Beneficial Effect of Pretreatment Hyperosmolality on Outcome in Severe Traumatic Brain Injury: Evidence from a South Korean Multicenter Registry and Propensity Score Matching Analysis.

BACKGROUND: Hyperosmolar therapy has long been a cornerstone in managing increased intracranial pressure and improving outcomes in severe traumatic brain injury (TBI). This therapy hinges on elevating serum osmolality, creating an osmotic gradient that draws excess water from the brain's cellular and interstitial compartments and effectively reducing cerebral edema. Given this information, we hypothesized that the serum hyperosmolality prior to any treatment could significantly impact the clinical outcomes of patients with severe TBI, potentially mitigating secondary cerebral edema after trauma. METHODS: Data were extracted from the Korean Multi-center Traumatic Brain Injury data bank, encompassing 4628 patients with TBI admitted between January 2016 and December 2018. Of these, 507 patients diagnosed with severe TBI (Glasgow Coma Scale score < 9) were selected for comprehensive analysis across four data domains: clinical, laboratory, initial computed tomography scan, and treatment. Serum osmolality was assessed prior to treatment, and the hyperosmolar group was defined by a pretreatment serum osmolality exceeding 320 mOsm/L, whereas favorable outcomes were characterized by a modified Rankin Scale score of ≤ 3 at 6 months after trauma. Multivariate regression with receiver operating characteristic curve analysis and propensity score matching were used to dissect the data set. RESULTS: Multivariate analysis showed serum osmolality is significantly associated with clinical outcome in patients with severe TBI (p < 0.001). The optimal cutoff value for predicting favorable outcome was 331 mOsm/L, with a sensitivity of 38.9% and a specificity of 87.7%. Notably, the propensity score matching analysis comparing patients with pretreatment serum hyperosmolality with those without indicated a markedly improved functional outcome in the former group (32.5% vs 18.8%, p = 0.025). CONCLUSIONS: The present study has uncovered a significant correlation between the pretreatment serum osmolality and the clinical outcomes of patients with severe TBI. These findings offer a novel perspective, indicating that a serum hyperosmolality prior to any treatment might potentially have a neuroprotective effect in patients with severe TBI.

Comparison of laser and traditional lancing devices for capillary blood sampling in patients with diabetes mellitus and high bleeding risk.

PURPOSE: Despite the importance of self-monitoring blood glucose (SMBG) for management of diabetes mellitus (DM), frequent blood sampling is discouraged by bleeding risk due to dual-antiplatelet agent therapy (DAPT) or thrombocytopenia. METHODS: We compared the bleeding time (BT) of sampling by using a laser-lancing-device (LMT-1000) and a conventional lancet in patients with DM and thrombocytopenia or patients undergoing DAPT. BT was measured using the Duke method, and pain and satisfaction scores were assessed using numeric rating scale (NRS) and visual analog scale (VAS). The consistency in the values of glucose and glycated-hemoglobin (HbA1c) sampled using the LMT-1000 or lancet were compared. RESULTS: The BT of sampling with the LMT-1000 was shorter than that with the lancet in patients with thrombocytopenia (60s vs. 85s, P = 0.024). The NRS was lower and the VAS was higher in laser-applied-sampling than lancet-applied sampling in the DAPT-user group (NRS: 1 vs. 2, P = 0.010; VAS: 7 vs. 6, P = 0.003), whereas the group with thrombocytopenia only showed improvement in the VAS score (8 vs. 7, P = 0.049). Glucose and HbA1c sampled by the LMT-1000 and lancet were significantly correlated in both the DAPT-user and the thrombocytopenia groups. CONCLUSION: The LMT-1000 can promote SMBG by shortening BT in subject with thrombocytopenia and by increasing satisfaction score, as well as by showing reliable glucose and HbA1c value.

Usefulness of the 4A's test for detecting delirium in critically ill patients: a multicenter prospective observation study.

