Comparison of the efficacy and adverse effects of unilateral or bilateral botulinum toxin injections for adductor spasmodic dysphonia: a systematic review and meta-analysis.

PURPOSE: This study aims to aggregate and analyze existing clinical evidence to compare the efficacy and adverse effects of unilateral or bilateral botulinum toxin injections for the treatment of adductor spasmodic dysphonia (ADSD). METHODS: Reports from non-randomized controlled trials and cohort studies pertaining to the efficacy and adverse effects of unilateral and bilateral botulinum toxin injections for ADSD were identified and retrieved from four electronic databases from inception to July 2023. The meta-analysis employed fixed or random effects models to assess pooled relative risks (RR), mean differences (MDs), and standard mean differences (SMDs) with their corresponding 95% confidence intervals (CIs). RESULTS: We included two non-randomized controlled trials and seven cohort studies comprising 854 total patients. Meta-analysis of the included studies showed that bilateral botulinum toxin injections associated with a longer duration of vocal improvement (MD = - 2.89, 95% CI - 3.13 to - 2.65, I2 = 0%, P < 0.00001). However, bilateral botulinum toxin injections associated with an increase in adverse effects, including a longer duration of breathy voice quality (SMD = - 0.51, 95% CI - 0.79 to - 0.22, I2 = 35%, P = 0.0005) and a higher occurrence of swallowing difficulties (RR = 0.46, 95% CI 0.35 to 0.11, I2 = 0%, P < 0.00001). CONCLUSION: Bilateral botulinum toxin injections for ADSD showed a longer duration of vocal improvement, a longer breathy voice duration and a higher dysphagia occurrence and duration than unilateral injections.

The impact of preoperative nutritional status on postoperative outcomes: an insight from Geriatric Nutritional Risk Index in elderly pancreaticoduodenectomy patients.

BACKGROUND: Malnutrition is not uncommon among the elderly undergoing pancreatoduodenectomy (PD) and is related to increased complications. Previous studies have shown that the Geriatric Nutritional Risk Index (GNRI) predicts outcomes in various populations. Nevertheless, the research exploring the correlation between GNRI and postoperative outcomes in PD is scarce. This study aimed to investigate the preoperative malnutrition, as measured by GNRI, on outcomes in elderly patients undergoing PD. MATERIALS AND METHODS: This retrospective analysis enrolled 144 elderly patients underwent PD for periampullary tumors from November 2016 to December 2021. Patients were stratified based on the GNRI value: high/moderate nutrition risk (GNRI ≤ 92, N = 54), low nutrition risk (92 < GNRI ≤ 98, N = 35), and no nutrition risk (GNRI > 98, N = 55). Perioperative outcomes and postoperative surgical complications were compared between these groups. Univariate and multivariate analyses were performed on major postoperative complications and prolonged postoperative length of stay (PLOS). RESULTS: Patients in the high/moderate risk group were significantly older, with lower BMI (P = 0.012), higher mortality rate (11.1%, P = 0.024), longer PLOS (P < 0.001), and higher incidence of over grade IIIB complications (37.0%, P = 0.001), Univariate and multivariate analyses showed the high/moderate risk GNRI group (OR 3.61, P = 0.032), increased age (OR 1.11, P = 0.014) and operative time over 8 h (OR 3.04, P = 0.027) were significantly associated with increased major postoperative complications. The high/moderate risk GNRI group was also a significant predictor for prolonged PLOS (OR 3.91, P = 0.002). CONCLUSIONS: Preoperative GNRI has the potential to be a predictive tool for identifying high-risk elderly patients and monitoring nutritional status preoperatively to improve postoperative surgical outcomes following PD.

Near-infrared cholangiography can increase the chance of success in laparoscopic approaches to common bile duct stones, even with previous abdominal surgery.

