Cox Proportional Hazards Model Analysis Research Articles

SCG2: A Prognostic Marker That Pinpoints Chemotherapy and Immunotherapy in Colorectal Cancer.

BackgroundFluorouracil (FU)-based chemotherapy regimens are indispensable in the comprehensive treatment of colorectal cancer (CRC). However, the heterogeneity of treated individuals and the severe adverse effects of chemotherapy results in limited overall benefit.MethodsFirstly, Weighted gene co-expression network analysis (WGCNA) identified modules tightly associated with chemotherapy response. Then, the in-house cohort and prognostic cohorts from TCGA and GEO were subjected to Cox proportional hazards model and survival analysis to ascertain the predictable function of SCG2 on the prognosis of CRC patients. Finally, we performed In vitro experiments, functional analysis, somatic mutation, and copy number variation research to explore the biological characteristics of SCG2.ResultsWe identified red and green as the modules most associated with chemotherapy response, in which SCG2 was considered a risky factor with higher expression predicting poorer prognosis. SCG2 expression in the APC non-mutation group was remarkably higher than in the mutation group. The mutation frequencies of amplified genes differed significantly between different SCG2 expression subgroups. Besides, CRC cell lines with SCG2 knockdown have reduced invasive, proliferative, and proliferative capacity. We discovered that the SCG2 high expression subgroup was the immune hot type and considered more suitable for immunotherapy.ConclusionThis study demonstrates the clinical significance and biological characteristics of SCG2, which could serve as a promising biomarker to identify patients who may benefit from chemotherapy and immunotherapy.

A retrospective cohort study on COVID-19 at 2 Los Angeles hospitals: Older age, low triage oxygenation, and chronic kidney disease among the top risk factors associated with in-hospital mortality.

Los Angeles, California became a warzone of COVID-19 infections with up to one death every 10 minutes at the end of 2020. As resources thinned, and ICU beds and ventilators became scarce, physicians began agonizing over potentially rationing medical care. In this study, we conducted a retrospective cohort analysis of 7,429 confirmed COVID-19 positive patients from two community hospitals in Los Angeles, California between March 16, 2020 and June 9, 2021. We applied the Cox proportional hazards regression model to determine the risk factors most strongly associated with in-hospital mortality. Using the multivariable Cox proportional hazards model, there was a higher hazard ratio (HR) for mortality in patients who were older (age ≥60 years) [HR 2.189, 95% CI 1.991–2.407, p<0.001], had low triage oxygenation < 90% [HR 1.439, 95% CI 1.339–1.546, p<0.001], had chronic kidney disease (CKD) [HR 1.348, 95% CI 1.234–1.496, p = 0.001)], and who were obese (BMI ≥ 30 kg/m^2) [HR 1.221, 95% CI 1.155–1.340, p = 0.003)]. Overall, our study concluded that age ≥ 60 years, low triage oxygenation less than 90%, chronic kidney disease, and obesity were the top patient characteristics associated with increased mortality for both the univariate and multivariate Cox proportional hazards model analyses. Furthermore, by separating our data set into a development and validation set, we created a novel prediction tool to forecast in-hospital mortality and achieved 86% accuracy.

Effect of Obesity on Left Ventricular Remodeling and Clinical Outcome in Chinese Patients With Hypertrophic Cardiomyopathy: Assessed by Cardiac MRI.

Obesity is highly prevalent in patients with hypertrophic cardiomyopathy (HCM) and believed to influence its phenotype. To explore the effects of obesity on left ventricular (LV) remodeling and long-term clinical course in Chinese patients with HCM. Longitudinal. A total of 247 patients with HCM classified according to body mass index (BMI) (normal weight: BMI=18.0-22.9kg/m2 [N=90]; overweight: BMI=23.0-24.9kg/m2 [N=58]; and obese: BMI ≥ 25 kg/m2 [N=99]). 3.0 T/Balanced steady-state free precession sequence and phase-sensitive inversion recovery late gadolinium enhancement (LGE) sequence. LV function and geometry were measured. LV peak strain analysis was performed. The presence and percentage of LGE in the LV were recorded. The endpoints including heart failure, sudden cardiac death, and overall composite outcome were assessed during a median follow-up of 4.1 years (interquartile range, 3.0-6.2 years). One-way analysis of variance, Kruskal-Wallis test, or chi-square test; Pearson correlation coefficient (r); multivariable linear regression analysis; Kaplan-Meier survival analysis; and Cox proportional hazards model analysis were conducted. A two-tailed P-value < 0.05 was considered statistically significant. Obese patients exhibited a significant progressive increase in LV mass compared with normal-weight patients. The magnitude of all LV strain indices gradually and significantly decreased as BMI increased, whereas LV ejection fraction was not significantly different among BMI groups (P=0.364). Multivariable linear regression analysis showed that obesity had a significant association with impaired strain indices as well as with indexed LV mass. Multivariable Cox model analysis retained obesity as an independent marker for future endpoints, and conveyed a > 3-fold increase in risk compared with patients with normal weight (hazard ratio, 3.04; 95% confidence interval, 1.07-6.57). Obesity is an important environmental modifier that is associated with adverse LV remodeling and is independently associated with future clinical outcomes in Chinese patients with HCM. 3 TECHNICAL EFFICACY: Stage 2.

