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The success of checkpoint inhibitors (CPIs) for cancer has been tempered by immune-related adverse effects including colitis. CPI-induced colitis is hallmarked by expansion of resident mucosal IFNγ cytotoxic CD8+ T cells, but how these arise is unclear. Here, we track CPI-bound T cells in intestinal tissue using multimodal single-cell and subcellular spatial transcriptomics (ST). Target occupancy was increased in inflamed tissue, with drug-bound T cells located in distinct microdomains distinguished by specific intercellular signaling and transcriptional gradients. CPI-bound cells were largely CD4+ T cells, including enrichment in CPI-bound peripheral helper, follicular helper, and regulatory T cells. IFNγ CD8+ T cells emerged from both tissue-resident memory (TRM) and peripheral populations, displayed more restricted target occupancy profiles, and co-localized with damaged epithelial microdomains lacking effective regulatory cues. Our multimodal analysis identifies causal pathways and constitutes a resource to inform novel preventive strategies.
Subject(s)
Colitis , Immune Checkpoint Inhibitors , Colitis/chemically induced , Colitis/immunology , Colitis/pathology , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/pharmacology , Humans , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/metabolism , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/drug effects , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/metabolism , Animals , Intestinal Mucosa/metabolism , Intestinal Mucosa/immunology , Intestinal Mucosa/pathology , Intestinal Mucosa/drug effects , Interferon-gamma/metabolism , Female , Single-Cell Analysis , MiceABSTRACT
Background/Aims@#We investigated the clinical practice patterns of post-polypectomy colonoscopic surveillance among Korean endoscopists. @*Methods@#In a web-based survey conducted between September and November 2021, participants were asked about their preferred surveillance intervals and the patient age at which surveillance was discontinued. Adherence to the recent guidelines of the U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) was also analyzed. @*Results@#In total, 196 endoscopists completed the survey. The most preferred first surveillance intervals were: a 5-year interval after the removal of 1–2 tubular adenomas 10 adenomas, 5–10 SSLs, and SSLs with dysplasia. In piecemeal resections of large polyps ( > 20 mm), surveillance colonoscopy was mostly preferred after 1 year for adenomas and 6 months for SSLs. The mean USMSTF guideline adherence rate was 30.7%. The largest proportion of respondents (40.8%–55.1%) discontinued the surveillance at the patient age of 80–84 years. @*Conclusions@#A significant discrepancy was observed between the preferred post-polypectomy surveillance intervals and recent international guidelines. Individualized measures are required to increase adherence to the guidelines.
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Purpose@#This study aimed to assess the feasibility of texture analysis using preoperative magnetic resonance imaging (MRI) for assessing the recurrence risk of endometrial cancer after hysterectomy. @*Materials and Methods@#Eighty-five patients who underwent surgery and had pathologically confirmed endometrial cancer were considered in this study. Histographic parameters (perfusion ratio, integrated density, skewness, and kurtosis) and gray-level co-occurrence matrix textural parameters (angular second moment, contrast, correlation, entropy, and inverse difference moment) obtained from normalized perfusion mapping and apparent diffusion coefficient (ADC) maps of pelvic MRI were correlated with pathological features, including tumor type, International Federation of Gynecology and Obstetrics staging, tumor-involved lymph node metastasis, and recurrence after hysterectomy. @*Results@#In distinctions between type I and II endometrial cancers, the histogram analysis of the perfusion map revealed significant differences in tumor area (p = 0.014), perfusion ratio (p = 0.001), integrated density (p = 0.042), entropy (p = 0.001) on the perfusion map, and energy (p = 0.004) and entropy (p = 0.007) on the ADC map. The assessment of the relationship with recurrence revealed significant differences in contrast (p = 0.013), and entropy (p < 0.001) on the perfusion map, and energy (p < 0.001) and entropy (p = 0.003) on the ADC map. Entropy obtained via texture analysis demonstrated associations between integrated density and linear correlation, with notable differences observed between type I (R 2 = 0.363) and type II (R 2 = 0.471) endometrial cancer subtypes (p = 0.010). @*Conclusion@#The parameters obtained through a texture analysis on preoperative MRI could be employed as potential quantitative predictors for the assessment of the recurrence risk in endometrial cancer after hysterectomy.