BACKGROUND: The treatment of common bile duct (CBD) stones with minimally invasive surgery (MIS) is more technical demanding than laparoscopic cholecystectomy (LC), especially in patients with history of previous abdominal surgery, cholangitis or cholecystitis. Near-infrared (NIR) cholangiography via systemic or biliary tree administration of indocyanine green (ICG), which enhances the visualization of the biliary tree anatomy, may increase the reassurance of CBD localization. The aim of this study was to identify the benefit of near-infrared cholangiography for laparoscopic common bile duct exploration (LCBDE). METHODS: Three groups of CBD stone patients were included in this retrospective study depending on the surgical methods: 1) open choledocholithotomy (OCC), 2) laparoscopic choledocholithotomy (LCC), and 3) near-infrared cholangiography-assisted laparoscopic choledocholithotomy (NIR-CC). For the NIR-CC group, either 3 ml (concentration: 2.5 mg/mL) of ICG were intravenously administered or 10 ml (concentration: 0.125 mg/mL) of ICG were injected directly into the biliary tree. The enhancement rate of the cystic duct (CD), CBD, the upper and lower margin of the CBD were compared using white light image. RESULTS: A total of 187 patients with a mean age of 68.3 years were included (OCC, n = 56; LCC, n = 110; NIR-CC, n = 21). The rate of previous abdominal surgery was significantly lower in the LCC group. The conversion rate was similar between the LCC and the NIR CC groups (p = 0.746). The postoperative hospital stay was significantly longer in the OCC group. No differences in morbidity and mortality were found between the three groups. In the NIR-CC group, the localization of CBD was as high as 85% compared to 24% with white light imaging. CONCLUSIONS: Near-infrared cholangiography helps increase the chance of success in minimally invasive approaches to CBD stones even in patients with previous abdominal surgeries, without increasing the rate of conversion.

Ticagrelor in Patients with Stable Coronary Disease and Diabetes.

BACKGROUND: Patients with stable coronary artery disease and diabetes mellitus who have not had a myocardial infarction or stroke are at high risk for cardiovascular events. Whether adding ticagrelor to aspirin improves outcomes in this population is unclear. METHODS: In this randomized, double-blind trial, we assigned patients who were 50 years of age or older and who had stable coronary artery disease and type 2 diabetes mellitus to receive either ticagrelor plus aspirin or placebo plus aspirin. Patients with previous myocardial infarction or stroke were excluded. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria. RESULTS: A total of 19,220 patients underwent randomization. The median follow-up was 39.9 months. Permanent treatment discontinuation was more frequent with ticagrelor than placebo (34.5% vs. 25.4%). The incidence of ischemic cardiovascular events (the primary efficacy outcome) was lower in the ticagrelor group than in the placebo group (7.7% vs. 8.5%; hazard ratio, 0.90; 95% confidence interval [CI], 0.81 to 0.99; P = 0.04), whereas the incidence of TIMI major bleeding was higher (2.2% vs. 1.0%; hazard ratio, 2.32; 95% CI, 1.82 to 2.94; P<0.001), as was the incidence of intracranial hemorrhage (0.7% vs. 0.5%; hazard ratio, 1.71; 95% CI, 1.18 to 2.48; P = 0.005). There was no significant difference in the incidence of fatal bleeding (0.2% vs. 0.1%; hazard ratio, 1.90; 95% CI, 0.87 to 4.15; P = 0.11). The incidence of an exploratory composite outcome of irreversible harm (death from any cause, myocardial infarction, stroke, fatal bleeding, or intracranial hemorrhage) was similar in the ticagrelor group and the placebo group (10.1% vs. 10.8%; hazard ratio, 0.93; 95% CI, 0.86 to 1.02). CONCLUSIONS: In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, those who received ticagrelor plus aspirin had a lower incidence of ischemic cardiovascular events but a higher incidence of major bleeding than those who received placebo plus aspirin. (Funded by AstraZeneca; THEMIS ClinicalTrials.gov number, NCT01991795.).

Short-term outcomes after minimally invasive versus open pancreaticoduodenectomy in elderly patients: a propensity score-matched analysis.

BACKGROUND: To date, the evidence on the safety and benefits of minimally invasive pancreatoduodenectomy (MIPD) in elderly patients is still controversy. This study aim to compare the risk and benefit between MIPD and open pancreatoduodenectomy (OPD) in elderly patients. METHODS: From 2016 to 2020, we retrospective enrolled 26 patients underwent MIPD and other 119 patients underwent OPD. We firstly compared the baseline characteristics, 90-day mortality and short-term surgical outcomes of MIPD and OPD. Propensity score matching was applied for old age patient (≥ 65-year-old vs. < 65-year-old) for detail safety and feasibility analysis. RESULTS: Patients received MIPD is significantly older, had poor performance status, less lymph node harvest, longer operation time, less postoperative hospital stay (POHS) and earlier drain removal. After 1:2 propensity score matching analysis, elderly patients in MIPD group had significantly poor performance status (P = 0.042) compared to OPD group. Patients receiving MIPD had significantly shorter POHS (18 vs. 25 days, P = 0.028), earlier drain removal (16 vs. 21 days, P = 0.012) and smaller delay gastric empty rate (5.9 vs. 32.4% P = 0.036). There was no 90-day mortality (0% vs. 11.8%, P = 0.186) and pulmonary complications (0% vs. 17.6%, P = 0.075) in MIPD group, and the major complication rate is comparable to OPD group (17.6% vs. 29.4%, P = 0.290). CONCLUSION: For elderly patients, MIPD is a feasible and safe option even in patients with inferior preoperative performance status. MIPD might also provide potential advantage for elderly patients in minimizing pulmonary complication and overall mortality over OPD.