The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) is a robust and reliable instrument for discerning delirium within the specific context of the intensive care unit (ICU). Nonetheless, the CAM-ICU is burdened by various limitations, including a protracted learning curve and the need for frequent daily administration. The 4 A's Test (4AT) was formulated to assess delirium in hospitalized patients and may have distinct advantages over the CAM-ICU, particularly regarding practical applicability within the ICU bundle. This study was performed to assess the utility of the 4AT in detecting delirium in critically ill patients. This multicenter prospective observational study involved critically ill patients at four academic tertiary care hospitals in South Korea from June 2021 to September 2022. In total, 274 patients (median age, 64 years; 56.9% men) were included, and 75 (27.4%) developed delirium. The 4AT showed good performance in detecting ICU delirium (area under the curve, 0.879; P < 0.001). The 4AT showed a sensitivity of 74.0%, specificity of 95.4%, positive predictive value of 77.5%, negative predictive value of 94.6%, and accuracy of 91.7% for ICU detection of delirium. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the CAM-ICU for detecting ICU delirium were 71.3%, 97.1%, 83.8%, 94.1%, and 92.6%, respectively. The 4AT showed acceptable reliability and validity for detecting ICU delirium in critically ill patients. Because the 4AT is simpler and easier to learn, this scale could be a useful alternative to the CAM-ICU for detecting delirium in critically ill patients.

Altered pattern of theta and gamma oscillation to visual stimuli in patients with postconcussion syndrome.

Although many patients with mild traumatic brain injury (mTBI) suffer from postconcussional syndrome (PCS) including abnormal emotional responses, most conventional imaging studies fail to detect any causative brain lesion. We hypothesized that event-related electroencephalography (EEG) recordings with time-frequency analysis would show a distinguishable pattern in patients with mTBI with PCS compared with normal healthy controls. EEG signals were collected from a total of 18 subjects: eight patients with mTBI with PCS and 10 healthy control subjects. The signals were recorded while the subjects were presented with affective visual stimuli, including neutral, pleasant, and unpleasant emotional cues. Event-related spectral perturbation analysis was performed to calculate frontal midline theta activity and posterior midline gamma activity, followed by statistical analysis to identify whether patients with mTBI with PCS have distinct patterns of theta or gamma oscillations in response to affective stimuli. Compared with the healthy control group, patients with mTBI with PCS did not show a significant increase in the power of frontal theta activity in response to the pleasant stimuli, indicating less susceptibility toward pleasant cues. Moreover, the patient group showed attenuated gamma oscillatory activity, with no clear alteration in gamma oscillations in response to either pleasant or unpleasant cues. This study demonstrates that patients with mTBI with PCS exhibited altered patterns of oscillatory activities in the theta and gamma bands in response to affective visual stimuli compared with the normal control group. The current finding implicates that these distinguishable patterns of brain oscillation may represent the mechanism behind various psychiatric symptoms in patients with mTBI.NEW & NOTEWORTHY Patients with mild traumatic brain injury (mTBI) with postconcussional syndrome (PCS) exhibited altered patterns of changes in oscillatory activities in the theta and gamma bands in response to visual affective stimuli. Distinguishable patterns of brain oscillation may represent the mechanism behind various psychiatric symptoms in patients with mTBI.

Hair Loss: A Well-Known Yet Understudied Symptom in Parkinson's Disease Patients During Dopaminergic Therapy.

OBJECTIVE: Hair loss has been reported to occur during dopaminergic therapy in patients with Parkinson's disease. The mechanism by which dopaminergic therapy induces hair loss is not well understood. Dopamine receptors are present in the hair follicle, where they regulate melanin production. However, the role of dopamine receptors in hair growth is still not well understood. This study aimed to evaluate the prevalence of hair loss and identify factors associated with complaints of hair loss in patients with Parkinson's disease. METHODS: A cross-sectional design involving 495 Parkinson's disease patients was applied to evaluate hair loss status. Patients completed a questionnaire, and scalp/hair examinations were performed. Patients with underlying conditions that could affect hair loss and those prescribed medications known to increase the risk of hair loss were excluded. Finally, 291 patients (58.8%) were included for analysis. RESULTS: Among the 495 patients, 138 (27.9%) reported hair loss. Interestingly, more than half of the patients who complained of hair loss (79 out of 138) did not utilize treatments such as hair products, massage, dietary modifications, or alopecia medications. Hair inspection by a single investigator revealed objective hair loss in 263 patients (53.1%). An analysis of factors associated with hair loss complaints showed that the intake of dopaminergic medications with a levodopa-equivalent daily dose > 448 mg was associated with complaints of hair loss. CONCLUSION: Dopaminergic medication is associated with hair loss complaints in Parkinson's disease patients.