Kidney function deterioration is dependent on blood pressure levels: 11.2year follow-up in diabetic patients.

There is little evidence of how blood pressure level over 10years affects the decline of estimated glomerular filtration rate (eGFR) in diabetic patients. The Japanese primary prevention of atherosclerosis with aspirin for diabetes (JPAD) trial was a multicenter, randomized, clinical trial done from 2002 to 2008. After completion of the JPAD trial, we followed up the patients until 2019 as a cohort study. We defined late-stage kidney disease (LSKD) as eGFR < 30ml/min/1.73m2 or hemodialysis. Based on the mean value of systolic blood pressure (SBP) obtained average 7 times during the follow-up, we divided the patients into three groups: a high SBP group (n = 607, SBP ≥ 140mm Hg); a moderate SBP group (n = 989, 140 > SBP ≥ 130mm Hg); or a low SBP group (n = 913, SBP < 130mm Hg). There was no significant deference in the mean eGFR among the high SBP, moderate SBP and low SBP groups on registration. The incidence rate of LSKD was significantly higher in the high SBP (HR 2.02, 95% CI 1.36-3.01) and moderate SBP (HR 1.54, 95% CI 1.07-2.20) groups than in the low SBP group (Log-Rank P = 0.0018). Cox proportional hazards model analysis revealed that the high SBP (HR, 1.57, P = 0.049) and moderate SBP (HR, 1.52, P = 0.037) were independent factors after adjustment for proteinuria ≥ ± , age ≥ 65years, men, body mass index ≥ 24kg/m2, duration of diabetes ≥ 7.0years, statin usage, eGFR ≥ 60ml/min/1.73m2, hemoglobin A1c ≥ 7.2%, and smoking status. Our 11.2year follow-up study demonstrated that mean SBP was independently associated with the progression to LSKD in diabetic patients. These findings may become new evidence that SBP less than 130mm Hg is recommended for diabetic patients to prevent progression to LSKD.

Single-agent anti-PD-1 or combined with ipilimumab in patients with mucosal melanoma: an international, retrospective, cohort study

Mucosal melanoma (MM) is a rare melanoma subtype with distinct biology and poor prognosis. Data on the efficacy of immune checkpoint inhibitors (ICIs) are limited. We determined the efficacy of ICIs in MM, analyzed by primary site and ethnicity/race. A retrospective cohort study from 25 cancer centers in Australia, Europe, USA and Asia was carried out. Patients with histologically confirmed MM were treated with anti-programmed cell death protein 1 (PD-1) ± ipilimumab. Primary endpoints were response rate (RR), progression-free survival (PFS), overall survival (OS) by primary site (naso-oral, urogenital, anorectal, other), ethnicity/race (Caucasian, Asian, Other) and treatment. Univariate and multivariate Cox proportional hazards model analyses were conducted. In total, 545 patients were included: 331 (63%) Caucasian, 176 (33%) Asian and 20 (4%) Other. Primary sites included 113 (21%) anorectal, 178 (32%) urogenital, 206 (38%) naso-oral and 45 (8%) other. Three hundred and forty-eight (64%) patients received anti-PD-1 and 197 (36%) anti-PD-1/ipilimumab. RR, PFS and OS did not differ by primary site, ethnicity/race or treatment. RR for naso-oral was numerically higher for anti-PD-1/ipilimumab [40%, 95% confidence interval (CI) 29% to 54%] compared with anti-PD-1 (29%, 95% CI 21% to 37%). Thirty-five percent of patients who initially responded progressed. The median duration of response (mDoR) was 26 months (95% CI 18 months-not reached). Factors associated with short PFS were Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3 (P < 0.01), lactate dehydrogenase (LDH) more than the upper limit of normal (ULN) (P= 0.01), lung metastases (P < 0.01) and ≥1 previous treatments (P < 0.01). Factors associated with short OS were ECOG PS ≥1 (P < 0.01), LDH >ULN (P= 0.03), lung metastases (P < 0.01) and ≥1 previous treatments (P < 0.01). MM has poor prognosis. Treatment efficacy of anti-PD-1 ± ipilimumab was similar and did not differ by ethnicity/race. Naso-oral primaries had numerically higher response to anti-PD-1/ipilimumab, without difference in survival. The addition of ipilimumab did not show greater benefit over anti-PD-1 for other primary sites. In responders, mDoR was short and acquired resistance was common. Other factors, including site and number of metastases, were associated with survival.