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Purpose@#The purpose of this study was to evaluate the effectiveness of histographic analysis for the perfusion map of pelvic magnetic resonance imaging (MRI) in predicting remnant ovarian tissue in patients with ovarian endometriosis. @*Materials and Methods@#To generate the perfusion map, subtracted T1-weighted image (T1-WI) was divided by contrast enhanced T1-WI with using image analysis software ImageJ. Each region of interest (ROI) was quantified by outlining of the affected ovaries with endometrioma at the level with the largest area of normal ovary tissue and normal contralateral ovaries using the measurement tool on the software. Consequently, the number of ratios per each pixel comprising the perfusion map was scored from 0 (not perfused) to 1 (totally perfused). The pixel information, including area within ROI, mean with standard deviation of signal intensity, as well as integrated density of affected ovary with endometrioma, were compared with that of the normal ovary. Additionally, we compared the histogram according to the severity of the ovarian invasion. @*Results@#In comparison between the affected ovary with endometrioma and the normal ovary, the perfusion ratio of the normal ovary was higher than that of the affected ovary (0.48 ± 0.07 vs. 0.20 ± 0.12, p < 0.001), whereas the area within the ROI and the perfusion ratio was higher in the affected ovary. According to the severity of the endometrial invasion of the ovary based on the surgical findings, the area with the perfusion ratio between 0.4 and 0.8 (199.17 ± 163.15 vs. 528.00 ± 154.43, p = 0.003), perfusion ratio (0.11 ± 0.07 vs.0.27 ± 0.11, p = 0.012), and, and integrated density (187.33 ± 106.32 vs. 427.125 ± 132.24, p = 0.003) was lower in the group of severe invasion than those of the mild group and moderate invasion group. @*Conclusion@#The histographic analysis for the perfusion map of the pelvic MRI could be valuable in revealing the extent of the endometrial invasion and viable remnant ovarian tissue.
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Background@#The association between renal dysfunction and cardiovascular outcomes has yet to be determined in patients with hypertrophic cardiomyopathy (HCM). We aimed to investigate whether mildly reduced renal function is associated with the prognosis in patients with HCM. @*Methods@#Patients with HCM were enrolled at two tertiary HCM centers. Patients who were on dialysis, or had a previous history of heart failure (HF) or stroke were excluded. Patients were categorized into 3 groups by estimated glomerular filtration rate (eGFR): stage I (eGFR ≥ 90 mL/min/1.73 m2 , n = 538), stage II (eGFR 60–89 mL/min/1.73 m2 , n = 953), and stage III–V (eGFR < 60 mL/min/1.73 m2 , n = 265). Major adverse cardiovascular events (MACEs) were defined as a composite of cardiovascular death, hospitalization for HF (HHF), or stroke during median 4.0-year follow-up. Multivariable Cox regression model was used to adjust for covariates. @*Results@#Among 1,756 HCM patients (mean 61.0 ± 13.4 years; 68.1% men), patients with stage III–V renal function had a significantly higher risk of MACEs (adjusted hazard ratio [aHR], 2.71; 95% confidence interval [CI], 1.39–5.27; P = 0.003), which was largely driven by increased incidence of cardiovascular death and HHF compared to those with stage I renal function. Even in patients with stage II renal function, the risk of MACE (vs. stage I: aHR, 2.21’ 95% CI, 1.23–3.96; P = 0.008) and HHF (vs. stage I: aHR, 2.62; 95% CI, 1.23–5.58; P = 0.012) was significantly increased. @*Conclusion@#This real-world observation showed that even mildly reduced renal function (i.e., eGFR 60–89 mL/min/1.73 m2 ) in patients with HCM was associated with an increased risk of MACEs, especially for HHF.