Flow Void Analysis Using Different Thresholding Methods on a Choriocapillaris Optical Coherence Tomography Angiography Image Complemented with a Structural En Face Image.

PURPOSE: To investigate the flow characteristics using different thresholding methods on a choriocapillaris optical coherence tomography angiography (OCTA) image complemented with a structural En Face image. METHODS: The 42 choriocapillaris OCTA images from healthy subjects were obtained with swept-source OCTA device and the 3 × 3-mm area OCTA images were processed with ImageJ. Using a raw choriocapillaris OCTA image and structural En Face image, we adjusted the different structural signal intensity. Then, the raw images and adjusted images were binarized with a global threshold and an auto local threshold using the Phansalkar method at 1- or 2-intercapillary distance. Then, the mean area, number, and size of the flow void, were compared among the images using different thresholding methods. RESULTS: Mean flow void area, number, and size were different according to the different binarization method both in raw and adjusted images (all p < 0.001). The mean flow void area analyzed with global threshold method were well correlated with those with auto local threshold method both in raw and adjusted images (all intraclass correlations, >0.929). CONCLUSIONS: Flow void features varied according to the different binarization methods but showed good correlation. The flow void characteristics according to the different binarization methods should be considered for the analysis of the choriocapillaris OCTA images complemented with a structural En Face image.

Target blood pressure in Korean hemodialysis patients for optimal survival.

Background: Hypertension is a major cardiovascular risk factor in hemodialysis patients. This study identified the optimal blood pressure (BP) target for Korean hemodialysis patients using the Korean Renal Dialysis System (KORDS) dataset from the Korean Society of Nephrology and a pooled analysis for previous studies. Methods: Hemodialysis patients were classified according to their systolic (SBP) and diastolic BP (DBP) at intervals of 20 and 10 mmHg, respectively. As a primary and secondary outcome, all-cause mortality and cardiovascular mortality were evaluated. Subsequently, pooled analysis with previous literatures was performed. Results: Among 70,607 patients, 13,708 (19.4%) died in 2,426 days (interquartile range, 1,256-4,075 days). Mean SBP and DBP were 143.0 ± 19.6 and 78.5 ± 12.0 mmHg. In multivariable Cox regression, the patients with SBP of <120 and ≥180 mmHg showed 1.10- and 1.12-times increased risk of all-cause mortality compared to SBP of 120-140 mmHg. Meanwhile, DBP showed no significant association. In subgroup analysis, patients aged <70 years and without diabetes had a U-shaped SBP-mortality association. Cardiovascular mortality was increased in SBP of ≥160 mmHg compared to 120-140 mmHg, but it was not in <120 mmHg. Pooled analysis with previous studies mostly showed elevated risk in SBP of <120 mmHg, but the risks in 140-160 and 160-180 mmHg were not consistent. Conclusion: Extremely lowering BP (<120 mmHg) or uncontrolled hypertension (≥160 mmHg) should be avoided to optimize survival in Korean hemodialysis patients. Detailed analysis for patients with SBP of 120-160 mmHg should be studied further under uniform BP measurement, along with consideration of risk of intradialytic hypotension. Tailored recommendations regarding patient risk factors also should be considered.

Low Serum Creatinine as Well as High Serum Creatinine Is Associated with Prognosis of Patients with Cancer in End-of-Life.