Abstract 5280: TERT promoter mutations are an independent predictor of distant metastasis in Middle Eastern papillary thyroid microcarcinoma

Abstract Background: Papillary thyroid microcarcinomas (PTMCs) have been attributed to the recent increased incidence of thyroid cancer. Although indolent, a subset of PTMC could potentially develop distant metastasis (DM). This study aimed to evaluate the clinico-pathological features and molecular characteristics of PTMC and identify the risk factors for DM in PTMC patients from Middle Eastern ethnicity. Methods: We retrospectively analyzed 210 patients with histologically confirmed PTMC. Clinico-pathological associations for DM, BRAF mutation and TERT mutation were analyzed successfully in 184 patients. Multivariate analysis was performed using Cox proportional hazards model and logistic regression analysis. Results: Among the PTMC patients included in this cohort, DM was noted in 6.0%(11/184), whereas tumor relapse occurred in 29/184 (15.8%). Of the 11 cases with DM, lung metastasis occurred in 8 cases, bone metastasis in 2 cases and brain metastasis in 1 case. Presence of extrathyroidal extension and older age were significantly associated with DM. Molecular analysis showed BRAF V600E mutations to be the most frequent, being detected in 45.7% (84/184). TERT promoter mutations were detected in 16 (8.7%) cases and were significantly associated with DM and shorter metastasis-free survival in multivariate analysis. Conclusions: Our study indicates a surprisingly high frequency of TERT promoter mutation in Saudi patients with PTMC. Identifying TERT promoter mutations as an independent predictor of DM in patients with microcarcinoma could explain the inherent aggressive nature of PTMC from Middle Eastern ethnicity and magnify its role in patient risk stratification, which might help in improving therapeutic strategy for these patients. Citation Format: Saeeda Omer Ahmed, Abdul K. Siraj, Sandeep K. Parvathareddy, Kaleem Iqbal, Zeeshan Qadri, Maha Al-Rasheed, Sarah Siraj, Saravanan Thangavel, Roxanne Diaz, Allianah Benito, Ingrid F. Victoria, Khawla S. AlKuraya. TERT promoter mutations are an independent predictor of distant metastasis in Middle Eastern papillary thyroid microcarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5280.

Risk factors for prolonged time to hospital discharge after ambulatory cholecystectomy under general anaesthesia. A retrospective cohort study

BackgroundAlthough predictive models have already integrated demographic factors and comorbidities as risk factors for a prolonged hospital stay, factors related to anaesthesia management in ambulatory surgery have not been yet characterized. This study aims to identify anaesthetic factors associated with a prolonged discharge time in ambulatory surgery. MethodsAll clinical records of patients who underwent ambulatory cholecystectomy in a French University Hospital (Hôpital Saint Antoine, Paris) between January 1st, 2012 and December 31st, 2018 were retrospectively reviewed. The primary endpoint was the discharge time, defined as the time between the end of surgery and discharge. A multivariable Cox proportional-hazards model was fitted to investigate the factors associated with a prolonged discharge time. ResultsFive hundred and thirty-five (535) patients were included. The median time for discharge was 150 min (interquartile range – IQR [129−192]). A bivariable analysis highlighted a positive correlation between discharge timeline and the doses-weight of ketamine and sufentanil. In the multivariable Cox proportional hazards model analysis, the anaesthesia-related factors independently associated with prolonged discharge time were the dose-weight of ketamine in interaction with the dose weight of sufentanil (HR 0.10 per increment of 0.1 mg/kg of ketamine or 0.2 μg/kg of sufentanil, CI 95% [0.01–0.61], p = 0.013) and the non-use of a non-steroidal anti-inflammatory drug (NSAID) (HR 0.81 [0.67–0.98], p = 0.034). Twenty patients (4%) had unscheduled hospitalization following surgery. ConclusionAnaesthesia management, namely the use of ketamine and the non-use of NSAID, affects time to hospital discharge.

Natural History Trajectories of Frailty in Community-Dwelling Older Japanese Adults.

