Purpose: Programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors have shown efficacy in metastatic esophageal squamous cell carcinoma (ESCC) therapy. However, data is still limited regarding neoadjuvant immunotherapy for operable ESCC. Materials and Methods: Patients with clinical stage T2 or T3 and N0 ESCC received three cycles of nivolumab therapy every two weeks before surgical resection. The primary endpoint is major pathologic responses (MPR) rate (≤ 10% of residual viable tumor [RVT]). Results: Total 20 patients completed the planned nivolumab therapy. Among them, 17 patients underwent surgery as protocol, showing MPR in two patients (MPR rate, 11.8%), including one pathologic complete response, on conventional pathologic response evaluation. Pathologic response was re-evaluated using the immune-related pathologic response criteria based on immune-related RVT (irRVT). Three patients were classified as immunologic major pathologic response (iMPR; ≤ 10% irRVT, iMPR rate: 17.6%), five as pathologic partial response (> 10% and < 90% irRVT), and nine as pathologic nonresponse (≥ 90% irRVT). The combined positive score (CPS) for PD-L1 in the baseline samples was predictable for iMPR, with the probability as 37.5% in CPS ≥ 10 (3/8) and 0% in CPS < 10 (0/9). Conclusion Although the efficacy of neoadjuvant nivolumab therapy was modest in unselected ESCC patients, further researches on neoadjuvant immunotherapy are necessary in patients with PD-L1 expressed ESCC.

Positional headache refers to a headache that worsens or improves with changes in posture. It is often secondary in nature, associated with various pathologies that may have serious consequences if left undiagnosed or untreated. The authors report a patient who complained of severe positional headache and was diagnosed with concurrent reversible cerebral vasoconstriction syndrome and vertebral artery dissection, thus highlighting the importance of considering such conditions in a patient with postural headaches.

Purpose: To assess the agreement between anterior segment measurements obtained using swept-source optical coherence tomography (Anterion®, Heidelberg Engineering Inc., Heidelberg, Germany) and Scheimpflug partial coherence interferometry (Pentacam HR®, OCULUS, Wetzlar, Germany). Methods: We analyzed the anterior and posterior corneal keratometry, Cartesian astigmatism (J0), oblique astigmatism (J45), anterior chamber depth (ACD), and central corneal thickness (CCT) measurements obtained using the two devices in 65 eyes of 43 subjects. Results: The mean differences between the anterior flat K, anterior steep K, anterior mean K, anterior J0, anterior J45, posterior flat K, posterior steep K, posterior mean K, posterior J0, posterior J45, ACD, and CCT measurements were -0.13 ± 0.34, -0.02 ± 0.33, -0.05 ± 0.31, -0.03 ± 0.39, -0.06 ± 0.35, 0.12 ± 0.09, 0.07 ± 0.08, 0.10 ± 0.06, -0.02 ± 0.14, 0.01 ± 0.16, 0.04 ± 0.06, and -3.51 ± 7.42, respectively. All measurements except posterior J0 and J45 had interclass correlation coefficients greater than 0.75. Conclusions The mean differences and 95% limits of agreement in this study are consistent with previously reported values. There was a high level of agreement between Anterion® and Pentacam HR®. However, considering the statistically significant differences and limits of agreement for certain measurements, caution should be exercised when assuming interchangeability between these devices.

Background: Subclinical left ventricular diastolic dysfunction (LVDD) is an emerging consequence of increased insulin resistance, and dyslipidemia is one of the few correctable risk factors of LVDD. This study evaluated the role of mean and visit-to-visit variability of lipid measurements in risk of LVDD in a healthy population. Methods: This was a 3.7-year (interquartile range, 2.1 to 4.9) longitudinal cohort study including 2,817 adults (median age 55 years) with left ventricular ejection fraction >50% who underwent an annual or biannual health screening between January 2008 and July 2016. The mean, standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), and average real variability of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB), non-HDL-C, and triglycerides were obtained from three to six measurements during the 5 years preceding the first echocardiogram. Results: Among the 2,817 patients, 560 (19.9%) developed LVDD. The mean of no component of lipid measurements was associated with risk of LVDD. CV (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.10 to 1.67), SD (HR, 1.27; 95% CI, 1.03 to 1.57), and VIM (HR, 1.26; 95% CI, 1.03 to 1.55) of LDL-C and all the variability parameters of apoB were significantly associated with development of LVDD. The association between CV-LDL and risk of LVDD did not have significant interaction with sex, increasing/decreasing trend at baseline, or use of stain and/or lipid-modifying agents. Conclusion The variability of LDL-C and apoB, rather than their mean, was associated with risk for LVDD.