Super-Selective Intra-Arterial Indocyanine Green Administration for Near-Infrared Fluorescence-Based Positive Staining of Hepatic Segmentation: A Feasibility Study.

BACKGROUND: Despite the increasing number of laparoscopic hepatic procedures for the resection of hepatocellular carcinoma (HCC), intraoperative tumor localization and demarcation remains challenging in comparison to open surgery. In this study, we evaluated the feasibility of positive liver segment staining through the super-selective intra-arterial indocyanine green (ICG) administration. METHODS: Eight patients presenting with a single HCC underwent an interventional vascular procedure followed by laparoscopic surgery. A microcatheter was advanced into the hepatic artery branches perfusing the HCC followed by digital subtraction angiography and angiography computed tomography (angio-CT). Patients were then transferred to the operating room, and a laparoscopic hepatectomy was performed under ultrasound guidance. A 5 mL bolus of ICG with a concentration of .125 mg/mL was injected through the microcatheter, and a near-infrared laparoscope was used to detect the fluorescence signal to assess the correspondence between the fluorescence-based demarcation and the intraoperative ultrasound-based demarcation. RESULTS: The duration for the angiography procedure was 32.7 +/- 5.3 min, and it took 242 +/- 118 min from the end of angiography procedure until the start of the surgical procedure. In all cases, the fluorescent liver segment was corresponding to the angio-CT findings. In 6/8 cases, fluorescence imaging was considered helpful in the identification of the resection line. In 3 patients, the resection line was changed according to the positively stained liver segment. CONCLUSION: We successfully demonstrated the feasibility of the super-selective intra-arterial ICG administration for fluorescence-based positive staining of hepatic segmentation during laparoscopic surgery for HCC (NCT04266548).

Getting to an ImprOved Understanding of Low-Density Lipoprotein-Cholesterol and Dyslipidemia Management (GOULD): Methods and baseline data of a registry of high cardiovascular risk patients in the United States.

BACKGROUND: Guidelines for managing patients with atherosclerotic cardiovascular disease (ASCVD) recommend statin therapy initially. Target levels/goals for low-density lipoprotein-cholesterol (LDL-C) were initially included, subsequently de-emphasized in 2013, and then re-introduced as thresholds, leading to confusion in clinical practice. We designed a multicenter, observational registry of patients with ASCVD, to describe and track LDL-C treatment patterns in the United States over time. METHODS: Patients with ASCVD receiving any pharmacologic lipid-lowering therapy were eligible for enrollment in one of three cohorts: 1) currently receiving a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i), or not receiving PCSK9i with 2) LDL-C 70-99 mg/dL, or 3) LDL-C ≥100 mg/dL. Patients undergo a 1-year retrospective chart review, followed by chart reviews and phone interviews every 6 months for 2 years. RESULTS: A total of 5006 patients were enrolled at 119 centers. Mean age was 68 years, 40% of patients were female, 86% were white, 80% had coronary artery disease, and 33% had type 2 diabetes mellitus. Among those not on a PCSK9i, high-intensity statins and ezetimibe were utilized in only 44% and 9%, respectively. Among women vs men, only 36.6% vs 48.2% received high-intensity statins (P < .001). Among patients on a PCSK9i, only one-third were receiving a statin, suggesting statin intolerance is a driver of PCSK9i use at present. CONCLUSION: Our data on current practice in the US continue to illustrate that high-intensity statins and ezetimibe are underutilized in at-risk patients outside of clinical trials, particularly women. This study will track temporal changes in treatment patterns and identify opportunities for improvement in lipid management in patients with ASCVD.

The GAMMA concept (gastrointestinal activity manipulation to modulate appetite) preliminary proofs of the concept of local vibrational gastric mechanical stimulation.

