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Prader-Willi syndrome (PWS) is characterized by hypotonia, distinctive facial features, hyperphagia, obesity, short stature, hypogonadism, intellectual disability, and behavior problems. Uncontrolled hyperphagia can lead to dangerous food-seeking behavior and with life-threatening obesity. Severe obesity is prone to obstructive sleep apnea (OSA) and can lead to cor pulmonale. This study reports on a case involving a 21-year-old man with PWS who developed OSA due to severe obesity, which led to cor pulmonale, a life-threatening complication. Multidisciplinary care provided in the intensive care unit included weight reduction, ventilation support, antipsychotics, sedative drugs, rehabilitation, and meticulous skin care. The patient did recover. To prevent severe obesity in adults with PWS, hyperphagia must be controlled, and the patient must also be managed by an endocrinologist throughout childhood.

Transitions to a new principal are common, especially within urban public schools, and potentially highly disruptive to a school's culture and operations. We use longitudinal data from New York City to investigate if the effect of principal transitions differs by whether the incoming principal was hired externally or promoted from within the school. We take advantage of variation in the timing of principal transitions within an event-study approach to estimate the causal effect of principal changes. Changing principals has an immediate negative effect on student test scores that is sustained over several years regardless of whether hired internally or externally. However, externally hired principals lead to an increase in teacher turnover and a decline in perceptions of the school's learning environment, whereas transitions to an internally promoted principal have no such effects. This pattern of results raises important questions about leadership transitions and the nature of principal effects on school quality.

A complete denture, consisting of teeth and a gum base, is a standard device used to restore masticatory and esthetic functions in patients with complete edentulism. The different colors and mechan...

PurposeAnalysis of circulating tumor DNA (ctDNA) in blood could allow noninvasive genetic analysis of primary tumors. Although there have been unmet needs for noninvasive methods in patients with primary central nervous system lymphoma (PCNSL), it is still not determined whether plasma ctDNA analysis could be useful for patients with PCNSL. Materials and MethodsTargeted deep sequencing of 54 genes was performed in cell-free DNA isolated from plasma samples collected pretreatment, during treatment, and at the end of treatment in 42 consecutively diagnosed PCNSL patients between January 2017 and December 2018.ResultsTargeted sequencing of plasma cell-free DNA detected somatic mutations representing ctDNA in 11 cases (11/41, 27%). The detection of ctDNA was not related to the concentration of cell-free DNA or tumor volume. The mutation profiles of these 11 cases varied between patients. The most frequently mutated gene was PIM1 (4/11, 36.4%), whereas KMT2D, PIK3CA, and MYD88 were each observed in three patients (3/11, 27%). The mutations of 13 genes were concordantly found in primary tumor tissue and plasma ctDNA, giving a detection sensitivity of 45%. During the serial tracking of seven patients with complete response, the disappearance of ctDNA mutations was found in four patients, whereas three patients had detected ctDNA mutation at the end of treatment. ConclusionThe plasma ctDNA mutation analysis still has limited value for surveillance and predicting treatment outcomes of PCNSL because the detection efficiency was lower than other systemic lymphomas. Thus, analytical platforms should be improved to overcome anatomical hurdles associated with PCNSL.

Because of paucity of published data, we evaluated the 2-year major clinical outcomes between early invasive (EI) and delayed invasive (DI) strategies according to the stage of chronic kidney disease (CKD) in patients with non-ST-segment elevation myocardial infarction (NSTEMI), who underwent a successful newer-generation drug-eluting stent (DES) implantation.A total of 8241 NSTEMI patients were recruited from the Korea Acute Myocardial Infarction Registry (KAMIR). Based on baseline estimated glomerular filtration rate (eGFR; ≥90, 60-89, 30-59, and30 mL/min/1.73 mAfter multivariable-adjusted and propensity score-adjusted analyses, the cumulative incidence of MACE (group A, p = 0.139 and p = 0.103, respectively; group B, p = 0.968 and p = 0.608, respectively; group C, p = 0.111 and p = 0.196, respectively; group D, p = 0.882 and p = 0.571, respectively), all-cause death, re-MI, and any repeat revascularization was similar between the EI and DI groups in the 4 different renal function groups.In the era of newer-generation DES, EI and DI strategies showed comparable major clinical outcomes in patients with NSTEMI and CKD during a 2-year follow-up period. However, to confirm these results, further randomized, large-scale, long-term follow-up studies are needed.

The thalamic connectivity system, with the thalamus as the central node, enables transmission of the brain’s neural computations via extensive connections to cortical, subcortical and cerebellar regions. Emerging reports suggest deficits in this system across multiple psychiatric disorders, making it a unique network of high translational and transdiagnostic utility in mapping neural alterations that potentially contribute to symptoms and disturbances in psychiatric patients. However, despite considerable research effort, it is still debated how this system contributes to psychiatric disorders. This review characterizes current knowledge regarding thalamic connectivity system deficits in psychiatric disorders, including schizophrenia, bipolar disorder, major depressive disorder and autism spectrum disorder, across multiple levels of the system. We identify the presence of common and distinct patterns of deficits in the thalamic connectivity system in major psychiatric disorders and assess their nature and characteristics. Specifically, this review assembles evidence for the hypotheses of 1) thalamic microstructure, particularly in the mediodorsal nucleus, as a state marker of psychosis; 2) thalamo-prefrontal connectivity as a trait marker of psychosis; and 3) thalamo-somatosensory/parietal connectivity as a possible marker of general psychiatric illness. Furthermore, possible mechanisms contributing to thalamocortical dysconnectivity are explored. We discuss current views on the contributions of cerebellar-thalamic connectivity to the thalamic connectivity system and propose future studies to examine its effects at multiple levels, from the molecular (e.g., glutamatergic) to the behavioral (e.g., cognition), to gain a deeper understanding of the mechanisms that underlie the disturbances observed in psychiatric disorders.

Wilson disease (WD) is a relatively common genetic hepatic disease in children that is characterized by excessive copper accumulation, predominantly in the liver and brain. It is an autosomal recessive disease caused by the mutation of ATP7B that is potentially fatal if diagnosed late or untreated owing to degenerative aspects in the brain. In the early phase of WD, its initial presentation may include a mild hepatic involvement. WD may be overlooked as a cause of liver disease due to severe obesity, but should not be excluded from the differential diagnosis. We report a case of WD with severe obesity and fatty liver diagnosed in the early phase by targeted gene panel sequencing. We reviewed the endocrine problems associated with WD. Early suspicion of WD is important to improve prognosis.

Contains fulltext : 249977.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as β blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66·8 years [SD 11·0], 893 [23·9%] women; 1863 [49·9%] in the empagliflozin group, 1867 [50·1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0·75 [95% CI 0·65-0·86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0·85 [0·69-1·06]) and for doses of 50% or more of the target dose (HR 0·67 [0·52-0·88]; p(interaction)=0·18). A similar result was seen for β blockers at doses of less than 50% of the target dose (HR 0·66 [0·54-0·80]) and for doses of 50% or more of the target dose (HR 0·81 [0·66-1·00]; p(interaction)=0·15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus β blocker plus MRA (given combination HR 0·73 [0·61-0·88]; not given combination HR 0·76 [0·62-0·94]; p(interaction)=0·77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company.