Background: The prognosis of end-of-life patients is challenging, and clinicians have attempted to predict survival more accurately. High serum creatinine (sCr) levels are associated with lower survival rates in patients with various cancers; however, low sCr levels are commonly expected in patients with terminal cancer because of muscle wasting and malnutrition. Therefore, we investigated the prevalence of low and high sCr levels and their association with survival duration in patients with terminal cancer in a palliative care unit. Methods: We analyzed the medical records of 280 patients admitted to a palliative care unit. Patients were divided into low (<0.5 mg/dL), normal (0.5-1.2 mg/dL), and high (>1.2 mg/dL) sCr groups. Kaplan-Meier survival curves using sCr levels were plotted and compared using the log-rank test. Using stepwise selection, a multivariable Cox proportional hazards model was used to identify the significant prognostic factors. Results: The median survival durations in the high-, low-, and normal-sCr groups were 9.57 days, 22.26 days, and 27.51 days, respectively. Multivariable Cox proportional hazard model identified that males (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.16-2.85), poor performance status (HR, 3.43; 95% CI, 1.12-10.54), total parenteral nutrition use (HR, 1.84; 95% CI, 1.09-3.1), high sCr (HR, 2.74; 95% CI, 1.52-4.94), and low sCr (HR, 1.22; 95% CI, 1.07-1.43) were significantly associated with a shorter survival time. Conclusion: Low and high serum creatinine levels were significantly associated with poor survival in patients with cancer at the end-of-life stage. Therefore, readily available and simple biomarkers may help plan advanced care in palliative care settings.

Additive impact of diabetes and sarcopenia on all-cause and cardiovascular mortality: A longitudinal nationwide population-based study.

OBJECTIVE: Diabetes mellitus (DM) and sarcopenia (SP) are growing public health concerns in an aging society, which share common pathophysiological mechanisms and are associated with serious health consequences. We investigated the impact of DM and SP on all-cause and cardiovascular mortalities in a longitudinal nationwide population-based study. METHODS: The study analyzed data from the Korea National Health and Nutrition Examination Survey conducted between 2008 and 2011, including information on appendicular skeletal muscle mass data. Mortality data up to December 2020 were retrieved from the National Death Registry. RESULTS: Among the 17,920 participants, 14,737 (82.2 %) had neither DM nor SP (DM-/SP-), 1349 (7.5 %) had only DM (DM+/SP-), 1425 (8.0 %) had only SP (DM-/SP+), and 409 (2.3 %) had both DM and SP (DM+/SP+). Compared to the DM-/SP- group, the DM-/SP+ and DM+/SP+ groups demonstrated increased all-cause mortality with adjusted hazard ratios (HRs) of 1.47 (95 % confidence interval [CI]: 1.14-1.89) and 1.85 (95 % CI: 1.28-2.69), respectively, while the DM+/SP- group did not (HR 1.29, 95 % CI: 0.97-1.74). The DM+/SP+ group demonstrated the highest risk of overall mortality (p-for-trend <0.001). Compared to the DM-/SP- group, only the DM+/SP+ group demonstrated increased cardiovascular mortality with HRs of 2.10 (95 % CI: 1.11-4.00) while the DM+/SP- (HR 1.35, 95 % CI: 0.79-2.30) and DM-/SP+ (HR 1.42, 95 % CI: 0.84-2.43) groups did not. CONCLUSIONS: The coexistence of DM and SP additively increased the risk of all-cause and cardiovascular mortality. Individuals with either disease may require more careful management to prevent the development of the other disease to reduce mortality.

A Novel Anthropometric Parameter, Weight-Adjusted Waist Index Represents Sarcopenic Obesity in Newly Diagnosed Type 2 Diabetes Mellitus.

Background: As the metabolic significance of sarcopenic obesity (SO) is revealed, finding an appropriate index to detect SO is important, especially for type 2 diabetes mellitus (T2DM) patients with accompanying metabolic dysfunction. Methods: Participants (n=515) from the Korea Guro Diabetes Program were included to compare how well waist circumference (WC), waist hip ratio (WHR), waist height ratio (WHtR), and the weight-adjusted waist index (WWI) predict SO in newly diagnosed T2DM patients. Sarcopenia was defined based on guidelines from the 2019 Asian Working Group for Sarcopenia as both low muscle mass (appendicular skeletal muscle [ASM]/height2 <7.0 kg/m2 for men, <5.4 kg/m2 for women) and strength (handgrip strength <28.0 kg for men, <18.0 kg for women) and/or reduced physical performance (gait speed <1.0 m/sec). Obesity was defined as a WC ≥90 cm in men and ≥85 cm in women. The WHR, WHtR, and WWI were calculated by dividing the WC by the hip circumference, height, and √ weight, respectively. Results: The WC, WHR, and WHtR correlated positively with the fat and muscle mass represented by truncal fat amount (TFA) and ASM, whereas the WWI was proportional to the TFA and inversely related to ASM. Of the four indices, the WWI showed the highest area under the receiver operative characteristic curve for SO. The WWI also exhibited a positive correlation with albuminuria and the mean brachial-ankle pulse wave velocity, especially in patients aged ≥65 years. Conclusion: The WWI is the preferable anthropometric index for predicting SO in T2DM patients, and it might be a proper index for predicting cardiometabolic risk factors in elderly people.

