Adjuvant Chemoradiation in Resected Biliary Adenocarcinoma: Evaluation of SWOG S0809 with a Large National Database.

BACKGROUND: There is a paucity of evidence supporting the use of adjuvant radiation therapy in resected biliary cancer. Supporting evidence for use comes mainly from the small SWOG S0809 trial, which demonstrated an overall median survival of 35 months. We aimed to use a large national database to evaluate the use of adjuvant chemoradiation in resected extrahepatic bile duct and gallbladder cancer. METHODS: Using the National Cancer Database, we selected patients from 2004 to 2017 with pT2-4, pN0-1, M0 extrahepatic bile duct or gallbladder adenocarcinoma with either R0 or R1 resection margins, and examined factors associated with overall survival (OS). We examined OS in a cohort of patients mimicking the SWOG S0809 protocol as a large validation cohort. Lastly, we compared patients who received chemotherapy only with patients who received adjuvant chemotherapy and radiation using entropy balancing propensity score matching. RESULTS: Overall, 4997 patients with gallbladder or extrahepatic bile duct adenocarcinoma with available survival information meeting the SWOG S0809 criteria were selected, 469 of whom received both adjuvant chemotherapy and radiotherapy. Median OS in patients undergoing chemoradiation was 36.9 months, and was not different between primary sites (p = 0.841). In a propensity score matched cohort, receipt of adjuvant chemoradiation had a survival benefit compared with adjuvant chemotherapy only (hazard ratio 0.86, 95% confidence interval 0.77-0.95; p = 0.004). CONCLUSION: Using a large national database, we support the findings of SWOG S0809 with a similar median OS in patients receiving chemoradiation. These data further support the consideration of adjuvant multimodal therapy in resected biliary cancers.

Targeting NLRP3 signaling reduces myocarditis-induced arrhythmogenesis and cardiac remodeling.

BACKGROUND: Myocarditis substantially increases the risk of ventricular arrhythmia. Approximately 30% of all ventricular arrhythmia cases in patients with myocarditis originate from the right ventricular outflow tract (RVOT). However, the role of NLRP3 signaling in RVOT arrhythmogenesis remains unclear. METHODS: Rats with myosin peptide-induced myocarditis (experimental group) were treated with an NLRP3 inhibitor (MCC950; 10 mg/kg, daily for 14 days) or left untreated. Then, they were subjected to electrocardiography and echocardiography. Ventricular tissue samples were collected from each rat's RVOT, right ventricular apex (RVA), and left ventricle (LV) and examined through conventional microelectrode and histopathologic analyses. In addition, whole-cell patch-clamp recording, confocal fluorescence microscopy, and Western blotting were performed to evaluate ionic currents, intracellular Ca2+ transients, and Ca2+-modulated protein expression in individual myocytes isolated from the RVOTs. RESULTS: The LV ejection fraction was lower and premature ventricular contraction frequency was higher in the experimental group than in the control group (rats not exposed to myosin peptide). Myocarditis increased the infiltration of inflammatory cells into cardiac tissue and upregulated the expression of NLRP3; these observations were more prominent in the RVOT and RVA than in the LV. Furthermore, experimental rats treated with MCC950 (treatment group) improved their LV ejection fraction and reduced the frequency of premature ventricular contraction. Histopathological analysis revealed higher incidence of abnormal automaticity and pacing-induced ventricular tachycardia in the RVOTs of the experimental group than in those of the control and treatment groups. However, the incidences of these conditions in the RVA and LV were similar across the groups. The RVOT myocytes of the experimental group exhibited lower Ca2+ levels in the sarcoplasmic reticulum, smaller intracellular Ca2+ transients, lower L-type Ca2+ currents, larger late Na+ currents, larger Na+-Ca2+ exchanger currents, higher reactive oxygen species levels, and higher Ca2+/calmodulin-dependent protein kinase II levels than did those of the control and treatment groups. CONCLUSION: Myocarditis may increase the rate of RVOT arrhythmogenesis, possibly through electrical and structural remodeling. These changes may be mitigated by inhibiting NLRP3 signaling.