BackgroundThe gap between the average life expectancy and healthy life expectancy remains wide. Understanding the natural history of frailty development is necessary to prevent and treat frailty to overcome this gap. This study elucidated the trajectories of 5 frailty assessment components using group-based multitrajectory modeling.MethodsOverall, 845 community-dwelling older adults (aged 65–91 years; 433 males and 412 females) who underwent longitudinal frailty assessments at least 3 times were included in the analysis. The mean follow-up period (±SD, range) was 7.1 (±2.3, 3.8–11.3) years. In each wave, the physical frailty was assessed for the following 5 partially modified components of the Cardiovascular Health Study criteria: shrinking, weakness, exhaustion, slowness, and low activity. Using group-based multitrajectory modeling, we identified subgroups that followed distinctive trajectories regarding the 5 frailty components.ResultsFive frailty trajectory groups were identified: weakness-focused frail progression group (Group 1 [G1]; 10.9%), robust maintenance group (Group 2 [G2]; 43.7%), exhaustion-focused prefrail group (Group 3 [G3]; 24.3%), frail progression group (Group 4 [G4]; 6.7%), and low activity–focused prefrail group (Group 5 [G5]; 14.4%). The Cox proportional hazards model analysis showed that G1, G4, and G5 had significantly higher mortality risks after adjusting for sex and age (G2 was the reference group).ConclusionBased on the natural history of frailty, the 5 distinctive trajectory groups showed that some individuals remained robust, while others remained predominantly prefrail or progressed primarily owing to physical mobility decline. Therefore, identifying individuals belonging to these progressive frailty groups and providing interventions according to the characteristics of each group may be beneficial.

VEGFR-C mutation serves as a potential negative predictor for immunotherapy in metastatic melanoma.

e21593 Background: Immune checkpoint blockade has shown significant promise as an anticancer treatment and anti–CTLA-4 treatment prolongs overall survival in patients with melanoma. Vascular endothelial growth factor-C (VEGF-C), a member of the VEGF gene family, has been characterised as a prime mediator of lymphangiogenesis and angiogenic growth factors that promote the growth and metastasis of neoplasms. Previous studies provided evidence that VEGF-C correlated with poorer survival in melanoma. We aimed to determine the association of VEGF-C mutations with melanoma survival to immune checkpoint inhibitors (ICI). Methods: Data from Allen study (n = 110, anti- CTLA-4 therapy) was obtained and analyzed. Meanwhile, we extracted skin cutaneous melanoma (SKCM) RNA data from The Cancer Genome Atlas (TCGA). In survival analysis, Kaplan-Meier curves were compared by log-rank test, and the hazard ratio (HR) was determined through a multivariable Cox regression model. Using the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm, the relative proportions of 22 types of infiltrating immune cells were determined in TCGA cohort. Results: In Allen cohort, the frequency of VEGFR-C mutation was 5.45% (6 in 110). Meanwhile, the frequency of VEGFR-C mutation in TCGA cohort was 7.37% (33 in 448). VEGFR-C-mutant (VEGFR-C-mut) group showed a poorer progression-free survival (PFS) (HR, 2.34; 95%CI, 1.01 to 5.4, p = 0.041) and overall survival (OS) (HR, 2.84, 95%CI, 1.22 to 6.62, p = 0.012) than the VEGFR-C-wild (VEGFR-C-wt) group, based on results of the log-rank test and Kaplan-Meier analysis. Moreover, COX proportional hazards model analysis showed VEGFR-C mutation was associated with poorer PFS (HR, 2.54; 95%CI, 1.04-6.25, p = 0.0042;) and OS (HR, 3.25; 95%CI, 1.30-8.12, p = 0.0117) compared with VEGFR-C-wt. In addition, we identified that the levels of naive B cells and resting CD4+ memory T cells were more abundant in VEGFR-C-mut group according to CIBERSORT algorithm. Conclusions: In our study, the frequency of VEGFR-C mutation in melanoma was investigated in Allen and TCGA cohorts, which might provide useful information to guide precision medicine. VEGFR-C mutation may serve as a potential negative predictor of response to anti-CTL4 treatment in melanoma via higher levels of naive B cells and resting CD4+ memory T cells.

