analysis was performed using a second series from 2019 to 2020. RESULTS: Postoperative DI occurred in 40 of 159 included patients. Twelve patients required inpatient desmopressin treatment and 20 patients needed desmopressin prescription after discharge. The potential predictors of requiring any desmopressin use included higher peak sodium (Na) level (p = 0.007), lower minimum Na level (p = 0.043), and higher peak urine output (p = 0.006), but these were not supported by external validation. The predictors of requiring desmopressin after discharge included higher peak Na (p = 0.040) and minimum Na levels (p = 0.048), which were supported by external ROC validation showing areas under curve of 0.787, 0.611, and 0.898 for peak Na (p = 0.036), minimum Na (p = 0.460), and peak Na - minimum Na levels (p < 0.001), respectively. A criterion of peak Na ≥ 150 mmol/L or peak Na - minimum Na ≥ 10 predicted the need of desmopressin prescription after discharge. A postoperative management algorithm was proposed. CONCLUSION: The required treatments for patients with postoperative DI following endoscopic sellar surgery are heterogenous. Elevated peak Na and large peak Na-minimum Na levels in the perioperative period predicted requiring desmopressin after hospital discharge. Patients with peak Na <150 mmol/L and peak Na-minimum Na <10 can be safely discharged without desmopressin prescription.

A Prediction Model for Tumor Recurrence in Stage II-III Colorectal Cancer Patients: From a Machine Learning Model to Genomic Profiling.

BACKGROUND: Colorectal cancer (CRC) is one of the most prevalent malignant diseases worldwide. Risk prediction for tumor recurrence is important for making effective treatment decisions and for the survival outcomes of patients with CRC after surgery. Herein, we aimed to explore a prediction algorithm and the risk factors for postoperative tumor recurrence using a machine learning (ML) approach with standardized pathology reports for patients with stage II and III CRC. METHODS: Pertinent clinicopathological features were compiled from medical records and standardized pathology reports of patients with stage II and III CRC. Four ML models based on logistic regression (LR), random forest (RF), classification and regression decision trees (CARTs), and support vector machine (SVM) were applied for the development of the prediction algorithm. The area under the curve (AUC) of the ML models was determined in order to compare the prediction accuracy. Genomic studies were performed using a panel-targeted next-generation sequencing approach. RESULTS: A total of 1073 patients who received curative intent surgery at the National Cheng Kung University Hospital between January 2004 and January 2019 were included. Based on conventional statistical methods, chemotherapy (p = 0.003), endophytic tumor configuration (p = 0.008), TNM stage III disease (p < 0.001), pT4 (p < 0.001), pN2 (p < 0.001), increased numbers of lymph node metastases (p < 0.001), higher lymph node ratios (LNR) (p < 0.001), lymphovascular invasion (p < 0.001), perineural invasion (p < 0.001), tumor budding (p = 0.004), and neoadjuvant chemoradiotherapy (p = 0.025) were found to be correlated with the tumor recurrence of patients with stage II-III CRC. While comparing the performance of different ML models for predicting cancer recurrence, the AUCs for LR, RF, CART, and SVM were found to be 0.678, 0.639, 0.593, and 0.581, respectively. The LR model had a better accuracy value of 0.87 and a specificity value of 1 in the testing set. Two prognostic factors, age and LNR, were selected by multivariable analysis and the four ML models. In terms of age, older patients received fewer cycles of chemotherapy and radiotherapy (p < 0.001). Right-sided colon tumors (p = 0.002), larger tumor sizes (p = 0.008) and tumor volumes (p = 0.049), TNM stage II disease (p < 0.001), and advanced pT3-4 stage diseases (p = 0.04) were found to be correlated with the older age of patients. However, pN2 diseases (p = 0.005), lymph node metastasis number (p = 0.001), LNR (p = 0.004), perineural invasion (p = 0.018), and overall survival rate (p < 0.001) were found to be decreased in older patients. Furthermore, PIK3CA and DNMT3A mutations (p = 0.032 and 0.039, respectively) were more frequently found in older patients with stage II-III CRC compared to their younger counterparts. CONCLUSIONS: This study demonstrated that ML models have a comparable predictive power for determining cancer recurrence in patients with stage II-III CRC after surgery. Advanced age and high LNR were significant risk factors for cancer recurrence, as determined by ML algorithms and multivariable analyses. Distinctive genomic profiles may contribute to discrete clinical behaviors and survival outcomes between patients of different age groups. Studies incorporating complete molecular and genomic profiles in cancer prediction models are beneficial for patients with stage II-III CRC.