Colon Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the United States. Management of disseminated metastatic CRC involves various active drugs, either in combination or as single agents. The choice of therapy is based on consideration of the goals of therapy, the type and timing of prior therapy, the mutational profile of the tumor, and the differing toxicity profiles of the constituent drugs. This manuscript summarizes the data supporting the systemic therapy options recommended for metastatic CRC in the NCCN Guidelines for Colon Cancer.

Ventricular response as a predictor of the termination of sustained paroxysmal atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained atrial arrhythmia. Accurate detection of the timing and possibility of AF termination is vital for optimizing rhythm and rate control strategies. The present study evaluated whether the ventricular response (VR) in AF offers a distinctive electrocardiographic indicator for predicting AF termination. METHODS: Patients experiencing sustained paroxysmal AF for more than 3 h were observed using 24-h ambulatory Holter monitoring. VR within 5 min before AF termination (VR 0-5 min, BAFT) was compared with VR observed during the 60th to 65th min (VR 60-65 min, BAFT) and the 120th to 125th min (VR 120-125 min, BAFT) before AF termination. Maximum and minimum VRs were calculated on the basis of the average of the highest and lowest VRs across 10 consecutive heartbeats. RESULTS: Data from 37 episodes of paroxysmal AF revealed that the minimum VR0-5 min, BAFT (64 ± 20 bpm) was significantly faster than both the minimum VR120-125 min, BAFT (56 ± 15 bpm) and the minimum VR60-65 min, BAFT (57 ± 16 bpm, p < .05). Similarly, the maximum VR0-5 min, BAFT (158 ± 49 bpm) was significantly faster than the maximum VR120-125 min, BAFT (148 ± 45 bpm, p < .05). In the daytime, the minimum VR0-5 min, BAFT (66 ± 20 bpm) was significantly faster than both the minimum VR60-65 min, BAFT (58 ± 17 bpm) and minimum VR120-125 min, BAFT (57 ± 15 bpm, p < .05). However, the mean and maximum VR0-5 min, BAFT in the daytime were similar to the mean and maximum VR120-125 min in the daytime, respectively. At night, the minimum, mean, and maximum VR0-5 min, BAFT were similar to the minimum, mean, and maximum VR120-125 min, respectively. CONCLUSIONS: Elevated VR rates during AF episodes may be predictors for the termination of AF, especially during the daytime and in patients with nondilated left atria. These findings may guide the development of clinical approaches to rhythm control in AF.

Empagliflozin suppressed cardiac fibrogenesis through sodium-hydrogen exchanger inhibition and modulation of the calcium homeostasis.

BACKGROUND: The novel sodium-glucose co-transporter 2 inhibitor (SGLT2i) potentially ameliorates heart failure and reduces cardiac arrhythmia. Cardiac fibrosis plays a pivotal role in the pathophysiology of HF and atrial myopathy, but the effect of SGLT2i on fibrogenesis remains to be elucidated. This study investigated whether SGLT2i directly modulates fibroblast activities and its underlying mechanisms. METHODS AND RESULTS: Migration, proliferation analyses, intracellular pH assay, intracellular inositol triphosphate (IP3) assay, Ca2+ fluorescence imaging, and Western blotting were applied to human atrial fibroblasts. Empagliflozin (an SGLT2i, 1, or 5 µmol/L) reduced migration capability and collagen type I, and III production. Compared with control cells, empagliflozin (1 µmol/L)- treated atrial fibroblasts exhibited lower endoplasmic reticulum (ER) Ca2+ leakage, Ca2+ entry, inositol trisphosphate (IP3), lower expression of phosphorylated phospholipase C (PLC), and lower intracellular pH. In the presence of cariporide (an Na+-H+ exchanger (NHE) inhibitor, 10 µmol/L), control and empagliflozin (1 µmol/L)-treated atrial fibroblasts revealed similar intracellular pH, ER Ca2+ leakage, Ca2+ entry, phosphorylated PLC, pro-collagen type I, type III protein expression, and migration capability. Moreover, empagliflozin (10 mg/kg/day orally for 28 consecutive days) significantly increased left ventricle systolic function, ß-hydroxybutyrate and decreased atrial fibrosis, in isoproterenol (100 mg/kg, subcutaneous injection)-induced HF rats. CONCLUSIONS: By inhibiting NHE, empagliflozin decreases the expression of phosphorylated PLC and IP3 production, thereby reducing ER Ca2+ release, extracellular Ca2+ entry and the profibrotic activities of atrial fibroblasts.