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Objective@#: Isoflurane, a widely used common inhalational anesthetic agent, can induce brain toxicity. The challenge lies in protecting neurologically compromised patients from neurotoxic anesthetics. Choline alfoscerate (L-α-Glycerophosphorylcholine, α-GPC) is recognized for its neuroprotective properties against oxidative stress and inflammation, but its optimal therapeutic window and indications are still under investigation. This study explores the impact of α-GPC on human astrocytes, the most abundant cells in the brain that protect against oxidative stress, under isoflurane exposure. @*Methods@#: This study was designed to examine changes in factors related to isoflurane-induced toxicity following α-GPC administration. Primary human astrocytes were pretreated with varying doses of α-GPC (ranging from 0.1 to 10.0 μM) for 24 hours prior to 2.5% isoflurane exposure. In vitro analysis of cell morphology, water-soluble tetrazolium salt-1 assay, quantitative real-time polymerase chain reaction, proteome profiler array, and transcriptome sequencing were conducted. @*Results@#: A significant morphological damage to human astrocytes was observed in the group that had been pretreated with 10.0 mM of α-GPC and exposed to 2.5% isoflurane. A decrease in cell viability was identified in the group pretreated with 10.0 μM of α-GPC and exposed to 2.5% isoflurane compared to the group exposed only to 2.5% isoflurane. Quantitative real-time polymerase chain reaction revealed that mRNA expression of heme-oxygenase 1 and hypoxia-inducible factor-1α, which were reduced by isoflurane, was further suppressed by 10.0 μM α-GPC pretreatment. The proteome profiler array demonstrated that α-GPC pretreatment influenced a variety of factors associated with apoptosis induced by oxidative stress. Additionally, transcriptome sequencing identified pathways significantly related to changes in isoflurane-induced toxicity caused by α-GPC pretreatment. @*Conclusion@#: The findings suggest that α-GPC pretreatment could potentially enhance the vulnerability of primary human astrocytes to isoflurane-induced toxicity by diminishing the expression of antioxidant factors, potentially leading to amplified cell damage.
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Purpose@#This study aimed to investigate the sustained effects of a 3-week equine-assisted activities and therapies (EAAT) program on motor function and muscle activity in children with cerebral palsy (CP). @*Methods@#Nine children with CP (aged 5–15 years, Gross Motor Function Classification System stages I–III) parti-cipated in the study. We assessed Gross Motor Function Measure-66 (GMFM-66) scores, Pediatric Balance Scale (PBS) scores, BioRescue static posturography (RM Ingenierie) findings, core-muscle activity, and body composition before, immediately after, and 3 months after EAAT. @*Results@#Of the nine included children, eight showed improvement in their GMFM-66 scores and six showed improvement in their PBS scores. No significant changes were observed in GMFM-66 and PBS scores immediately after the EAAT program compared to baseline. However, significant improvements were noted 3 months after EAAT in both GMFM-66 and PBS scores. Trunk skeletal muscle mass showed a significant increase immediately after EAAT. Balance, stability, and muscle activity during the gait cycle remained stable throughout the study. @*Conclusion@#This study suggests that a short-period EAAT program can lead to long-term improvements in gross motor function for children with CP.
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Purpose@#We investigated the current status of imaging studies for pediatric blunt cervical spine injury, and applied 3 clinical decision rules to children with blunt trauma of the head or neck in a pediatric emergency center in Korea. The rules included National Emergency X-Radiography Utilization Study (NEXUS) criteria, Canadian Cervical Spine Rule, and Pediatric Emergency Care Applied Research Network risk factors. @*Methods@#This was a retrospective study conducted on 399 children aged 15 years or younger who visited the center after the blunt trauma, and underwent cervical spine radiographs from January 2020 through December 2021. We examined the clinical characteristics per age groups (0-1, 2-5, 6-12, and 13-15 years). Using the 3 rules, we selected children with a potential need for imaging studies (PNI). For this purpose, we analyzed the absence of low-risk variables and the presence of high-risk variables. Predictive performances of the rules were measured for the imaging-confirmed cervical spine injury. @*Results@#The study population (n = 399) had a median age of 5.0 years (interquartile range, 2.0-9.0) and a 64.2% boys’ proportion. Fall (36.6%) was the most common injury mechanism. Two children had the cervical spine injuries. As per NEXUS criteria, Canadian Cervical Spine Rule, and Pediatric Emergency Care Applied Research Network risk factors, 72 (18.0%), 289 (72.4%), and 74 children (18.5%) were classified as those with PNI, respectively. Resultantly, 291 children (72.9%) were classified as having PNI whereas the other 108 (27.1%) were deemed to undergo unnecessary imaging. The 3 rules had nearly 100% sensitivity and negative predictive value, except a 50% sensitivity of NEXUS criteria. @*Conclusion@#Imaging studies can be minimized for children with blunt trauma of the head or neck who are deemed without PNI per the 3 current clinical decision rules. More elaborate criteria are needed to make a timely diagnosis.