A 49-year-old female patient was transferred to our hospital due to suspicion of severe adhesion and malignant tumours during surgery at a local hospital with an adnexal tumour a week ago. There was no history of gynaecological surgery before this surgery. On pelvic examination, a solid, fixed mass

Purpose K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods.Materials and Methods Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers).Results In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively.Conclusion The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

Rationale: The ability of peripheral blood biomarkers to assess COPD risk and progression is unknown. Genetics and gene expression may capture important aspects of COPD-related biology that predict...

Purpose To evaluate the correlation between vitamin D level and erectile dysfunction (ED) in male lower urinary tract symptoms (LUTS) patients. Materials and methods We analyzed data from 534 male patients who were tested for LUTS from 2014 to 2017. LUTS severity was classified into mild (≤7) or moderate to severe (≥8) based on total IPSS scores. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D [25(OH)D] level of less than 20 ng/mL. The severity of ED was dichotomized into mild (≥17 points) or moderate to severe (≤16 points) depending on total IIEF-5 scores. The association of the serum 25(OH)D level with moderate to severe ED was assessed using logistic regression analysis. Results In the entire cohort, moderate to severe ED was significantly associated with age ≥60 years (odds ratio [OR], 1.762; 95% confidence interval [CI], 1.011-3.073) and moderate to severe LUTS (OR, 2.075; 95% CI, 1.134-3.789), but not with serum 25(OH)D level (OR, 1.001; 95% CI, 0.979-1.023). Whereas, in the subgroup consisting of moderate to severe LUTS patients over 60 years (n=223), either low serum 25(OH)D level (OR, 0.944; 95% CI, 0.903-0.986) or vitamin D deficiency (OR, 2.949; 95% CI, 1.118-7.782) was the independent risk factor of moderate to severe ED as a result of each multivariate analysis. Conclusions Low vitamin D status closely correlated with moderate to severe ED in elderly men with moderate to severe LUTS.

BACKGROUND The 2020 European Society of Cardiology (ESC) guidelines recommend using the 0/1-hour and 0/2-hour algorithms over the 0/3-hour algorithm as the first and second choices of high-sensitivity cardiac troponin (hs-cTn)-based strategies for triage of patients with suspected acute myocardial infarction (AMI). PURPOSE To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms. DATA SOURCES PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020. (PROSPERO: CRD42020216479). STUDY SELECTION Prospective studies that evaluated the ESC 0/1-hour, 0/2-hour, or 0/3-hour algorithms in adult patients presenting with suspected AMI. DATA EXTRACTION The primary outcome was index AMI. Twenty unique cohorts were identified. Primary data were obtained from investigators of 16 cohorts and aggregate data were extracted from 4 cohorts. Two independent authors assessed each study for methodological quality. DATA SYNTHESIS A total of 32 studies (20 cohorts) with 30 066 patients were analyzed. The 0/1-hour algorithm had a pooled sensitivity of 99.1% (95% CI, 98.5% to 99.5%) and negative predictive value (NPV) of 99.8% (CI, 99.6% to 99.9%) for ruling out AMI. The 0/2-hour algorithm had a pooled sensitivity of 98.6% (CI, 97.2% to 99.3%) and NPV of 99.6% (CI, 99.4% to 99.8%). The 0/3-hour algorithm had a pooled sensitivity of 93.7% (CI, 87.4% to 97.0%) and NPV of 98.7% (CI, 97.7% to 99.3%). Sensitivity of the 0/3-hour algorithm was attenuated in studies that did not use clinical criteria (GRACE score

Background: With growing incidence of early gastric cancer (EGC), endoscopic submucosal dissection (ESD) is widely performed as a standard treatment for mucosal cancer. Due to the increasing application of ESD, the number of non-curative resection after ESD is also growing, leading to escalating number of patients who require additional gastrectomy with lymph node dissection after non-curative ESD. However, effects of ESD prior to surgery on technical difficulties during operation for EGC remain unclear. Therefore, this study aimed to determine the effect of non-curative ESD on short-term surgical outcomes in patients who underwent additional surgical treatment using propensity score matching method. Methods: To evaluate the effect of ESD on short-term surgical outcomes in patients who underwent additional surgical treatment after a non-curative ESD procedure, patients were divided into two groups: (1) those who underwent additional gastrectomy after non-curative resection of ESD [ESD + Surgery (ES) Group], and (2) those who underwent gastrectomy as the initial treatment [Surgery Only (SO) Group]. To minimize differences in baseline demographic features that could potentially be associated with short-term outcomes, propensity-scored matching analysis was performed. Results: After propensity-scored matching (1:1 matching), 140 patients altogether were selected and analyzed in this study. Complications were experienced by 18 (25.7%) patients in the ES group and 13 (18.6%) patients in the SO group, showing no significant (p

Background: It remains unclear whether P2Y 12 monotherapy, especially clopidogrel, following short-duration dual antiplatelet therapy (DAPT) is associated with favorable outcomes in patients undergoing complex percutaneous coronary intervention (PCI). Therefore, this study analyzed the efficacy and safety of P2Y 12 inhibitor monotherapy, mostly clopidogrel (78%), in complex PCI following short-term DAPT. Methods: The post-hoc analysis of the SMART-CHOICE trial involving 2,993 patients included 498 cases of complex PCIs, defined by at least one of the following features: 3 vessels treated, ≥ 3 stents implanted, ≥ 3 lesions treated, bifurcation with ≥ 2 stents implanted, and a total stent length of ≥ 60 mm. The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE), defined as the composite of all-cause death, myocardial infarction, and stroke. The primary safety endpoint included bleeding, defined as Bleeding Academic Research Consortium (BARC) types 2 to 5. Results: Complex PCI group had a higher risk of MACCE (4.0% vs. 2.3%, hazard ratio [HR] = 1.74, 95% confidence interval [CI]: 1.05–2.89, p = 0.033) and a similar risk of BARC types 2–5 bleeding (2.6% vs. 2.6%, HR = 1.02, 95% CI: 0.56–1.86, p = 0.939) compared with those without complex PCIs. Patients undergoing complex PCIs, followed by P2Y 12 inhibitor monotherapy and 12 months of DAPT exhibited similar rates of MACCE (3.8% vs. 4.2%, HR = 0.92, 95% CI: 0.38–2.21, p = 0.853). Conclusions: P2Y 12 inhibitor monotherapy, mostly clopidogrel, following 3 months of DAPT did not increase ischemic events in patients with complex PCIs.

Background The clinical features of pediatric rhabdomyolysis differ from those of the adults with rhabdomyolysis; however, multicenter studies are lacking. This study aimed to investigate the characteristics of pediatric rhabdomyolysis and reveal the risk factors for acute kidney injury (AKI) in such cases. Methods This retrospective study analyzed the medical records of children and adolescents diagnosed with rhabdomyolysis at 23 hospitals in South Korea between January 2007 and December 2016. Results Among 880 patients, those aged 3 to 5 years old composed the largest subgroup (19.4%), and all age subgroups were predominantly male. The incidence of AKI was 11.3%. Neurological disorders (53.6%) and infection (39.0%) were the most common underlying disorder and cause of rhabdomyolysis, respectively. The median age at diagnosis in the AKI subgroup was older than that in the non-AKI subgroup (12.2 years vs. 8.0 years). There were no significant differences in body mass index, myalgia, dark-colored urine, or the number of causal factors between the two AKI-status subgroups. The multivariate logistic regression model indicated that the following factors were independently associated with AKI: multiorgan failure, presence of an underlying disorder, strong positive urine occult blood, increased aspartate aminotransferase and uric acid levels, and reduced calcium levels. Conclusions Our study revealed characteristic clinical and laboratory features of rhabdomyolysis in a Korean pediatric population and highlighted the risk factors for AKI in these cases. Our findings will contribute to a greater understanding of pediatric rhabdomyolysis and may enable early intervention against rhabdomyolysis-induced AKI.

