Survival of advanced/recurrent gastrointestinal stromal tumors treated with tyrosine kinase inhibitors in Taiwan: a nationwide registry study.

BACKGROUND: Most gastrointestinal stromal tumors (GISTs) harbor c-KIT or PDGFRA mutations. Administration of tyrosine kinase inhibitors (TKIs) has significantly improved the survival of patients with GISTs. We aimed to evaluate the clinical outcome of advanced or recurrent GIST patients in Taiwan. METHODS: Patients diagnosed between 2010 and 2020 were enrolled. The collected data included baseline characteristics, treatment pattern, treatment outcome, genetic aberrations and survival status. Progression-free survival (PFS) and overall survival (OS) were analyzed and plotted with the Kaplan-Meier method. Cox regression analysis was used to analyze the prognostic factors of survival. RESULTS: A total of 224 patients with advanced or recurrent GISTs treated with TKIs were enrolled. All patients received imatinib treatment. Ninety-three and 42 patients received sunitinib and regorafenib treatment, respectively. The 48-month PFS and OS rates for patients treated with imatinib were 50.5% and 79.5%, respectively. c-KIT exon 9 and PDGFRA mutations were prognostic factors for a poor PFS and PDGFRA mutation was a prognostic factor for a poor OS in patients treated with imatinib in multivariate Cox regression analysis. The median PFS of patients who received sunitinib treatment was 12.76 months (95% confidence interval (CI), 11.01-14.52). Patients with c-KIT exon 9 mutations had a longer PFS than those with other genetic aberrations. The median PFS of patients treated with regorafenib was 7.14 months (95% CI, 3.39-10.89). CONCLUSIONS: We present real-world clinical outcomes for advanced GIST patients treated with TKIs and identify mutational status as an independent prognostic factor for patient survival.

Redefining aberrant P53 expression of gastric cancer and its distinct clinical significance among molecular-histologic subtypes.

BACKGROUND: Numerous studies have demonstrated a correlation between p53 overexpression and diminished survival in gastric cancer patients. However, conflicting findings exist, and we hypothesize that these discrepancies arise from the cancer's complexity and heterogeneity, coupled with a lack of consensus on aberrant p53 expression. METHODS: We enrolled a cohort of 187 patients with surgically resected gastric cancer. Patient categorization was based on Epstein-Barr virus (EBV), microsatellite instability (MSI), and Lauren classification (intestinal, diffuse and mixed). Utilizing an incremental algorithm, we evaluated p53 immunohistochemical (IHC) patterns in all 187 cases, while next-generation sequencing was successfully performed on 152 cases to identify TP53 mutations (mutTP53). RESULTS: MutTP53 was identified in 32 % of the 152 cases, comprising 36 missense, 5 nonsense, and 7 frameshift alterations. Missense mutations predominantly correlated with p53 overexpression, while nonsense and frameshifting alterations related to null expression. Trial calculations indicated that null expression and a p53 IHC cutoff at >40 % offered the best prediction of mutTP53 (kappa coefficient, 0.427), with the highest agreement (0.524) observed in diffuse type and the lowest (0.269) in intestinal type. Null expression and a p53 IHC cutoff at >10 %, but not mutTP53 per se, provided the optimal prediction of survival outcome (p = 0.043), particularly in diffuse type (p = 0.044). Multivariate analysis showed that aberrant p53 IHC expression was not an independent prognostic factor. CONCLUSIONS: P53 IHC patterns are predictive biomarkers for mutTP53 and gastric cancer outcomes, where a prerequisite involves a nuanced approach considering cutoff values and molecular-histologic subtyping.

Impact of preoperative frailty on the surgical and survival outcomes in older patients with solid cancer after elective abdominal surgery.