The reliability and validity of the Korean version of the reaching performance scale for stroke after translation and cross-cultural adaptation.

The reaching performance scale for stroke evaluates reach-to grasp movement of the upper extremity and compensatory movements. The objective of the study was to translate and cross-culturally adapt the reaching performance scale for stroke into Korean and assess its reliability and validity. An expert committee supervised the forward and backward translation and the final translated Korean version of reaching performance scale for stroke (K-RPSS). Ninety-eight individuals (mean age 63.63 ± 13.13 years), with hemiplegia after stroke (97.82 ± 191.50 weeks) were evaluated independently by physiatrist and occupational therapist using K-RPSS. Degree of the motor impairment and functional status of patients were evaluated with the Fugl-Meyer assessment for upper limb and manual function test. The K-RPSS demonstrated excellent intra-rater (intraclass correlation coefficient = 0.9865), inter-rater (intraclass correlation coefficient 0.9866) reliability, and internal consistency (Cronbach α = 0.977 for total score). The validity of K-RPSS was confirmed with strong correlation with Fugl-Meyer assessment and manual function test. The K-RPSS had ceiling effect and the 3 points is the score change needed to indicate a change in a patient. K-RPSS has been shown to be a reliable and valid tool for assessing the compensation and movement quality of the upper limb and trunk when performing a reach-to grasp task. The K-RPSS is expected to be used widely by Korean speaking clinicians and researchers.

Use of thyroid transcription factor 1 and napsin A to predict local failure and survival after Gamma Knife radiosurgery in patients with brain metastases from lung adenocarcinoma.

OBJECTIVE: Stereotactic radiosurgery (SRS), combined with contemporary targeted therapies and immunotherapies, has improved the overall survival of patients with lung adenocarcinoma (ADC). Given that histological subtypes reflect prognosis in patients with primary ADC, it is important to integrate pathological biomarkers to predict clinical outcomes after SRS in patients with brain metastases from lung ADC. Therefore, the authors investigated the prognostic relevance of various biomarkers of primary lung ADC for clinical outcomes after SRS. METHODS: A total of 95 patients with 136 brain metastases (1-4 oligometastases) who were treated with Gamma Knife radiosurgery between January 2017 and December 2020 were included. The Kaplan-Meier method and univariate and multivariate analyses using Cox proportional hazard regression models were used to identify prognostic factors for local control, survival, and distant brain control. RESULTS: Multivariate analysis revealed thyroid transcription factor 1 as an independent prognostic factor for local control (HR 0.098, 95% CI 0.014-0.698, p = 0.0203) and napsin A as a significant predictor of overall survival after SRS (HR 0.080, 95% CI 0.017-0.386, p < 0.01). In a subset analysis of epidermal growth factor receptor (EGFR) mutation, patients with EGFR exon 19 mutations showed better distant brain control than those with EGFR exon 21 mutations (p < 0.01). CONCLUSIONS: Pathological biomarkers of primary cancer should be considered to predict clinical outcomes after SRS in patients with lung ADC. Use of such biomarkers may help to provide personalized treatment to each patient, improving clinical outcomes after SRS.

Low Neutralizing Activities to the Omicron Subvariants BN.1 and XBB.1.5 of Sera From the Individuals Vaccinated With a BA.4/5-Containing Bivalent mRNA Vaccine.