BACKGROUND: Mechanical stimulation of the stretch receptors of the gastric wall can simulate the presence of indigested food leading to reduced food intake. We report the preliminary experimental results of an innovative concept of localized mechanical gastric stimulation. METHODS: In a first survival study, a biocompatible bulking agent was injected either in the greater curvature (n = 8) or in the cardia wall (n = 8) of Wistar rats. Six animals served as sham. Changes of bulking volume, leptin levels and weight gain were monitored for 3 months. In a second acute study, a micro-motor (n = 10; MM) or a size-paired inactive device (n = 10; ID) where applied on the cardia, while 10 additional rats served as sham. Serum ghrelin and leptin were measured at baseline and every hour (T0-T1-T2-T3), during 3 h. In a third study, 24 implants of various shapes and sizes were introduced into the gastric subserosa of 6 Yucatan pigs. Monthly CT scans and gastroscopies were done for 6 months. RESULTS: Weight gain in the CW group was significant lower after 2 weeks and 3 months when compared to the shame and GC (p = 0.01/p = 0.01 and p = 0.048/p = 0.038 respectively). Significant lower increase of leptin production occurred at 2 weeks (p = 0.01) and 3 months (p = 0.008) in CW vs. SG. In the MM group significant reduction of the serum ghrelin was seen after 3 h. Leptin was significantly increased in both MM and ID groups after 3 h, while it was significantly reduced in sham rats. The global device retention was 43.5%. Devices with lower profile and with a biocompatible coating remained more likely in place without complications. CONCLUSIONS: Gastric mechanical stimulation induced a reduced weight gain and hormonal changes. Low profile and coated devices inserted within the gastric wall are more likely to be integrated.

Serum asprosin levels and bariatric surgery outcomes in obese adults.

BACKGROUND/OBJECTIVES: Asprosin is a novel fasting-induced glucogenic and orexigenic protein hormone. The clinical function of asprosin in obesity is currently unknown. This study investigated the association between asprosin abundance and the outcome of bariatric surgery. SUBJECTS/METHODS: Patients with body mass index more than 35 kg/m2 were recruited for the Obesity and Clock for Elegant Aging Registry in 2011-2016. Body weight changes, blood sugar, and asprosin were assessed in 117 patients receiving bariatric surgery and 57 non-obese subjects as normal control. Primary outcomes of excess weight loss percentage at 6 months after bariatric surgery were determined at follow-up. RESULTS: Asprosin levels were significantly higher in obese patients than in non-obese subjects (2360 ± 5094 vs. 307 ± 832 ng/ml, p < 0.0001). Multivariate analyses showed a significant association of asprosin abundance with excess body weight loss percentage at 6 months after surgery (p < 0.0001). After adjusted for age, sex, smoking, HbA1c, cholesterol, and triglyceride, serum asprosin level was the only independent predictor of 6 months excess weight loss percentage after bariatric surgery. Asprosin levels decreased significantly 6 months after bariatric surgery (162.2 ± 169.1 ng/ml). Furthermore, there was no association between asprosin and serum glucose levels in our study. CONCLUSION: This study provides novel evidence that higher asprosin concentrations before bariatric surgery were associated with the weight reduction magnitude at 6 months after surgery. Further studies are warranted to investigate whether asprosin has direct functions to modulate body weight regulation in humans after bariatric surgery.

Elevated heme impairs macrophage phagocytosis in endometriosis.

Endometriosis (EMS) is a chronic inflammatory disease characterized by the presence of extrauterine endometrial tissues. It has been previously reported that the refluxed blood containing viable endometrial tissues and the defective elimination of peritoneal macrophages in the pelvic cavity may involve in EMS pathogenesis. However, the mechanism by which macrophages exhibit attenuated phagocytic capability in EMS remains undetermined. Herein, we found that heme, the byproduct of lysed erythrocytes, accumulated abnormally in the peritoneal fluid (PF) of patients with EMS (14.22 µmol/L, 95% confidence interval (CI): 12.54-16.71), compared with the EMS-free group (9.517 µmol/L, 95% CI: 8.891-10.1053). This abnormal accumulation was not associated with the color of PF, phase of the menstrual cycle or severity of the disease. The reduced phagocytic ability of peritoneal macrophages (pMφs) was observed in the EMS group. Consistently, a high-concentration (30 µmol/L) heme treatment impaired EMS-pMφs phagocytosis more than a low-concentration (10 µmol/L) heme treatment. A similar phenomenon was observed in the EMS-free control pMφs (Ctrl-pMφs) and the CD14+ peripheral monocytes (CD14+ Mos). These results indicated that a high heme concentration exhibits a negative effect on macrophage phagocytosis, which supplements the mechanism of impaired scavenger function of pMφs in EMS.