Oral Anticoagulants in Patients with Atrial Fibrillation and Active Cancer.

Background: Atrial fibrillation (AF) is associated with an increased risk of heart failure, death and thromboembolism. AF is prevalent in patients with cancer. Although current guidelines suggest the application of oral anticoagulants (OACs) for thromboembolic event prevention in high-risk AF patients, owing to the high thromboembolic and bleeding risks of active-cancer patients, there is no consensus on the use of OACs in such a population. Therefore, we conducted this retrospective cohort study to investigate the applicability of the CHA 2 DS 2 -VASc score and to evaluate the efficacy and safety outcomes of OAC therapy in active-cancer patients with AF. Methods: This retrospective cohort study enrolled patients diagnosed with cancer at National Cheng Kung University Hospital between November 2012 and August 2019. The primary outcomes included all-cause mortality, thromboembolic events (stroke/transient ischemic attack and systemic emboli), acute myocardial infarction (AMI), hospitalization for HF and major bleeding events. Results: We enrolled 2429 patients with active cancer. Among these patients, 1060 patients (43.6%) had AF. After 1:2 propensity score matching, 690 cancer patients with AF were enrolled for the final analysis, grouped as follows: 225 patients taking OACs and 465 patients without OAC treatment. The OAC-treated group had lower all-cause mortality than the patients without OAC treatment (all-cause mortality rate in OAC treatment vs. non-OAC treatment: 24.4% vs. 37.4%, hazard ratio 0.58 [95% confidence interval (CI) 0.43-0.78], p < 0.001). However, there was no difference in thromboembolic events, myocardial infarction or heart failure hospitalization between the OAC-treated and non-OAC-treated groups. Importantly, the risk of major bleeding composition (i.e., major gastrointestinal bleeding and intracranial hemorrhage) was similar between these two groups. Moreover, the CHA 2 DS 2 -VASc score could not predict thromboembolic events in the enrolled active-cancer patients with AF (OR 1.23, 95% CI 0.98-1.56). Conclusions: OAC treatment may significantly reduce the risk of death, without safety concerns, in active-cancer patients with AF. OAC treatment may not prevent thromboembolic events in patients with active cancer and AF. However, we found that OAC treatment is associated with improved prognosis without increasing the risks of major bleeding, despite several limitations in this study. Further studies are required to determine the optimal use of anticoagulation therapy in this high-risk population.

Hospice delivery models and survival differences in the terminally ill: a large cohort study.

OBJECTIVE: A common difficulty at the end of life (EOL) is to determine an appropriate service model, such as hospice share care (HSC), hospice inpatient care (HIC) and hospice home care (HHC). This study aimed to recommend the appropriate hospice delivery model based on the physical, psychosocial and spiritual needs of patients referred for hospice care. METHODS: This cohort study included patients who received only one kind of hospice delivery model between 2006 and 2020. Data were analysed with descriptive statistics, Fisher's exact test, non-parametric analysis of variance, Kaplan-Meier curves and Cox proportional hazards model that determined the patients' clinical characteristics for a hospice delivery model and overall survival. RESULTS: A total of 8874 hospice patients were recruited, of which 7076 (79.7%) were HSC patients, 918 (10.4%) were HIC patients and 880 (9.9%) were HHC patients. There were significant differences in the physical symptoms and demographic, psychosocial and spiritual factors among the three groups (p<0.001). The patients who received the HHC were less to have dyspnoea (18.5%) and dysphagia (28.7%). The HIC patients showed higher severity of symptoms and experienced greater psychosocial distress (73.2%). The HSC is appropriate for noncancer patients . Patients with cancer were associated with less dyspnoea (32.4%) and dysphagia (46.5%). Patients with lung cancer who received the HHC had better survival than those who received other types of hospice care (HR=0.75, 95% CI: 0.66 to 0.86, p<0.001). CONCLUSIONS: This study provides guidance regarding the appropriate hospice service model, based on individualised palliative needs, targeting improvement in EOL care.