The continuous emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants has provided insights for updating current coronavirus disease 2019 (COVID-19) vaccines. We examined the neutralizing activity of Abs induced by a BA.4/5-containing bivalent mRNA vaccine against Omicron subvariants BN.1 and XBB.1.5. We recruited 40 individuals who had received a monovalent COVID-19 booster dose after a primary series of COVID-19 vaccinations and will be vaccinated with a BA.4/5-containing bivalent vaccine. Sera were collected before vaccination, one month after, and three months after a bivalent booster. Neutralizing Ab (nAb) titers were measured against ancestral SARS-CoV-2 and Omicron subvariants BA.5, BN.1, and XBB.1.5. BA.4/5-containing bivalent vaccination significantly boosted nAb levels against both ancestral SARS-CoV-2 and Omicron subvariants. Participants with a history of SARS-CoV-2 infection had higher nAb titers against all examined strains than the infection-naïve group. NAb titers against BN.1 and XBB.1.5 were lower than those against the ancestral SARS-CoV-2 and BA.5 strains. These results suggest that COVID-19 vaccinations specifically targeting emerging Omicron subvariants, such as XBB.1.5, may be required to ensure better protection against SARS-CoV-2 infection, especially in high-risk groups.

Association of plasma brain-derived neurotrophic factor levels and frailty in community-dwelling older adults.

Brain-derived neurotrophic factor (BDNF), an exercise-induced neurotrophin, is an important factor in memory consolidation and cognitive function. This study evaluates the association between plasma BDNF levels and frailty in community-dwelling older adults. Plasma BDNF levels were analyzed in a total of 302 individuals aged 70-84 years from the Korean Frailty and Aging Cohort Study. There were 30 (9.9%) participants with frailty. They were older and had a higher prevalence of dementia and depression than those without frailty. There were no differences in the proportion of male sex between the frail and non-frail groups. Plasma BDNF levels were significantly lower in participants with frailty than in those without frailty. The presence of frailty was significantly associated with plasma BDNF levels (odds ratio 0.508, 95% confidence interval 0.304-0.849) as well as age, hemoglobin, and the presence of dementia, and depression. After adjustment for confounding factors, the significant association between plasma BDNF and frailty was maintained (0.495, 0.281-0.874). This association remained consistent after exclusion of individuals with dementia, depression, stroke, diabetes, and osteoporosis. Plasma BDNF levels were significantly associated with frailty in community-dwelling older adults. Our study may suggest the possible role of BDNF as a novel biomarker of frailty.

Myocardial Infarction, Stroke, and All-Cause Mortality according to Low-Density Lipoprotein Cholesterol Level in the Elderly, a Nationwide Study.

BACKGROUND: We assessed the myocardial infarction (MI), stroke, and all-cause death risks during follow-up according to the low-density lipoprotein cholesterol (LDL-C) levels among older adults. METHODS: The Korean National Health Insurance Service datasets (2002 to 2020) were used for this population-based cohort study. The hazards of MI, stroke, and all-cause mortality during follow-up were analyzed according to LDL-C level in individuals aged ≥65 years without baseline cardiovascular diseases (n=1,391,616). RESULTS: During a mean 7.55 years, 52,753 MIs developed; 84,224 strokes occurred over a mean 7.47 years. After a mean 8.50 years, 233,963 died. A decrease in LDL-C was associated with lower hazards of MI and stroke. The decreased hazard of stroke in lower LDL-C was more pronounced in statin users, and individuals with diabetes or obesity. The hazard of all-cause death during follow-up showed an inverted J-shaped pattern according to the LDL-C levels. However, the paradoxically increased hazard of mortality during follow-up in lower LDL-C was attenuated in statin users and individuals with diabetes, hypertension, or obesity. In statin users, lower LDL-C was associated with a decreased hazard of mortality during follow-up. CONCLUSION: Among the elderly, lower LDL-C was associated with decreased risks of MI and stroke. Lower LDL-C achieved by statins in the elderly was associated with a decreased risk of all-cause death during follow-up, suggesting that LDL-C paradox for the premature death risk in the elderly should not be applied to statin users. Intensive statin therapy should not be hesitated for older adults with cardiovascular risk factors including diabetes.

Ultrasonographic index for the diagnosis of non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease.