Introduction Despite of the routine use of erythropoietin in hemodialysis patients to correct anemia, its administration route's effects on hemoglobin variability and cardiovascular events remain elusive. Herein, we determined different erythropoietin administration routes' effects on hemoglobin variability in hemodialysis patients and the associated factors of hemoglobin variability and cardiovascular events. Methods This is a post hoc analysis of a prospective, controlled, randomized, unblinded study with 78 Korean hemodialysis patients receiving intravenous (n = 40) or subcutaneous (n = 38) erythropoietin therapy. We evaluated hemoglobin variability by calculating the frequency of hemoglobin measurements outside the target range during all visits. The high-frequency group was defined by those with hemoglobin variability over the median value (25%) while the low-frequency group was defined by those with hemoglobin variability of Results In this analysis, 37 patients (51.1%) were males, and the mean age was 50.6 ± 12.5 years. The frequency of the value being outside the target hemoglobin range was higher in the subcutaneous group compared to the intravenous group (p = 0.03). The low-frequency group required significantly lower erythropoietin doses compared to the high-frequency group. In the adjusted Cox analysis, the parameter high group was a significant independent risk factor for cardiovascular events (p = 0.03). Conclusion The risk out of the target hemoglobin range increased with subcutaneous administration compared with intravenous erythropoietin administration in hemodialysis patients. An increased frequency of the value being outside the target hemoglobin range was also associated with an increased risk of cardiovascular events.

Introduction A pericardial effusion (PE) has a variable etiology and the primary role is diagnosis of metastatic malignancy. We analyzed the PE cytology in a large cohort in accordance with the international system for reporting serous fluid cytopathology (ISRSFC) and evaluated the long‐term patient outcomes. Methods PE specimens from 2010 to 2014 with an available clinical history, cytologic data, and pericardial biopsy results were collected. Results A total of 574 PE specimens were obtained from 486 patients, representing 1.5% (574/38,589) of all body fluid specimens. Three hundred and eighty‐two (66.6%) cases were “negative,” 54 (9.4%) cases were “atypia of undetermined significance,” 10 (1.7%) cases were “suspicious for malignancy,” and 128 (22.3%) cases were “malignancy”. The most common origin for malignant PE was the lung (82.1%), in both men (70.5%) and women (50.6%). Breast cancer (20%) in women and gastric cancer (4.9%) in men were the second most common malignant PE, respectively. The mean interval from the occurrence of malignant PE to death was 10.06 months (range; 0–116.03 months, median 3.5 months), and the 1‐year survival rate was 16.7%. In addition, the 1‐year survival rates after malignant PE onset were 0% for gastric cancer, 13.9% for lung cancer, 19.8% for breast cancer, and 21.1% for the other cancers (p = 0.011). Conclusion Our present study is the first to our knowledge to classify the pericardial fluid from 574 cases in accordance with the recently published ISRSFC, and to present the long‐term outcomes of patients with malignant PE at the same time. Moreover, we report for the first time that it is gastric and not lung cancer patients that have the poorest prognosis after the occurrence of malignant PE., Our study report the long‐term outcomes of patients with malignant pericardial effusion. In addition, most common malignant pericardial effusion was lung cancer and gastric cancer showed the poorest survival prognosis after the occurrence of malignant pericardial effusion.

Evidence for the utility of medications in settings lacking randomized trial data can come from studies of treatment persistence. The present study was undertaken to examine patterns of medication use in systemic lupus erythematosus (SLE) using data from a large multicenter longitudinal cohort.Prospectively collected data from the Asia Pacific Lupus Collaboration cohort including disease activity (SLE Disease Activity Index 2000 [SLEDAI-2K]) and medication details, captured at every visit from 2013-2018, were used. Medications were categorized as glucocorticoids (GCs), antimalarials (AM), and immunosuppressants (IS). Cox regression analyses were performed to determine the time-to-discontinuation of medications, stratified by SLE disease activity.Data from 19,804 visits of 2,860 patients were analyzed. Eight medication categories were observed: no treatment; GC, AM, or IS only; GC plus AM; GC plus IS; AM plus IS; and GC plus AM plus IS (triple therapy). Triple therapy was the most frequent pattern (31.4% of visits); single agents were used in 21% of visits, and biologics in only 3%. Time-to-discontinuation analysis indicated that medication persistence varied widely, with the highest treatment persistence for AM and lowest for IS. Patients with a time-adjusted mean SLEDAI-2K score of ≥10 had lower discontinuation of GCs and higher discontinuation of IS.Most patients received combination treatment. GC persistence was high, while IS persistence was low. Patients with high disease activity received more medication combinations but had reduced IS persistence, consistent with limited utility. These data confirm unmet need for improved SLE treatments.

Background: In recent decades, laparoscopic liver resection (LLR) has been gradually adopted at high-volume centers, particularly for hepatocellular carcinoma and liver metastasis. However, LLR in patients with gallbladder cancer (GBC) is a controversial issue, and there are few studies of LLR for GBC. Our aim was to compare the outcomes of patients who underwent laparoscopic or open liver resection for GBC. Materials and Methods: All patients admitted with stage II or III GBC requiring liver resection, together with cholecystectomy and lymphadenectomy, were analyzed retrospectively. Patients with thickness of the resected liver specimen >2 cm in pathology reports were included. Results: A total of 56 patients with stage II or III GBC were included in this study; 23 (41.1%) underwent laparoscopic surgery and 33 (58.9%) underwent open surgery. Propensity score matching was performed using a 1:1 matching scheme. After matching, 12 patients were included in each group. The preoperative characteristics of both groups were similar, as were the operative times (laparoscopic versus open group: 237.5 minutes versus 272.5 minutes, respectively; P = .319) and blood loss (300 mL versus 275 mL, respectively; P = .307). The laparoscopic group had a significantly shorter postoperative hospital stay than the open surgery group (4.5 days versus 8 days, respectively; P = .012). There were no major complications in either group. There was no difference between the groups in the number of lymph nodes harvested at surgery (P = .910). There were no differences between the two groups in disease-free (P = .503) or overall (P = .719) survival. Conclusion: LLR extended to GBC provides outcomes similar to those of open surgery. With increasing experience, LLR can be a viable alternative to open surgery for GBC.

Aims Familial hypercholesterolemia (FH) is currently a worldwide health issue. Understanding the characteristics of patients is important for proper diagnosis and treatment. This study aimed to analyze the phenotypic and genetic features, including threshold cholesterol levels, of Korean patients with FH. Methods A total of 296 patients enrolled in the Korean FH registry were included, according to the following criteria: low-density lipoprotein-cholesterol (LDL-C) ＞190 mg/dL with tendon xanthoma or family history compatible with FH, or LDL-C ＞225 mg/dL. DNA sequences of three FH-associated genes were obtained using whole-exome or target exome sequencing. Threshold cholesterol levels for differentiating patients with FH/pathogenic variant (PV) carriers and predictors of PVs were identified. Results Of the 296 patients, 104 had PVs and showed more obvious clinical findings, including higher cholesterol levels. PV rates ranged from 30% to 64% when patients were categorized by possible or definite type according to the Simon Broome criteria. Frequent PV types included missense variants and copy number variations (CNVs), while the most frequent location of PVs was p.P685L in LDLR. The threshold LDL-C levels for patient differentiation and PV prediction were 177 and 225 mg/dL, respectively. Younger age, tendon xanthoma, and higher LDL-C levels were identified as independent predictors of PVs, while traditional cardiovascular risk factors were predictors of coronary artery disease. Conclusions Korean patients with FH had variable PV rates depending on diagnostic criteria and distinctive PV locations. The reported threshold LDL-C levels pave the way for efficient patient care in this population.

Purpose The role of epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) in the management of persistent subsolid nodules (SSNs) is unclear. This study aimed to investigate the impact of EGFR-TKIs on concurrent SSNs in patients with stage IV non–small cell lung cancer (NSCLC).Materials and Methods Patients who received an EGFR-TKI for at least 1 month for stage IV NSCLC and had concurrent SSN(s) that had existed for at least 3 months on chest computed tomography were included in this retrospective study. Size change of each nodule before and after EGFR-TKI therapies were evaluated using a cutoff value of 2 mm; increase (≥ 2 mm), decrease (≤ –2 mm), and no change (–2 mm < size change < +2 mm).Results A total of 77 SSNs, 51 pure ground-glass (66.2%) and 26 part-solid nodules (33.8%), were identified in 59 patients who received gefitinib (n=45) and erlotinib (n=14). Among 58 EGFR mutation analysis performed for primary lung cancer, 45 (77.6%) were EGFR mutant. The proportions of decrease group were 19.5% (15/77) on per-nodule basis and 25.4% (15/59) on per-patient basis. Four SSNs (5.2%) disappeared completely. On per-patient based multivariable analysis, EGFR exon 19 deletion positivity for primary lung cancer was associated with a decrease after initial EGFR-TKI therapy (adjusted odds ratio, 4.29; 95% confidence interval, 1.21 to 15.29; p=0.025).Conclusion Approximately 20% of the concurrent SSNs decreased after the initial EGFR-TKI therapy. EGFR exon 19 deletion positivity for primary lung cancer was significantly associated with the size change of concurrent SSNs.

OBJECTIVE Brainstem cavernous malformations (CMs) often require resection due to their aggressive natural history causing hemorrhage and progressive neurological deficits. The authors report a novel intraoperative neuromonitoring technique of direct brainstem somatosensory evoked potentials (SSEPs) for functional mapping intended to help guide surgery and subsequently prevent and minimize postoperative sensory deficits. METHODS Between 2013 and 2019 at the Stanford University Hospital, intraoperative direct brainstem stimulation of primary somatosensory pathways was attempted in 11 patients with CMs. Stimulation identified nucleus fasciculus, nucleus cuneatus, medial lemniscus, or safe corridors for incisions. SSEPs were recorded from standard scalp subdermal electrodes. Stimulation intensities required to evoke potentials ranged from 0.3 to 3.0 mA or V. RESULTS There were a total of 1 midbrain, 6 pontine, and 4 medullary CMs—all with surrounding hemorrhage. In 7/11 cases, brainstem SSEPs were recorded and reproducible. In cases 1 and 11, peripheral median nerve and posterior tibial nerve stimulations did not produce reliable SSEPs but direct brainstem stimulation did. In 4/11 cases, stimulation around the areas of hemosiderin did not evoke reliable SSEPs. The direct brainstem SSEP technique allowed the surgeon to find safe corridors to incise the brainstem and resect the lesions. CONCLUSIONS Direct stimulation of brainstem sensory structures with successful recording of scalp SSEPs is feasible at low stimulation intensities. This innovative technique can help the neurosurgeon clarify distorted anatomy, identify safer incision sites from which to evacuate clots and CMs, and may help reduce postoperative neurological deficits. The technique needs further refinement, but could potentially be useful to map other brainstem lesions.

Vitamin D as a prohormone is converted into the active form in vivo and binds to vitamin D receptors, exercising a wide range of biological functions. Recent studies strongly support that vitamin D supplementation is associated with reduced cancer risk and a good prognosis. Gastrointestinal cancer is the leading cause of cancer-related deaths worldwide. The key role of vitamin D in the development of gastrointestinal cancer has been observed. Moreover, Vitamin D can also affect innate immunity and perform anti-inflammation and anti-infection actions. Given the intimate relationship between cancer and inflammation, we herein summarize epidemiological and preclinical studies of vitamin D and the underlying mechanism of its action in inflammation, gastric and colorectal cancer by our group and other researchers. A beneficial effect of vitamin D in cancer and inflammatory disease has been supported by different studies. More controlled and larger clinical trials are needed before a reliable conclusion and realization of vitamin D supplementation in the adjunct treatment of gastrointestinal inflammation and cancer.

Proximal junctional problems are among the potential complications of surgery for adult spinal deformity (ASD) and are associated with higher morbidity and increased rates of revision surgery. The diverse manifestations of proximal junctional problems range from proximal junctional kyphosis (PJK) to proximal junctional failure (PJF). Although there is no universally accepted definition for PJK, the most common is a proximal junctional angle greater than 10° that is at least 10° greater than the preoperative measurement. PJF represents a progression from PJK and is characterized by pain, gait disturbances, and neurological deficits. The risk factors for PJK can be classified according to patient-related, radiological, and surgical factors. Based on an understanding of the modifiable factors that contribute to reducing the risk of PJK, prevention strategies are critical for patients with ASD.

Background While several randomized trials have shown conflicting results regarding the comparative effectiveness of on- and off-pump coronary arterial bypass grafting (CABG), research on long-term outcomes in large-scale, real-world clinical settings are limited. We sought to examine the comparative effectiveness of on- and off-pump CABG in a real-world clinical setting. Methods Using the nationwide claims database of the Korean National Health Insurance Service, we identified patients who underwent isolated CABG from 2004 to 2013. Propensity-score matching with multivariable adjustment was used to assemble a cohort of patients with similar baseline characteristics. Results Among 23,828 patients, 12,639 in the off-pump (53.0%) and 11,189 in the on-pump (47.0%) groups were enrolled. After matching, 6,483 pairs were included in the final analysis. At 30 days, there was no significant difference in adjusted mortality between the off- and on-pump groups (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.87-1.16). During long-term follow-up (100% complete; median 5.3yrs, maximum 13.2yrs), however, off-pump CABG was associated with a higher risk of mortality than on-pump CABG (HR, 1.09; 95% CI, 1.03-1.15). The risks of myocardial infarction (MI) (HR, 1.3; 95% CI, 1.16-1.45) and repeat revascularization (HR, 1.50; 95% CI, 1.37-1.63) were also significantly higher in the off-pump CABG group than in the on-pump CABG group, while the stroke risk was similar inter-groups (HR, 0.99; 95% CI, 0.87-1.13). Conclusions In this contemporary, nationwide, clinical practice claim registry, off-pump CABG was associated with higher long-term risks of mortality, MI, and repeat revascularization than on-pump CABG.

Adenosine triphosphate potassium sensitive channels provide endogenous myocardial protection via coupling of cell membrane potential to myocardial metabolism. Adenosine triphosphate potassium sensitive channel openers, such as diazoxide, mimic ischemic preconditioning, prevent cardiomyocyte swelling, preserve myocyte contractility after stress, and provide diastolic protection. We hypothesize that diazoxide combined with hyperkalemic cardioplegia provides superior myocardial protection compared with cardioplegia alone during prolonged global ischemia in a large animal model.Twelve pigs were randomized to global ischemia for 2 hours with a single dose of cold blood (4:1) hyperkalemic cardioplegia alone (n = 6) or with diazoxide (500 μmol/L) (n = 6) and reperfused for 1 hour. Cardiac output, myocardial oxygen consumption, left ventricular developed pressure, left ventricular ejection fraction, diastolic function, myocardial troponin, myoglobin, markers of apoptosis, and left ventricular infarct size were compared.Four pigs in the cardioplegia alone group could not be weaned from cardiopulmonary bypass. There were no differences in myoglobin, troponin, or apoptosis between groups. Diazoxide preserved cardiac output versus control (74.5 vs 18.4 mL/kg/min, P = .01). Linear mixed regression modeling demonstrated that the addition of diazoxide to cardioplegia preserved left ventricular developed pressure by 36% (95% confidence interval, 9.9-61.5; P .01), dP/dt max by 41% (95% confidence interval, 14.5-67.5; P .01), and dP/dt min by 33% (95% confidence interval, 8.9-57.5; P = .01). It was also associated with higher (but not significant) myocardial oxygen consumption (3.7 vs 1.4 mL ODiazoxide preserves systolic and diastolic ventricular function in a large animal model of prolonged global myocardial ischemia. Diazoxide as an adjunct to hyperkalemic cardioplegia may allow safer prolonged ischemic times during increasingly complicated cardiac procedures.

Negative affect is a fundamental dimension of human emotion. When extreme, it contributes to a variety of adverse outcomes—from physical and mental illness to divorce and premature death. Mechanistic work in animals and neuroimaging research in humans and monkeys has begun to reveal the broad contours of the neural circuits governing negative affect, but the relevance of these discoveries to everyday distress remains incompletely understood. Here we used a combination of approaches— including neuroimaging assays of threat anticipation and emotional face perception and >10,000 momentary assessments of emotional experience—to demonstrate that individuals showing greater activation in a cingulo-opercular circuit during an anxiety-eliciting laboratory paradigm experience lower levels of stressor-dependent distress in their daily lives (n=202-208). Extended amygdala activation was not significantly related to momentary negative affect. These observations provide a framework for understanding the neurobiology of negative affect in the laboratory and in the real world.STATEMENT OF RELEVANCEAnxiety, sadness, and other negative emotions are hallmarks of the human condition. When extreme, they contribute to a variety of adverse outcomes—from physical and mental illness to divorce and premature death—pointing to the need to develop a better understanding of the underlying brain circuitry. Recent work has begun to reveal the neural systems governing negative affect, but the relevance of these tantalizing laboratory discoveries to the real world has remained unclear. Here we used a combination of brain imaging and smartphone-based survey techniques to show that individuals marked by greater activation in a cingulo-opercular circuit during an anxiety-promoting laboratory paradigm tend to experience diminished distress in response to everyday stressors. These observations provide new insights into the brain systems most relevant to moment-by-moment fluctuations in negative mood, underscoring the importance of more recently evolved cortical association areas.

Objectives The presence of a fistula between the thoracic aorta and the esophagus is a rare and highly fatal condition. This study aimed to evaluate the outcomes of the surgical treatment of an aortoesophageal fistula (AEF). Methods We retrospectively reviewed patients with AEF who underwent surgery at our institution. Results Between 2007 and 2018, a total of 10 patients who underwent surgery for AEF. The mean age was 63 ± 12 years, and 6 patients were men. Four patients had primary AEFs and 6 patients had secondary AEFs (3 graft replacements and 3 thoracic endovascular aortic repairs). The timing of AEF since graft replacement or thoracic endovascular aortic repairs was 21.6 ± 27 days. We performed aortic replacement with a prosthetic graft (4 patients) or a homograft (5 patients) and extra-anatomical bypass due to a previous aortic graft infection (1 patient). As a treatment of the esophagus, we conducted primary repair in 7 of 10 patients. The median lengths of hospital and intensive care unit stay were 59 days (range, 9-225 days) and 6.3 days (range, 1-87 days), respectively. Seven patients achieved oral feeding after a median 10.3 postoperative days (range, 7-78 postoperative days). Two of the 10 patients died of sepsis at 9 and 74 days postoperatively. Conclusions The strategy for patients with AEF should be individualized. Our surgical strategy for AEF, which includes simultaneous aortic graft replacement and primary repair of esophagus in the same operative field, is feasible and promising.

Background/aims The endoscopic step-up approach is accepted as the preferred treatment for complicated or symptomatic walled-off necrosis (WON). Direct endoscopic necrosectomy (DEN) is an effective therapeutic option, but few reports describe long-term follow-up in this patient population. Thus, we aim to assess the long-term outcomes of DEN following severe necrotizing pancreatitis. Methods The data of all acute pancreatitis patients who underwent DEN following endoscopic transmural drainage from six referral centers between 2007 and 2017 were retrospectively collected. Results Sixty patients (76.7% male, mean age 48.3 years) underwent a median of 4 sessions of DEN starting at a median of 45.5 days after the onset of acute pancreatitis. Clinical success was achieved in 51 patients (85%), with a 35% complication rate and a 5% mortality rate. Using multivariate analysis, the risk factor associated with DEN failure or major DEN complications requiring intervention or surgery was an identified bacterial/fungal WON infection (odds ratio, 19.3; 95% confidence interval, 1.5 to 261.7). During the median follow-up period of 27 months, complicated WON recurrence was observed in 5.3% of patients, and long-term complications occurred in 24.6% of patients (four exocrine insufficiency, nine newly developed diabetes mellitus, one recurrent small bowel obstruction, one chylous ascites). Conclusions Considering that long-term complications are similar to those observed after pancreatectomy, DEN should be performed meticulously while minimizing damage to the viable pancreatic parenchyma with adequate antibiotic escalation.

Background: Olecranon fractures are common in motorcycle accidents, falls, or in direct elbow injury. In cases of transverse olecranon fracture, surgery is frequently required in adults. The aim of this study is to compare the biomechanical durability of suture anchor fixation in olecranon fractures to conventional tension band wiring technique in saw bones. Methods: 12 plastic saw bones were divided into 3 groups: tension band wiring fixation, modified Cha-Batman method, and a modified simple suture method using a suture anchor. After fixation, cyclic load tests were conducted for 1,000 cycles, at 5 Hz with a force of 10 N to 250 N. After cycling loading, the extent of displacement was measured using a non-contact coordinate measuring instrument, and statistical analysis performed. Results: The average displacement was significantly smaller in the modified Cha-Bateman method (1.4 mm) than in the tension band wiring method (3.8 mm, p = 0.007) and the modified simple suture method using suture anchor (3.3 mm, p = 0.012). There was no significant difference in displacement between tension band wiring fixation and the modified simple suture method (p = 0.564). Conclusions: This study provides a biomechanical basis for the hypothesis that the suture anchor technique in weak bone model could obtain results comparable to those of conventional tension band wiring. In particular, the modified Cha-Bateman method, showed stronger biomechanical properties than the tension band wiring method and modified simple suture method using a suture anchor. The current study could also provide pilot data that can be used in future experiments.

Klippel-Trenaunay syndrome (KTS) is a rare complex vascular syndrome with limb hypertrophy. KTS is diagnosed if at least two of the three features of capillary malformation, venous malformation, and soft tissue and/or bone overgrowth are present. Of these, capillary malformation (i.e., port-wine stain) is the most commonly observed feature but may be absent in atypical KTS. We herein report a case of atypical KTS with venous malformation and unilateral soft tissue hypertrophy.