BACKGROUND: Frailty is common in older patients with cancer; however, its clinical impact on the survival outcomes has seldom been examined in these patients. This study aimed to investigate the association of frailty with the survival outcomes and surgical complications in older patients with cancer after elective abdominal surgery in Taiwan. METHODS: We prospectively enrolled 345 consecutive patients aged ≥65 years with newly diagnosed cancer who underwent elective abdominal surgery between 2016 and 2018. They were allocated into the fit, pre-frail, and frail groups according to comprehensive geriatric assessment (CGA) findings. RESULTS: The fit, pre-frail, and frail groups comprised 62 (18.0%), 181 (52.5%), and 102 (29.5%) patients, respectively. After a median follow-up of 48 (interquartile range, 40-53) months, the mortality rates were 12.9%, 31.5%, and 43.1%, respectively. The adjusted hazard ratio was 1.57 (95% confidence interval [CI], 0.73-3.39; p = 0.25) and 2.87 (95% CI, 1.10-5.35; p = 0.028) when the pre-frail and frail groups were compared with the fit group, respectively. The frail group had a significantly increased risk for a prolonged hospital stay (adjusted odds ratio, 2.22; 95% CI, 1.05-4.69; p = 0.022) compared with the fit group. CONCLUSION: Pretreatment frailty was significantly associated with worse survival outcomes and more surgical complications, with prolonged hospital stay, in the older patients with cancer after elective abdominal surgery. Preoperative frailty assessment can assist physicians in identifying patients at a high risk for surgical complications and predicting the survival outcomes of older patients with cancer.

Secreted frizzled-related protein 4 induces gastric cancer progression and resistance to cisplatin and oxaliplatin via ß-catenin dysregulation.

INTRODUCTION: Gastric cancer is the 5th most common cancer and 3rd leading cause of cancer-related death worldwide. There are three main ways to treat gastric cancer: surgical resection, radiation therapy, and drug therapy. Furthermore, combinations of two to three regimens can improve survival. However, the survival outcomes of chemotherapy in advanced gastric cancer patients are still unsatisfactory. Unfortunately, no widely useful biomarkers have been verified to predict the efficacy of chemotherapy for locally advanced gastric cancer. METHODS: An MTT assay was used to determine the cell viability after cisplatin or oxaliplatin treatment. Western blotting and immunohistochemistry were utilized to examine the sFRP4 level and associated signaling pathways. Immunofluorescence staining was utilized to analyze the location of ß-catenin. Colony formation and Transwell assays were used to analyze the functions related with cisplatin, oxaliplatin and sFRP4. RESULTS: We have found that gastric cancer patients treated with combinations of 5-fluorouracil (5-FU) and cisplatin regimens have better survival rates than those treated with 5-FU-based chemotherapy alone. Secreted frizzled-related protein 4 (sFRP4) was selected as a potential target from stringent analysis and intersection of 5-FU and cisplatin resistance-related gene sets. sFRP4 was shown to be overexpressed in clinical gastric tumor tissues and positively correlated with a worse survival rate. In addition, sFRP4 and ß-catenin were upregulated in cisplatin-resistant and oxaliplatin-resistant gastric cancer cells compared to parental cells. Immunofluorescence staining and nuclear fractionation showed that ß-catenin translocated from the cytosol into the nucleus. Moreover, sFRP4 was detected in the conditioned medium of these resistant cells, which indicates that sFRP4 might have an extracellular role in chemotherapy resistance. Increased migration capacity and dysregulation of epithelial-mesenchymal transition-related markers, which might result from the dysregulation of sFRP4, were observed in cisplatin-resistant and oxaliplatin-resistant gastric cancer cells. DISCUSSION/CONCLUSION: In summary, sFRP4 might play a critical role in resistance to cisplatin and oxaliplatin, cell metastasis and poor prognosis in gastric cancer via the Wnt-ß-catenin pathway. Investigations of the molecular mechanism underlying sFRP4-modulated cancer progression and chemotherapeutic outcomes can provide additional therapeutic strategies for gastric cancer.

Curriculum mapping of accredited pharmacy programs in the United States.

INTRODUCTION: No current guidance exists to inform the content area credit hours for doctor of pharmacy (PharmD) programs in the United States (US). METHODS: Public websites were accessed for all Accreditation Council for Pharmacy Education (ACPE) accredited PharmD programs in the US to record the credit hours devoted to drug therapy, clinical skills, experiential learning, scholarship, social and administrative sciences, physiology/pathophysiology, pharmacogenomics, medicinal chemistry, pharmacology, pharmaceutics, and pharmacokinetics/pharmacodynamics in the didactic curricula. Due to the high prevalence of programs that integrate drug therapy, pharmacology, and medicinal chemistry into a single course, we subdivided programs based upon whether drug therapy courses were "integrated" or "non-integrated." A regression analyses was conducted to explore the relationship between each content area and North American Pharmacist Licensure Examination (NAPLEX) pass rates and residency match rates. RESULTS: Data were available for 140 accredited PharmD programs. Drug therapy had the highest credit hours in programs with both integrated and non-integrated drug therapy courses. Programs with integrated drug therapy courses had significantly more credit hours in experiential and scholarship and fewer credit hours in stand-alone courses for pathophysiology, medicinal chemistry, and pharmacology. Credit hours in content areas did not predict NAPLEX pass rate nor residency match success rate. CONCLUSIONS: This is the first comprehensive description of all ACPE accredited pharmacy schools with credit hours broken down by content areas. While content areas did not directly predict success criteria, these results may still be useful to describe curricular norms or inform the design of future pharmacy curricula.

