Cox Proportional Hazards Model Analysis Research Articles

Tuberculosis notifications in regional Victoria, Australia: Implications for public health care in a low incidence setting.

Regionality is often a significant factor in tuberculosis (TB) management and outcomes worldwide. A wide range of context-specific factors may influence these differences and change over time. We compared TB treatment in regional and metropolitan areas, considering demographic and temporal trends affecting TB diagnosis and outcomes. Retrospective analyses of data for patients notified with TB in Victoria, Australia, were conducted. The study outcomes were treatment delays and treatment outcomes. Multivariable Cox proportional hazard model analyses were performed to investigate the effect of regionality in the management of TB. Six hundred and eleven (7%) TB patients were notified in regional and 8,163 (93%) in metropolitan areas between 1995 and 2019. Of the 611 cases in the regional cohort, 401 (66%) were overseas-born. Fifty-one percent of the overseas-born patients in regional Victoria developed TB disease within five years of arrival in Australia. Four cases of multidrug-resistant tuberculosis were reported in regional areas, compared to 97 cases in metropolitan areas. A total of 3,238 patients notified from 2012 to 2019 were included in the survival analysis. The time follow-up for patient delay started at symptom onset date, and the event was the presentation to the healthcare centre. For healthcare system delay, follow-up time began at the presentation to the healthcare centre, and the event was commenced on TB treatment. Cases with extrapulmonary TB in regional areas have a non-significantly longer healthcare system delay than patients in metropolitan (median 64 days versus 54 days, AHR = 0.8, 95% CI 0.6-1.0, P = 0.094). Tuberculosis in regional Victoria is common among the overseas-born population, and patients with extrapulmonary TB in regional areas experienced a non-significant minor delay in treatment commencement with no apparent detriment to treatment outcomes. Improving access to LTBI management in regional areas may reduce the burden of TB.

Persistent or Recurrent Disease in Thyroid Cancer Survivors Who Have Elevated Serum Antithyroglobulin Antibodies

ObjectiveDetection of residual differentiated thyroid cancer is important but difficult. A variety of imaging modalities and biochemical markers has been used with moderately good success. We hypothesized that elevated perioperative serum antithyroglobulin antibody (TgAb) levels would also be a predictive marker for persistent or recurrent thyroid cancer. MethodsWe performed a retrospective analysis of 277 differentiated thyroid cancer survivors divided into 2 groups: (1) those with low or normal serum TgAb (TgAb−) and (2) those with elevated serum TgAb (TgAb+). All patients were seen at one major academic medical center. Patients were followed for a median of 7.54 years. ResultsPatients in the TgAb+ group were more likely to have positive lymph nodes at initial surgery, to be assigned to a higher American Joint Committee on Cancer stage, and to have significantly higher incidence of persistent/recurrent disease. The higher incidence of persistent/recurrent cancer was significant under univariable and multivariable (including TgAb status, age, and sex) Cox proportional hazards model analysis. ConclusionWe conclude that individuals with elevated serum TgAb at the outset should be followed with a higher index of suspicion for persistent/recurrent thyroid cancer.

Prognostic value of C-reactive protein to albumin ratio for mortality in acute kidney injury

BackgroundInflammation plays an important role in the development of acute kidney injury (AKI). However, there are few studies exploring the prognostic influence of C-reactive protein to albumin ratio (CAR) among AKI patients. In this study, we investigated whether CAR could be a useful marker to predict the mortality of AKI.MethodsA total of 358 AKI patients were extracted from the Medical Information Mart for Intensive Care III (MIMIC III) database. C-reactive protein (CRP) and albumin were measured at ICU admission. The clinical outcome was 365-day mortality. Cox proportional hazards model and Kaplan-Meier survival analysis were conducted to evaluate the association between CAR and outcome.ResultsCompared with patients in the survival group, nonsurvivors had higher CAR levels. The area under the receiver operating characteristic (ROC) curve of CAR was higher than that of CRP and albumin for mortality (0.64 vs. 0.63, 0.59, respectively). The cut-off point of CAR for mortality was 7.23. In Cox proportional-hazard regression analysis, CAR (hazards ratio (HR) =2.04, 95% confidence interval (CI) =1.47-2.85, p < 0.001 for higher CAR) and Simplified Acute Physiology Score II (HR = 1.02, 95%CI = 1.00-1.03, p = 0.004) were independent predictors of 365-day mortality.ConclusionsOur study demonstrated that a higher level of CAR was associated with 365-day mortality in AKI patients.