Background: Liver biopsy is a gold standard for the diagnosis of non-alcoholic steatohepatitis (NASH), but has several disadvantages including invasiveness, high cost, and sampling error. Ultrasonography (US) is a noninvasive imaging modality widely used in non-alcoholic fatty liver disease (NAFLD) patients. This study aimed: (I) to assess the feasibility of US in the prediction of NASH and (II) to develop various US indices combining US parameters and laboratory data for the detection of NASH in NAFLD patients and to compare the diagnostic performance of them. Methods: Sixty patients who underwent liver biopsy, gray-scale US [hepatorenal index (HRI) and shear-wave elastography (SWE)], and Fibroscan [controlled attenuation parameter (CAP) and transient elastography (TE)] for the evaluation of NASH were included. Patients were classified according to the NAFLD Activity Score (NAS) into the NASH (NAS ≥5) and non-NASH (NAS <5) groups. The diagnostic performance of HRI, CAP, SWE, TE, and laboratory data for grading steatosis, lobular inflammation, ballooning degeneration, and fibrosis was evaluated. After the identification of laboratory data that were independently associated with NASH through univariable and multivariable logistic regression analyses, various US indices were developed by combining US parameters with or without these laboratory data. The diagnostic performance of the US indices was assessed with obtaining area under the curve (AUC) and compared using DeLong test. Results: Twenty-five NASH and 35 non-NASH patients were included. The mean AUCs for grading steatosis were 0.871 using HRI and 0.583 using CAP. The mean AUCs for grading fibrosis and ballooning degeneration were 0.777 and 0.729 using SWE and 0.830 and 0.708 using TE, respectively. Aspartate aminotransferase (AST) was the only significant laboratory data associated with NASH (OR, 1.019; P=0.032). Using AST, the mean AUCs for grading lobular inflammation and ballooning degeneration were 0.712 and 0.775, respectively. Among various US indices, the index consisting of gray-scale US parameters (SWE and HRI) and AST showed the best diagnostic performance for the detection of NASH in NAFLD patients (AUC =0.806). Conclusions: The index combining gray-scale US parameters and AST is useful for the detection of NASH and may be used to exclude the need for liver biopsy in NAFLD patients.

Duration of Humoral Immunity and Cross-Neutralizing Activity Against the Alpha, Beta, and Delta Variants After Wild-Type Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Prospective Cohort Study.

A prospective cohort study was conducted for adults with a diagnosis of with coronavirus disease 2019 (COVID-19). Convalescent blood samples were obtained 4, 6, and 11 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The seropositivity of anti-spike antibody was maintained in all patients (100%) until 11 months after COVID-19 diagnosis. Neutralizing antibody levels against wild-type SARS-CoV-2 gradually decreased but remained positive in >50% of patients 11 months after diagnosis: in 98.5% (67 of 68) at 4 months, 86.8% (46 of 53) at 6 months, and 58.8% (40 of 68) at 11 months. However, cross-neutralizing activity against the Beta and Delta variants was attenuated 2.53-fold and 2.93-fold, respectively, compared with the wild-type strain.

Implications of fasting plasma glucose variability on the risk of incident peripheral artery disease in a population without diabetes: a nationwide population-based cohort study.

BACKGROUND: Diabetes have been known as a traditional risk factor of developing peripheral artery disease (PAD). However, the study evaluating the impact of long-term glycemic variability on the risk of developing PAD is limited, especially in a general population without diabetes. METHODS: We included 152,931 individuals without diabetes from the Korean National Health Insurance Service-Health Screening Cohort. Fasting plasma glucose (FPG) variability was measured using coefficient variance (FPG-CV), standard deviation (FPG-SD), and variability independent of the mean (FPG-VIM). RESULTS: A total of 16,863 (11.0%) incident cases of PAD were identified during a median follow-up of 8.3 years. Kaplan-Meier curves showed a progressively increasing risk of PAD in the higher quartile group of FPG variability than in the lowest quartile group (log rank P < 0.001). Multivariable Cox proportional hazard analysis showed the hazard ratio for PAD prevalence as 1.11 (95% CI 1.07-1.16, P < 0.001) in the highest FPG-CV quartile than in the lowest FPG-CV quartile after adjusting for confounding variables, including mean FPG. Similar degree of association was shown in the FPG-SD and FPG-VIM. In sensitivity analysis, the association between FPG variability and the risk of developing PAD persisted even after the participants were excluded based on previously diagnosed diseases, including stroke, coronary artery disease, congestive heart failure, chronic kidney disease, or current smokers or drinkers. Subgroup analysis demonstrated that the effects of FPG variability on the risk of PAD were more powerful in subgroups of younger age, regular exercisers, and those with higher income. CONCLUSIONS: Increased long-term glycemic variability may have a significant prognostic effect for incident PAD in individuals without diabetes.