Cancer survivorship and risk of pregnancy complications, adverse obstetric outcomes, and maternal morbidities in female adolescents and young adults: a nationwide population-based study from Taiwan.

BACKGROUND: Cancer treatment in female adolescent and young adult (AYA) cancer survivors (i.e., those diagnosed between 15 and 39 years of age) may adversely affect multiple bodily functions, including the reproductive system. METHODS: We initially assembled a retrospective, nationwide population-based cohort study by linking data from two nationwide Taiwanese data sets. We subsequently identified first pregnancies and singleton births to AYA cancer survivors (2004-2018) and select AYA without a previous cancer diagnosis matched to AYA cancer survivors for maternal age and infant birth year. RESULTS: The study cohort consisted of 5151 and 51,503 births to AYA cancer survivors and matched AYA without a previous cancer diagnosis, respectively. The odds for overall pregnancy complications (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.01-1.18) and overall adverse obstetric outcomes (OR, 1.07; 95% CI, 1.01-1.13) were significantly increased in survivors compared with matched AYA without a previous cancer diagnosis. Specifically, cancer survivorship was associated with an increased risk of preterm labour, labour induction, and threatened abortion or threatened labour requiring hospitalisation. CONCLUSIONS: AYA cancer survivors are at increased risk for pregnancy complications and adverse obstetric outcomes. Efforts to integrate individualised care into clinical guidelines for preconception and prenatal care should be thoroughly explored.

Reply to Graziosi et al. Rationale in the Use of Adjuvant Chemotherapy in pT3N0M0 Gastric Cancer Resected Patients. Comment on "Chen et al. Prognostic Factors and the Role of Adjuvant Chemotherapy in Pathological Node-Negative T3 Gastric Cancer. J. Pers. Med. 2023, 13, 553".

We appreciate the authors very much for their interest in our article "Prognostic factors and the role of adjuvant chemotherapy in pathological node-negative T3 gastric cancer" [...].

Clinical Benefits of Laparoscopic Adhesiolysis during Peritoneal Dialysis Catheter Insertion: A Single-Center Experience.

Background and Objectives: In peritoneal dialysis (PD) therapy, intra-abdominal adhesions (IAAs) can cause catheter insertion failure, poor dialysis function, and decreased PD adequacy. Unfortunately, IAAs are not readily visible to currently available imaging methods. The laparoscopic approach for inserting PD catheters enables direct visualization of IAAs and simultaneously performs adhesiolysis. However, a limited number of studies have investigated the benefit/risk profile of laparoscopic adhesiolysis in patients receiving PD catheter placement. This retrospective study aimed to address this issue. Materials and Methods: This study enrolled 440 patients who received laparoscopic PD catheter insertion at our hospital between January 2013 and May 2020. Adhesiolysis was performed in all cases with IAA identified via laparoscopy. We retrospectively reviewed data, including clinical characteristics, operative details, and PD-related clinical outcomes. Results: These patients were classified into the adhesiolysis group (n = 47) and the non-IAA group (n = 393). The clinical characteristics and operative details had no remarkable between-group differences, except the percentage of prior abdominal operation history was higher and the median operative time was longer in the adhesiolysis group. PD-related clinical outcomes, including incidence rate of mechanical obstruction, PD adequacy (Kt/V urea and weekly creatinine clearance), and overall catheter survival, were all comparable between the adhesiolysis and non-IAA groups. None of the patients in the adhesiolysis group suffered adhesiolysis-related complications. Conclusions: Laparoscopic adhesiolysis in patients with IAA confers clinical benefits in achieving PD-related outcomes comparable to those without IAA. It is a safe and reasonable approach. Our findings provide new evidence to support the benefits of this laparoscopic approach, especially in patients with a risk of IAAs.

Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer with Peritoneal Carcinomatosis: Additional Information Helps to Optimize Patient Selection before Surgery.

(1) Background: The prognosis of gastric cancer-associated peritoneal carcinomatosis (GCPC) is poor, with a median survival time of less than six months, and current systemic chemotherapy, including targeted therapy, is ineffective. Despite growing evidence that cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for GCPC improves overall survival (OS), optimal patient selection remains unclear. We aimed to evaluate preoperative clinical factors and identify indicative factors for predicting postoperative OS in patients with GCPC undergoing CRS-HIPEC. (2) Methods: We retrospectively reviewed 44 consecutive patients with GCPC who underwent CRS-HIPEC between May 2015 and May 2021. Data on demographics and radiologic assessment were collected and analyzed. (3) Results: Elevated preoperative serum neutrophil-to-lymphocyte ratio > 4.4 (p = 0.003, HR = 3.70, 95% CI = 1.55-8.79) and number of computed tomography risks > 2 (p = 0.005, HR = 3.26, 95% CI = 1.33-7.98) were independently indicative of OS post-surgery. A strong correlation was observed between intraoperative peritoneal cancer index score and number of computed tomography risks (r = 0.534, p < 0.0001). Two patients after CRS-HIPEC ultimately achieved disease-free survival for more than 50 months. (4) Conclusions: Our experience optimizes GCPC patients' selection for CRS-HIPEC, may help to improve outcomes in the corresponding population, and prevent futile surgery in inappropriate patients.

Prognostic Factors and the Role of Adjuvant Chemotherapy in Pathological Node-Negative T3 Gastric Cancer.

The role of adjuvant chemotherapy in pathological T3N0M0 (pT3N0M0) gastric cancer (GC) remains unclear. The aim of this study was to analyze the prognostic factors of patients with pT3N0M0 GC and to clarify which ones could benefit from adjuvant chemotherapy. A total of 137 patients with pT3N0M0 GC were recruited between 1994 and 2020. Clinicopathological factors and adjuvant chemotherapy regimens were retrospectively collected. Prognostic factors of disease-free survival (DFS) and cancer-specific survival (CSS) were determined using univariate and multivariate analyses. The chemotherapy group was younger (p = 0.012), had had more lymph nodes retrieved (p = 0.042) and had higher percentages of vascular invasion (p = 0.021) or perineural invasion (p = 0.030) than the non-chemotherapy group. There were no significant differences in DFS (p = 0.222) and CSS (p = 0.126) between patients treated with or without adjuvant chemotherapy. Stump cancer, tumor size and perineural invasion were associated with higher rates of recurrence. Tumor size was an independent prognostic factor for DFS (hazard ratio, 4.55; confidence interval, 1.59-12.99; p = 0.005) and CSS (hazard ratio, 3.97; confidence interval, 1.38-11.43; p = 0.011). Tumor size independently influenced survival outcomes in pT3N0M0 patients who underwent radical surgery with and without adjuvant chemotherapy.

Risk factors of recurrent secondary hyperparathyroidism after adequate primary surgical treatment.

Background: Secondary hyperparathyroidism (SHPT) is a common condition in patients with end-stage renal disease (ESRD) who are on dialysis. Parathyroidectomy is a treatment for patients when medical therapy has failed. Recurrence may occur and is indicated for further surgery in the era of improved quality of care for ESRD patients. Methods: We identified, 1060 patients undergoing parathyroidectomy from January, 2011 to June, 2020. After excluding patients without regular check-up at our institute, primary hyperparathyroidism, or malignancy, 504 patients were enrolled. Sixty-two patients (12.3%, 62/504) were then excluded due to persistent SHPT even after the first parathyroidectomy. We aimed to identify risk factors for recurrent SHPT after the first surgery. Results: During the study period, 20% of patients who underwent parathyroidectomy at our institute (in, 2019) was due to recurrence after a previous parathyroidectomy. There were 442 patients eligible for analysis of recurrence after excluding patients with the persistent disease (n = 62). While 44 patients (9.95%) had recurrence, 398 patients did not. Significant risk factors for recurrent SHPT within 5 years after the first parathyroidectomy, including dialysis start time to first operation time < 3 years (p = 0.046), postoperative PTH >106.5 pg/mL (p < 0.001), and postoperative phosphorus> 5.9 mg/dL (p = 0.016), were identified by multivariate analysis. Conclusions: The starting time of dialysis to first operation time < 3 years in the patients with dialysis, postoperative PTH> 106.5 pg/mL, and postoperative phosphorus> 5.9 mg/dL tended to have a higher risk for recurrent SHPT within 5 years after primary treatment.