Transfer of passive immunity and survival in Jersey heifer calves fed heat-treated pooled colostrum.

Acquisition of adequate transfer of passive immunity (ATPI) by calves depends on the absorption of sufficient mass of colostral immunoglobulin G (IgG). Several studies report conflicting evidence regarding the ability of feeding pooled colostrum to achieve ATPI. Pooling colostrum is practical and efficient for some dairies, and recommendations are required to prevent failure of transfer of passive immunity (FTPI) in calves following pooling. This study aimed to determine the effect of pooling colostrum on serum IgG concentrations, FTPI, and preweaning mortality in calves. A prospective study was performed on two conventional Jersey dairy farms where heat treatment of colostrum occurred in the same colostrum processing kitchen. Four to 10 cows contributed to colostrum pools. A sample of the colostrum pool fed to the calves and serum from calves at 24-72 h was collected for IgG concentration determination by single radial immunodiffusion assay. Multivariable and logistic regression analyses were performed to evaluate factors that predicated serum IgG concentrations and the probability of FTPI, respectively. A Cox proportional hazard model analysis was performed to determine risk factors for mortality over the preweaning period. A total of 164 calves fed 28 colostrum pools were enrolled. Birth weight, number of colostrum feedings and pool IgG concentrations were significant predictors of calf serum IgG concentrations at 24-72 h, whereas the number of colostrum feedings and age at bleeding to determine passive transfer status were not significant predictors of calf serum IgG concentrations at 24-72 h. The prevalence of FTPI was 4.9%. Birth weight, pool IgG concentrations, number of colostrum feedings, and age at bleeding to check for passive transfer status were not significant predictors of the probability of FTPI at 24-72 h. The incidence of mortality was 4.3%. Passive transfer status was not a predictor of mortality. Our study demonstrates the effect of pooling colostrum on serum IgG concentrations even in herds where colostrum with higher median colostrum IgG concentrations is fed to calves. The results emphasize the recommendations to assess pooled colostrum IgG concentrations before feeding calves.

Diagnostic and Prognostic Roles of C-Reactive Protein, Procalcitonin, and Presepsin in Acute Kidney Injury Patients Initiating Continuous Renal Replacement Therapy

For reducing the high mortality rate of severe acute kidney injury (AKI) patients initiating continuous renal replacement therapy (CRRT), diagnosing sepsis and predicting prognosis are essential. However, with reduced renal function, biomarkers for diagnosing sepsis and predicting prognosis are unclear. This study aimed to assess whether C-reactive protein (CRP), procalcitonin, and presepsin could be used to diagnose sepsis and predict mortality in patients with impaired renal function initiating CRRT. This was a single-center, retrospective study involving 127 patients who initiated CRRT. Patients were divided into sepsis and non-sepsis groups according to the SEPSIS-3 criteria. Of the 127 patients, 90 were in the sepsis group and 37 were in the non-sepsis group. Cox regression analysis was performed to determine the association between the biomarkers (CRP, procalcitonin, and presepsin) and survival. CRP and procalcitonin were superior to presepsin for diagnosing sepsis. Presepsin was closely related to the estimated glomerular filtration rate (eGFR) (r = -0.251, p = 0.004). These biomarkers were also evaluated as prognostic markers. Procalcitonin levels ≥3 ng/mL and CRP levels ≥31 mg/L were associated with higher all-cause mortality using Kaplan-Meier curve analysis. (log-rank test p = 0.017 and p = 0.014, respectively). In addition, procalcitonin levels ≥3 ng/mL and CRP levels ≥31 mg/L were associated with higher mortality in univariate Cox proportional hazards model analysis. In conclusion, a higher lactic acid, sequential organ failure assessment score, eGFR, and a lower albumin level have prognostic value to predict mortality in patients with sepsis initiating CRRT. Moreover, among these biomarkers, procalcitonin and CRP are significant factors for predicting the survival of AKI patients with sepsis-initiating CRRT.