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Background/Aims@#Patients with inflammatory bowel disease (IBD) are diagnosed with ankylosing spondylitis (AS) often. However, the disease course of patients with both IBD and AS is not well understood. This study aims to evaluate the effect of concomitant AS on IBD outcomes. @*Methods@#Among the 4,722 patients with IBD who were treated in 3 academic hospitals from 2004 to 2021, 55 were also diagnosed with AS (IBD-AS group). Based on patients’ electronic medical records, the outcomes of IBD in IBD-AS group and IBD group without AS (IBD-only group) were appraised. @*Results@#The proportion of patients treated with biologics or small molecule therapies was significantly higher in IBD-AS group than the proportion in IBD-only group (27.3% vs. 12.7%, P= 0.036). Patients with both ulcerative colitis and AS had a significantly higher risk of biologics or small molecule therapies than patients with only ulcerative colitis (P< 0.001). For univariable logistic regression, biologics or small molecule therapies were associated with concomitant AS (odds ratio, 4.099; 95% confidence interval, 1.863–9.021; P< 0.001) and Crohn’s disease (odds ratio, 3.552; 95% confidence interval, 1.590–7.934; P= 0.002). @*Conclusions@#Concomitant AS is associated with the high possibility of biologics or small molecule therapies for IBD. IBD patients who also had AS may need more careful examination and active treatment to alleviate the severity of IBD.
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Objective@#Pesticide poisoning is one of the leading causes of death, and it is important to classify high-risk patients. Lactate measurement could be used to assess the triage level and decide and prioritize treatment even within the same triage group. This study investigates whether point-of-care lactate measurement helps to triage pesticide poisoning patients in the emergency department (ED). @*Methods@#This retrospective study was done for pesticide poisoning patients between January 2018 to December 2021. Demographic data and laboratory results were collected by reviewing medical records. Statistical analysis was performed by dividing patients into death and survival groups. Univariable and multivariable logistic regression analyses were done. Receiver operating characteristic curves were obtained for variables with significant differences, and area under the curves (AUC) were calculated and compared. @*Results@#Among the 288 patients evaluated, there were 24 (8.33%) mortalities and 264 (91.67%) survivals during hospitalization. Age, the Acute Physiology and Chronic Health Evaluation II (APACHE-II) score, pH and base excess, and lactate levels were analyzed via univariable and multivariable logistic regression tests. We found that old age and high lactate were independent factors in predicting mortality for pesticide poisoning patients. AUCs with 95% confidence interval for age and lactate were 0.784 (0.653-0.915) and 0.803 (0.674-0.932), respectively. @*Conclusion@#Lactate measurement may be useful during triage of alert and consciousness patients presenting with pesticide poisoning and having stable vital signs in ED. This study has several limitations, and it is necessary to reconfirm the results through a well-designed prospective study.
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Purpose@#In patients with glufosinate poisoning, severe neurological symptoms may be closely related to a poor prognosis, but their appearance may be delayed. Therefore, this study aimed to determine whether the Acute Physiology and Chronic Health Evaluation II (APACHE II) score could predict the neurological prognosis in patients with glufosinate poisoning who present to the emergency room with alert mental status. @*Methods@#This study was conducted retrospectively through a chart review for patients over 18 years who presented to a single emergency medical center from January 2018 to December 2022 due to glufosinate poisoning. Patients were divided into groups with a good neurological prognosis (Cerebral Performance Category [CPC] Scale 1 or 2) and a poor prognosis (CPC Scale 3, 4, or 5) to identify whether any variables showed significant differences between the two groups. @*Results@#There were 66 patients (67.3%) with good neurological prognoses and 32 (32.8%) with poor prognoses. In the multivariate logistic analysis, the APACHE II score, serum amylase, and co-ingestion of alcohol showed significant results, with odds ratios of 1.387 (95% confidence interval [CI], 1.027–1.844), 1.017 (95% CI, 1.002–1.032), and 0.196 (95% CI, 0.040–0.948), respectively. With an APACHE II score cutoff of 6.5, the AUC was 0.826 (95% CI, 0.746–0.912). The cutoff of serum amylase was 75.5 U/L, with an AUC was 0.761 (95% CI, 0.652–0.844), and the AUC of no co-ingestion with alcohol was 0.629 (95% CI, 0.527–0.722). @*Conclusion@#The APACHE II score could be a useful indicator for predicting the neurological prognosis of patients with glufosinate poisoning who have alert mental status.