Risk factors for the recurrence of relapsing polychondritis

BackgroundAlthough the survival rates of patients with relapsing polychondritis (RP) have increased remarkably, the high recurrence rate remains a significant concern for physicians and patients. This retrospective study aimed to investigate the risk factors for RP recurrence.MethodsPatients with RP who presented to Kyoto University Hospital from January 2000 to March 2020 and fulfilled Damiani’s classification criteria were included. Patients were classified into recurrence and non-recurrence groups. Risk factors for RP recurrence were analysed using a Cox proportional hazards model, and Kaplan–Meier survival curves were drawn.ResultsThirty-four patients were included. Twenty-five patients (74%) experienced 64 recurrences (mean: 2.56 recurrences per patient). The median duration before the first recurrence was 202 [55−382] days. The median prednisolone dose at the initial recurrence was 10 [5−12.75] mg/day. Tracheal involvement was significantly more frequent in the recurrence group at the initial presentation (44.0% vs. 0.0%, p=0.0172) than in the non-recurrence group, and pre-treatment C-reactive protein levels were significantly higher in the recurrence group than in the non-recurrence group (4.7 vs 1.15 mg/dL, p=0.0024). The Cox proportional hazards model analysis revealed that tracheal involvement (hazard ratio [HR] 4.266 [1.535−13.838], p=0.0048), pre-treatment C-reactive protein level (HR 1.166 [1.040−1.308], p=0.0085), and initial prednisolone monotherapy (HR 4.443 [1.515−16.267], p=0.0056) may be associated with recurrence. The median time before the initial recurrence was significantly longer in patients who received combination therapy with prednisolone and immunosuppressants or biologics (400 vs. 70 days, p=0.0015).ConclusionsTracheal involvement, pre-treatment C-reactive protein level, and initial prednisolone monotherapy were risk factors for recurrence in patients with RP. Initial combination therapy with prednisolone and immunosuppressants may delay recurrence.

Different Effects of Antibiotics on Klebsiella pneumoniae and Escherichia coli Resistance Induced by Antibiotics: A Retrospective Study from China.

Objective: The main objective was to assess the correlation between antibiotic use and carbapenem-resistant Klebsiella pneumoniae (CRKP) and carbapenem-resistant Escherichia coli (CREC) induction by antibiotics. Materials and Methods: A retrospective cohort study was conducted from January 2017 to December 2020. This study included patients with K. pneumoniae and E. coli. Kaplan-Meier analysis and Cox proportional hazard model were used to estimate the hazard of carbapenem-resistant Enterobacterales (CRE), whereas restricted cubic spline regression was used to visualize the hazard of CRE by antibiotics at different doses. Results: Two thousand fifty-six K. pneumoniae patients and 3,243 E. coli patients were included. After Cox proportional hazard model analysis, carbapenems or 1st-cephalospoins or penicillin monotherapy, male and ICU admission were associated with CRKP. CREC was associated with quinolone monotherapy. Time-to-event analysis indicated that carbapenem, β-lactamase inhibitor mixtures, and quinolones were associated with higher 30-day CRKP hazards than other antibiotics (χ2 = 33.670, p < 0.001). Further restricted cubic spline regression analysis found that the hazard of CRKP induction decreased with the increased dose of β-lactamase inhibitor mixtures, but there was no significant change in the hazard ratio of CRKP induction with the increased dose of quinolones. Moreover, there was an obvious characteristic of "parabolic curve" for the hazard of CREC induction due to β-lactamase inhibitor mixtures, and the hazard value gradually increased with the dose, reached the maximum at 24 g, and finally gradually decreased from 26 g. Conclusions: Rational use of antibiotics should be implemented and antimicrobial stewardship policies should be adjusted according to the characteristics of each hospital.

Metabolic dysfunction-associated fatty liver disease predicts new onset of chronic kidney disease better than fatty liver or nonalcoholic fatty liver disease.

Possible associations of chronic kidney disease (CKD) with fatty liver (FL) and nonalcoholic fatty liver disease (NAFLD) have recently been focused on. Metabolic dysfunction-associated fatty liver disease (MAFLD), defined as FL with overweight/obesity, type 2 diabetes mellitus or metabolic abnormalities, has been proposed as a new feature of chronic liver disease. However, the relationship between MAFLD and new onset of CKD has not been fully addressed. We investigated the associations of FL, NAFLD and MAFLD with the development of CKD, defined as an estimated glomerular filtration rate (eGFR) <60mL/min/1.73 m2 or positive for urinary protein, over a 10-year period in 28 890 Japanese subjects who received annual health examinations. After exclusion of subjects with no data for abdominal ultrasonography and subjects with CKD at baseline, a total of 13 159 subjects (men 8581, women 4578; mean age 48 years) were recruited. The prevalence of FL, NAFLD and MAFLD was 34.6% (men 45.1%, women 15.1%), 32.8% (men 42.7%, women 14.5%) and 32.3% (men 42.4%, women 13.4%), respectively. During the 10-year follow-up period, 2163 subjects (men 1475, women 688) had new onset of CKD. Multivariable Cox proportional hazards model analyses showed that MAFLD [hazard ratio 1.12 (95% confidence interval 1.02-1.26); P=.027] but not FL or NAFLD was an independent risk factor for new onset of CKD after adjustment of age, sex, eGFR, current smoking habit, ischemic heart disease, diabetes mellitus, overweight/obesity, hypertension and dyslipidemia. The addition of MAFLD [continuous net reclassification improvement (NRI) 0.154, integrated discrimination improvement (IDI) 0.0024] to traditional risk factors without metabolic abnormalities significantly improved the discriminatory capacity better than did the addition of FL (NRI 0.138, IDI 0.0018) or NAFLD (NRI 0.132, IDI 0.0017). MAFLD is modestly and independently associated with new onset of CKD and predicts the risk for development of CKD better than FL or NAFLD.