MET Mutation Is a Potential Therapeutic Target for Advanced Endometrial Cancer.

An optimal therapeutic regimen for endometrial cancer with extra-uterine metastasis is unavailable. This study aims to improve our understanding of the genomic landscape of advanced endometrial cancer and identify potential therapeutic targets. The clinical and genomic profiles of 81 patients with stage III or IV endometrial cancer were integrated. To identify genomic aberrations associated with clinical outcomes, Cox proportional hazard regression was used. The impacts of the genomic aberrations were validated in vitro and in vivo. The mutation status of MET, U2AF1, BCL9, PPP2R1A, IDH2, CBL, BTK, and CHEK2 were positively correlated with poor clinical outcomes. MET mutations occurred in 30% of the patients who presented with poor overall survival (hazard ratio, 2.606; 95% confidence interval, 1.167~5.819; adjusted p-value, 0.067). Concurrent MET and KRAS mutations presented with the worst outcomes. MET mutations in hepatocyte growth factor (HGF)-binding (58.1%) or kinase (16.2%) domains resulted in differential HGF-induced c-MET phosphorylation. Different types of MET mutations differentially affected tumor growth and displayed different sensitivities to cisplatin and tyrosine kinase inhibitors. MET N375S mutation is a germline variant that causes chemoresistance to cisplatin, with a high incidence in Eastern Asia. This study highlights the ethnic differences in the biology of the disease, which can influence treatment recommendations and the genome-guided clinical trials of advanced endometrial cancer.

A Simplified Diagnostic Classification Scheme of Chemotherapy-Induced Peripheral Neuropathy.

Background and Objective. The main purpose of this study was to develop a simple automatic diagnostic classification scheme for chemotherapy-induced peripheral neuropathy. METHODS: This was a prospective cohort study that enrolled patients with colorectal or gynecologic cancer post chemotherapy for more than 1 year. The patients underwent laboratory examinations (nerve conduction studies and quantitative sensory tests), and a questionnaire about the quality of life. An unsupervised classification algorithm was used to classify the patients into groups using a small number of variables derived from the laboratory tests. A panel of five neurologists also diagnosed the types of neuropathies according to the laboratory tests. The results by the unsupervised classification algorithm and the neurologists were compared. RESULTS: The neurologists' diagnoses showed much higher rates of entrapment syndromes (66.1%) and radiculopathies (55.1%) than polyneuropathy (motor/sensory: 33.1%/29.7%). A multivariate analysis showed that the questionnaire was not significantly correlated with the results of quantitative sensory tests (r = 0.27) or the neurologists' diagnoses (r = 0.27) or the neurologists' diagnoses (. CONCLUSION: The results of our unsupervised classification algorithm based on three variables of laboratory tests correlated well with the neurologists' diagnoses.

Kidney Stone History and Adverse Outcomes After Percutaneous Coronary Intervention.