Anal Carcinoma, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

This discussion summarizes the NCCN Clinical Practice Guidelines for managing squamous cell anal carcinoma, which represents the most common histologic form of the disease. A multidisciplinary approach including physicians from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology is necessary. Primary treatment of perianal cancer and anal canal cancer are similar and include chemoradiation in most cases. Follow-up clinical evaluations are recommended for all patients with anal carcinoma because additional curative-intent treatment is possible. Biopsy-proven evidence of locally recurrent or persistent disease after primary treatment may require surgical treatment. Systemic therapy is generally recommended for extrapelvic metastatic disease. Recent updates to the NCCN Guidelines for Anal Carcinoma include staging classification updates based on the 9th edition of the AJCC Staging System and updates to the systemic therapy recommendations based on new data that better define optimal treatment of patients with metastatic anal carcinoma.

Effect of macrophage migration inhibitory factor on pulmonary vein arrhythmogenesis through late sodium current.

AIMS: Macrophage migration inhibitory factor (MIF), a pleiotropic inflammatory cytokine, is highly expressed in patients with atrial fibrillation (AF). Inflammation increases the risk of AF and is primarily triggered by pulmonary vein (PV) arrhythmogenesis. This study investigated whether MIF can modulate the electrical activity of the PV and examined the underlying mechanisms of MIF. METHODS AND RESULTS: A conventional microelectrode, a whole-cell patch clamp, western blotting, and immunofluorescent confocal microscopy were used to investigate electrical activity, calcium (Ca2+) regulation, protein expression, ionic currents, and cytosolic reactive oxygen species (ROS) in rabbit PV tissue and isolated single cardiomyocytes with and without MIF incubation (100 ng/mL, treated for 6 h). The MIF (100 ng/mL)-treated PV tissue (n = 8) demonstrated a faster beating rate (1.8 ± 0.2 vs. 2.6 ± 0.1 Hz, P < 0.05), higher incidence of triggered activity (12.5 vs. 100%, P < 0.05), and premature atrial beat (0 vs. 100%, P < 0.05) than the control PV tissue (n = 8). Compared with the control PV cardiomyocytes, MIF-treated single PV cardiomyocytes had larger Ca2+ transients (0.6 ± 0.1 vs. 1.0 ± 0.1, ΔF/F0, P < 0.05), sarcoplasmic reticulum Ca2+ content (0.9 ± 0.20 vs. 1.7 ± 0.3 mM of cytosol, P < 0.05), and cytosolic ROS (146.8 ± 5.3 vs. 163.7 ± 3.8, ΔF/F0, P < 0.05). Moreover, MIF-treated PV cardiomyocytes exhibited larger late sodium currents (INa-Late), L-type Ca2+ currents, and Na+/Ca2+ exchanger currents than the control PV cardiomyocytes. KN93 [a selective calcium/calmodulin-dependent protein kinase II (CaMKII) blocker, 1 µM], ranolazine (an INa-Late inhibitor, 10 µM), and N-(mercaptopropionyl) glycine (ROS inhibitor, 10 mM) reduced the beating rates and the incidence of triggered activity and premature captures in the MIF-treated PV tissue. CONCLUSION: Macrophage migration inhibitory factor increased PV arrhythmogenesis through Na+ and Ca2+ dysregulation through the ROS activation of CaMKII signalling, which may contribute to the genesis of AF during inflammation. Anti-CaMKII treatment may reverse PV arrhythmogenesis. Our results clearly reveal a key link between MIF and AF and offer a viable therapeutic target for AF treatment.

Relationship Between Pharyngeal Residues Assessed by Bolus Residue Scale or Normalized Residue Ratio SCALE and Risk of Aspiration in Head and Neck Cancer Who Underwent Videofluoroscopy.