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Mastocytosis is a heterogeneous neoplasm characterized by accumulation of neoplastic mast cells in various organs. There are three main types: cutaneous mastocytosis (CM), systemic mastocytosis (SM), and mast cell sarcoma. CM mainly affects children and is confined to the skin, whereas SM affects adults and is characterized by extracutaneous involvement, with or without cutaneous involvement. Most cases of SM have an indolent clinical course; however, some types of SM have aggressive behavior and a poor prognosis. Recent advances in the understanding of the molecular changes in SM have changed the diagnosis and treatment of aggressive and advanced SM subtypes. The International Consensus Classification and World Health Organization refined the diagnostic criteria and classification of SM as a result of accumulation of clinical experience and advances in molecular diagnostics. Somatic mutations in the KIT gene, most frequently KIT D816V, are detected in 90% of patients with SM. Expression of CD30 and any KIT mutation were introduced as minor diagnostic criteria after the introduction of highly sensitive screening methods. SM has a wide spectrum of clinical features, and only a few drugs are effective at treating advanced SM. Currently, the mainstay of SM treatment is limited to the management of chronic symptoms related to release of mast cell mediators. Small-molecule kinase inhibitors targeting the KIT-downstream and KIT-independent pathways were recently approved for treating advanced SM. I describe recent advances in diagnosis of SM, and review the currently available and emerging therapeutic options for SM management.
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Mesenchymal stromal cells (MSCs) have attracted scientific and medical interest due to their self-renewing properties, pluripotency, and paracrine function. However, one of the main limitations to the clinical application of MSCs is their loss of efficacy after transplantation in vivo. Various bioengineering technologies to provide stem cell niche-like conditions have the potential to overcome this limitation. Here, focusing on the stem cell niche microenvironment, studies to maximize the immunomodulatory potential of MSCs by controlling biomechanical stimuli, including shear stress, hydrostatic pressure, stretch, and biophysical cues, such as extracellular matrix mimetic substrates, are discussed. The application of biomechanical forces or biophysical cues to the stem cell microenvironment will be beneficial for enhancing the immunomodulatory function of MSCs during cultivation and overcoming the current limitations of MSC therapy.
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Background@#Interscalene brachial plexus block (ISB) is a common regional technique to manage acute postoperative pain for arthroscopic rotator cuff tear repair. However, rebound pain may compromise its overall benefit. Our aim was to investigate the primary hypothesis that perineural and intravenous dexamethasone have different effects on rebound pain after resolution of ISB for arthroscopic rotator cuff tear repair. @*Methods@#Patients aged ≥ 20 years scheduled for elective arthroscopic rotator cuff tear repair under general anesthesia with preoperative ISB were included. The participants were randomized to receive dexamethasone either perineurally (perineural group) or intravenously (intravenous group). In the perineural group, patients received ISB with 12 mL of 0.5% ropivacaine containing 5 mg of dexamethasone; simultaneously, 1 mL of 0.9% normal saline was administered intravenously. In the intravenous group, patients received ISB with 12 mL of 0.5% ropivacaine; simultaneously, 1 mL of dexamethasone 5 mg was administered intravenously. The primary outcome was the difference in the pain score (0–10 on numeric rating scale) between before and after ISB resolution. The secondary outcomes were the incidence of rebound pain; onset, duration, and intensity of rebound pain; time to the first analgesic request; and pain-related sleep disturbance. @*Results@#A total of 71 patients were randomized to either perineural group (n = 36) or intravenous group (n = 35). After block resolution, pain scores increased significantly more in the perineural group (mean ± standard deviation, 4.9 ± 2.1) compared to the intravenous group (4.0 ± 1.7, P = 0.043). The duration of ISB was more prolonged in the perineural group (median [interquartile range], 19.9 [17.2–23.1] hours) than the intravenous group (15.1 [13.7–15.9] hours, P < 0.001). The incidence of rebound pain and pain-related sleep disturbance during the first postoperative week was significantly higher in the perineural group than in the intravenous group (rebound pain: 44.4% vs. 20.0%, P = 0.028; sleep disturbance: 55.6% vs. 25.7%, P = 0.011). The duration and intensity of rebound pain were similar between the two groups. @*Conclusion@#Although perineural dexamethasone provided longer postoperative analgesia, intravenous dexamethasone was more beneficial in reducing pain increase after ISB resolution, incidence of rebound pain, and pain-related sleep disturbance.