Association of preoperative frailty and postoperative delirium in older cancer patients undergoing elective abdominal surgery: A prospective observational study in Taiwan.

BACKGROUND: Postoperative delirium (POD) is a common surgical complication in elderly patients. As frailty is a relatively novel concept, its clinical significance for POD has seldom been examined. This study aimed to investigate the association between frailty and POD in aged cancer patients undergoing elective abdominal surgery in Taiwan. METHODS: We prospectively enrolled 345 consecutive patients aged ≥65 years with newly diagnosed cancer who underwent elective abdominal surgery between 2016 and 2018. Frailty assessment was performed using the Comprehensive Geriatric Assessment (CGA). POD was assessed daily using the Confusion Assessment Method from postoperative day 1 until discharge. Patients were allocated into fit and frail groups. RESULTS: POD occurred in 19 (5.5%) of 345 patients. POD incidence was 1.6%, 3.1%, 4.8%, 11.5%, and 10.0% in patients with 0, 1, 2, 3, and 4+ frail conditions, respectively, which presented a positive linear correlation among patients with an increased number of frail conditions and POD incidence. Based on CGA, 159 (46.1%) and 186 (53.9%) patients were allocated to fit and frail groups, respectively. POD incidence was 2.5% and 8.1% for the fit and frail groups, respectively. Frailty status was an independent risk factor for POD occurrence in multivariate analysis. CONCLUSION: Our study identified frailty as an independent risk factor for POD in aged Taiwanese cancer patients undergoing elective abdominal surgery. Given the high prevalence of frailty among older cancer patients, preoperative assessment is important to identify high risk of POD and to improve the quality of postoperative care.

Risk factors and effect of postoperative delirium on adverse surgical outcomes in older adults after elective abdominal cancer surgery in Taiwan.

BACKGROUND: Postoperative delirium (POD) is a common complication in older adults, with unknown epidemiology and effects on surgical outcomes in Asian geriatric cancer patients. This study evaluated incidence, risk factors, and association between adverse surgical outcomes and POD after intra-abdominal cancer surgery in Taiwan. METHODS: Overall, 345 patients aged ≥65 years who underwent elective abdominal cancer surgery at a medical center in Taiwan were prospectively enrolled. Delirium was assessed daily using the Confusion Assessment Method. Univariate and multivariate logistic regression analyses investigated risk factors for POD occurrence and estimated the association with adverse surgical outcomes. RESULTS: POD occurred in 19 (5.5%) of the 345 patients. Age ≥73 years, Charlson comorbidity index ≥3, and operative time >428 min were independent predictors for POD occurrence. Patients presenting with one, two, and three risk factors had 4.1-fold (95% confidence interval [CI], 0.4-35.8, p = 0.20), 17.4-fold (95% CI, 2.2-138, p = 0.007), and 30.8-fold likelihood (95% CI, 2.9-321, p = 0.004) for POD occurrence, respectively. Patients with POD had a higher probability of prolonged hospital stay (adjusted odds ratio [OR] 2.8; 95% CI, 1.0-8.1; p = 0.037), intensive care stay (adjusted OR: 3.9; 95% CI, 1.5-10.5; p = 0.008), 30-day readmission (adjusted OR 3.1; 95% CI, 1.1-9.7; p = 0.039), and 90-day postoperative death (adjusted OR: 4.2; 95% CI, 1.0-17.7; p = 0.041). CONCLUSION: POD occurrence was significantly associated with adverse surgical outcomes in geriatric patients undergoing elective abdominal cancer surgery, highlighting the importance of early POD identification in geriatric patients to improve postoperative care quality.

A novel technique of sutureless omentopexy during dual-incision laparoscopic peritoneal dialysis catheter insertion to prevent catheter dysfunction due to omental wrapping.