Dysphagia affects 60-75% of patients treated for head and neck cancer (HNC). We aimed to evaluate the association between residue severity and airway invasion severity using a videofluoroscopic swallowing study and identify risk factors for poor penetration-aspiration outcomes in patients with dysphagia treated for HNC. Penetration-Aspiration Scale (PAS) was used to assess airway invasion severity, while residue severity was assessed using both the Bolus Residue Scale (BRS) for residue location and the Normalized Residue Ratio Scale (NRRS) for residue amount. Relevant covariates were adjusted in the logistic regression models to account for potential confounding. Significantly higher abnormal PAS was reported for increased piriform sinus NRRS (NRRSp) [odds ratio (OR), 4.81; p = 0.042] with liquid swallowing and increased BRS value (OR, 1.52; p = 0.014) for semi-liquid swallowing in multivariate analysis. Tumor location, older age, and poorer Functional Oral Intake Scale (FOIS) were significant factors for abnormal PAS in both texture swallowings. After adjusting for confounding factors (sex, age, and FOIS score), NRRS model in liquid swallowing (area under the curve [AUC], 0.83; standard error = 0.04, 95% confidence interval [CI]: 0.75, 0.91) and BRS in semi-liquid swallowing (AUC, 0.83; SE = 0.04; 95% CI: 0.76, 0.91) predicted abnormal PAS. The results indicate that while assessing residue and swallowing aspiration in patients with HNC, it is important to consider age, tumor location, and functional swallowing status. The good predictability of abnormal PAS with BRS and NRRS indicated that residue location and amount were both related to the aspiration event in patients with HNC.

Effects of photobiomodulation as an adjunctive treatment in chronic obstructive pulmonary disease: a narrative review.

Chronic obstructive pulmonary disease (COPD) is a disease characterized by chronic airway inflammation and remodeling and lung parenchymal inflammation and destruction, which result in many pulmonary and extrapulmonary manifestations. The anti-inflammatory effect of photobiomodulation (PBM) has been reported in previous studies. This review was conducted to evaluate the direct effect of PBM on lung inflammation in COPD. The other effects of PBM on modulation of peripheral and respiratory muscle metabolism and angiogenesis in lung tissues were also discussed. The databases of PubMed, Cochrane Library, and Google Scholar were searched to find the relevant studies. Keywords included PBM and related terms, COPD-related signs, and lung inflammation. A total of 12 articles were selected and reviewed in this study. Based on the present review, PBM is helpful in reducing lung inflammation through decreasing the inflammatory cytokines and chemokines at multiple levels and increasing anti-inflammatory cytokines. In addition, PBM also improves both peripheral and respiratory muscle metabolism and promote angiogenesis. This review demonstrated that PBM is a promising adjunctive treatment modality for COPD management which merits further validation.

Electrical and Structural Insights into Right Ventricular Outflow Tract Arrhythmogenesis.

The right ventricular outflow tract (RVOT) is the major origin of ventricular arrhythmias, including premature ventricular contractions, idiopathic ventricular arrhythmias, Brugada syndrome, torsade de pointes, long QT syndrome, and arrhythmogenic right ventricular cardiomyopathy. The RVOT has distinct developmental origins and cellular characteristics and a complex myocardial architecture with high shear wall stress, which may lead to its high vulnerability to arrhythmogenesis. RVOT myocytes are vulnerable to intracellular sodium and calcium overload due to calcium handling protein modulation, enhanced CaMKII activity, ryanodine receptor phosphorylation, and a higher cAMP level activated by predisposing factors or pathological conditions. A reduction in Cx43 and Scn5a expression may lead to electrical uncoupling in RVOT. The purpose of this review is to update the current understanding of the cellular and molecular mechanisms of RVOT arrhythmogenesis.

Glucagon-like Peptide-1 Receptor Activation Reduces Pulmonary Vein Arrhythmogenesis and Regulates Calcium Homeostasis.