Immunological Role of TP53 Somatic Mutation Classification in Human Cancers.

TP53 is a very common tumor suppressor gene and has implicated in various cancers. A systematic immunological analysis of TP53 somatic mutation classification in multiple cancers is still lacking. To assess the immunological value of TP53 somatic mutation classification in various cancers, we integrated a series of bioinformatics methods to analyze the role of TP53 gene across the public databases, such as UCSC Xena, Cancer Cell Line Encyclopedia (CCLE), Ensembl, and Genotype-Tissue Expression (GTEx). The results revealed that the TP53 expression level had significant difference in tumor tissues and normal tissues, and it had a high expression level in most malignant tumors. Moreover, the missense mutation is the most common type of TP53 mutation in most cancers. In addition, the Cox proportional hazards model analysis and Kaplan-Meier (KM) survival analysis demonstrated that the TP53 expression is a high-risk factor in brain lower-grade glioma (LGG), prostate adenocarcinoma (PRAD), and uterine carcinosarcoma (UCS), which is opposite in uterine corpus endometrial carcinoma (UCEC). Besides, compared to the TP53 nontruncating mutation classification samples, we found that TP53 truncating mutation samples had lower TP53 expression levels in certain types of cancer. Notably, TP53 was associated with the mismatch repair (MMR) gene in some cancers which contained truncating or nontruncating mutation. Based on the classification of truncating or nontruncating mutation, we also discovered that TP53 expression was positively or negatively correlated with the immune score, stromal score, and the levels of immune cell infiltration in different cancers. Our research reveals an overarching landscape of immunological value on TP53 status in various malignant tumors. According to our results, we demonstrate that TP53 also plays an immunological role in various cancers.

P780 Prognosis and optimal treatment for 5-aminosalicylic acid-intolerant patients with Ulcerative Colitis

Abstract Background 5-aminosalicylic acid (5-ASA) is widely used as a first-line treatment for ulcerative colitis (UC), but intolerance sometimes occurs. 5-ASA-intolerance was considered a risk factor for colectomy in UC patients, but no reports have examined which treatment is suitable to avoid colectomy in 5-ASA-intolerant UC patients. This is the first report describing a treatment strategy for 5-ASA-intolerant UC. The aims of this study were to determine the optimal therapeutic strategy in 5-ASA-intolerant UC patients. Methods This retrospective cohort study involved patients who were newly diagnosed as having UC after January 2010 and who received oral 5-ASA agents. Patients were considered 5-ASA-intolerant when they fulfilled two or more of the following conditions: (1) paradoxical aggravation of colitis on introducing oral 5-ASA agents or allergic reactions to the agents; (2) obvious improvement of abdominal symptoms after discontinuation of 5-ASA agents; (3) positive drug-induced lymphocyte stimulation test (DLST) for at least two formulations of 5-ASA; (4) adverse events following re-challenge with 5-ASA agents; and (5) severe adverse events owing to 5-ASA agents. Results Of 950 UC patients with a history of 5-ASA administration, 213 (22.4%) were considered 5-ASA-intolerant. Five-year colectomy-free survival was significantly lower in 5-ASA-intolerant patients compared with 5-ASA-tolerant patients (73% vs. 84%, respectively). From the multivariate Cox proportional hazards model analysis in the 5-ASA-intolerant patient cohort, thiopurine use was shown to contribute to avoidance of colectomy in 5-ASA-intolerant patients (hazard ratio = 0.25; 95% confidence interval, 0.13–0.47; P &amp;lt; 0.001); however, 5-ASA-intolerant patients were also likely to be thiopurine-intolerant compared with 5-ASA-tolerant patients (27% vs. 15%, respectively; P = 0.04). Calcineurin inhibitor use was associated with an increased risk of colectomy (hazard ratio = 4.80; 95% confidence interval, 2.24–10.3; P &amp;lt; 0.001), while treatment with systemic corticosteroids and biologics did not affect the colectomy rate (hazard ratio = 1.07; 95% confidence interval, 0.60–1.91; P = 0.81). Conclusion Treatment with thiopurines demonstrated the potential to improve the prognosis in 5-ASA-intolerant patients. However, it should be noted that thiopurine intolerance was more frequent in 5-ASA-intolerant patients. Compared to biologics, calcineurin inhibitors may not contribute to avoidance of colectomy, and biologics may be preferred for intractable patients with 5-ASA intolerance. This is the first report describing a treatment strategy for 5-ASA-intolerant UC, and we believe it will have many implications in clinical practice.