Objective:To assess the long-term outcome and influencing factors of laparoscopic Heller myotomy plus Dor fundoplication(LHM+ Dor) for achalasia by a single operator.Methods:Fifty-four patients who underwent LHM+ Dor consecutively from January 2011 to December 2019 were retrospectively reviewed. Those who had already undergone surgical or endoscopic myotomy and who were complicated with cancer were ruled out. Symptom inquiry and esophagogram were conducted both before and after surgery for assessing surgical results. Esophagoscopy, esophageal manometry and 24 h pH monitoring were performed before surgery, and the effects of these preoperative factors on the long-term outcome were analyzed.Results:All patients had dysphagia for average 6.5 years, ranging from 0.5-30.0 years. Intra-operative mucosal perforation occurred in 4(7.4%) patients, and there were no postoperative morbidity and mortality. At a median follow-up of 5.2 years, the morbidity of dysphagia decreased from 100% before surgery to 5.5% after surgery( P<0.001), Eckardt scores from 4.85±1.64 to 0.71±1.08( P=0.000). After surgery, 94.4% of patients had excellent and good relief of symptoms and good control of gastroesophageal reflux, the morbidity of heartburn being 3.7%. At 5 years after surgery, the probability of being symptoms free(Eckardt score≤1) was 91.7% in patients without preoperative night cough, compared to 54.6% in those with preoperative night cough( P=0.047). The probability was 92.3% in patients with grade Ⅰ and Ⅱ dilation of the esophagus and 79.0% in patients with grade Ⅲ and Ⅳ dilation( P=0.027). At multivariate analysis, heavier esophageal dilation was the independent predicator for poor symptom control after surgery. Conclusion:LHM+ Dor can be safely performed and durably relieve achalasia symptoms. Severe esophageal dilation before surgery is an independent predictor of a poor response to surgery.

Purpose: The aim of this study was to evaluate the association between the severity of hyperechoic pancreas (HP) on ultrasonography (US) and glycemic progression. Methods: In total, 1,386 participants who underwent abdominal US as part of health examinations between December 2008 and May 2014 were included in this retrospective study. We classified pancreatic echogenicity on a 4-point scale, and compared it using two distinct criteria: fatty pancreas (FP) 1 criterion (normal vs. ≥mild HP) and FP2 criterion (normal/mild HP vs. ≥moderate HP). According to the presence of nonalcoholic fatty liver disease (NAFLD), participants were subdivided into four groups: non-NAFLD and non-HP, isolated NAFLD, isolated HP, and HP with NAFLD. Glycemic progression was defined as progression from normoglycemia to prediabetes or diabetes or progression from prediabetes to diabetes. Results: During the follow-up (median, 5.9 years), 262 of the 1,386 participants developed glycemic progression. Using FP2, the probability of glycemic progression across the four subgroups showed cumulative aggravation for NAFLD and HP (all P<0.05). Isolated HP showed a higher probability of glycemic progression than isolated NAFLD according to FP2 (P<0.001). The highest probability of glycemic progression was observed in patients with both NAFLD and HP (P<0.001). The hazard ratio for glycemic progression increased with the severity of HP. Conclusion Increasing severity of HP on US was found to be significantly correlated with glycemic progression. Moreover, isolated HP of moderate or greater severity predicted glycemic progression independent of NAFLD.

As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified