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A 48-year-old man came with a left-sided headache that was compatible with diagnostic criteria of cluster headache. Left oculomotor nerve palsy developed 2 weeks after headache onset. Magnetic resonance imaging showed wall thickening and enhancement by contrast material in the lateral aspect of the left cavernous sinus, consistent with a possible inflammatory lesion. The patient reported the almost complete remission of the pain and diplopia after steroid therapy. We speculate that Tolosa-Hunt syndrome should be included as a cause of cluster-like headaches.

Neurofibromatosis type 1 (NF1) is an autosomal-dominant genetic disease that predisposes affected individuals to tumors. Neurofibroma and malignant peripheral nerve sheath tumor (MPNST) are examples of PNSTs that occur either sporadically or as part of hereditary neurocutaneous diseases such as NF1. We treated three patients with NF1 who presented with different PNSTs. All patients underwent surgical resection, and pathologic findings indicated neurofibroma, atypical neurofibroma, and MPNST, respectively. We managed each case based on its pathology. The patient with MPNST died after chemoradiotherapy; the other patients did not experience recurrence for several months.

OBJECTIVE We investigated (1) the associations of pre-stroke aspirin use with thrombus burden, infarct volume, hemorrhagic transformation, early neurological deterioration (END), and functional outcome, and (2) whether stroke subtypes modify these associations in first-ever ischemic stroke. METHODS This multicenter magnetic resonance imaging (MRI)-based study included 5,700 consecutive patients with acute first-ever ischemic stroke, who did not undergo intravenous thrombolysis or endovascular thrombectomy, from May 2011 through February 2014. Propensity score-based augmented inverse probability weighting was performed to estimate adjusted effects of pre-stroke aspirin use. RESULTS The mean age was 67 years (41% women), and 15.9% (n = 907) were taking aspirin before stroke. Pre-stroke aspirin use (vs nonuse) was significantly related to a reduced infarct volume (by 30%), particularly in large artery atherosclerosis stroke (by 45%). In cardioembolic stroke, pre-stroke aspirin use was associated with a ~50% lower incidence of END (adjusted difference = -5.4%, 95% confidence interval [CI] = -8.9 to -1.9). Thus, pre-stroke aspirin use was associated with ~30% higher likelihood of favorable outcome (3-month modified Rankin Scale score

Background and ObjectivesWe evaluated the association between admission glycated hemoglobin (HbA1c) and subsequent risk of composite vascular events, including stroke, myocardial infarction (MI), and vascular death, in patients with acute ischemic stroke and diabetes.MethodsPatients who had a TIA or an acute ischemic stroke within 7 days of symptom onset and diabetes were included in a retrospective cohort design using the stroke registry of the Clinical Research Center for Stroke in Korea. The association between admission HbA1c and composite vascular events, including stroke, MI, and vascular death, during 1-year follow-up was estimated using the Fine-Gray model. The risk of composite vascular events according to the ischemic stroke subtype was explored using fractional polynomial and linear-quadratic models.ResultsOf the 18,567 patients, 1,437 developed composite vascular events during follow-up. In multivariable analysis using HbA1c as a categorical variable, the risk significantly increased at a threshold of 6.8%–7.0%. The influence of admission HbA1c level on the risk of composite vascular events was pronounced particularly among those in whom fasting glucose at admission was ≤130 mg/dL. The optimal ranges of HbA1c associated with minimal risks for composite vascular events were lowest for the small vessel occlusion subtype (6.6 [95% confidence internal [CI], 6.3–6.9]) compared to the large artery atherosclerosis (7.3 [95% CI, 6.8–7.9]) or the cardioembolic subtype (7.4 [95% CI, 6.3–8.5]).DicussionIn patients with ischemic stroke and diabetes, the risks of composite vascular events were significantly associated with admission HbA1c. The optimal range of admission HbA1c was below 6.8%–7.0% and differed according to the ischemic stroke subtype.

This study identified single nucleotide polymorphisms (SNPs) that affect the body weight of chickens. Analysis of body weight showed that the Cornish breed had the highest body weight, and the Korean native chicken (Gray Brown) had the lowest body weight. TSH is composed of an α-subunit and a β-subunit, and the TSH-β gene encoding the β-subunit has been reported to be associated with obesity. In chickens, it is located on chromosome 26 and is reported to be associated with growth. The calcium-sensing receptor gene (CaSR) plays a role in the regulation of extracellular calcium homeostasis and is responsible for calcium absorption in the urinary tract, which affects the eggshell quality in poultry. It was shown that TSH-β was strongly correlated with weight in Cornish and Korean native (Gray Brown) chickens, particularly in those with the CC trait. However, CaSR showed no association with body weight in poultry; it was associated with calcium and the eggshell. Thus, selection for TSH-β can be used to produce individuals with more favorable traits in terms of body weight.

BackgroundNo study has thoroughly compared the effectiveness of combined antiplatelet treatments (other than clopidogrel–aspirin) versus clopidogrel–aspirin or aspirin alone for early secondary prevention in acute ischaemic stroke.MethodsWe identified patients with acute, minor, non-cardiogenic ischaemic stroke treated with aspirin alone, clopidogrel–aspirin or other combination treatment. Propensity scores considering the inverse probability of treatment weighting were used to adjust for baseline imbalances. The primary outcome was the composite of all strokes (ischaemic or haemorrhagic), myocardial infarction and all-cause mortality at 3 months.ResultsAmong 12 234 patients (male: 61.9%; age: 65.5±13 years) who met the eligibility criteria, aspirin, clopidogrel–aspirin and other combination treatments were administered in 52.2%, 42.9% and 4.9% of patients, respectively. In the crude analysis, the primary outcome event at 3 months occurred in 14.5% of the other combination group, 14.4% of the aspirin group and 13.0% of the clopidogrel–aspirin group. In the weighted Cox proportional hazards analysis, the 3-month primary outcome event occurred less frequently in the clopidogrel–aspirin group than in the other combination group (weighted HR: 0.82 (0.59–1.13)), while no association was found between the aspirin group (weighted HR: 1.04 (0.76–1.44)) or other combination group and the 3-month primary outcome.ConclusionOther combined antiplatelet treatment, compared with aspirin alone or clopidogrel–aspirin, was not associated with reduced risks of primary composite vascular events or recurrent stroke during the first 3 months after stroke. Therefore, the results suggest that other combination treatments, particularly the cilostazol-based combination, may not be effective alternatives for clopidogrel–aspirin to prevent early vascular events in patients with acute minor stroke. Further exploration in clinical trials will be needed.

Given the role of comorbid conditions in the pathophysiology of HFpEF, we aimed to identify and rank the importance of comorbid conditions associated with post-hospitalization outcomes of older adults hospitalized for HFpEF. We examined data from 4605 Medicare beneficiaries hospitalized in 2007–2014 for HFpEF based on ICD-9-CM codes for acute diastolic heart failure (428.31 or 428.33). To identify characteristics with high importance for prediction of mortality, all-cause rehospitalization, rehospitalization for heart failure, and composite outcome of mortality or all-cause rehospitalization up to 1 year, we developed boosted decision tree ensembles for each outcome, separately. For interpretability, we estimated hazard ratios (HRs) and 95% confidence intervals (CI) using Cox proportional hazards models. Age and frailty were the most important characteristics for prediction of mortality. Frailty was the most important characteristic for prediction of rehospitalization, rehospitalization for heart failure, and the composite outcome of mortality or all-cause rehospitalization. In Cox proportional hazards models, a 1-SD higher frailty score (0.1 on theoretical range of 0–1) was associated with a HR of 1.27 (1.06–1.52) for mortality, 1.16 (1.07–1.25) for all-cause rehospitalization, 1.24 (1.14–1.35) for HF rehospitalization, and 1.15 (1.07–1.25) for the composite outcome of mortality or all-cause rehospitalization. In conclusion, frailty is an important predictor of mortality and rehospitalization in adults aged [Formula: see text] 66 years with HFpEF.

Purpose: We assessed the clinical feasibility of C-reactive protein to lymphocyte ratio (CLR) as a determinant of survival in patients with non-small cell lung cancer (NSCLC) undergoing curative surgical resection. Methods: A retrospective study was conducted on patients with stage I and II NSCLC undergoing curative resection. Demographic and clinical variables, including CLR, were collected and analyzed. The Cox proportional hazards model was used to calculate hazard ratios for overall survival (OS) and cancer-specific survival (CSS). The Mann-Whitney U test was used to compare differences between two independent groups. Results: The median age of the patients was 69.0 years, and male patients comprised 63.9% of all patients. A total of 164 (75.9%) patients were categorized as having stage I disease and 52 (24.1%) as having stage II disease. Using the multivariate Cox model, age (hazard ratio [HR] 1.08, p

In recent years, various methods of measuring body temperature have been developed using wireless biosensors to facilitate an early detection of pregnancy and parturition in cows. However, there are no studies on real-time monitoring of cattle body temperature throughout pregnancy. Therefore, we investigated the daily mean ruminal temperature in pregnant cows throughout pregnancy using a ruminal bio-capsule sensor and then evaluated the temperature variation between pregnant and non-pregnant cows. In pregnant cows, the mean and standard deviation of ruminal temperature was 38.86 ± 0.17℃. Ruminal temperature in pregnant cows slowly decreased until 180 to 190 days after artificial insemination and after that, the temperature increased dramatically until just before parturition. Furthermore, the means ruminal temperature was significantly different between pregnant and nonpregnant cows. The mean and standard deviation of ruminal temperature were as follows: 38.68 ± 0.01℃ from days 80 to 100, 38.78 ± 0.02℃ from days 145 to 165, 38.99 ± 0.45℃ from days 200 to 220, 39.14 ± 0.38℃ from days 250 to 270 before parturition. Therefore, our results could provide useful data for early detection of pregnancy and parturition in Korean cows.

Background: Protease-activated protein-2 (PAR2) has been reported to regulate hepatic insulin resistance condition in type 2 diabe tes mice. However, the mechanism of lipid metabolism through PAR2 in obesity mice have not yet been examined. In liver, Fork head box O1 (FoxO1) activity induces peroxisome proliferator-activated receptor γ (PPARγ), leading to accumulation of lipids and hyperlipidemia. Hyperlipidemia significantly influence hepatic steatoses, but the mechanisms underlying PAR2 signaling are com plex and have not yet been elucidated. Methods: To examine the modulatory action of FoxO1 and its altered interaction with PPARγ, we utilized db/db mice and PAR2-knockout (KO) mice administered with high-fat diet (HFD). Results: Here, we demonstrated that PAR2 was overexpressed and regulated downstream gene expressions in db/db but not in db+ mice. The interaction between PAR2/β-arrestin and Akt was also greater in db/db mice. The Akt inhibition increased FoxO1 activity and subsequently PPARγ gene in the livers that led to hepatic lipid accumulation. Our data showed that FoxO1 was negatively con trolled by Akt signaling and consequently, the activity of a major lipogenesis-associated transcription factors such as PPARγ in creased, leading to hepatic lipid accumulation through the PAR2 pathway under hyperglycemic conditions in mice. Furthermore, the association between PPARγ and FoxO1 was increased in hepatic steatosis condition in db/db mice. However, HFD-fed PAR2-KO mice showed suppressed FoxO1-induced hepatic lipid accumulation compared with HFD-fed control groups. Conclusion: Collectively, our results provide evidence that the interaction of FoxO1 with PPARγ promotes hepatic steatosis in mice. This might be due to defects in PAR2/β-arrestin-mediated Akt signaling in diabetic and HFD-fed mice.

Aortobronchial fistula (ABF) induced by an infected pseudoaneurysm of the thoracic aorta is a life-threatening condition. As surgical treatment is associated with significant mortality and morbidity, thoracic endovascular aneurysm repair (TEVAR) may be an alternative for the treatment of ABF. However, the long-term durability of this intervention is largely unknown and the recurrence of ABF is a potential complication. We experienced a case of recurrent ABF after stent grafting as an early procedure for an infected pseudoaneurysm of the thoracic aorta. Remnant ABF, bronchial and/or aortic wall erosion, vasa vasorum connected with ABF, and recurrent local inflammation of the thin aortic wall around ABF might cause recurrent hemoptysis. As a result, we suggest that TEVAR should be considered as a bridge therapy for the initial treatment of ABF resulting from an infected pseudoaneurysm, and that several options, such as second-stage surgery, should be considered to prevent the recurrence of ABF.

Background Acute acquired comitant esotropia (AACE) is a type of strabismus characterized by a sudden onset of large angle esotropia with diplopia, which often occurs in children after infancy, teenagers, and young adolescents. However, studies on the surgical outcomes of only adults are rare. The purpose of this article is to analyze the surgical outcomes for adult patients diagnosed with AACE. Methods Medical records of 24 patients who had undergone surgery for AACE were retrospectively analyzed. The main outcome measures were the final motor and sensory success rate after surgery and factors affecting motor and sensory outcomes. Motor success was considered alignment within 8 prism diopter (PD) at both near and distance and sensory success was stereoacuity ≥ 60 sec/arc. Results The preoperative mean esodeviation angles were 33.1 ± 10.4 PD at distance and 33.3 ± 11.2 PD at near. The mean period of postoperative follow up was 7.5 ± 4.5 months (range 1–8 months). The postoperative mean esodeviation angles at final follow-up time were 3.4 ± 6.1 PD at distance and 3.8 ± 6.7 PD at near. The surgical motor success rate at final follow-up was 79.2% (19/24). The sensory success rate at final follow-up was 50.0% (12/24). The factor affecting the motor outcome was the type of surgery (p p Conclusions Surgery type appears to affect surgical motor outcomes in adults with AACE. Although the sensory outcome was favorable, it seems that regaining bifoveal fixation takes time.

We evaluated the clinical course of asymptomatic and mildly symptomatic patients with laboratory-confirmed coronavirus disease (COVID-19) admitted to community treatment centers (CTCs) for isolation in South Korea. Of 632 patients, 75 (11.9%) had symptoms at admission, 186 (29.4%) were asymptomatic at admission but developed symptoms during their stay, and 371 (58.7%) remained asymptomatic during their entire clinical course. Nineteen (3.0%) patients were transferred to hospitals, but 94.3% (573/613) of the remaining patients were discharged from CTCs upon virologic remission. The mean virologic remission period was 20.1 days (SD + 7.7 days). Nearly 20% of patients remained in the CTCs for 4 weeks after diagnosis. The virologic remission period was longer in symptomatic patients than in asymptomatic patients. In mildly symptomatic patients, the mean duration from symptom onset to virologic remission was 11.7 days (SD + 8.2 days). These data could help in planning for isolation centers and formulating self-isolation guidelines.

Background/Aims: Sarcopenia and erectile dysfunction (ED) are associated with poor health and quality of life in older men. We investigate the association be tween sarcopenia and severe ED in community-dwelling older men. Methods: We prospectively assessed sarcopenia and ED in 519, community-dwelling, older men (mean age, 74.0) in Pyeongchang, Korea, in 2016 to 2017. Sarcopenia was based on muscle mass, grip strength, and gait speed according to the Asian Working Group consensus algorithm. Severe ED was defined as 5-item Interna tional Index of Erectile Function questionnaire score under 8. Logistic regres sions were used to study associations between incident severe ED and sarcopenia, after adjusting age, cardiovascular risk factors, depression, and polypharmacy. Results: The prevalence of severe ED was 52.4% and that of sarcopenia was 31.6%. At baseline, the prevalence of severe ED was higher in men with sarcopenia than in those without (73.2% vs. 42.8%; adjusted odds ratio [aOR], 1.89; 95% confidence interval [CI], 1.18 to 3.03; p = 0.008). Slow gait speed (aOR, 2.80; 95% CI, 1.18 to 6.62; p = 0.019) and decreased muscle mass (aOR, 2.54; 95% CI, 1.11 to 5.81; p = 0.027) were associated with the incidence of severe ED, while decreased grip strength (aOR, 0.76; 95% CI, 0.30 to 1.91; p = 0.564) was not. Conclusions: Sarcopenia was associated with severe ED. Slow gait speed, and de creased muscle mass was independently associated with incident severe ED at 1 year. Further research is warranted to examine whether an intervention targeting these components can prevent severe ED.

ObjectiveTo improve epidemiologic knowledge of neurologic deterioration (ND) in patients with acute ischemic stroke (AIS).MethodsIn this prospective observational study, we captured ND prospectively in 29,446 patients with AIS admitted to 15 hospitals in Korea within 7 days of stroke onset. ND was defined as an increase in NIH Stroke Scale (NIHSS) score ≥2 (total), or ≥1 (motor or consciousness), or any new neurologic symptoms. Change in incidence rate after stroke onset, causes, factors associated with ND, modified Rankin Scale (mRS) score at 3 months and 1 year, and a composite of stroke, myocardial infarction, and all-cause death at 1 year were assessed.ResultsND occurred in 4,299 (14.6%) patients. The highest rate, 6.95 per 1,000 person-hours incidence, was within the first 6 hours, which decreased to 2.09 within 24–48 hours, and 0.66 within 72–96 hours after stroke onset. Old age, female sex, diabetes, early arrival, large artery atherosclerosis as a stroke subtype, high NIHSS scores, glucose level, systolic blood pressure, leukocytosis at admission, recanalization therapy, TIA without a relevant lesion, and steno-occlusion of relevant arteries were associated with ND. The causes were stroke progression (71.8%) followed by recurrence (8.5%). Adjusted relative risks (95% CI) for poor outcome (mRS 3–6) at 3 months and 1 year were 1.75 (1.70–1.80) and 1.70 (1.65–1.75), respectively. The adjusted hazard ratio (95% CI) for the composite event was 1.59 (1.45–1.74).ConclusionsND should be taken into consideration as a factor that may influence the outcome in acute ischemic stroke.

Background Delirium is a major risk factor for poor recovery after surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). It is unclear whether preoperative physical performance tests improve delirium prediction. Objective To examine whether physical performance tests can predict delirium after SAVR and TAVR, and adapt an existing delirium prediction rule for cardiac surgery, which includes Mini-Mental State Examination (MMSE), depression, prior stroke, and albumin level. Design Prospective cohort, 2014-2017. Setting Single academic center. Subjects A total of 187 patients undergoing SAVR (n=77) or TAVR (n=110). Methods The Short Physical Performance Battery (SPPB) score was calculated based on gait speed, balance, and chair stands (range: 0-12 points, lower scores indicate poor performance). Delirium was assessed using the Confusion Assessment Method. We fitted logistic regression to predict delirium using SPPB components and risk factors of delirium. Results Delirium occurred in 35.8% (50.7% in SAVR and 25.5% in TAVR). The risk of delirium increased for lower SPPB scores: 10-12 (28.2%), 7-9 (34.5%), 4-6 (37.5%) and 0-3 (44.1%) (p-for-trend=0.001). A model that included gait speed

Background & Aims Endoplasmic reticulum (ER) stress is one of the major causes of hepatic insulin resistance through increasing de novo lipogenesis. Forkhead box O6 (FoxO6) is a transcription factor mediating insulin signalling to glucose and lipid metabolism, therefore, dysregulated FoxO6 is involved in hepatic insulin resistance. In this study, we elucidated the role of FoxO6 in ER stress‐induced hepatic lipogenesis. Methods Hepatic ER stress responses and lipogenesis were monitored in mice overexpressed with constitutively active FoxO6 allele and FoxO6‐null mice. In the in vitro study, HepG2 cells overexpressing constitutively active FoxO6 were treated with palmitate, and then alterations in ER stress and lipid metabolism were measured. Results FoxO6 activation induced hepatic lipogenesis and the expression of ER stress‐inducible genes. The expression and transcriptional activity of peroxisome proliferator‐activated receptor γ (PPARγ) were significantly increased in constitutively active FoxO6 allele. Interestingly, we found that the active FoxO6 physically interacted with C/EBP homologous protein (CHOP), an ER stress‐inducible transcription factor, which was responsible for PPARγ expression. Palmitate treatment caused the expression of ER stress‐inducible genes, which was deteriorated by FoxO6 activation in HepG2 cells. Palmitate‐induced ER stress led to PPARγ expression through interactions between CHOP and FoxO6 corresponding to findings in the in vivo study. On the other hand, the expression of PPARα and β‐oxidation were decreased in constitutively active FoxO6 allele which implied that lipid catabolism is also regulated by FoxO6. Conclusion Our data present significant evidence demonstrating that CHOP and FoxO6 interact to induce hepatic lipid accumulation through PPARγ expression during ER stress.

In the mass outbreak of the 2019 novel coronavirus disease pandemic, the Daegu Medical Association managed to control and reduce the number of victims in Daegu successfully. More than 6,000 people were diagnosed in this city within a four-week period, and both medical system breakdown and increasing mortality were imminent. However, we minimized fatalities despite this explosive outbreak in a short time. The collaboration between the Daegu Medical Association and the local government may provide a reference model for overcoming regional outbreaks in the global pandemic era. We can prevent the shortage of medical resources by recruiting volunteer doctors and nurses early through public awareness campaigns. We can overcome the first massive outbreak using several new diagnostic and therapeutic systems such as the drive-through diagnosis system, telephonic counseling for self-quarantine patients by volunteer doctors, and therapeutic living centers. Both sharing the process of collaboration with the public system and summarizing the factors can provide useful information for building effective response systems to cope with the ongoing local outbreak of COVID-19 and any future epidemics of infectious diseases.

Secondary cluster-like headache has been reported in association with various underlying diseases. A 20-year-old man came with right-sided headache that started 1 month ago. Initially, his headache was compatible with diagnostic criteria of episodic cluster headache. Magnetic resonance imaging showed multiple enhancement lesions in right frontal bone and periorbital area. With bone marrow biopsy, we confirmed that B-lymphoblastic leukemia relapsed. We describe an unusual case with cluster-like headache caused by acute lymphocytic leukemia infiltration of periorbital tissue.

Objectives The aim of this study was to examine the value of frailty to predict in-hospital major bleeding and determine its impact on mid-term mortality following transcatheter (TAVR) or surgical (SAVR) aortic valve replacement. Background Bleeding complications are harbingers of mortality and major morbidity in patients undergoing TAVR or SAVR. Despite the high prevalence of frailty in this population, little is known about its effects on bleeding risk. Methods A post hoc analysis was performed of the multinational FRAILTY-AVR (Frailty Aortic Valve Replacement) cohort study, which prospectively enrolled older adults ≥70 years of age undergoing TAVR or SAVR. Trained researchers assessed frailty using a questionnaire and physical performance battery pre-procedure and ascertained clinical data from the electronic health record. The primary endpoint was major or life-threatening bleeding during the index hospitalization, and the secondary endpoint was units of packed red blood cells transfused. Results The cohort consisted of 1,195 patients with a mean age of 81.3 ± 6.0 years. The incidence of life-threatening bleeding, major bleeding with a clinically apparent source, and major bleeding without a clinically apparent source was, respectively, 3%, 6%, and 9% in the TAVR group and 8%, 10%, and 31% in the SAVR group. Frailty measured using the Essential Frailty Toolset was an independent predictor of major bleeding and packed red blood cell transfusions in both groups. Major bleeding was associated with a 3-fold increase in 1-year mortality following TAVR (odds ratio: 3.40; 95% confidence interval: 2.22 to 5.21) and SAVR (odds ratio: 2.79; 95% confidence interval: 1.25 to 6.21). Conclusions Frailty is associated with post-procedural major bleeding in older adults undergoing TAVR and SAVR, which is in turn associated with a higher risk for mid-term mortality.

Background We aimed to assess the clinical characteristics of sarcopenia by the original and revised European Working Group on Sarcopenia in Older People (EWGSOP 1 and 2), and to propose a new sarcopenia phenotype score (SPS) to improve relevance of clinical outcomes. Methods Analyses were performed in 1408 older adults of the Aging Study of PyeongChang Rural Area, a community‐based cohort in Korea. For sarcopenia definitions, we used EWGSOP 1, EWGSOP 2, and SPS, a new index counting number of abnormal domains among components of grip strength, gait speed, or muscle mass. Frailty status by the frailty index and the Cardiovascular Health Study frailty score was compared with sarcopenia measures. Prediction ability for composite outcome combining death and institutionalization due to functional decline was assessed among sarcopenia measures. Results Generally, sarcopenia spectrum by both EWGSOP 1 and 2 was associated with worse functional status in parameters of geriatric assessments. However, population who were considered as sarcopenic by EWGSOP 1, but not by EWGSOP 2, showed increased risk of composite outcome and worse frailty status, compared with people who were classified as not sarcopenic by both EWGSOP 1 and 2. With SPS, dose–response relationship was observed with both frailty status and outcome prediction. Prediction for composite outcome was better in SPS than in EWGSOP 2 classification. Conclusions A new SPS might be used to classify sarcopenic burden in older adults to resolve possible inconsistencies in phenotype correlation and outcome prediction of EWGSOP 2 criteria.

BackgroundHigh tumor mutation burden (TMB) has been associated with benefit to immunotherapy in multiple tumor types. However, the prevalence of hypermutated breast cancer is not well described. The aim of this study is to evaluate frequency, mutational patterns, and genomic profile of hypermutated breast cancer.Patients and MethodsWe used de-identified data from individuals with primary or metastatic breast cancer from six different publicly available genomic studies. The prevalence of hypermutated breast cancer was determined among 3969 patients’ samples that underwent whole exome sequencing or gene panel sequencing. Samples were classified as having high TMB if they had ≥10 mutations per megabase (mut/Mb). An additional 8 patients were identified from a Dana-Farber Cancer Institute cohort for inclusion in the hypermutated cohort. Among patients with high TMB, the mutational patterns, and genomic profile were determined. A subset of patients was treated with regimens containing PD-1 inhibitors.ResultsThe median TMB was 2.63 mut/Mb. Median TMB significantly varied according to tumor subtype (HR-/HER2-> HER2+ > HR+/HER2-,p< 0.05) and sample type (metastatic > primary,p2.2×10−16). Hypermutated tumors were found in 198 patients (5%), with an enrichment in metastatic versus primary tumors (8.4% versus 2.9%, p = 6.5 × 10−14). APOBEC activity (59.2%), followed by mismatch repair deficiency (MMRd; 36.4%), were the most common mutational processes among hypermutated tumors. Three patients with hypermutated breast cancer—including two with a dominant APOBEC activity signature and one with a dominant MMRd signature—treated with pembrolizumab-based therapies derived an objective and durable response to therapy.ConclusionHypermutation occurs in 5% of all breast cancers, with an enrichment in metastatic tumors. Different mutational signatures are present in this population, with APOBEC activity being the most common dominant process. Preliminary data suggest that hypermutated breast cancers are more likely to benefit from PD-1 inhibitors.Key MessageHigh tumor mutation burden is found in 5% of all breast cancers and is more common in metastatic tumors. While different mutational signatures are present in hypermutated tumors, APOBEC activity is the most common dominant process. Preliminary data suggest that those tumors are more likely to benefit from PD-1 inhibitors.

ObjectiveStroke is a devastating and costly disease; however, there is a paucity of information on long-term costs and on how they differ according to 3-month modified Rankin scale (mRS) score, which is a primary outcome variable in acute stroke intervention trials.MethodsWe analyzed a prospective multicenter stroke registry (Clinical Research Collaboration for Stroke in Korea) database through linkage with claims data from the National Health Insurance Service with follow-up to December 2016. Healthcare expenditures were converted into daily cost individually, and annual and cumulative costs up to 5 years were estimated and compared according to the 3-month mRS score.ResultsBetween January 2011 and November 2013, 11,136 patients were enrolled in the study. The mean age was 68 years, and 58% were men. The median follow-up period was 3.9 years (range 0–5 years). Mean cumulative cost over 5 years was $117,576 (US dollars [USD]); the cost in the first year after stroke was the highest ($38,152 USD), which increased markedly from the cost a year before stroke ($8,718 USD). The mean 5-year cumulative costs differed significantly according to the 3-month mRS score (p < 0.001); the costs for a 3-month mRS score of 0 or 5 were $53,578 and $257,486 USD, respectively. Three-month mRS score was an independent determinant of long-term costs after stroke.ConclusionsWe show that 3-month mRS score plays an important role in the prediction of long-term costs after stroke. Such estimates relating to 3-month mRS categories may be valuable when undertaking health economic evaluations related to stroke care.

A 46-year-old man presented with a progressive headache lasting for 2 weeks. Initial lumbar puncture revealed a pressure of 31 cm H20 and 30 white cells. His symptoms had worsened despite the treatment of intracranial hypertension. Visual field exam showed marked peripheral constriction and the fundus showed marked papilledema. Cytological analysis of cerebrospinal fluid demonstrated positive for metastatic carcinoma. We report a case of a patient with meningeal carcinomatosis who developed isolated intracranial hypertension with papilledema.

Background and Purpose— There is a paucity of information about the role of resting heart rate in the prediction of outcome events in patients with ischemic stroke with atrial fibrillation. We aimed to investigate the relationships between the level and variability of heart rate in the acute stroke period and stroke recurrence and mortality after acute ischemic stroke in patients with atrial fibrillation. Methods— Acute patients with ischemic stroke who had atrial fibrillation and were hospitalized within 48 hours of stroke onset were identified from a multicenter prospective stroke registry database. The acute stroke period was divided into early (within 24 hours of hospitalization) and late (72 hours to 7 days from onset) stages, and data on heart rate in both stages were collected. Moreover, the level and variability of heart rate were assessed using mean values and coefficients of variation. Outcome events were prospectively monitored up to 1 year after the index stroke. Results— Among 2046 patients eligible for the early acute stage analysis, 102 (5.0%) had a stroke recurrence, and 440 (21.5%) died during the first year after stroke. A statistically significant nonlinear J-shaped association was observed between mean heart rate and mortality ( P P >0.1 for quadratic and overall effect). The nonlinear and overall effects of the coefficients of variation of heart rate were not significant for all outcome variables. The same results were observed in the late acute stage analysis (n=1576). Conclusions— In patients with atrial fibrillation hospitalized for acute ischemic stroke, the mean heart rate during the acute stroke period was not associated with stroke recurrence but was associated with mortality (nonlinear, J-shaped association). The relationships between heart rate and outcomes were not observed with respect to heart rate variability.

Objectives: Several factors associated with the prognosis of patients with NSCLC have been reported in the literature; however, most of these factors cannot be examined preoperatively. In this study, the clinical utility of platelet parameters in patients with NSCLC who underwent curative resection was evaluated. Materials and Methods: A retrospective study on patients with NSCLC who underwent curative resection from July 2006 to September 2016 was conducted. The Cox proportional hazard regression model was applied to evaluate the variables that demonstrated effects on disease-free and overall survival (DFS and OS). Results: A total of 116 patients with NSCLC were analyzed. There were 15 patients with plateletcrit greater than 0.2755%, and 101 patients whose plateletcrit was 0.2755% or lower. Multivariate analysis identified plateletcrit higher than 0.2755% (hazard ratio [HR] = 4.18, 95% confidence interval [CI] = 1.54-11.34, P =0.004), patient age of 65 years or more (HR = 4.02, 95% CI = 1.67-9.66, P = 0.001), and stage II or IIIA disease (HR = 2.95, 95% CI = 1.26-6.87, P = 0.012) as independent factors for OS that predicted a poor prognosis. Multivariate analysis identified plateletcrit higher than 0.2755% (HR = 4.07, 95% CI = 1.52-10.94, P = 0.005), stage II or IIIA disease (HR = 5.38, 95% CI = 2.71-10.66, P < 0.001) and non-adenocarcinoma (HR = 1.92, 95% CI = 1.02-3.59, P = 0.040) as independent prognostic factors for DFS that predicted a poor prognosis. Conclusion: Our results suggest a potential role of preoperative plateletcrit as an independent prognostic marker for patients with resectable NSCLC.

Background It is unclear whether women diagnosed with acute ischemic stroke (AIS) have worse outcome after adjusting for several confounding factors such as age, initial stroke severity, and risk factors. In this study, we investigated sex disparities in long-term functional outcome after AIS. Methods We recruited patients with AIS prospectively registered in the Clinical Research Collaboration for Stroke in Korea database of Dong-A University Stroke Center between 2015 and 2018. We reviewed the patients’ clinical demographics, living type (alone or cohabitating), laboratory and radiological findings, stroke severity, stroke subtype, and cardiovascular risk profile. We compared the long-term functional outcomes between men and women using the modified Rankin Scale score at 90 days and 1 year after AIS. Results A total of 2,711 patients with AIS were enrolled in this study. Women comprised 38.9% (1,055) of all participants. Compared with men, women were significantly older (72.7±11.6 vs.65.6±12.2, P

Background and Purpose— This study aimed to compare the effectiveness of dual antiplatelet therapy with clopidogrel plus aspirin (DAPT) with that of aspirin monotherapy (AM) in patients with acute, nonminor, and noncardioembolic stroke. Methods— Using a prospective, nationwide, multicenter stroke registry database, acute (within 24 hours of onset), nonminor (baseline National Institutes of Health Stroke Scale score, 4–15), and noncardioembolic stroke patients were identified. Propensity scores using inverse probability of treatment weighting were used to adjust baseline imbalances between the DAPT and AM groups. A primary outcome measure was a composite of all types of stroke (ischemic and hemorrhagic), myocardial infarction, and all-cause mortality within 3 months of stroke onset. Results— Among the 4461 patients meeting the eligibility criteria (age, 69±13 years; men, 57.7%), 52.5% (n=2340) received AM, and 47.5% (n=2121) received DAPT. The primary outcome event was not significantly different between the DAPT group and the AM group (20.9% versus 22.6%, P =0.13). The event rates of all types of stroke were also not different between the 2 groups (19.3% versus 20.1%, P =0.35), while all-cause mortality was significantly lower in the DAPT group than in the AM group (3.4% versus 4.9%, P =0.02). In the propensity-weighted Cox proportional hazards models with robust estimation, DAPT did not reduce the risk of the primary outcome event (hazards ratio, 0.91; 95% CI, 0.79–1.04) but did reduce the risk of all-cause mortality (0.69; 0.49–0.97). There was no treatment heterogeneity among the predefined subgroups, although the potential benefits of DAPT were suggested in subpopulations of moderate-to-severe relevant arterial stenosis and relatively severe deficits (National Institutes of Health Stroke Scale score, 12–15). Conclusions— Compared to AM, clopidogrel plus aspirin did not reduce the risk of the primary outcome event during the first 3 months after a nonminor, noncardioembolic, ischemic stroke.

Background and Purpose— Brain areas associated with functional improvement differ between acute and chronic phases after stroke. This study investigated brain areas associated with language function, according to time after stroke. Methods— Patients with aphasia after stroke were divided into subacute (≤3 months after stroke, 17 patients) and chronic groups (>12 months after stroke, 23 patients). Voxel-wise linear regression analyses in each group were conducted by using fractional anisotropy mapping in diffusion tensor images as a dependent variable, while scores of spontaneous speech, comprehension, repetition, and naming were used as independent variables. Results— Structural connectivity in the left dorsal pathway (eg, superior temporal gyrus, inferior parietal lobule, and superior longitudinal fasciculus) was positively associated with spontaneous speech, repetition, and naming, whereas structural connectivity in the corona radiata, internal capsule, and corpus callosum of the right hemisphere was negatively associated with language function in the subacute phase. Comprehension was associated with the left superior temporal gyrus and the right corona radiata in the subacute phase and the right corpus callosum in the chronic phase ( P FWE Conclusions— More lateralized language function related to the dorsal pathway was influenced in the bilateral brain areas in the subacute phase but not in the chronic phase. Less lateralized language function related to the ventral pathway was influenced in the bilateral brain areas during both subacute and chronic phases after stroke.

Background: Frailty is associated with a higher risk for adverse outcomes after aortic valve replacement (AVR) for severe aortic valve stenosis, but whether or not frail patients derive differential benefit from transcatheter (TAVR) versus surgical (SAVR) AVR is uncertain. Methods: We linked adults ≥65 years old in the US CoreValve HiR trial (High-Risk) or SURTAVI trial (Surgical or Transcatheter Aortic-Valve Replacement in Intermediate-Risk Patients) to Medicare claims, February 2, 2011, to September 30, 2015. Two frailty measures, a deficit-based and phenotype-based frailty index (FI), were generated. The treatment effect of TAVR versus SAVR was evaluated within FI tertiles for the primary end point of death and nondeath secondary outcomes, using multivariable Cox regression. Results: Of 1442 (linkage rate =60.0%) individuals included, 741 (51.4%) individuals received TAVR and 701 (48.6%) received SAVR (mean age 81.8±6.1 years, 44.0% female). Although 1-year death rates in the highest FI tertiles (deficit-based FI 36.7% and phenotype-based FI 33.8%) were 2- to 3-fold higher than the lowest tertiles (deficit-based FI 13.4%; hazard ratio, 3.02 [95% CI, 2.26–4.02], P P P >0.05). Results remained consistent across individual trials, frailty definitions, and when considering the nonlinked trial data. Conclusions: Two different frailty indices based on Fried and Rockwood definitions identified individuals at higher risk of death and functional impairment but no differential benefit from TAVR versus SAVR.

We investigated the association between dietary habits, evaluated using the modified Mini Dietary Assessment Index for Koreans (MDA), and lipid control among patients aged ≥20 years who had used pravastatin for dyslipidemia for 6 months. Participants were administered questionnaires regarding sociodemographic characteristics and lifestyle factors. Odds ratios and 95% confidence intervals for the control of low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) at 6 months for each category of the modified MDA items were calculated through multivariate logistic regression analysis. The odds for controlled LDL-C was higher among those who consumed cholesterol-rich foods &lt, 1 time/week (3.27, 1.25–8.57) than for those who did so ≥4 times/week. The odds for controlled TG was higher among those who always consumed dairy products (2.96, 1.36–6.44), ate protein-rich foods three times/day (2.94, 1.06–8.10), and had a regular eating schedule (3.02, 1.30–7.00) than among those who did not have any of these. The odds for controlled TC was higher among those with a regular eating schedule (3.47, 1.55–7.76) than among their counterparts. Patients with dyslipidemia should consume less cholesterols, consume more dairy and protein-rich foods, and follow a regular eating schedule to control lipid profiles.

How does vaccination against foot-and-mouth disease (FMD) affect pregnant cows? Vaccination is the most effective method of preventing the spread of FMD, but it is linked to sporadic side effects, such as abortion and premature birth, which result in economic loss. In this study, ruminoreticular temperature and body activity were measured before and after FMD vaccination using a ruminoreticular biocapsule sensor in Hanwoo cows at different stages of pregnancy. Compared to the unvaccinated groups, the ruminoreticular temperature increased 12 h after vaccination in the vaccinated groups. This increase in temperature is significantly correlated to vaccination. Compared to the nonpregnant and early pregnancy groups, the ruminoreticular temperature of the late pregnancy group increased sharply by more than 40 °C. Moreover, in nonpregnant and early pregnancy groups, a rapid increase in body activity was observed after FMD vaccinations. Of the 73 pregnant vaccinated cows in the study, a total of five cases had side effects (four abortions and one premature birth). Therefore, changes in the ruminoreticular temperature and activity in pregnant cows can be used as raw data to further clarify the association of FMD vaccination with the loss of a fetus and possibly predict abortion, miscarriage, and premature birth following FMD vaccination.

Photoacoustic (PA) imaging is used widely in cancer diagnosis. However, the availability of PA agents has not made great progress due to the limitations of the one currently in use, porphyrin. Porphyrin–Micelle (PM), developed by synthesizing porphyrin and PEG-3.5k, confirmed the amplification of the PA agent signal, and added binding affinity in an LNCaP model by attaching prostate-specific membrane antigen PSMA. Compared to the previously used porphyrin, a superior signal was confirmed, and the potential of PMP was confirmed when it showed a signal superior to that of hemoglobin at the same concentration. In addition, in the in vivo mouse experiment, it was confirmed that the signal in the LNCaP xenograft model was stronger than that in the PC-3 xenograft model, and the PMP signal was about three times higher than that of PM and porphyrin.

Mitral regurgitation (MR) is the most common heart disease in small-breed dogs. Mitral repair, which comprise artificial chorda tendineae implantation and mitral annuloplasty, has become the mainstay of treatment in the veterinary field. We report on two small dogs who underwent mitral repair surgery for MR. A Hegar dilator was used during mitral annuloplasty for accurate and reproducible surgery. In both cases, mitral regurgitant flow almost disappeared after surgery, and clinical signs improved. The treatment regimen was terminated 3 months after the surgery. We concluded that using a Hegar dilator may facilitate mitral valve repair surgery.

BackgroundRestricted mean survival time analysis offers an intuitive and robust summary of treatment effect compared with HRs.ObjectiveTo examine the effect of intensive versus standard blood pressure (BP) control on death or cardiovascular events in type 2 diabetes.DesignSecondary analysis of the Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial.Setting77 sites in the USA and Canada.Participants4733 adults with type 2 diabetes at high risk for cardiovascular events.InterventionsSystolic BP target MeasurementsComposite endpoint of death, non-fatal myocardial infarction or non-fatal stroke.ResultsThe mean event-free survival time over 5 years (1825 days) was similar between intensive and standard BP control (1716 vs 1714 days; mean difference, 1.3 (95% CI −18.1 to 20.7) days). However, intensive BP treatment was more beneficial for those assigned to standard glycaemic control (1725 vs 1697 days; mean difference, 28.1 (95% CI 0.4 to 55.9) days), but not for those assigned to intensive glycaemic control (1706 vs 1731 days; mean difference, −25.2 (95% CI −52.3 to 1.9) days) (p=0.008 for interaction). In subgroup analysis, the mean event-free survival time difference between intensive and standard BP treatment was −76.0 (95% CI –131.8 to –20.3) days for those with cognitive impairment and 21.8 (95% CI −24.0 to 67.5) days for those with normal cognitive function (p=0.008 for interaction). The effect was not different by age, sex and baseline cardiovascular disease status.ConclusionsIntensive BP treatment may reduce death and cardiovascular events among patients with type 2 diabetes receiving standard glycaemic treatment and without cognitive impairment.Trial registration numberNCT00000620; Post-results.

Purpose Evaluate differences in eye care utilization among patients with glaucoma by race and socioeconomic status (SES). Design Retrospective cohort study. Participants Representative 5% sample of Medicare beneficiaries aged > 65 years with continuous part A/B enrollment between January 1, 2014, and July 1, 2014, at least 1 diagnosis code for glaucoma within that period, and a glaucoma diagnosis in the Chronic Conditions Warehouse before January 1, 2014. Methods The following race/ethnicity categories were defined in our cohort: non-Hispanic White, Black/African American, Hispanic, and Asian/Pacific Islander. Low SES was defined as having 2 or more enrollment-based low-income indicators (dual eligibility for Medicare/Medicaid, Part D limited income subsidies, and eligibility for Part A and B State buy-in). Negative binomial regression analyses were carried out to compare relative rate ratios (RRs) of eye care utilization among racial groups stratified by low and non-low SES. Main Outcome Measures Measured from July 1, 2014, to December 31, 2016: eye examinations and eye care–related office visits; eye care–related inpatient and emergency department (ED) encounters; eye care–related nursing home and home-visit encounters; visual field and retinal nerve fiber OCT tests; glaucoma lasers and surgeries. Results Among 78 526 participants with glaucoma, mean age was 79.1 years (standard deviation, 7.9 years), 60.9% were female, 78.4% were non-Hispanic White, and 13.8% met enrollment-based criteria for low-SES. Compared with White beneficiaries, Blacks had lower counts of outpatient visits (RR, 0.92; 95% confidence interval [CI], 0.90–0.93), visual field (VF) tests (RR, 0.92; 95% CI, 0.90–0.94), but more inpatient/ED encounters (RR, 2.42; 95% CI, 1.55–3.78) and surgeries (RR, 1.14; 95% CI, 1.03–1.27). Hispanics had fewer outpatient visits (RR, 0.97; 95% CI, 0.95–0.98) and retinal nerve fiber layer (RNFL) OCT tests (RR, 0.89; 95% CI, 0.86–0.93), but more inpatient/ED encounters (RR, 2.32; 95% CI, 1.18–4.57) and selective laser trabeculoplasty (SLT) (RR, 1.25; 95% CI, 1.11–1.42) versus non-Hispanic Whites. In the non-low SES group, Black versus White disparities persisted in outpatient visits (RR, 0.93; 95% CI, 0.92–0.95), VF (RR, 0.96; 95% CI, 0.94–0.98), RNFL OCT (RR, 0.81; 95% CI, 0.78–0.83), and inpatient/ED encounters (RR, 2.57; 95% CI, 1.55–4.26). Conclusions Disparities were found in eye care utilization among Black and Hispanic patients with glaucoma. These differences persisted among Blacks after stratification by SES, suggesting that systemic racism may be an independent driver in this population.

OBJECTIVE To evaluate whether prestroke glucose control is associated with functional outcomes in patients with acute large vessel occlusive stroke and diabetes who underwent intra-arterial thrombectomy (IAT). RESEARCH DESIGN AND METHODS From the Clinical Research Center for Stroke–Korea registry, we included patients with emergent large vessel occlusive stroke with diabetes who underwent IAT between January 2009 and March 2020. The association between the HbA1c level at admission and functional outcomes (modified Rankin Scale at 3 months after the index stroke) was assessed. RESULTS A total of 1,351 patients were analyzed. Early neurological deterioration was more common in patients with higher levels of HbA1c at admission (P = 0.02 according to HbA1c quintiles, P = 0.003 according to an HbA1c cutoff value of 7.0%) than in those with lower HbA1c levels. Higher HbA1c levels at admission were significantly associated with decreased odds of favorable functional outcomes at a threshold of 7.0–7.1%. The association was consistently observed in subgroups divided according to age, sex, stroke subtype, occlusion site, degree of recanalization, thrombolysis modalities, time from symptom onset to groin puncture, and treatment period. CONCLUSIONS Prestroke glucose control with a target HbA1c of ≤7.0% may be beneficial for neurological recovery in patients with diabetes undergoing IAT for large vessel occlusive stroke, regardless of stroke subtype, bridging intravenous thrombolysis, occlusion site, degree of recanalization, and treatment period.

Background: Although chest radiographs have not been utilised well for classifying stroke subtypes, they could provide a plethora of information on cardioembolic stroke. This study aimed to develop a deep convolutional neural network that could diagnose cardioembolic stroke based on chest radiographs. Methods: Overall, 4,064 chest radiographs of consecutive patients with acute ischaemic stroke were collected from a prospectively maintained stroke registry. Chest radiographs were randomly partitioned into training/validation (n = 3,255) and internal test (n = 809) datasets in an 8:2 ratio. A densely connected convolutional network (ASTRO-X) was trained to diagnose cardioembolic stroke based on chest radiographs. The performance of ASTRO-X was evaluated using the area under the receiver operating characteristic curve. Gradient-weighted class activation mapping was used to evaluate the region of focus of ASTRO-X. External testing was performed with 750 chest radiographs of patients with acute ischaemic stroke from 7 hospitals. Findings: The areas under the receiver operating characteristic curve of ASTRO-X were 0.86 (95% confidence interval [CI], 0.83–0.89) and 0.82 (95% CI, 0.79–0.85) during the internal and multicentre external testing, respectively. The gradient-weighted class activation map demonstrated that ASTRO-X was focused on the area where the left atrium was located. Compared with cases predicted as non-cardioembolism by ASTRO-X, cases predicted as cardioembolism by ASTRO-X had higher left atrial volume index and lower left ventricular ejection fraction in echocardiography. Interpretation: ASTRO-X, a deep neural network developed to diagnose cardioembolic stroke based on chest radiographs, demonstrated good classification performance and biological plausibility. Funding Grant No. 14–2020–046 and 08–2016–051 from the Seoul National University Bundang Research Fund and NRF-2020M3E5D9079768 from the National Research Foundation of Korea.

Background: postoperative atelectasis is a significant clinical problem during thoracic surgery with one-lung ventilation. Intraoperative deep neuromuscular blockade can improve surgical conditions, but an increased risk of residual paralysis may aggravate postoperative atelectasis. Every patient was verified to have full reversal before extubation. We compared the effect of deep versus moderate neuromuscular blockade on postoperative atelectasis quantitatively using chest computed tomography. Methods: patients undergoing thoracic surgery were randomly allocated to two groups: moderate neuromuscular blockade during surgery (group M) and deep neuromuscular blockade during surgery (group D). The primary outcome was the proportion and the volume of postoperative atelectasis measured by chest computed tomography on postoperative day 2. The mean values of the repeatedly measured intraoperative dynamic lung compliance during surgery were also compared. Result: the proportion of postoperative atelectasis did not differ between the groups (1.32 [0.47–3.20]% in group M and 1.41 [0.24–3.07]% in group D, p = 0.690). The actual atelectasis volume was 38.2 (12.8–61.4) mL in group M and 31.9 (7.84–75.0) mL in group D (p = 0.954). Some factors described in the lung protective ventilation were not taken into account and might explain the atelectasis in both groups. The mean lung compliance during one-lung ventilation was higher in group D (26.6% in group D vs. 24.1% in group M, p = 0.026). Conclusions: intraoperative deep neuromuscular blockade did not affect postoperative atelectasis when compared with moderate neuromuscular blockade if full reversal was verified.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by thunderclap headache with reversible vasoconstriction of the cerebral arteries. RCVS has been reported to occur in various clinical settings. However, RCVS triggered by blood transfusion is rare. A 50-year-old woman had severe anemia and received multiple blood transfusions. She developed thunderclap headache after transfusion. Cerebral artery vasoconstrictions were demonstrated by magnetic resonance angiography and transfemoral cerebral angiography. RCVS might be triggered by red blood cell transfusion in patients with severe anemia.

Risk stratification tools are useful to provide appropriate clinical care for older patients with pneumonia. This study aimed to compare a Frailty Index (FI) with pneumonia severity measures, CURB-65, and the Pneumonia Severity Index (PSI), for predicting mortality and persistent disability after pneumonia.Single-center prospective cohort study.The study included 190 patients aged ≥65 years who were hospitalized with pneumonia at a university hospital in Korea between October 2019 and September 2020.At admission, a 50-item deficit-accumulation FI (range: 0-1), CURB-65 (range: 0-5), and PSI (range: 0-395) scores were calculated. The outcomes were death and a composite outcome of death or decline in ability to perform daily activities and physical task 6 months later.The median age was 79 years (interquartile range: 74-85), and 70 (36.8%) patients were women. The patients who died (n = 53) had higher FI (median, 0.46 vs 0.20; P.011), CURB-65 score (median, 3 vs 2; P = .001), and PSI score (median, 149 vs 116; P.001) than those who did not. The C-statistics (95% confidence intervals) for 6-month mortality were 0.69 (0.61-0.77) for the FI, 0.62 (0.53-0.71) for CURB-65, and 0.71 (0.62-0.79) for the PSI (P = .019). The C-statistics for the 6-month composite outcome were 0.73 (0.65-0.81) for the FI, 0.64 (0.55-0.73) for CURB-65, and 0.69 (0.60-0.77) for the PSI (P = .096). The C-statistics improved when the FI was added to CURB-65 (from 0.64 to 0.74; P = .003) and to the PSI (from 0.69 to 0.75; P = .044) for the composite outcome.Measuring frailty provides additive value to widely used pneumonia severity measures in predicting death or persistent hospitalization-associated disability in older adults after pneumonia hospitalization. Early recognition of frailty may be useful to identify those who require in-hospital and post-acute care interventions for functional recovery.

Electronic frailty indices based on data from administrative claims and electronic health records can be used to estimate frailty in large populations of older adults with cancer where direct frailty measures are lacking. The objective of this study was to use the electronic Veterans Affairs Frailty Index (VA-FI-10)—developed and validated to measure frailty in the national United States (US) VA Healthcare System—to estimate the prevalence and impact of frailty in older US veterans newly treated for multiple myeloma (MM) with contemporary therapies. We designed a retrospective cohort study of 4924 transplant-ineligible veterans aged ≥ 65 years initiating MM therapy within VA from 2004 to 2017. Initial MM therapy was measured using inpatient and outpatient treatment codes from pharmacy data in the VA Corporate Data Warehouse. In total, 3477 veterans (70.6%) were classified as frail (VA-FI-10 &gt, 0.2), with 1510 (30.7%) mildly frail (VA-FI-10 &gt, 0.2–0.3), 1105 (22.4%) moderately frail (VA-FI-10 &gt, 0.3–0.4), and 862 (17.5%) severely frail (VA-FI-10 &gt, 0.4). Survival and time to hospitalization decreased with increasing VA-FI-10 severity (log-rank p-value &lt, 0.001), the VA-FI-10 predicted mortality and hospitalizations independently of age, sociodemographic variables, and measures of disease risk. Varying data sources and assessment periods reclassified frailty severity for a substantial portion of veterans but did not substantially affect VA-FI-10’s association with mortality. Our study supports use of the VA-FI-10 in future research involving older veterans with MM and provides insights into its potential use in identifying frailty in clinical practice.

Sensorineural hearing loss due to ototoxic drugs remains as a conflict as the treatment option with aminoglycosides. Ototoxic mouse model was produced with the administration of ototoxic drugs aminoglycoside kanamycin and loop-diuretic furosemide, thus validation of auditory function of the mouse model is needed to determine the efficacy of the drugs. Kanamycin sulfate 550 mg/kg (VWR life sciences, PA, USA) and furosemide 130 mg/kg (Lasix, Handok, Korea) were administered through subcutaneous and intraperitoneal injection respectively. Auditory brainstem response and distortion otoacoustic emission tests were performed on days 3,5,7,10,14 post administration of the ototoxic drug. Thresholds in response to the stimulus given in the auditory brainstem recordings and distortion otoacoustic emission tests were obtained. The hearing threshold shift to high stimulus intensity was observed post administration of the ototoxic drug. Latency of the ABR peak waves were recorded and analyzed, latency delay was observed as hearing threshold increases. These findings will further support in the application of this animal model in various studies regarding ototoxic hearing loss.

Vaccination against foot-and-mouth disease is the most common method for preventing the spread of the disease, the negative effects include miscarriage, early embryo death, lower milk production, and decreased growth of fattening cattle. Therefore, in this study, we analyze the side effects of vaccination by determining the acute immune response and ovulation rate after vaccinating cows for foot-and-mouth disease. The test axis was synchronized with ovulation using 100 Hanwoo (Bos taurus coreanae) cows from the Gyeongsangbuk-do Livestock Research Institute, only individuals with estrus confirmed by ovarian ultrasound were used for the test. All test axes were artificially inseminated 21 days after the previous estrus date. The control group was administered 0.9% normal saline, the negative control was injected intramuscularly with lipopolysaccharide (LPS, 0.5 µg/kg), and the test group was administered a foot-and-mouth disease virus vaccine (FMDV vaccine, bioaftogen, O and A serotypes, inactivated vaccine) 2, 9, and 16 days before artificial insemination. White blood cells and neutrophils increased significantly 1 day after vaccination, and body temperature in the rumen increased for 16 h after vaccination. Ovulation was detected 1 day after artificial fertilization by ovarian ultrasound. The ovulation rates were as follows: control 89%, LPS 60%, FMDV vaccine (−2 d) 50%, FMDV vaccine (−9 d) 75%, and FMDV vaccine (−16 d) 75%. In particular, the FMDV vaccine (−2 d) test group confirmed that ovulation was delayed for 4 days after artificial insemination. In addition, it was confirmed that it took 9 days after inoculation for the plasma contents of haptoglobin and serum amyloid A to recover to the normal range as the main acute immune response factors. The conception rate of the FMDV vaccine (−2 d) group was 20%, which was significantly lower than that of the other test groups.

Background It remains unclear whether physicians' attitudes toward timely management of elevated blood pressure affect the risk of stroke recurrence. Methods and Results From a multicenter stroke registry database, we identified 2933 patients with acute ischemic stroke who were admitted to participating centers in 2011, survived at the 1‐year follow‐up period, and returned to outpatient clinics ≥2 times after discharge. As a surrogate measure of physicians' attitude, individual treatment intensification (TI) scores were calculated by dividing the difference between the frequencies of observed and expected medication changes by the frequency of clinic visits and categorizing them into 5 groups. The association between TI groups and the recurrence of stroke within 1 year was analyzed using hierarchical frailty models, with adjustment for clustering within each hospital and relevant covariates. Mean±SD of the TI score was −0.13±0.28. The TI score groups were significantly associated with increased risk of recurrent stroke compared with Group 3 (TI score range, −0.25 to 0); Group 1 (range, −1 to −0.5), adjusted hazard ratio (HR) 13.43 (95% CI, 5.95–30.35); Group 2 (range, −0.5 to −0.25), adjusted HR 4.59 (95% CI, 2.01–10.46); and Group 4 (TI score 0), adjusted HR 6.60 (95% CI, 3.02–14.45); but not with Group 5 (range, 0–1), adjusted HR 1.68 (95% CI, 0.62–4.56). This elevated risk in the lowest TI score groups persisted when confining analysis to those with hypertension, history of blood pressure‐lowering medication, no atrial fibrillation, and regular clinic visits and stratifying the subjects by functional capacity at discharge. Conclusions A low TI score, which implies physicians' therapeutic inertia in blood pressure management, was associated with a higher risk of recurrent stroke. The TI score may be a useful performance indicator in the outpatient clinic setting to prevent recurrent stroke.