Background Kissing aneurysms are situated on the same artery but have separate points of origin. Open surgical strategies for access from opposing directions may be technically problematic. Recent advances in protective devices and coiling techniques have compelled the present study, aimed at technical aspects and procedural outcomes of coil embolization in this setting. Methods Data prospectively accruing between May 2001 and May 2020 were systematically reviewed, assessing clinical and morphologic outcomes of coil embolization in 36 patients with 72 kissing aneurysms. Results Lesions most often involved paraclinoid internal carotid artery (n = 22), followed by anterior communicating artery (n = 7). Single-stage coil embolization of both aneurysms took place in nearly all patients (n = 35). Microcatheter tips for selecting paired aneurysms were usually directed opposite to one another (32 of 36, 88.9%), applying protective devices (i.e., balloons or stents) to 1 or both aneurysms in 21 patients (58.3%). Balloons were placed in 9 patients, often when treating first aneurysms and largely for second aneurysms as well (7 of 9, 77.8%). Stents deployed in 14 patients involved first and second aneurysms equally. Two patients required balloon of stent combinations. No procedure-related morbidity or mortality resulted. In follow-up of 68 aneurysms (mean: 40.2 ± 28.1 months) after coiling, 86.8% (59 of 68) showed sustained complete saccular occlusion. Conclusions Strategies for endovascular treatment of kissing aneurysms rely heavily on characteristics that the paired aneurysms display. Properly conducted single-stage coil embolization is a safe and effective method of treating such lesions.

Summary Background In patients with acute myocardial infarction receiving potent antiplatelet therapy, the bleeding risk remains high during the maintenance phase. We sought data on a uniform unguided de-escalation strategy of dual antiplatelet therapy (DAPT) from ticagrelor to clopidogrel after acute myocardial infarction. Methods In this open-label, assessor-masked, multicentre, non-inferiority, randomised trial (TALOS-AMI), patients at 32 institutes in South Korea with acute myocardial infarction receiving aspirin and ticagrelor without major ischaemic or bleeding events during the first month after index percutaneous coronary intervention (PCI) were randomly assigned in a 1:1 ratio to a de-escalation (clopidogrel plus aspirin) or active control (ticagrelor plus aspirin) group. Unguided de-escalation without a loading dose of clopidogrel was adopted when switching from ticagrelor to clopidogrel. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or bleeding type 2, 3, or 5 according to Bleeding Academic Research Consortium (BARC) criteria from 1 to 12 months. A non-inferiority test was done to assess the safety and efficacy of de-escalation DAPT compared with standard treatment. The hazard ratio (HR) for de-escalation versus active control group in a stratified Cox proportional hazards model was assessed for non-inferiority by means of an HR margin of 1·34, which equates to an absolute difference of 3·0% in the intention-to-treat population and, if significant, a superiority test was done subsequently. To ensure statistical robustness, additional analyses were also done in the per-protocol population. This trial is registered at ClinicalTrials.gov, NCT02018055. Findings From Feb 26, 2014, to Dec 31, 2018, from 2901 patients screened, 2697 patients were randomly assigned: 1349 patients to de-escalation and 1348 to active control groups. At 12 months, the primary endpoints occurred in 59 (4·6%) in the de-escalation group and 104 (8·2%) patients in the active control group (pnon-inferiority Interpretation In stabilised patients with acute myocardial infarction after index PCI, a uniform unguided de-escalation strategy significantly reduced the risk of net clinical events up to 12 months, mainly by reducing the bleeding events. Funding ChongKunDang Pharm, Medtronic, Abbott, and Boston Scientific.

Dermal melanocytic disorders present as bluish pigmentation on the skin. Several entities including Mongolian spot, aberrant Mongolian spot, nevus of Ota, and nevus of Ito have been reported. It is often difficult to distinguish between the different entities from their overlapping features. Although they share similar etiologies and histologic findings, their co-morbidities and prognosis differ. In this paper, we report four cases of dermal melanocytic disorders of which we were not able to make a clear-cut diagnosis. Also, we briefly review the dermal melanocytic disorders.

Periostin plays a crucial role in fibrosis, which is involved in kidney aging. A few studies have shown that lipid metabolism is involved in kidney aging. We investigated the role of periostin in lipid metabolism during kidney aging. Renal function, fibrosis, and inflammatory markers were studied using urine, blood, and tissue samples from wild-type (WT) C57BL/6 mice and Postn-null mice of 2 and 24 months of age. Lipids were quantitatively profiled using liquid chromatography-tandem mass spectrometry in the multiple reaction monitoring mode. Renal function was worse and tubular atrophy/interstitial fibrosis, periostin expression, and inflammatory and fibrotic markers were more severe in aged WT mice than in young WT mice. In aged Postn-null mice, these changes were mitigated. Thirty-five differentially regulated lipids were identified. Phosphatidylcholines, cholesteryl ester, cholesterol, ceramide-1-phosphate, and CCL5 expression were significantly higher in aged WT mice than in aged Postn-null mice. Particularly, linoleic acid, linolenic acid, arachidonic acid, and docosahexaenoic acid differed strongly between the two groups. Lysophosphatidylcholine acyltransferase 2, which converts lysophosphatidylcholine to phosphatidylcholine, was significantly higher in aged WT mice than in aged Postn-null mice. Periostin expression in the kidneys increased with age, and periostin ablation delayed aging. Changes in lipids and their metabolism were found in Postn-null mice. Further research on the precise mechanisms of and relationships between lipid expression and metabolism, kidney aging, and periostin expression is warranted.

Objectives: This study aimed to evaluate the degree of satisfaction of cancer patients and to understand their motives for visiting Korean Medicine Hospital in order to increase satisfaction with Korean medicine among cancer patients.Methods: Data collection was conducted in the form of a survey of 100 inpatients who responded to a self-report questionnaire. Independent t-test and analysis of variance (ANOVA) were used for data analysis.Results: The main reason for visiting Korean Medicine Hospital was to prevent metastasis or recurrence of cancer. Patients showed the highest satisfaction with acupuncture and moxibustion. The average degree of satisfaction related to the doctor service was, on a 5-point scale, 4.80, and that of using procedure was 4.68.Conclusion: Most of the cancer patients are satisfied with the medical services in Korean Medicine Hospital. There were no significant differences in satisfaction degree by gender, age, or occupation.