Glucagon-like peptide-1 (GLP-1) receptor agonists are associated with reduced atrial fibrillation risk, but the mechanisms underlying this association remain unclear. The GLP-1 receptor agonist directly impacts cardiac Ca2+ homeostasis, which is crucial in pulmonary vein (PV, the initiator of atrial fibrillation) arrhythmogenesis. This study investigated the effects of the GLP-1 receptor agonist on PV electrophysiology and Ca2+ homeostasis and elucidated the potential underlying mechanisms. Conventional microelectrodes and whole-cell patch clamp techniques were employed in rabbit PV tissues and single PV cardiomyocytes before and after GLP-1 (7-36) amide, a GLP-1 receptor agonist. Evaluations were conducted both with and without pretreatment with H89 (10 µM, an inhibitor of protein kinase A, PKA), KN93 (1 µM, an inhibitor of Ca2+/calmodulin-dependent protein kinase II, CaMKII), and KB-R7943 (10 µM, an inhibitor of Na+/Ca2+ exchanger, NCX). Results showed that GLP-1 (7-36) amide (at concentrations of 1, 10, and 100 nM) reduced PV spontaneous activity in a concentration-dependent manner without affecting sinoatrial node electrical activity. In single-cell experiments, GLP-1 (7-36) amide (at 10 nM) reduced L-type Ca2+ current, NCX current, and late Na+ current in PV cardiomyocytes without altering Na+ current. Additionally, GLP-1 (7-36) amide (at 10 nM) increased sarcoplasmic reticulum Ca2+ content in PV cardiomyocytes. Furthermore, the antiarrhythmic effects of GLP-1 (7-36) amide on PV automaticity were diminished when pretreated with H89, KN93, or KB-R7943. This suggests that the GLP-1 receptor agonist may exert its antiarrhythmic potential by regulating PKA, CaMKII, and NCX activity, as well as modulating intracellular Ca2+ homeostasis, thereby reducing PV arrhythmogenesis.

Ketogenic Diet Regulates Cardiac Remodeling and Calcium Homeostasis in Diabetic Rat Cardiomyopathy.

A ketogenic diet (KD) might alleviate patients with diabetic cardiomyopathy. However, the underlying mechanism remains unclear. Myocardial function and arrhythmogenesis are closely linked to calcium (Ca2+) homeostasis. We investigated the effects of a KD on Ca2+ homeostasis and electrophysiology in diabetic cardiomyopathy. Male Wistar rats were created to have diabetes mellitus (DM) using streptozotocin (65 mg/kg, intraperitoneally), and subsequently treated for 6 weeks with either a normal diet (ND) or a KD. Our electrophysiological and Western blot analyses assessed myocardial Ca2+ homeostasis in ventricular preparations in vivo. Unlike those on the KD, DM rats treated with an ND exhibited a prolonged QTc interval and action potential duration. Compared to the control and DM rats on the KD, DM rats treated with an ND also showed lower intracellular Ca2+ transients, sarcoplasmic reticular Ca2+ content, sodium (Na+)-Ca2+ exchanger currents (reverse mode), L-type Ca2+ contents, sarcoplasmic reticulum ATPase contents, Cav1.2 contents. Furthermore, these rats exhibited elevated ratios of phosphorylated to total proteins across multiple Ca2+ handling proteins, including ryanodine receptor 2 (RyR2) at serine 2808, phospholamban (PLB)-Ser16, and calmodulin-dependent protein kinase II (CaMKII). Additionally, DM rats treated with an ND demonstrated a higher frequency and incidence of Ca2+ leak, cytosolic reactive oxygen species, Na+/hydrogen-exchanger currents, and late Na+ currents than the control and DM rats on the KD. KD treatment may attenuate the effects of DM-dysregulated Na+ and Ca2+ homeostasis, contributing to its cardioprotection in DM.

Class I HDAC modulates angiotensin II-induced fibroblast migration and mitochondrial overactivity.

BACKGROUND: Inhibition of histone deacetylases (HDACs) attenuates cardiac fibrosis. In this study, we evaluated whether the inhibition of class I HDACs can attenuate angiotensin II (ANG II)-induced fibrogenesis and mitochondrial malfunction through its effects on reactive oxygen species (ROS) and calcium dysregulation in human cardiac fibroblasts (CFs). METHODS: Seahorse XF24 extracellular flux analyser, fluorescence staining, Western blotting, HDAC activity assays and Transwell migration assay were used to study mitochondrial respiration, adenosine triphosphate (ATP) production, mitochondrial calcium uptake and ROS, HDAC expression and activity and fibroblast activity in CFs without (control) or with ANG II (100 nM) and/or MS-275 (HDAC class 1 inhibitor, 10 µM) for 24 h. RESULTS: ANG II increased HDAC activity without changing protein expression in CFs. Compared with controls, ANG II-treated CFs had greater migration activity, higher ATP production, maximal respiration and spare capacity with higher mitochondrial Ca2+ uptake and ROS generation, which was attenuated by the administration of MS-275. ANG II activated CFs by increasing mitochondrial calcium content and ATP production, which may be caused by increased HDAC activity. Inhibition of HDAC1 attenuated the effects of ANG II by reducing mitochondrial ROS generation and calcium overload. CONCLUSIONS: Modulating mitochondrial function by regulation of HDAC may be a novel strategy for controlling CF activity.