P696 Design and rationale for the multicentre, randomised, controlled VERDICT trial to determine the optimal treatment target in patients with ulcerative colitis

Abstract Background Symptoms, endoscopy, histology, and biomarkers are used to evaluate disease activity and response to therapy in ulcerative colitis (UC). Histologic disease activity may persist in ~25% of patients with normal-appearing endoscopic mucosa, and observational studies demonstrate an association between the achievement of histologic remission (vs endoscopic remission alone) and a lower risk of complications. These findings suggest that histologic remission may be a distinct treatment target. The aim of the VERDICT trial is to determine the optimal treatment target in UC to inform clinical practice and future drug development. Methods The primary objective of the multicentre, randomised, controlled VERDICT trial (Figure 1) is to determine whether a treatment target of corticosteroid (CS)-free symptomatic + endoscopic + histologic remission is superior to CS-free symptomatic remission alone in moderately to severely active UC (Mayo rectal bleeding subscore [RBS] ≥1; Mayo endoscopic score [MES] ≥2). Patients are randomised to 3 treatment targets (2:3:5 ratio): CS-free symptomatic remission (Mayo RBS = 0) (Group 1); CS-free endoscopic remission (MES ≤1) + symptomatic remission (Group 2); or CS-free histologic remission (Geboes score &amp;lt;2B.0) + endoscopic remission + symptomatic remission (Group 3). Therapy is administered according to a treatment algorithm that is dependent on each patient’s existing UC treatment regimen at study entry (Figures 2-4). Early introduction of vedolizumab and dose escalation to a maximum of 300 mg every 4 weeks until the assigned treatment target is reached are central to each algorithm. There are 3 opportunities, 16 weeks apart (weeks 16, 32, or 48), to achieve the treatment target. Urine, stool, mucosa, and serum samples are collected at these follow-up time points and at baseline for subsequent biomarker and prediction model development. Results The primary efficacy outcome is the time from treatment target achievement to a UC-related complication, defined as a UC-related hospitalisation, colectomy, need for rescue therapy, or treatment-related or other complication. This composite outcome will be compared among treatment target Groups 1 and 3 using the Cox proportional hazard model analysis. The trial was initiated in September 2020, and 660 patients are planned for enrolment. Of these, ~50% are currently enrolled at 55 sites across 10 North American and European countries. Prespecified interim analyses will be conducted when the first 50 patients in each group reach weeks 16, 32, and 48. Conclusion The VERDICT trial in active UC is designed to determine the optimal treatment target to inform clinical practice, drug trials, and future evidence-based recommendations.

OP21 COVID-19 morbidity/mortality and vaccination against SARS-CoV-2 in patients with Inflammatory Bowel Disease in Poland: Nationwide Data