Comparison of novel methods in two-way enriched clinical trial design.

Two-way enriched design (TED) is a novel approach addressing placebo response in clinical trials. It is a two-stage, randomized, placebo-controlled trial design with enrichment in placebo non-responders and treatment responders at the second stage. All data from the first stage and data from placebo non-responders and treatment responders in the second stage are used for the final analysis of the treatment effect. The existing methods for the analysis of TED data include score tests with one, two, and three degrees of freedom. All these methods are only applicable to binary outcomes. However, there is an interest in continuous outcomes in clinical trials in psychiatry. In this manuscript, we apply some novel methods, including a repeated measures model, a weighted repeated measures model with weights from propensity score, and weights from K-means clustering, to analyze TED data for both binary outcomes and continuous outcomes. The simulation study indicates that the repeated measures model performs consistently well in preserving the type I error and achieving the minimum mean standard error as well as a higher power. The performance of the weighted repeated measures model with weights from K-means clustering improves with increasing sample size. Investigators can choose from these analytic approaches under different scenarios.

Inverse relationship of serum albumin to the risk of venous thromboembolism among acutely ill hospitalized patients: Analysis from the APEX trial.

Hypoalbuminemia is a common finding and independent predictor for unfavorable prognosis. The prognostic value of albumin measurement for short-term VTE prediction in hospitalized patients remains unclear. In the APEX trial (ClinicalTrials.gov identifier: NCT01583218), medical inpatients were randomized to receive either extended-duration betrixaban or shorter-duration enoxaparin and followed for 77 days. Baseline albumin concentrations were obtained in 7266 subjects with evaluable VTE endpoints. The association of baseline albumin to VTE was assessed, with adjustment for patient characteristics, thromboprophylaxis, and biomarkers for fibrinolysis and inflammation (ie, D-dimer and C-reactive protein [CRP]). VTE risk refinement was evaluated by incorporation of albumin to well-validated risk assessment models. A stepwise increase in the risk of VTE (P < .0001) was observed with lower levels of albumin. Patients at the bottom albumin quartile (<35 g/L) had a two-fold greater odds for developing VTE compared with the top quartile (≥42 g/L) (OR = 2.119 [95% CI, 1.592-2.820]; adjusted OR = 2.079 [1.485-2.911]). The odds for VTE increased by 1.368 (95% CI, 1.240-1.509) times per SD decrement of albumin (5.24 g/L). Compared with the propensity score-matched pairs of patients with albumin ≥35 g/L, patients with albumin <35 g/L had a greater risk of VTE (OR = 1.623 [1.260-2.090]; adjusted OR = 1.658 [1.209-2.272]). Albumin measurement also refined VTE risk discrimination and reclassification after inclusion in the risk assessment models. In conclusion, acutely ill hospitalized patients with low serum albumin had an increased VTE risk through 77 days. VTE risk assessment models for medical inpatients should consider incorporation of baseline albumin measurement.

Toward the Total Synthesis of Scabrosins: Synthesis of a Desulfur-scabrosin Skeleton and Its Stereoisomers.

The enantioselective synthesis of a desulfur-scabrosin skeleton was reported. The synthesis began from 3-(hydroxymethyl)phenol, and key steps include asymmetric nucleophilic epoxidation, a Mitsunobu reaction using a sulfonamide as the nucleophile, the construction of a pyrrolidine ring by intramolecular nucleophilic substitution, and inversion of configuration through base-induced keto-enol isomerization. Additionally, two isomers of the carbon skeleton were also obtained via an alternative ring-closing strategy.

Fluorescence lymphangiography-guided full-thickness oncologic gastric resection.