A Single Baseline Amyloid Positron Emission Tomography Could Be Sufficient for Predicting Alzheimer's Disease Conversion in Mild Cognitive Impairment.

ObjectiveBaseline amyloid burden in mild cognitive impairment (MCI) has been linked to conversion to Alzheimer’s disease (AD), but the comparison of baseline and longitudinal changes in amyloid burden for predicting AD remains unresolved. The objectives of this study aimed to compare the prognostic ability of baseline and longitudinal changes in amyloid burden in MCI patients. MethodsSeventy-five individuals with MCI were recruited and examined annually by clinical interviews for a mean follow-up of 24 months (range, 11.6–42.0). [18F]Florbetaben positron emission tomography (PET) scans were performed. T1-weighted 3D volumes were acquired for co-registration, and to define regions of interest. We examined whether baseline and longitudinal amyloid burden changes can improve AD conversion by Cox proportional hazard model analysis and receiver operating characteristic (ROC) curve analysis. ResultsCox proportional hazards model analysis showed that baseline amyloid burden was significantly associated with increased risk of conversion to AD (hazard ratio [HR]=10.0; 95% confidence interval [CI], 1.15–85.39; p=0.04), but longitudinal amyloid burden changes was not (HR=0.2; 95% CI, 0.02–1.18; p=0.07). When predicting AD, longitudinal amyloid burden changes had better ROC accuracy of 65.2% (95% CI, 48.4–82.0) than baseline amyloid burden of 59.6% (95% CI, 40.3–79.0), without statistical significance in pairwise comparison. ConclusionA single baseline amyloid PET could be sufficient in the prediction of AD conversion in MCI.

Influence of inpatient rehabilitation after crisis in patients with myasthenia gravis: A retrospective cohort study using a nationwide administrative database in Japan

BackgroundGrowing evidence indicates that carefully programmed rehabilitation can improve symptoms in patients with myasthenia gravis (MG). However, evidence on rehabilitation to aid in recovery from a myasthenic crisis is lacking. This study aimed to examine the association between inpatient rehabilitation and recovery in the activities of daily living (ADL) after a myasthenic crisis. MethodsWe retrospectively identified patients hospitalized due to myasthenic crisis in a nationwide administrative database in Japan. Patients were divided into two groups based on the intensity of rehabilitation after weaning from mechanical ventilation. We evaluated the influence of rehabilitation on recovery in the ADL by comparing the two groups in Kaplan–Meier and Cox proportional hazard model analyses. ResultsWe extracted the data of 437 cases treated from April 1, 2016 to March 31, 2020. High-intensity rehabilitation was associated with delayed recovery in the ADL on Kaplan–Meier analysis (p = 0.024, log-rank test). A similar result was obtained after adjusting for covariates in the Cox proportional hazard model analysis (hazard ratio: 0.69; 95% confidence interval: 0.48–0.99; p = 0.043). ConclusionsHigh-intensity rehabilitation performed in current inpatient settings may not contribute to recovery in the ADL after a myasthenic crisis in patients with MG. Despite this study's large sample size, further research is necessary to reach firm conclusions.

Effects of age and gender on body composition indices as predictors of mortality in middle-aged and old people

To determine whether body composition indices interact with age and gender as a predictor of all-cause mortality, 1200 participants at least 40 years of age were recruited in 2009 and 2010. A multi-frequency bioelectrical impedance analysis device was used to measure each participant’s body composition indices, including the fat mass index (FMI), fat free mass index (FFMI), skeletal muscle mass index (SMMI), and visceral fat area index (VFAI). A baseline questionnaire was used to collect demographic information about lifestyle habits, socioeconomic status, and medical conditions. All claimed records of death from 2009 to 2018 in the National Health Insurance Research Databank were identified. The all-cause mortality rate was 8.67% after a mean follow-up period of 5.86 ± 2.39 person-years. The Cox proportional hazard model analysis showed significantly negative associations between FFMI or SMMI with all-cause mortality in the total group and those aged geq 65 y/o. The FFMI and SMMI were negative predictors of mortality in both genders. The FMI and VFAI were positive predictors of mortality exclusively in females. In conclusion, the SMMI is a better predictor of mortality than the BMI, FMI, and FFMI, especially in older adults. A higher fat mass or visceral fat distribution may predict higher mortality in females.