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Background@#Menorrhagia is a common cause of iron deficiency anemia (IDA) in premenopausal women. However, the effects of menorrhagia on IDA in premenopausal women have been underestimated compared to those on other IDA-related disorders (IRDs) such as gastrointestinal malignancies (GIMs). To better understand the relationship between menorrhagia and IDA in premenopausal women, we analyzed the National Health Insurance Service-National Health Information Database (NHIS-NHID). @*Methods@#From 2005 to 2008, data about women between the age of 20 and 59 years were extracted from the NHIS-NHID to create a propensity score-matched case (IDA) and control group. The annual incidence of IDA was calculated per age group. A 10-year follow up of the study population was determined to detect IRDs in case and control groups. We compared the risk of detection (ROD) of IRDs, including GIM and gynecological disorders associated with menorrhagia - leiomyoma of uterus (LM) and adenomyosis (AM), in the case and the control group. @*Results@#From 2005 to 2008, women diagnosed with IDA (n = 535,249) and healthy women as a control group (n = 1,070,498) were identified from the NHIS-NHID. The annual incidence of IDA was 767.4 (2005), 948.7 (2006), 981.6 (2007), and 897.7 (2008) per 100,000 women.The age distribution of IDA was similar each year; IDA was common in women aged 30–39 years (36–37%) and 40–49 years (30–32%), and its incidence was significantly decreased in women aged 50–59 years (< 10%). The ROD of IRDs were significantly higher in the IDA group than in the control group (LM: 20.8% vs. 6.9%, AM: 5.6% vs. 1.6%, and GIM: 2.6% vs.0.7%). The corresponding hazard ratios were 3.89 (95% confidence interval [CI], 3.85–3.93) for LM, 4.99 (95% CI, 4.90–5.09) for AM, and 3.43 (95% CI, 3.32–3.55) for GIM. The ROD of the IRDs varied; the ROD of LM in the IDA group increased with age and decreased in the age group 50–59 years. AM was more frequently detected in women with IDA aged 30–39 years and less in women older than 40 years. The frequency of GIM increased with age. @*Conclusion@#In this study, we found that the gynecologic disease is the main cause of IDA in premenopausal women. Gynecological evaluations should be performed more actively in the clinic to prevent and control IDA and IRDs.
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Objective@#Venom-induced coagulopathy (VIC) is a common snakebite complication that can cause life-threatening hemorrhage. Previous studies have shown that snake venom can cause a decrease in the erythrocyte sedimentation rate (ESR), but this has not been investigated in actual clinical practice. This study evaluated the clinical utility of erythrocyte sedimentation rate as a predictive factor for VIC in patients with a poisonous snakebite. @*Methods@#From January 2012 to December 2021, this study performed a retrospective study of patients with venomous snakebites presenting to a tertiary emergency department. The demographic and laboratory data were collected through a chart review. The patients were divided into two groups, VIC and NoVIC groups. Logistic regression analysis was performed to identify the factors that predicted the presence of VIC, and the receiver operating characteristic (ROC) curve was drawn. @*Results@#One hundred and fifty-three patients were enrolled, and 31 patients (20.3%) developed VIC. The VIC group had significantly lower ESR than the NoVIC group (5.1±5.6 vs. 14.8±13.8; P<0.001). Logistic regression analysis showed that the decreased ESR was associated with the occurrence of coagulopathy (odds ratio, 0.957; 95% confidence interval, 0.917-0.999; P=0.045). The area under the curve was 0.701 in the ROC curve, and the cutoff value was set to 4.5 mm/hr. @*Conclusion@#ESR measured upon arrival at the emergency department was available to predict venom-induced coagulopathy in snakebite patients.