BACKGROUND: We aimed to assess the feasibility of a novel hybrid endoscopic/laparoscopic non-exposed, full-thickness, single-wall gastric resection technique guided by a fluorescence lymphangiography to identify the lymphatic pathway and the sentinel node basin. METHODS: Eight large white pigs (4 acute and 4 survival models) were included. Indocyanine green was injected submucosally around a pseudo-tumor at four points (1 ml, 0.1 mg/ml). The lymphatic spreading pathway was identified by the means of near-infrared (NIR) laparoscopic camera, and the resection line was planned outside of the fluorescent signals, to include all the potential lymphatic channels. Lymph node (LN) dissection was performed at greater curvature side and the infrapyloric area preserving the infragastric artery for all pigs. At the lesser curvature, 3-4 branches of the gastric artery were preserved in all acute and in two survival (group A), while in the remaining animals, 1-2 branches were preserved (group B). Perfusion of the remaining stomach was examined by NIR angiography. The gastric motility and function were evaluated by the means of a dynamic MRI immediately after the procedure and repeated after 1 week in surviving animals. RESULTS: The hybrid full-thickness resection with bilateral sentinel LN basin dissection were successfully performed with no intra-operative or post-operative complications. The removed specimen was including all the area with florescent signal. The remaining stomach demonstrated a good perfusion at the NIR angiography. The dynamic MRI revealed a preserved emptying function in the acute animals and in the group A, and a loss of function in the group B. CONCLUSIONS: Fluorescence-lymphangiography guided hybrid resection was feasible to remove a relatively large part of the stomach including the lymphatic spreading pathway and sentinel basin. The extent of dissection in the lesser curvature side can affect the post-operative function and further researches are warranted to optimize the concept.

Incident Type 2 Myocardial Infarction in a Cohort of Patients Undergoing Coronary or Peripheral Arterial Angiography.

BACKGROUND: Despite growing recognition of type 2 myocardial infarction (T2MI; related to supply/demand mismatch), little is known about its risk factors or its association with outcome. METHODS: A single-center cohort of patients undergoing coronary or peripheral angiography with or without intervention was prospectively enrolled and followed for incident type 1 and T2MI, and major adverse cardiovascular events (MACE, a composite of all-cause death, nonfatal myocardial infarction [MI], heart failure, stroke, transient ischemic attack, peripheral arterial complication, and cardiac arrhythmia), as well. T2MI was adjudicated using criteria from the Third Universal Definition of MI. Baseline characteristics, blood samples, and angiography information were obtained. Major end points subsequent to first MI were assessed using landmark analyses to compare the rates of first events only where everyone with a prior history of any MACE before MI were censored and adjusted for follow-up times. Cox proportional hazard models were used for time-to-event analyses with age and sex forced into all models and additional covariates evaluated by using the stepwise option for the selection. RESULTS: One thousand two hundred fifty-one patients were enrolled and followed for a median of 3.4 years. Of these patients, 152 (12.2%) had T2MI during follow-up; T2MI was frequently recurrent. Multivariable predictors of T2MI were older age, lower systolic blood pressure, history of coronary artery disease, heart failure, chronic obstructive pulmonary disease, diabetes mellitus, nitrate use, and elevated concentrations of glucose, N-terminal pro-B type natriuretic peptide, and cystatin C. Patients with T2MI had higher rates of subsequent adverse events than those without T2MI (per 100 person-years: MACE, 53.7 versus 21.1, P<0.001; all-cause death, 23.3 versus 3.3, P<0.001; cardiovascular death, 17.5 versus 2.6, P<0.001; heart failure events, 22.4 versus 7.4, P<0.001); these rates are similar to those seen in patients with type 1 MI. Incident diagnosis of T2MI strongly predicted risk for subsequent MACE (adjusted hazard ratio, 1.90; 95% confidence interval, 1.46-2.48; P<0.001), all-cause death (adjusted hazard ratio, 2.96; 95% confidence interval, 2.01-4.36; P<0.001), and cardiovascular death (adjusted hazard ratio, 2.16; 95% confidence interval, 1.36-3.43; P=0.001). CONCLUSIONS: T2MI is common and associated with poor prognosis. Studies evaluating treatment strategies for management of T2MI are needed. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00842868.

Association of insurance type with receipt of oral anticoagulation in insured patients with atrial fibrillation: A report from the American College of Cardiology NCDR PINNACLE registry.