BACKGROUND: Omental wrapping (OW) is the leading cause of obstruction of the peritoneal dialysis (PD) catheter, which interferes with dialysis treatment. Routinely or selectively performing omentopexy during laparoscopic PD catheter placement has been suggested to prevent OW. However, most of the published techniques for performing this adjunctive procedure require additional incisions and suturing. Herein, we aimed to report our experience in performing omentopexy with a sutureless technique during dual-incision PD catheter insertion. We also performed a comparative analysis to assess the benefit/risk profile of routine omentopexy in these patients. METHODS: This retrospective study enrolled 469 patients who underwent laparoscopic PD catheter insertion. Their demographic characteristics and operative details were collected from the database of our institution. Omentopexy was performed by fixing the inferior edge of the omentum to the round ligament of the liver using titanium clips. For analysis, the patients were divided into the omentopexy group and the non-omentopexy group. We also reviewed the salvage management and outcomes of patients who experienced OW. RESULTS: The patients were categorized into the omentopexy (n = 81) and non-omentopexy (n = 388) groups. The patients in the non-omentopexy group had a higher incidence of OW, whereas no patient in the omentopexy group experienced this complication (5.2% vs. 0.0%, p = 0.033). The median operative time was 27 min longer in patients who underwent omentopexy than in those who did not [100 (82-118) min vs. 73 (63-84) min, p < 0.001]. One patient had an intra-abdominal hematoma after omentopexy and required salvage surgery to restore catheter function. The complication rate of omentopexy was 1.2% (1/81). CONCLUSION: Sutureless omentopexy during laparoscopic PD catheter insertion is a safe and reliable technique that does not require additional incisions and suturing. Routinely performing omentopexy provides clinical benefits by reducing the risk of catheter dysfunction due to OW.

Gastroesophageal Reflux Disease Symptoms after Laparoscopic Sleeve Gastrectomy: A Retrospective Study.

(1) Background: Laparoscopic sleeve gastrectomy (LSG) is widely performed in bariatric surgery. However, the prevalence and risk factors of gastroesophageal reflux disease (GERD) symptoms after LSG remain unclear to date. This study aimed to identify risk factors of GERD after LSG. (2) Methods: We conducted a retrospective study at Linkou Chang Gung Memorial Hospital and reviewed 296 patients who underwent LSG from 2016 to 2019. A total of 143 patients who underwent preoperative esophagogastroduodenoscopy and completed the 12-month postoperative follow-up were enrolled. Patients' demographic data, comorbidities, and postoperative weight loss results were recorded for analysis. The GerdQ questionnaire was used to assess GERD after LSG. (3) Results: There were eight surgical complications (5.6%) among the 143 studied patients (median age, 36 years; 56 (39.2%) men; median body weight 105.5 kg; median body mass index [BMI], 38.5 kg/m2). Twenty-three patients (16.1%) developed de novo GERD symptoms. GERD was significantly associated with older age (p = 0.022) and lower BMI (<35 kg/m2, p = 0.028). In multiple logistic regression analysis, age and BMI were significantly associated with GERD. (4) Conclusions: LSG is a safe and effective weight loss surgery. In our study, it led to 16.1% of de novo GERD symptoms, which were significantly related to older age and lower BMI (<35 kg/m2).

Mechanism Underlying Metformin Action and Its Potential to Reduce Gastric Cancer Risk.

Diabetes mellitus is associated with a high risk of developing gastric cancer (GC). Metformin, which is conventionally used to treat type 2 diabetes, induces AMP-activated protein kinase signaling and suppresses gluconeogenesis. Recent studies have reported that metformin is associated with beneficial effects in cancer prevention and treatment owing to its anti-tumor effects. This makes metformin a potential medication for GC therapy. However, contradicting reports have emerged regarding the efficacy of metformin in reducing the risk of GC. This review summarizes the impact of metformin on mitigating GC risk by analyzing clinical databases. The mechanism underlying the anti-tumor effect of metformin on GC is also discussed.

Optimal Timing of Cholecystectomy for Patients with Concurrent Acute Cholecystitis and Acute Cholangitis after Successful Biliary Drainage by Interventional Endoscopic Retrograde Cholangiopancreatography.