Ceramide modulates electrophysiological characteristics and oxidative stress of pulmonary vein cardiomyocytes.

BACKGROUND: Ceramide is involved in regulating metabolism and energy expenditure, and its abnormal myocardial accumulation may contribute to heart injury or lipotoxic cardiomyopathy. Whether ceramide can modulate the electrophysiology of pulmonary veins (PVs) remains unknown. MATERIALS AND METHODS: We used conventional microelectrodes to measure the electrical activity of isolated rabbit PV tissue preparations before and after treatment with various concentrations of ceramide with or without H2 O2 (2 mM), MitoQ, wortmannin or 740 YP. A whole-cell patch clamp and fluorescence imaging were used to record the ionic currents, calcium (Ca2+ ) transients, and intracellular reactive oxygen species (ROS) and sodium (Na+ ) in isolated single PV cardiomyocytes before and after ceramide (1 µM) treatment. RESULTS: Ceramide (0.1, 0.3, 1 and 3 µM) reduced the beating rate of PV tissues. Furthermore, ceramide (1 µM) suppressed the 2 mM H2 O2 -induced faster PV beating rate, triggered activities and burst firings, which were further reduced by MitoQ. In the presence of wortmannin, ceramide did not change the PV beating rate. The H2 O2 -induced faster PV beating rate could be counteracted by MitoQ or wortmannin with no additive effect from the ceramide. Ceramide inhibited pPI3K. Ceramide reduced Ca2+ transients, sarcoplasmic reticulum Ca2+ contents, L-type Ca2+ currents, Na+ currents, late Na+ currents, Na+ -hydrogen exchange currents, and intracellular ROS and Na+ in PV cardiomyocytes, but did not change Na+ -Ca2+ exchange currents. CONCLUSION: C2 ceramide may exert the distinctive electrophysiological effect of modulating PV activities, which may be affected by PI3K pathway-mediated oxidative stress, and might play a role in the pathogenesis of PV arrhythmogenesis.

Characterizing impact of positive lymph node number in endometrial cancer using machine-learning: A better prognostic indicator than FIGO staging?

BACKGROUND: Number of involved lymph nodes (LNs) is a crucial stratification factor in staging of numerous disease sites, but has not been incorporated for endometrial cancer. We evaluated whether number of involved LNs provide improved prognostic value. PATIENTS AND METHODS: Patients diagnosed with node-positive endometrial adenocarcinoma without distant metastasis were identified in the National Cancer Database. We trained a machine-learning based model of overall survival. Shapley additive explanation values (SHAP) based on the model were used to identify cutoffs of number of LNs involved. Results were validated using a Cox proportional hazards regression model. RESULTS: We identified 11,381 patients with endometrial cancer meeting the inclusion criteria. Using the SHAP values, we selected the following thresholds: 1-3 LNs, 4-5 LNs, and 6+ LNs. The 3-year OS was 82.0% for 1-3 LNs, 74.3% for 4-5 LNs (hazard ratio [HR] 1.38; p < 0.001), and 59.9% for 6+ LNs (HR 2.23; p < 0.001). On univariate Cox regression, PA nodal involvement was a significant predictor of OS (HR 1.20; p < 0.001) but was not significant on multivariate analysis when number of LNs was included (HR 1.05; p = 0.273). Additionally, we identified an interaction between adjuvant therapy and number of involved LNs. Patients with 1-3 involved LNs had 3-year OS of 85.2%, 78.7% and 74.2% with chemoradiation (CRT), chemotherapy, and radiation, respectively. Patients with 6+ involved LNs had 3-yr OS of 67.8%, 49.6%, and 48.9% with CRT, chemotherapy, and radiation, respectively (p < 0.001). CONCLUSION: Number of involved LNs is a stronger prognostic and predictive factor compared to PA node involvement.

Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Rectal Cancer focuses on management of malignant polyps and resectable nonmetastatic rectal cancer because important updates have been made to these guidelines. These recent updates include redrawing the algorithms for stage II and III disease to reflect new data supporting the increasingly prominent role of total neoadjuvant therapy, expanded recommendations for short-course radiation therapy techniques, and new recommendations for a "watch-and-wait" nonoperative management technique for patients with cancer that shows a complete response to neoadjuvant therapy. The complete version of the NCCN Guidelines for Rectal Cancer, available online at NCCN.org, covers additional topics including risk assessment, pathology and staging, management of metastatic disease, posttreatment surveillance, treatment of recurrent disease, and survivorship.

Comparison of the O-RADS and ADNEX models regarding malignancy rate and validity in evaluating adnexal lesions.

OBJECTIVE: This study aimed to compare the ability of the O-RADS and ADNEX models to classify benign or malignant adnexal lesions. METHODS: This retrospective single-center study included women who underwent surgery for adnexal lesions. Two gynecologists independently categorized the adnexal lesions according to the O-RADS and ADNEX models. Four additional readers were included to validate the new quick-access O-RADS flowchart. RESULTS: Among the 322 patients included in this study, 264 (82.0%) had a benign diagnosis, and 58 (18.0%) had a malignant diagnosis. The malignant rates of O-RADS 2, O-RADS 3, O-RADS 4, and O-RADS 5 were 0%, 3.0%, 37.7%, and 78.9%, respectively. The AUC of the O-RADS in the 322 patients was 0.93. On comparing the O-RADS and ADNEX models in the remaining 281 patients, the AUCs of the O-RADS, ADNEX model with CA125, and ADNEX model without CA125 were 0.92, 0.95, and 0.94, respectively. When setting a uniform cutoff of ≥ 10% (≥ O-RADS 4) to predict malignancy, the O-RADS had higher sensitivity than the ADNEX model (96.6% vs. 91.4%), and relatively similar specificity. In addition, the readers with the quick-access flowchart spent less time categorizing O-RADS than the readers with only the original O-RADS table (mean analysis time: 99 min 15 s vs. 111 min 55 s). CONCLUSIONS: The O-RADS classification of the adnexal lesions as benign or malignant was comparable to that of the ADNEX model and had higher sensitivity at the 10% cutoff value. A quick-access O-RADS flowchart was helpful in O-RADS categorization and might shorten the analysis time. KEY POINTS: • Both O-RADS and ADNEX models had good diagnostic performance in distinguishing adnexal malignancy, and O-RADS had higher sensitivity than ADNEX model in uniform 10% cutoff to predict malignancy. • Quick-access O-RADS flowchart was developed to help review O-RADS classification and might help reduce the analysis time.

Effect of antidiabetic drugs on the risk of atrial fibrillation: mechanistic insights from clinical evidence and translational studies.

Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF), which is the most common sustained arrhythmia and is associated with substantial morbidity and mortality. Advanced glycation end product and its receptor activation, cardiac energy dysmetabolism, structural and electrical remodeling, and autonomic dysfunction are implicated in AF pathophysiology in diabetic hearts. Antidiabetic drugs have been demonstrated to possess therapeutic potential for AF. However, clinical investigations of AF in patients with DM have been scant and inconclusive. This article provides a comprehensive review of research findings on the association between DM and AF and critically analyzes the effect of different pharmacological classes of antidiabetic drugs on AF.

Maintenance Therapy for Preventing Endometrioma Recurrence after Endometriosis Resection Surgery - A Systematic Review and Network Meta-analysis.