Abstract Background According to the international recommendations, patients with inflammatory bowel disease (IBD) should be vaccinated against SARS-CoV-2 at the earliest opportunity to do so. The aim of this study was to assess the morbidity and mortality from COVID-19 in the adult IBD population in Poland with respect to their vaccination status. Methods We conducted a retrospective analysis of administrative health claims collected by the National Health Fund, the sole public payer in Poland. We identified adult IBD patients as of December 31th, 2021 who had at least two or more records with K50 or K51 code and two or more prescriptions for IBD drugs reimbursed or else intestinal surgery preceding the record. The vaccination status in 2021 was assessed using the database maintained by the Ministry of Health. We examined the vaccination process against SARS-CoV-2 among IBD patients along with morbidity and mortality from COVID-19. We conducted a Cox proportional hazard model analysis to determine the hazard ratio of SARS-CoV-2 infection, hospitalization and death in respect to the vaccination status during the autumn wave of the COVID-19 pandemic (October–December 2021). Results As of December 31th, 2021 there were 93 068 adult patients diagnosed with IBD. The vaccination rate in IBD patients was significantly higher than in the general population of Poland (72.1% vs 63.8%; p&amp;lt;0.001) and grew with age, reaching the top value among those aged 70-79 years (88.2%) [Figure 1]. 87 353 IBD patients were included into the Cox proportional hazard analysis of autumn pandemic wave, during which there were 4 042 registered COVID-19 cases in IBD population. The peak value of a weekly average of incidence rate of COVID-19 was lower for vaccinated IBD patients (7.4/10000) than for unvaccinated ones (13.0/10000). The risk of being infected was significantly lower for vaccinated IBD patients (HR 0.53; 95%CI 0.5-0.57; p&amp;lt;0.001). The cumulative risk of being positively tested for COVID-19 shows Figure 2. The most notable protective effect of vaccination against SARS-CoV-2 was found in patients aged 60-69 years (HR 0.47; 95%CI 0.39-0.55) and in those aged 80 years and above (HR 0.44; 95%CI 0.32-0.63). The risk of hospitalization due to COVID-19 was also significantly lower among the vaccinated IBD patients (HR 0.48; 95%CI 0.31-0.74, p&amp;lt;0.0001). The risk of death due to COVID-19 was more than 3 times decreased in vaccinated IBD patients in comparison to the remaining IBD population (HR 0.29, 95%CI 0.17-0.43, p&amp;lt;0.001) [Table 1]. Conclusion Adult patients with IBD were more likely to get vaccinated against SARS-COV-2 than adults in the general population of Poland. The vaccination significantly decreased the risk of the infection, hospitalization and death due to COVID-19.

Second-line drug resistance markers as proxy indicators of time to sputum culture conversion among second-line drug resistant tuberculosis patients tested in Uganda: A cross-sectional study

Background Increased tuberculosis disease burden arises as a result of low treatment success rates stemming from the emergence of second-line drug resistance. We aimed at determining the usefulness of second-line drug (SLD) resistance markers as proxy indicators of time to sputum culture conversion; a renowned predictor of Tuberculosis treatment outcome, among SLD-resistant tuberculosis (TB) patients tested at the Uganda National TB Reference Laboratory (NTRL). Methods A cross-sectional study was conducted on 72 bacteriologically confirmed SLD resistant TB patients with datasets including culture conversion time and second line probe assay mutation profiles between 01/06/2017 and 31/12/2019. The data were then imported into STATA v15 for descriptive statistical analysis, Univariate cox proportional hazard model analysis and Kaplan-Meier survival curves at a 5% level of significance; p-value ≤0.05. Results Results indicate the median time was achieved at 3 (0–12) months across the studied patients. The rrs G1484T mutation associated with conferring drug resistance to injectable agents was observed to have the shortest median conversion time of 1.5 months, longest by the gryB E540D at 5 months. A single mutation in the gryA gene locus showed higher converted proportions 70.8% (58.9–81.0) than those that had two 8.3% (3.1–17.3) or three 2.7% (0.3–10.0) mutations. Conclusions The studied second-line drug resistance markers had no statistically significant association with the time to sputum culture conversion, although increased drug resistance levels reduced the converted proportions and stressed the need to utilize molecular diagnostics data and other crucial variables to better comprehend proxy indicators of SLD resistant tuberculosis management.

Superior survival for breast-conserving therapy over mastectomy in patients with breast cancer: A population-based SEER database analysis across 30 years.

It has been believed that breast-conserving therapy (lumpectomy plus adjuvant radiation, Lum + RT) and mastectomy without radiation (Mast + NoRT) have equivalent survival outcomes. However, there is a need to re-evaluate the role of lumpectomy plus adjuvant radiation due to changed breast cancer management over time. This study aimed to conduct a population-based study that compare long-term oncologic survival outcomes after Lum + RT vs Mast + NoRT. The Surveillance, Epidemiology and End Results database was used to identify female breast cancer patients with a primary localized breast cancer diagnosis from 1988 to 2018. The standardized incidence/mortality ratio (SIR/SMR) for breast cancer recurrence (BCR) and breast cancer-specific death (BSD) was estimated by the SEER*Stat program. Cumulative incidences of BCR and BSD were assessed using Gray's method. We evaluated the effects of Lum + RT vs. Mast + NoRT on breast cancer recurrence-free survival (BRFS) and breast cancer-specific survival (BCSS). Fine-Gray competing risk model analyses, propensity score-adjusted Kaplan-Meier analyses and Cox proportional hazards model analyses were applied. A total of 205,788 women were included in the study. Patients who underwent Lum + RT had higher SIR of BCR (4.14 [95% confidence interval, CI: 3.94-4.34] vs. 1.11 [95% CI: 1.07-1.14]) and lower SMR (9.89 [95% CI: 9.71-10.08] vs. 17.07 [95% CI: 16.82-17.33]) than patients who underwent Mast + NoRT. Lum + RT was associated with higher competing risk of BCR (adjusted hazard ratio [HR]: 1.996, 95% CI: 1.925-2.069, p < 0.001) and lower competing risk of BSD when compared to Mast + RT (adjusted HR: 0.584, 95% CI: 0.572-0.597, p < 0.001). Multivariate Cox regression analysis revealed similar results (adjusted HR after PSW for BRFS: 1.792, 95% CI 1.716-1.871, p < 0.001; adjusted HR after PSW for BCSS: 0.706, 95% CI 0.688-0.725, p < 0.001). These findings persisted in the sensitivity and subgroup analyses. The present study further confirmed superior long-term survival with lumpectomy plus adjuvant radiation over mastectomy independent of patient characteristics including age, race, time period, historic subtype, tumor size, historic grade and stage, indicating that this benefit may result from the treatment itself.

PS-BPP03-4: METABOLIC DYSFUNCTION-ASSOCIATED FATTY LIVER DISEASE (MAFLD) PREDICTS NEW ONSET OF CHRONIC KIDNEY DISEASE BETTER THAN DOES FATTY LIVER OR NAFLD

Background: 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. Methods: We investigated the associations of FL, NAFLD and MAFLD with the development of CKD, defined as estimated glomerular filtration rate (eGFR) &lt; 60 mL/min/1.73m2 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/women: 8,581/4,578, mean age: 48 years) were recruited. Results: The prevalences of FL, NAFLD and MAFLD were 34.6% (men/women: 45.1%/15.1%), 32.8% (men/women: 42.7%/14.5%) and 32.3% (men/women: 42.4%/13.4%), respectively. During the 10-year follow-up period, 2,163 subjects (men/women: 1,475/688) had new onset of CKD. Multivariable Cox proportional hazard model analyses showed that MAFLD (hazard ratio [95% confidence interval]: 1.12 [1.02–1.26], p = 0.027), 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). Conclusions: MAFLD is independently associated with new onset of CKD and predicts the risk for development of CKD better than does FL or NAFLD.

Value of Intraplaque Neovascularization on Contrast-Enhanced Ultrasonography in Predicting Ischemic Stroke Recurrence in Patients With Carotid Atherosclerotic Plaque.