Background Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). Methods From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. Results In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; P

PURPOSE Adjuvant chemotherapy after D2 gastrectomy is standard for resectable locally advanced gastric cancer (LAGC) in Asia. Based on positive findings for perioperative chemotherapy in European phase III studies, the phase III PRODIGY study (ClinicalTrials.gov identifier: NCT01515748 ) investigated whether neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 could improve outcomes versus standard treatment in Korean patients with resectable LAGC. PATIENTS AND METHODS Patients 20-75 years of age, with Eastern Cooperative Oncology Group performance status 0-1, and with histologically confirmed primary gastric or gastroesophageal junction adenocarcinoma (clinical TNM staging: T2-3N+ or T4Nany) were randomly assigned to D2 surgery followed by adjuvant S-1 (40-60 mg orally twice a day, days 1-28 every 6 weeks for eight cycles; SC group) or neoadjuvant DOS (docetaxel 50 mg/m2, oxaliplatin 100 mg/m2 intravenously day 1, S-1 40 mg/m2 orally twice a day, days 1-14 every 3 weeks for three cycles) before D2 surgery, followed by adjuvant S-1 (CSC group). The primary objective was progression-free survival (PFS) with CSC versus SC. Two sensitivity analyses were performed: intent-to-treat and landmark PFS analysis. RESULTS Between January 18, 2012, and January 2, 2017, 266 patients were randomly assigned to CSC and 264 to SC at 18 Korean study sites; 238 and 246 patients, respectively, were treated (full analysis set). Follow-up was ongoing in 176 patients at data cutoff (January 21, 2019; median follow-up 38.6 months [interquartile range, 23.5-62.1]). CSC improved PFS versus SC (adjusted hazard ratio, 0.70; 95% CI, 0.52 to 0.95; stratified log-rank P = .023). Sensitivity analyses confirmed these findings. Treatments were well tolerated. Two grade 5 adverse events (febrile neutropenia and dyspnea) occurred during neoadjuvant treatment. CONCLUSION PRODIGY showed that neoadjuvant DOS chemotherapy, as part of perioperative chemotherapy, is effective and tolerable in Korean patients with LAGC.

Objective Thyroid immune-related adverse events (irAEs) have been reported to have prognostic significance among patients with cancer treated with anti-programmed cell death-1 (PD1) and anti-programmed death-ligand 1 monotherapies. We evaluated the clinical course and predictors of thyroid irAEs in relation to outcomes of patients with advanced cancer treated with combination anti-PD1/anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Methods We conducted a regional study and identified patients with advanced cancer who received ≥1 cycle of combination anti-PD1/anti-CTLA4 between 2015 and 2019 in Hong Kong. Thyroid function tests (TFTs) were monitored every 3 weeks. Thyroid irAE was defined by ≥2 abnormal TFTs after initiation of combination anti-PD1/anti-CTLA4 in the absence of other causes. Results One hundred and three patients were included (median age: 59 years; 71.8% men). About 45% had prior anti-PD1 exposure. Upon median follow-up of 6.8 months, 17 patients (16.5%) developed thyroid irAEs, where 6 initially presented with thyrotoxicosis (overt, n = 4; subclinical, n = 2) and 11 with hypothyroidism (overt, n = 2; subclinical, n = 9). Eventually, 10 patients (58.8%) required continuous thyroxine replacement. Systemic steroid was not required in all cases. Prior anti-PD1 exposure (odds ratio, 3.67; 95% CI, 1.19–11.4; P = .024) independently predicted thyroid irAEs. Multivariable Cox regression analysis revealed that occurrence of thyroid irAEs was independently associated with better overall survival (adjusted hazard ratio, 0.34; 95% CI, 0.17–0.71; P = .004). Conclusion Thyroid irAEs are common in routine clinical practice among patients with advanced cancer treated with anti-PD1/anti-CTLA4 combination and might have potential prognostic significance. Regular TFT monitoring is advised for timely treatment of thyroid irAEs to prevent potential morbidities.

OBJECTIVE The most catastrophic symptom of proximal junctional failure (PJF) following long instrumented fusion surgery for adult spinal deformity (ASD) is neurological deficits. Although previous reports have shown that PJF usually developed during the early postoperative period, some patients showed late neurological deficits. The aim of this study was to report the incidence, characteristics, and surgical outcomes of PJF with late neurological deficits. METHODS Patients surgically treated for ASD at a single institution were retrospectively reviewed. Among them, the patients requiring revision surgery for newly developed neurological deficits at least 6 months after the initial surgery were included. Patient demographic, radiographic, surgical, and clinical data were investigated. Neurological status was assessed using the Frankel grading system. RESULTS PJF with late neurological deficits developed in 18 of 385 patients (4.7%). The mean age at the onset of neurological deficits was 72.0 ± 6.0 years, and the median time from the initial surgery was 4.5 years. The most common pathology of PJF was adjacent disc degeneration and subsequent canal stenosis (11 patients). Five patients showed disc degeneration with aseptic bone destruction. Fractures at the upper instrumented vertebra (UIV), UIV + 1, and UIV + 2 occurred in 2, 3, and 2 patients, respectively. Ossification of the yellow ligament, which had not been found at the first surgery, was identified in 6 patients. Eight patients showed improvement of their neurological deficits and 10 patients showed no improvement by the final follow-up. Perioperative major complications occurred in 8 of 18 patients. CONCLUSIONS The incidence of PJF with late neurological deficits following ASD surgery was 4.7% in this cohort. The patients showed several morphological features. After revision surgery, perioperative complications were common and the prognosis for improved neurological status was not favorable.

Previous epidemiological studies have demonstrated that the lower serum concentration of vitamin D was associated with elevated risk of open-angle glaucoma (OAG). However, few studies have examined the association between aqueous humor vitamin D concentrations and OAG. Hence, we investigated the relationship between 25-hydroxyvitamin D (25(OH)D) concentrations in aqueous humor and OAG. We measured 25(OH)D concentrations in aqueous humor and serum of 126 patients who underwent cataract surgery. 36 were patients with OAG and 90 were control patients. The 25(OH)D concentrations were measured using Elecsys Vitamin D Total Kits with the Cobas e602 module (Roche Diagnostics, Mannheim, Germany), an electrochemiluminescence assay. Multiple linear regression analysis was performed to investigate factors associated with serum and aqueous humor 25(OH)D concentrations. Patients with OAG had significantly lower 25(OH)D concentrations in aqueous humor than control patients. Serum 25(OH)D concentrations were higher in patients with OAG than in the control, but this was not statistically significant. 25(OH)D concentrations in aqueous humor of patients with OAG were significantly associated with axial length but not with glaucoma severity, which was determined by the retinal nerve fiber layer thickness or mean deviation. Vitamin D concentrations in aqueous humor of patients with OAG were significantly lower than those in patients without OAG.

Slow-cycling/dormant cancer cells (SCCs) have pivotal roles in driving cancer relapse and drug resistance. A mechanistic explanation for cancer cell dormancy and therapeutic strategies targeting SCCs are necessary to improve patient prognosis, but are limited because of technical challenges to obtaining SCCs. Here, by applying proliferation-sensitive dyes and chemotherapeutics to non-small cell lung cancer (NSCLC) cell lines and patient-derived xenografts, we identified a distinct SCC subpopulation that resembled SCCs in patient tumors. These SCCs displayed major dormancy-like phenotypes and high survival capacity under hostile microenvironments through transcriptional upregulation of regulator of G protein signaling 2 (RGS2). Database analysis revealed RGS2 as a biomarker of retarded proliferation and poor prognosis in NSCLC. We showed that RGS2 caused prolonged translational arrest in SCCs through persistent eukaryotic initiation factor 2 (eIF2α) phosphorylation via proteasome-mediated degradation of activating transcription factor 4 (ATF4). Translational activation through RGS2 antagonism or the use of phosphodiesterase 5 inhibitors, including sildenafil (Viagra), promoted ER stress-induced apoptosis in SCCs in vitro and in vivo under stressed conditions, such as those induced by chemotherapy. Our results suggest that a low-dose chemotherapy and translation-instigating pharmacological intervention in combination is an effective strategy to prevent tumor progression in NSCLC patients after rigorous chemotherapy.

BACKGROUND: Although home care workers (HCWs) are increasingly caring for adults with heart failure (HF), many feel unprepared and lack HF training. To serve as the foundation for a future educational intervention, we aimed to elicit HCWs’ HF educational needs. METHODS: We partnered with the largest healthcare union in the US to recruit 41 HCWs employed by 17 home care agencies. Using the nominal group technique, we asked HCWs to respond to 3 questions: When caring for a HF patient: (1) What information do you want? (2) What symptoms worry you? (3) What situations do you struggle with? Participants ranked their responses by priority. Data were consolidated by question. RESULTS: For question 1, participants ranked HF signs and symptoms most highly, followed by HF treatment and medications. For question 2, chest pain was most worrisome, followed by neurologic changes and shortness of breath. For question 3, participants struggled with encouraging patients to follow a heart-specific diet. CONCLUSIONS: HCWs expressed a need to learn more about signs and symptoms of HF and ways to assist patients with HF self-care. These findings can inform the development of a HF training program for HCWs that specifically addresses their expressed needs.

BACKGROUND Obstructive sleep apnoea (OSA) episode related blood pressure (BP) surge may mediate the association of OSA with cardiovascular disease. However, BP is not measured during a clinical sleep study. METHOD We tested the feasibility of incorporating the Caretaker physiological monitor, which utilizes a novel continuous beat-to-beat (b-b) BP monitoring technology, into polysomnography (PSG) and aimed to characterize BP surges related to obstructive respiratory events. B-b BP was concurrently collected and merged with PSG data on a posthoc basis. We compared BP surge between mean respiratory (apnoea, hypopnea and desaturation-alone events) and nonrespiratory events (spontaneous or leg movement-related arousals). We examined the association of the degree of oxygen desaturation with BP surge in a given respiratory event combining all events. A total of 17 consecutive patients (12 men, mean 52 years old, nine diagnostic and eight split-night PSGs) undergoing clinically indicated PSG were included after excluding one patient with poor signal quality due to excessive movement. RESULTS Caretaker was well tolerated. Mean respiratory BP surge ranged from 5 to 19 mmHg [Median (IQR) = 13.9 (9.5--16.2)]. Mean BP surge between the respiratory and nonrespiratory events was similar [13.8 (4.5) vs. 14.9 (5.3) mmHg, P = 0.13]. Accounting for the count distribution of desaturation/BP surge data pair events, there was a linear correlation between the degree of oxygen desaturation and BP surge (R = 0.57, P

Background/aims We investigated the effect of metabolic dysfunction-associated fatty liver disease (MAFLD) on future mortality and cardiovascular disease (CVD) using a prospective community-based cohort study. Methods Individuals from two community-based cohorts who were 40 to 70 years old were prospectively followed for 16 years. MAFLD was defined as a high fatty liver index (FLI ≥60) plus one of the following conditions: overweight/obesity (body mass index ≥23 kg/m2), type 2 diabetes mellitus, or ≥2 metabolic risk abnormalities. Nonalcoholic fatty liver disease (NAFLD) was defined as FLI ≥60 without any secondary cause of hepatic steatosis. Results Among 8,919 subjects (age 52.2±8.9 years, 47.7% of males), 1,509 (16.9%) had MAFLD. During the median follow-up of 15.7 years, MAFLD independently predicted overall mortality after adjustment for confounders (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.05 to 1.69) but NAFLD did not (HR, 1.20; 95% CI, 0.94 to 1.53). MAFLD also predicted CVD after adjustment for age, sex, and body mass index (HR, 1.35; 95% CI, 1.13 to 1.62), which lost its statistical significance by further adjustments. Stratified analysis indicated that metabolic dysfunction contributed to mortality (HR, 1.51; 95% CI, 1.21 to 1.89) and CVD (HR, 1.27; 95% CI, 1.02 to 1.59). Among metabolic dysfunctions used for defining MAFLD, type 2 diabetes mellitus in MAFLD increased the risk of both mortality (HR, 2.07; 95% CI, 1.52 to 2.81) and CVD (HR, 1.42; 95% CI, 1.09 to 1.85). Conclusions MAFLD independently increased overall mortality. Heterogeneity in mortality and CVD risk of subjects with MAFLD may be determined by the accompanying metabolic dysfunctions.

During the present COVID-19 pandemic, transplantation of donor lungs with a history of COVID-19 infection is a critical issue. Donor-derived virus infection and graft dysfunction are possible after transplantation. However, use of such lungs could save the lives of patients requiring emergency transplantation. We successfully transplanted lungs from a brain-dead donor who had recovered from SARS-CoV-2 into a severe respiratory failure patient supported with ECMO who needed an emergency transplant. At the 3-month follow-up, our patient showed no evidence of COVID-19 transmission or graft dysfunction.

OBJECTIVE The objective of this study was to evaluate the feasibility and complications of the over-the-arch (OTA) technique for screw insertion into the C1 lateral mass in patients in whom conventional techniques (i.e., posterior arch [PA] and inferior lateral mass [ILM]) are not feasible due to 1) PA with a very small height (< 3.5 mm), 2) a caudally tilted PA blocking the inferior part of the C1 lateral mass, or 3) loss of height at the ILM (< 3.5 mm). METHODS The authors reviewed the medical records of 60 patients who underwent C1 screw fixation with the OTA technique (13 screws) and the PA/ILM technique (107 screws) between 2011 and 2019. Vertebral artery (VA) injuries, screw malposition, and bony union were radiologically assessed. Clinical outcome measures, including Neck Disability Index (NDI), Japanese Orthopaedic Association (JOA) scale score, and occipital neuralgia, were recorded. RESULTS Thirteen OTA screws were successfully inserted without any major complications. NDI and JOA scale scores did not show significant differences between the two groups at final follow-up. No VA injuries were recognized during screw insertion. There was no evidence of ischemic damage to the VA or bony erosion in the occiput or atlas. Medial wall violation was observed in 1 screw (7.7%); however, no C0–1, C1–2, or lateral wall violations were observed. No patients developed new-onset neuralgia postoperatively after C1 fixation with the OTA technique. CONCLUSIONS The OTA technique was safe and useful for C1 screw fixation in patients in whom conventional techniques could not be employed.

Background/Aims: Rapid percutaneous coronary intervention (PCI) is the cornerstone of treatment for ST-elevation myocardial infarction (STEMI). However, there have been conflicting results regarding the differences in clinical outcomes between on-hours and off-hours presentation in STEMI patients. We aimed to examine the difference in long-term outcomes between off-hours and on-hours PCI in patients with STEMI.Methods: The characteristics and clinical outcomes of 5,364 STEMI patients between November 2011 and June 2015 from the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH) registry were analyzed. Patients were divided into two groups: the off-hours group (weekdays from 6:01 PM to 7:59 AM, weekends, and legal holidays) and the on-hours group (weekdays from 8:00 AM to 6:00 PM). Major adverse cardiac and cerebrovascular events (MACCEs) were defined as a composite of allcause mortality, non-fatal myocardial infarction, any revascularization, cerebrovascular accident, and stent thrombosis. The primary endpoint was the occurrence of MACCEs, and all other clinical outcomes were analyzed.Results: A total of 3,119 patients (58.1%) underwent primary PCI due to STEMI during off-hours and 2,245 patients (41.9%) during on-hours. At 36 months, the clinical outcomes of the off-hours group were similar to those of the on-hours group in both the unadjusted and propensity score weighting-adjusted analyses.Conclusions: Our analysis revealed that the long-term outcomes in STEMI patients admitted to hospitals during off-hours were similar to outcomes of those admitted during on-hours.