Impact of non-alcoholic fatty liver disease on the risk of sarcopenia: a nationwide multicenter prospective study.

BACKGROUND AND AIMS: Despite the association between sarcopenia and non-alcoholic fatty liver disease (NAFLD), no study has evaluated the predictive role of NAFLD in sarcopenia. We investigated impact of NAFLD on the risk of low muscle mass (LMM) and low muscle strength (LMS) in a nationwide multicenter study. METHODS: A total of 1595 community-dwelling people aged 70-84 years were followed for 2 years in the Korean Frailty and Aging Cohort Study. Muscle mass was estimated by dividing appendicular skeletal muscle mass (ASM) by body mass index (BMI). Muscle strength was measured as handgrip strength (HGS) divided by BMI. The sex-specific lowest quintiles of ASM/BMI and HGS/BMI of the study population were used as cutoffs for LMM and LMS, respectively. The risk of LMM and LMS were assessed according to hepatic steatosis index (HSI) and fatty liver index (FLI) quartiles. RESULTS: As HSI quartiles increased, the LMM risk increased gradually, after adjusting for age, sex, lifestyle factors, comorbidities, and several causative factors (insulin resistance, inflammation, and vitamin D) (Q4 vs. Q1 OR [95% CI] 3.46 [2.23-5.35]). The increased risk of LMS was even higher according to HSI quartiles (Q4 vs. Q1 5.81 [3.67-9.21]). Multivariate analyses based on FLI showed similar results. People with NAFLD (HSI > 36) were at higher risk of developing LMM and LMS compared to those without (1.65 [1.19-2.31] and 2.29 [1.61-3.26], respectively). CONCLUSIONS: The presence of NAFLD may predict future risk of LMM and LMS, with greater impact on LMS than on LMM.

Increased Risk of Type 2 Diabetes in Patients With Thyroid Cancer After Thyroidectomy: A Nationwide Cohort Study.

CONTEXT: Abnormal thyroid function after thyroidectomy and subsequent thyroid-stimulating hormone suppression can have detrimental effects on glucose homeostasis in patients with thyroid cancer. OBJECTIVE: To investigate whether thyroidectomy increases the risk of type 2 diabetes in patients with thyroid cancer and to explore the association between levothyroxine dosage and type 2 diabetes risk. METHODS: A retrospective population-based cohort study using the Korean National Health Insurance database. We included 36 377 thyroid cancer patients without known diabetes who underwent thyroidectomy between 2004 and 2013. Matched subjects with nonthyroid cancer were selected using 1:1 propensity score matching. The main outcome measure was newly developed type 2 diabetes mellitus. RESULTS: Patients with thyroid cancer who underwent thyroidectomy had a higher risk of developing type 2 diabetes mellitus than the matched controls (hazard ratio [HR] 1.43, 95% CI 1.39-1.47). Among patients with thyroid cancer, when the second quartile group (in terms of the mean levothyroxine dosage; 101-127 µg/day) was considered the reference group, the risk of type 2 diabetes mellitus increased in the first quartile (<101 µg/day; HR 1.45, 95% CI 1.36-1.54) and fourth quartile groups (≥150 µg/day; HR 1.37, 95% CI 1.29-1.45); meanwhile, the risk decreased in the third quartile group (128-149 µg/day; HR 0.91, 95% CI 0.85-0.97). CONCLUSION: Patients with thyroid cancer who underwent thyroidectomy were more likely to develop type 2 diabetes mellitus than the matched controls. There was a U-shaped dose-dependent relationship between the levothyroxine dosage and type 2 diabetes mellitus risk.