Early vs Delayed Surgery for Esophageal Cancer During the COVID-19 Pandemic.

During the coronavirus disease 2019 pandemic, national guidelines recommended that elective surgery for esophageal cancer be deferred by 3 months when hospital resources are limited. The impact of this delay on patient outcomes is unknown. We sought to evaluate the survival of patients with stage I and II/III esophageal cancer who undergo early vs delayed treatment. Using the National Cancer Database from 2010 to 2017, multivariable Cox proportional hazards modeling and propensity score-matched analysis were employed to compare survival of patients with stage I esophageal cancer who received early (0 to 4 weeks after diagnosis) vs delayed esophagectomy (12 to 16 weeks) and of patients with stage II/III esophageal cancer who-after receiving timely chemoradiation (0 to 4 weeks after diagnosis)-underwent early (9 to 17 weeks) vs delayed esophagectomy (21 to 29 weeks). For stage I esophageal cancer, 226 (41.7%) patients underwent early esophagectomy, and 316 (58.3%) patients underwent delayed esophagectomy. Propensity score matching created 2 groups of 134 patients with early or delayed esophagectomy, whose 5-year survival was comparable (hazard ratio [HR] 65.0% [95% confidence interval (CI) 55.2% to 73.2%] vs HR 65.1% [95% CI 55.6% to 73.1%], p = 0.50). For stage II/III esophageal cancer, 1,236 (86.1%) patients underwent early esophagectomy, and 200 (13.9%) underwent delayed esophagectomy. Propensity score matching created 2 groups of 130 patients; the early esophagectomy group had improved 5-year survival compared with the delayed esophagectomy group (HR 41.6% [95% CI 32.1% to 50.8%] vs HR 22.9% [95% CI 14.9% to 31.8%], p = 0.006). Early esophagectomy was associated with similar survival compared with delayed esophagectomy for patients with stage I esophageal cancer. For patients with stage II/III esophageal cancer, early esophagectomy was associated with improved survival relative to delayed esophagectomy.

MR elastography as a biomarker for prediction of early and late recurrence in HBV-related hepatocellular carcinoma patients before hepatectomy

PurposeTo investigate the diagnostic performance of preoperative MR elastography (MRE) in predicting early recurrence (ER) and late recurrence (LR) of HCC after hepatectomy. MethodIn total, 180 patients (median age, 52 years; interquartile range, 41–50 years; 161 men) who underwent conventional MRI and MRE before hepatectomy between December 2014 and April 2020 were retrospectively recruited. A preoperative clinic-radiologic model and a combined postoperative clinic-pathologic and radiologic model were built using quantitatively MRE-derived stiffnesses, and image features to predict tumor ER and LR after hepatectomy. The Cox proportional hazards model and ROC analyses were used to identify the value of parameters to predict ER and LR. ResultsSeventy-three (40.5%) and 16 (8.9%) developed ER and LR after hepatectomy, respectively. For prediction of ER, the preoperative model integrated higher tumor stiffness (TS) (hazard ratio [HR],1.142; p < 0.001) with AFP ≥ 400 ng/mL (HR,1.761; p = 0.022), multifocal tumors (HR,3.229; p < 0.001) and lower ADC (HR,0.998; p = 0.017) variables; and the postoperative model incorporated higher TS, microvascular invasion, multifocal tumors, Child-Pugh class and ADC predictors. The two models provided comparable predictive performance (pre- 0.812 vs. post- 0.834, p = 0.283). Moreover, TS alone had a high sensitivity (90.4%) for predicting ER. Liver stiffness (LS) (HR, 1.757; p < 0.001) was the only independent predictor for LR in multivariate analysis in both the pre- and postoperative models with high specificity (90.0%), and its AUC with an optimal cut-off of 3.62 kPa was 0.860. ConclusionsQuantitative MRE-based stiffness is a useful biomarker for preoperative prediction of ER and LR of HCC.

Role of serum surfactant protein-D as a prognostic predictor in fibrotic hypersensitivity pneumonitis.

Serum Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) are candidate diagnostic and activity markers for fibrotic hypersensitivity pneumonitis (HP), although their correlation with prognosis remains unclear. We aimed to evaluate the prognostic usefulness of serum KL-6 and SP-D in patients with fibrotic HP. This was a retrospective medical record review of 185 patients with fibrotic HP at a single center from 2005 to 2019. The baseline and minimum serum KL-6 and SP-D levels over two years were recorded. The contribution of KL-6 and SP-D levels to the incidence of progressive fibrosing interstitial lung disease (PF-ILD) and mortality were evaluated using multivariate analysis. The respective baseline and minimum levels were 1441 and 808 U/ml for KL-6 and 254 and 132ng/mL for SP-D. A high minimum SP-D level was significantly associated with a high incidence of PF-ILD by logistic regression, independent of baseline forced vital capacity and honeycombing. Similarly, a high minimum SP-D level was significantly associated with high mortality by Cox proportional hazard model analysis. The stratified minimum SP-D levels of <100, 100-200, and >200 revealed significantly distinct groups in the entire cohort, with PF-ILD incidence rates of 28%, 48%, and 74% and median survival times of 120, 74, and 45 months, respectively. High minimum SP-D levels over two years were correlated with an unfavorable prognosis in our cohort. Patient with consistently high SP-D levels during the clinical course may have a poor prognosis and be a candidate for early treatment intensification.

Hyperuricemia is associated with all-cause mortality among males and females: Findings from a study on Japanese community-dwelling individuals

BackgroundSerum uric acid (SUA) is a key determinant of cardiovascular diseases (CVDs). Studies have also shown that SUA independently impacts age-related health outcomes, although their findings differ between males and females. Furthermore, predictive data on all-cause mortality remain limited, particularly for the Japanese population. Thus, this study examined the association between SUA and survival prognosis among males and females based on a follow-up period of 7 or 19 years. MethodsThe study was based on 1,573 male (63 ± 14 years) and 1,980 female (65 ± 12 years) participants who participated in a Nomura Cohort Study in 2002 (Cohort 1) and 2014 (Cohort 2), and continued throughout the follow-up period. A basic resident register was referenced to derive the adjusted relative risk estimates for all-cause mortality. Finally, a Cox proportional hazards model analysis was conducted and was adjusted for possible confounders to estimate hazard ratios (HRs). 95% confidence intervals (CIs) were computed separately for male and female participants. ResultsOf the total 3,553 participants, 905 (25.5%) were deceased. Of these, 473 were male (30.1% of all males) and 432 were female (21.8% of all females). Hyperuricemia was defined in males with SUA levels of 8.5 mg/dL or higher, and in females with SUA levels of 7.5 mg/dL or higher, and was associated with a significantly increased HR for all-cause mortality (males: 1.67; 95% CI: 1.06–2.63; females: 2.17; 95% CI: 1.20–3.94). The data were further stratified based on age (< 65 years or ≥ 65 years), body mass index (BMI) (< 25.0 kg/m2 or ≥ 25.0 kg/m2), History of cardiovascular disease, estimated glomerular filtration rate (< 60 mL/min/1.73 m2 or ≥ 60 mL/min/1.73 m2), and presence of SUA-lowering medication. All stratified groups demonstrated a similar trend. The hyperuricemia group in particular reported a significant increase in HR. On the other hand, a U-shaped increase in HR was observed in those with BMI greater than 25 kg/m2 and SUA-lowering medication, but interaction effect was not significant. ConclusionsHyperuricemia is a key risk indicator for all-cause mortality in male and female community-dwelling individuals in Japan.

Circulating complement factor H levels are associated with disease severity and relapse in autoimmune hepatitis

Background & AimsThe complement system plays pivotal roles in innate immunity. Mannose-binding lectin-associated serine protease (MASP)-2 plays essential roles in the activation of the lectin complement pathway. Complement factor H acts as a critical negative regulator of the alternative complement pathway. The association of circulating MASP-2 and factor H with the clinical features of patients with autoimmune hepatitis (AIH) is unclear.MethodsA total of 63 patients with AIH were recruited for this study. The serum levels of MASP-2, factor H, and C3a were measured, and their associations with the clinical features of AIH were analyzed.ResultsThe circulating C3a levels were higher in patients with AIH than in the controls. The circulating MASP-2 and factor H levels were decreased depending on the severity of AIH. Multivariate logistic analysis showed that low circulating factor H levels were associated with features of severe AIH (odds ratio 0.36; 95% CI 0.15-0.84; p = 0.018). Multivariate Cox proportional hazards model analysis showed that low circulating factor H levels were associated with a high incidence of relapse (hazard ratio: 5.19; 95% CI 1.07–25.2; p = 0.041). Patients with low circulating factor H levels showed higher rates of relapse than the controls (log-rank, p = 0.006).ConclusionCirculating factor H levels were associated with severe disease and with the incidence of relapse, suggesting a role for the complement system in the pathophysiology of AIH.Lay summaryAutoimmune hepatitis is an immune-mediated liver disease. Despite effective treatments, patients often relapse, which can lead to clinical deterioration and adverse outcomes. Herein, we studied the importance of the complement system (a form of innate immunity) in patients with autoimmune hepatitis. We found that the levels of a protein called factor H, which regulates the complement system, could be a potential biomarker of disease severity and relapse, and could even have therapeutic potential for patients with AIH.