OBJECTIVE: To evaluate the efficacy of different hormone therapies in preventing postoperative endometrioma recurrence. DATA SOURCES: The MEDLINE, COCHRANE, and Embase electronic databases were searched from inception to 30 April 2021. METHODS OF STUDY SELECTION: Randomized controlled trials (RCTs) or cohort studies including reproductive age women with endometriosis undergoing ovarian cystectomy or excision of endometriotic lesions compared the effects of postoperative adjuvant therapy (gonadotropin-releasing hormone agonist [GnRHa]) and postoperative maintenance hormone interventions for more than 1 year (i.e., oral contraceptive pills [OCPs], dienogest [DNG], levonorgestrel-releasing intrauterine system [LNGIUS]) on endometrioma recurrence. TABULATION, INTEGRATION, AND RESULTS: Data collection and analysis of the data were independently performed 2 two reviewers. A total of 11 studies were included, of which 2 were RCTs, and 9 were cohort studies. There were 2394 patients with 6 interventions (cases: 1665, 69.6%) and expectant management (cases: 729, 30.4%). Relative treatment effects were estimated using network meta-analysis and ranked in descending order. The clinical effectiveness of these drugs (vs expectant management) was as follows: GnRHa plus DNG (odds ratio [OR], 0.04; 95% confidence interval [CI], 0.01-0.27), surface under the cumulative ranking (SUCRA) = 94.0; DNG (OR, 0.11; 95% CI, 0.04-0.32), SUCRA = 69.7; GnRHa plus OCP (OR, 0.12; 95% CI, 0.02-0.64), SUCRA = 63.4; GnRHa plus LNGIUS (OR, 0.13; 95% CI, 0.03-0.66), SUCRA = 59.4; and OCP (OR, 0.21; 95% CI, 0.13-0.36), SUCRA = 43.6. The effectiveness of GnRHa (OR, 0.47; 95% CI, 0.12-1.89), SUCRA = 17.3 was not significantly different from that of controls. CONCLUSION: In network meta-analysis, combined postoperative adjuvant therapy and longer maintenance hormone treatment are better than a single agent in preventing postoperative endometrioma recurrence. GnRHa plus DNG maintenance treatment might be the most effective intervention. Large-scale RCTs of these agents are still required.

Efficacy and Safety of "I-Stop-Mini Adjustable" Sling System versus Transobturator Midurethral "Obtryx" Sling System in Stress Urinary Incontinence: A Retrospective Cohort Study.

STUDY OBJECTIVE: To compare the safety, efficacy, and adverse events of the new mini-adjustable sling system "I-stop-mini" with transobturator midurethral slings "Obtryx" (Boston Scientific, Marlborough, MA) in women with stress urinary incontinence. DESIGN: A single-center, retrospective cohort study. SETTING: Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taiwan. PATIENTS: A total of 347 patients who underwent I-stop-mini or Obtryx for stress urinary incontinence treatment. INTERVENTIONS: Midurethral sling with either I-stop-mini or Obtryx. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were objective success and subjective cure rates between the 2 groups. Objective success was evaluated using a 1-hour pad test, and subjective cure was evaluated using a questionnaire score (Incontinence Impact Questionnaire, Urinary Distress Inventory, and International Consultation on Incontinence Questionnaire Short Form). Secondary outcomes were the evaluation of surgical outcomes, operative data, and adverse events between the 2 groups. In total, 171 of 200 I-stop-mini subjects and 127 of 147 Obtryx subjects completed 12 months of follow-up. Regarding the objective success between the I-stop-mini group and the Obtryx group, 1-month postoperative (3.6 ± 5.2 vs 3.9 ± 12.6; p = .765), 6-month postoperative (3.9 ± 5.1 vs 4.2 ± 12.6; p = .848), and 12-month postoperative (4.6 ± 5.6 vs 4.5 ± 13.6; p = .980) 1-hour pad tests showed no significant difference. The 12-month subjective cure rates decreased from 94.7% (1-month postoperative) to 91.2% (12-month postoperative) in the I-stop-mini group and 95.2% (1-month postoperative) to 85.0% (12-month postoperative) in the Obtryx group. Similar and durable efficacy was observed between the 2 groups. The I-stop-mini group had shorter operative times and hospital stays than the Obtryx group; however, both groups showed similar adverse event rates. CONCLUSION: The objective success and subjective cure rates of I-stop-mini did not differ to those of Obtryx. However, long-term data and further prospective studies on I-stop-mini are necessary to arrive at a definite conclusion.