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Background and Objectives@#The prognostic or safety implication of renin-angiotensinaldosterone system inhibitors (RASi) in hypertrophic cardiomyopathy (HCM) are not well established, mainly due to concerns regarding left ventricular outflow tract (LVOT) obstruction aggravation. We investigated the implications of RASi in a sizable number of HCM patients. @*Methods@#We enrolled 2,104 consecutive patients diagnosed with HCM in 2 tertiary university hospitals and followed up for five years. RASi use was defined as the administration of RASi after diagnostic confirmation of HCM. The primary and secondary outcomes were all-cause mortality and hospitalization for heart failure (HHF). @*Results@#RASi were prescribed to 762 patients (36.2%). During a median follow-up of 48.1months, 112 patients (5.3%) died, and 94 patients (4.5%) experienced HHF. Patients using RASi had less favorable baseline characteristics than those not using RASi, such as older age, more frequent history of comorbidities, and lower ejection fraction. Nonetheless, there was no difference in clinical outcomes between patients with and without RASi use (log-rank p=0.368 for all-cause mortality and log-rank p=0.443 for HHF). In multivariable analysis, patients taking RASi showed a comparable risk of all-cause mortality (hazard ratio [HR], 0.70, 95% confidence interval [CI], 0.43–1.14, p=0.150) and HHF (HR, 1.03, 95% CI, 0.63–1.70, p=0.900). In the subgroup analysis, there was no significant interaction of RASi use between subgroups stratified by LVOT obstruction, left ventricular (LV) ejection fraction, or maximal LV wall thickness. @*Conclusions@#RASi use was not associated with worse clinical outcomes. It might be safely administered in patients with HCM if clinically indicated.
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T cell recognition of SARS-CoV-2 antigens after vaccination and/or natural infection has played a central role in resolving SARS-CoV-2 infections and generating adaptive immune memory. However, the clinical impact of SARS-CoV-2-specific T cell responses is variable and the mechanisms underlying T cell interaction with target antigens are not fully understood. This is especially true given the virus rapid evolution, which leads to new variants with immune escape capacity. In this study, we used the Omicron variant as a model organism and took a systems approach to evaluate the impact of mutations on CD8+ T cell immunogenicity. We computed an immunogenicity potential score for each SARS-CoV-2 peptide antigen from the ancestral strain and Omicron, capturing both antigen presentation and T cell recognition probabilities. By comparing ancestral vs. Omicron immunogenicity scores, we reveal a divergent and heterogeneous landscape of impact for CD8+ T cell recognition of mutated targets in Omicron variants. While T cell recognition of Omicron peptides is broadly preserved, we observed mutated peptides with deteriorated immunogenicity that may assist breakthrough infection in some individuals. We then combined our scoring scheme with an in-silico mutagenesis, to characterise the position- and residue-specific theoretical mutational impact on immunogenicity. While we predict many escape trajectories from the theoretical landscape of substitutions, our study suggests that Omicron mutations in T cell epitopes did not develop under cell-mediated pressure. Our study provides a generalisable platform for fostering a deeper understanding of existing and novel variant impact on antigen-specific vaccine- and/or infection-induced T cell immunity.
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Purpose@#This study aimed to confirm the decision-making patterns for life-sustaining treatment (LST) and analyze medical service utilization changes after enforcement of the Life-Sustaining Treatment Decision-Making Act. @*Materials and Methods@#Of 1,237 patients who completed legal forms for life-sustaining treatment (hereafter called the LST form) at three academic hospitals and died at the same institutions, 1,018 cancer patients were included. Medical service utilization and costs were analyzed using claims data. @*Results@#The median time to death from completion of the LST form was three days (range, 0 to 248 days). Of these, 517 people died within two days of completing the document, and 36.1% of all patients prepared the LST form themselves. The frequency of use of the intensive care unit, continuous renal replacement therapy, and mechanical ventilation was significantly higher when the families filled out the form without knowing the patient’s intention. In the top 10% of the medical expense groups, the decision-makers for LST were family members rather than patients (28% patients vs. 32% family members who knew and 40% family members who did not know the patient’s intention). @*Conclusion@#The cancer patient’s own decision-making rather than the family’s decision was associated with earlier decision-making, less use of some critical treatments (except chemotherapy) and expensive evaluations, and a trend toward lower medical costs.
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Polycythemia vera (PV) is a rare myeloproliferative disease that causes elevated absolute red blood cell (RBC) mass due to uncontrolled RBC production. Moreover, this condition has been associated with a high risk of ischemic stroke and large vessel stenosis or occlusion, with many studies reporting cerebral infarction in PV patients. Despite these findings, there have been no reports on the vessel wall MRI (VW-MRI) findings of the narrowed vessels in PV-associated ischemic stroke patients. To the best of our knowledge, this is the first report in English regarding the carotid VW-MRI findings of a 30-year-old male diagnosed with PV after being hospitalized due to stroke.