BACKGROUND: It is poorly understood whether insurance type may be a major contributor to the underuse of oral anticoagulation (OAC) among patients with atrial fibrillation (AF), particularly for novel oral anticoagulants (NOACs). METHODS: We performed a retrospective cohort registry study of patients with insurance, AF, CHA2DS2-VASc ≥2, and at least one outpatient encounter recorded in the ACC NCDR's PINNACLE Registry between January 1, 2011 and December 31, 2014. We used hierarchical regression, adjusting for patient characteristics and clustering by physician, to evaluate the association of insurance type (Private, Military, Medicare, Medicaid, Other) with receipt of OAC (any OAC, warfarin, or NOAC). RESULTS: In 363,309 patients (age 75±10; 48% female), we found a significant difference in proportions of OAC and NOAC prescription across insurance types (OAC: Military 53%, Private 53%, Medicare 52%, Other 41%, Medicaid 41%, P<.001; NOAC: Military 24%, Private 19%, Medicare 17%, Other 17%, Medicaid 8%, P<.001). After adjustment for patient characteristics and facility, private, Medicaid, and other insurance were independently associated with a lower odds of OAC prescription relative to Medicare, but military insured patients were not significantly different. After adjustment, military and private insurance were independently associated with a higher odds of NOAC prescription relative to Medicare, while Medicaid and other insurance were associated with a lower odds of NOAC prescription. CONCLUSIONS: In a contemporary US AF population, there was significant variation of OAC prescription across insurance plans, with the highest among private and Medicare insured patients. These differences may indicate that insurance plan, and its associated pharmacy benefits, affect the pace of diffusion of new therapies.

Safety and efficacy of non-vitamin K oral anticoagulant for atrial fibrillation patients after percutaneous coronary intervention: A bivariate analysis of the PIONEER AF-PCI and RE-DUAL PCI trial.

BACKGROUND: The tradeoff in safety versus efficacy in substituting a non-vitamin K antagonist oral anticoagulant for a vitamin K antagonist (VKA) in the stented atrial fibrillation patient has not been quantitatively evaluated. METHODS: Based on summary data from the PIONEER AF-PCI and RE-DUAL PCI trials, 4 antithrombotic regimens were compared with VKA-based triple therapy: (1) rivaroxaban (riva) 15 mg daily + P2Y12 inhibitor, (2) riva 2.5 mg twice daily + P2Y12 inhibitor + aspirin, (3) dabigatran (dabi) 110 mg twice daily + P2Y12 inhibitor, and (4) dabi 150 mg twice daily + P2Y12 inhibitor. A bivariate model with a noninferiority margin of 1.38 was used to simultaneously assess safety and efficacy. The safety end point was major or clinically relevant nonmajor bleeding by International Society on Thrombosis and Haemostasis definitions. The efficacy end point was a thromboembolic event (myocardial infarction, stroke, or systemic embolism), death, or urgent revascularization. The bivariate outcome, a measure of risk difference in the net clinical outcome, was compared between antithrombotic regimens. RESULTS: All 4 non-vitamin K antagonist oral anticoagulant regimens were superior in bleeding and noninferior in efficacy compared with triple therapy with VKA. Riva 15 mg daily and 2.5 mg twice daily were associated with bivariate combined risk reductions of 5.6% (2.3%-8.8%) and 5.5% (2.1%-8.7%), respectively, and dabi 110 mg twice daily and 150 mg twice daily reduced the bivariate risk by 3.8% (0.5%-7.0%) and 6.3% (2.4%-9.8%), respectively. CONCLUSIONS: A bivariate analysis that simultaneously characterizes both risk and benefit demonstrates that riva- and dabi-based regimens were both favorable over VKA plus dual antiplatelet therapy among patients with atrial fibrillation undergoing PCI.

High-sensitivity C-reactive protein, low-density lipoprotein cholesterol and cardiovascular outcomes in patients with type 2 diabetes in the EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) trial.