Background: Concurrent acute cholecystitis and acute cholangitis is a unique clinical situation. We tried to investigate the optimal timing of cholecystectomy after adequate biliary drainage under this condition. Methods: From January 2012 to November 2017, we retrospectively screened all in-hospitalized patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and then identified patients with concurrent acute cholecystitis and acute cholangitis from the cohort. The selected patients were stratified into two groups: one-stage intervention (OSI) group (intended laparoscopic cholecystectomy at the same hospitalization) vs. two-stage intervention (TSI) group (interval intended laparoscopic cholecystectomy). Interrogated outcomes included recurrent biliary events, length of hospitalization, and surgical outcomes. Results: There were 147 patients ultimately enrolled for analysis (OSI vs. TSI, 96 vs. 51). Regarding surgical outcomes, there was no significant difference between the OSI group and TSI group, including intraoperative blood transfusion (1.0% vs. 2.0%, p = 1.000), conversion to open procedure (3.1% vs. 7.8%, p = 0.236), postoperative complication (6.3% vs. 11.8%, p = 0.342), operation time (118.0 min vs. 125.8 min, p = 0.869), and postoperative days until discharge (3.37 days vs. 4.02 days, p = 0.643). In the RBE analysis, the OSI group presented a significantly lower incidence of overall RBE (5.2% vs. 41.2%, p < 0.001) than the TSI group. Conclusions: Patients with an initial diagnosis of concurrent acute cholecystitis and cholangitis undergoing cholecystectomy after ERCP drainage during the same hospitalization period may receive some benefit in terms of clinical outcomes.

Assessing the causal relationships between gout and hypertension: a bidirectional Mendelian randomisation study with coarsened exposures.

OBJECTIVES: Observational studies have demonstrated associations between gout and hypertension, but whether they are causal remains unclear. Our work aims to assess the causal relationship between gout and hypertension. METHODS: We obtained genetic information from the Taiwan Biobank, including 88,347 participants and 686,439 single-nucleotide polymorphisms (SNPs). A novel model of Mendelian randomisation (MR) with coarsened exposures was used to examine the causality between the liability of gout on hypertension and vice versa, using 4 SNPs associated with gout and 10 SNPs associated with hypertension after removal of SNPs associated with measured confounders. The binary exposure (gout/hypertension) can be considered a coarsened approximation of a latent continuous trait. The inverse-variance weighted (IVW) and polygenic risk score (PRS) methods were used to estimate effect size. The MR analysis with coarsened exposures was performed with and without adjustments for covariates. RESULTS: Of the 88,347 participants, 3253 (3.68%) had gout and 11,948 (13.52%) had hypertension (men, 31.9%; mean age 51.1 [SD, 11.1] years). After adjusting to measured confounders, MR analysis with coarsened exposures showed a significant positive causal effect of the liability of gout on hypertension in both the IVW method (relative risk [RR], 1.10; 95% confidence interval [CI], 1.03-1.19; p = 0.0077) and the PRS method (RR, 1.10; 95% CI, 1.02-1.19; p = 0.0092). The result of causality was the same before and after involving measured confounders. However, there was no causal effect of the liability of hypertension on gout. CONCLUSIONS: In this study, we showed that the liability of gout has a causal effect on hypertension, but the liability of hypertension does not have a causal effect on gout. Adequate management of gout may reduce the risk of developing hypertension.

Characterization of a Droplet Containing the Clustered Magnetic Beads Manipulation by Magnetically Actuated Chips.

A magnetically actuated chip was successfully developed in this study to perform the purpose of transportation for a droplet containing clustered magnetic beads. The magnetic field gradient is generated by the chip of the two-layer 4 × 4 array micro-coils, which was commercially fabricated by printing circuit board (PCB) technology. A numerical model was first established to investigate the magnetic field and thermal field for such a micro-coil. Consequently, the numerical simulations were in reasonable agreement with the experimental results. Moreover, a theoretical analysis was derived to predict the dynamic behaviors of the droplets. This analysis will offer the optimal operation for such a magnetically actuated chip. This study aims to successfully implement the concept of "digital microfluidics" in "point-of-care testing" (POCT). In the future, the micro-coil chip will be of substantial benefit to genetic analysis and infectious disease detection.

Reply to Mazzei et al. Some Concerns from a Radiological Point of View. Comment on "Huang et al. Outcomes of Conversion Surgery for Metastatic Gastric Cancer Compared with In-Front Surgery plus Palliative Chemotherapy or In-Front Surgery Alone. J. Pers. Med. 2022, 12, 555".

We thank the authors for their interest in our article "Outcomes of Conversion Surgery for Metastatic Gastric Cancer Compared with In-Front Surgery Plus Palliative Chemotherapy or In-Front Surgery Alone" [...].