OBJECTIVE: To determine whether kidney stone history is associated with adverse outcomes after percutaneous coronary intervention (PCI). Kidney stone formers have an increased risk of developing coronary artery disease; however, whether these patients have worse cardiac outcomes is unknown. MATERIALS AND METHODS: We identified adult patients who underwent first-time PCI in Vanderbilt University Medical Center (VUMC) Synthetic Derivative from 2008 to 2016 (n = 11,289) and in a nationwide database of Taiwan (NHIRD) from 2005 to 2012 (n = 155,762). Odds ratios (ORs) of 30-day in-hospital mortality and hazard ratios (HRs) of 1-year and 3-year adverse outcomes associated with kidney stone history were estimated using a propensity score approach. RESULTS: Overall, 294 and 12,286 stone formers undergoing PCI were identified in the VUMC and NHIRD, respectively. After matching, stone formers at VUMC were at higher risks of 30-day in-hospital mortality (OR 2.79, 95% CI 1.15-6.69) and 1-year (HR 1.59, 95% CI 1.13-2.24) and 3-year (HR 1.36, 95% CI 1.02-1.81) myocardial infarction. In the NHIRD, kidney stone history was associated with 1-year (HR 1.12, 95% CI 1.03-1.21) and 3-year (HR 1.14, 95% CI 1.06-1.22) myocardial infarction. In a sensitivity analysis, stone formers undergoing kidney stone surgery were marginally associated with 30-day in-hospital mortality (OR 1.21, 95% CI 0.99-1.48) and were associated with 3-year myocardial infarction (HR 1.13, 95% CI 1.02-1.25). CONCLUSION: Kidney stone history is associated with poorer cardiac outcomes after PCI. Improving secondary cardiac prevention strategies after PCI may be necessary for patients with a history of kidney stone disease.

Health-related quality of life associated with different cancer treatments in Chinese breast cancer survivors in Taiwan.

We assessed the quality of life (QoL) associated with patient's characteristics and different cancer treatments among Chinese breast cancer survivors in Taiwan. A cross-sectional survey was conducted in 2017 where 193 patients with hormone receptor-positive/human epidermal growth factor receptor-2-negative metastatic breast cancer were recruited. Three QoL questionnaires were administered: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), its breast cancer supplementary measure (QLQ-BR23) and EQ-5D-5L. Multiple linear regression was performed to assess the association between QoL and cancer treatments, with adjustment for patient's characteristics. The mean age of study participants was 55.52 years. Simple linear regression showed that cancer stage and receiving chemotherapy were significantly associated with QoL scores (p < 0.05). Significant adverse effects of chemotherapy on QoL were found among early-stage cancer women (i.e., I or II), including poor cognitive and sexual functioning, and a higher symptom burden (i.e., dyspnoea, constipation, systematic therapy side effects). Multiple linear regression also revealed that receiving chemotherapy was significantly associated with poor QoL (e.g., lower functional health and higher symptom burden measured by the QLQ-BR23), compared to none chemotherapy (p < 0.05). Receiving chemotherapy was associated with poor QoL, especially among early-stage breast cancer patients.

Molecular damage and responses of oral keratinocyte to hydrogen peroxide.

BACKGROUND: Hydrogen peroxide (H2O2)-based tooth bleaching reagents have recently increased in popularity and controversy. H2O2 gel (3%) is used in a Nightguard for vital bleaching; transient tooth sensitivity and oral mucosa irritation have been reported. Genotoxicity and carcinogenicity have also been significant concerns. METHODS: We used primary cultured normal human oral keratinocytes (NHOKs) as an in vitro model to investigate the pathological effects to mitochondria functions on human oral keratinocytes exposed to different doses of H2O2 for different durations. RESULTS: An MTT assay showed compromised cell viability at a dose over 5 mM. The treatments induced nuclear DNA damage, measured using a single-cell gel electrophoresis assay. A real-time quantitative polymerase chain reaction showed H2O2 induced significant increase in mitochondrial 4977-bp deletion. Mitochondrial membrane potential and apoptosis assays suggested that oxidative damage defense mechanisms were activated after prolonged exposure to H2O2. Reduced intracellular glutathione was an effective defense against oxidative damage from 5 mM of H2O2. CONCLUSION: Our study suggests the importance for keratinocyte damage of the dose and the duration of the exposure to H2O2 in at-home-bleaching. A treatment dose ≥100 mM directly causes severe cytotoxicity with as little as 15 min of exposure.