AIMS: We sought to assess the risk of major adverse cardiovascular events (MACE) by utilizing high-sensitivity C-reactive protein (hsCRP) level and low-density lipoprotein cholesterol (LDL-C) in patients with type 2 diabetes and recent acute coronary syndrome. MATERIALS AND METHODS: Study participants enrolled in the EXAMINE trial (Clinical trials registration number: NCT00968708) and were stratified by baseline hsCRP levels (<1, 1-3 and >3 mg/L). They were also sub-divided into 4 groups according to baseline hsCRP (≤3 or >3 mg/L) and achieved LDL-C (<70 or ≥70 mg/dL) levels. Among 5380 patients, the MACE rate, a composite of cardiovascular death, non-fatal acute myocardial infarction and non-fatal stroke, was evaluated during the 30 months of follow-up. RESULTS: Cumulative incidence of MACE was 11.5% (119 events), 14.6% (209 events) and 18.4% (287 events) in patients with hsCRP levels of <1, 1 to 3 and >3 mg/L, respectively (P < .001). In patients with hsCRP >3 mg/L, the adjusted hazard ratio (95% confidence interval) was 1.42 (1.13, 1.78; P = .002) for MACE compared with patients with hsCRP <1 mg/L. MACE cumulative incidences were 11.0% (128 events), 14.4% (100 events), 15.6% (194 events) and 21.3% (182 events) in patients with low LDL-C and low hsCRP, low LDL-C and high hsCRP, high LDL-C and low hsCRP, and high LDL-C and high hsCRP levels, respectively (P < .001). CONCLUSIONS: Levels of hsCRP were associated with recurrent cardiovascular events in patients with type 2 diabetes and recent acute coronary syndrome, and this association appears to be independent of and additive to the achieved LDL-C level.

Image-guided video-assisted thoracoscopic small lung tumor resection using near-infrared marking.

BACKGROUND: Localization of non-visible, non-palpable small pulmonary nodules during video-assisted thoracoscopic surgery (VATS) remains challenging. We sought to investigate the feasibility and safety of image-guided video-assisted thoracoscopic surgery (iVATS) with near-infrared (NIR) marking in a hybrid operating room (OR). METHODS: Both localization and surgery were performed by a single team of thoracic surgeons. Diluted indocyanine green (ICG; quantity: 0.3-0.5 mL; dye concentration: 0.125 mg/mL) was injected percutaneously to pinpoint the tumor's location under cone beam computed tomography (CBCT) guidance using a laser-guided navigation system. Real-time fluorescence images were intraoperatively obtained using a NIR thoracoscopic camera to guide subsequent resection. RESULTS: Between March and December 2017, 26 patients underwent NIR marking of small pulmonary nodules for iVATS. The median tumor size was 7 mm (interquartile range [IQR] 5.3-10.8 mm), whereas their median distance from the pleural surface was 5 mm (IQR 0.3-10.5 mm). Seven nodules (35%) were solid, whereas 17 (65%) were ground-glass opacities. All lesions were identifiable on intraoperative CBCT. The median time required for NIR localization was 13 min. An NIR(+) "tattoo" was identified in all cases, and no intraoperative conversion to thoracotomy occurred. The final pathological diagnoses were primary lung cancer (n = 11), metastatic cancer (n = 6), and benign lung tumor (n = 9). Adverse events were not observed, and the median length of post-operative stay was 4 days (IQR 3-4 days). CONCLUSIONS: Our data show that iVATS with NIR marking is useful, has no adverse effects, and can successfully localize difficult-to-identify small pulmonary nodules.

Near-infrared cholecystocholangiography with direct intragallbladder indocyanine green injection: preliminary clinical results.

BACKGROUND: Near-infrared (NIR) fluorescence cholangiography by systemic administration of indocyanine green (ICG) enhances the visualization of the biliary tree anatomy. However, the simultaneous enhancement of liver parenchyma can disturb the visualization of critical details. We herein proposed a new technique of NIR cholecystocholangiography by intragallbladder ICG injection to increase the safety during laparoscopic cholecystectomy. METHODS: A total of 46 patients scheduled for laparoscopic cholecystectomy for symptomatic lithiasis (n = 21) or cholecystitis (n = 25) were enrolled. A fluorescence cholangiography by direct gallbladder injection of ICG was performed in all cases. Of them, the ICG was injected through a previously placed percutaneous transhepatic gallbladder drainage catheter (n = 18) or by intraoperative, percutaneous needle puncture of the gallbladder (n = 28). Visualization of biliary structures, including the cystic duct (CD), the common bile and hepatic ducts (CBD and CHD), the gallbladder neck, and the Hartmann's pouch (HP), was performed using White Light (served as control modality) and by NIR enhancement. RESULTS: Cholecystocholangiography provided a significantly higher rate of visualization of the CD in case of cholecystitis with mild adhesions, and an improved visualization of the HP, CBD, and CHD in case of severe inflammation, when compared to White Light observation. There were no benefits of NIR in case of non-inflamed lithiasis. CONCLUSIONS: Clinical translation of NIR cholecystocholangiography has been successful with a noise-free visualization of biliary anatomy. It can be considered in difficult cases to increase the safety of laparoscopic cholecystectomy.