Patients with a history of ischemic stroke are at risk for a second ischemic stroke. This study aimed to investigate the relationship between carotid plaque enhancement on perfluorobutane microbubble contrast-enhanced ultrasonography (CEUS) and future recurrent stroke, and to determine whether plaque enhancement can contribute to risk assessment for recurrent stroke compared with the Essen Stroke Risk Score (ESRS). This prospective study screened 151 patients with recent ischemic stroke and carotid atherosclerotic plaques at our hospital between August 2020 and December 2020. A total of 149 eligible patients underwent carotid CEUS, and 130 patients who were followed up for 15-27 months or until stroke recurrence were analyzed. Plaque enhancement on CEUS was investigated as a possible risk factor for stroke recurrence and as a possible adjunct to ESRS. During follow-up, 25 patients (19.2%) experienced recurrent stroke. Patients with plaque enhancement on CEUS had an increased risk of stroke recurrence events (22/73, 30.1%) compared to those without plaque enhancement (3/57, 5.3%), with an adjusted hazard ratio (HR) of 38.264 (95% confidence interval [CI]:14.975-97.767; P < 0.001) according to a multivariable Cox proportional hazards model analysis, indicating that the presence of carotid plaque enhancement was a significant independent predictor of recurrent stroke. When plaque enhancement was added to the ESRS, the HR for stroke recurrence in the high-risk group compared to that in the low-risk group (2.188; 95% CI, 0.025-3.388) was greater than that of the ESRS alone (1.706; 95% CI, 0.810-9.014). A net of 32.0% of the recurrence group was reclassified upward appropriately by the addition of plaque enhancement to the ESRS. Carotid plaque enhancement was a significant and independent predictor of stroke recurrence in patients with ischemic stroke. Furthermore, the addition of plaque enhancement improved the risk stratification capability of the ESRS.

Impact of sex and comorbid diabetes on hospitalization outcomes in acute pancreatitis: A large United States population-based study.

Data on the association between comorbid diabetes mellitus (DM) and acute pancreatitis (AP) remains limited. Utilizing a large, nationwide database, we aimed to examine the impact of comorbid diabetes mellitus on patients admitted for acute pancreatitis. This was a retrospective case-control study of adult patients with AP utilizing the National Inpatient Sample from 2015-2018, using ICD-10 codes. Hospitalization outcomes of patients admitted for AP with comorbid DM were compared to those without comorbid DM at the time of admission. The primary outcome was a mortality difference between the cohorts. Multivariable-adjusted cox proportional hazards model analysis was performed. Data was analyzed as both sex aggregated, and sex segregated. 940,789 adult patients with AP were included, of which 256,330 (27.3%) had comorbid DM. Comorbid DM was associated with a 31% increased risk of inpatient mortality (aOR: 1.31; p = 0.004), a 53% increased risk of developing sepsis (aOR: 1.53; p = 0.002), increased hospital length of stay (LOS) (4.5 days vs. 3.7 days; p < 0.001), and hospital costs ($9934 vs. $8486; p < 0.001). Whites admitted for AP with comorbid DM were at a 49% increased risk of mortality as compared to Hispanics (aOR: 1.49; p < 0.0001). Different comorbidities had sex-specific risks; men admitted for AP with comorbid DM were at a 28% increased risk of mortality (aOR: 1.28; p < 0.0001) as compared to women. Men with comorbid DM plus obesity or hypertension were also at increased risk of mortality as compared to women, whereas women with comorbid DM plus renal failure were at greater risk of mortality as compared to men. Comorbid DM appears to be a risk factor for adverse hospitalization outcomes in patients admitted for AP with male sex and race as additional risk factors. Future prospective studies are warranted to confirm these findings to better risk stratify this patient population.

Systemic immune-inflammation index during treatment predicts prognosis and guides clinical treatment in patients with nasopharyngeal carcinoma

PurposeSystemic immune-inflammation index (SII) has been demonstrated to be closely associated with the poor prognosis of nasopharyngeal carcinoma (NPC). However, the role of SII during treatment of NPC has not been reported. This study aimed to determine the prognostic value of SII during treatment for NPC patients.MethodsA total of 759 patients diagnosed with NPC were included in this retrospective study (393 in training cohort and 366 in validation cohort). The correlation between variables was analyzed by the chi-squared test, the Fisher’s exact test or the likelihood test. Kaplan–Meier method and log-rank test were used to analyze progression-free survival (PFS) and overall survival (OS). The independent prognostic factors were determined by multivariate analysis of Cox proportional hazards regression model. The uncontrolled risk was analyzed by Logistic regression. Receiver operating characteristic (ROC) curves were used to assess prognostic value.ResultsThe optimal cut-off point for the SII during treatment was 937.32. High SII during treatment group had higher uncontrolled risk than low SII during treatment group (p = 0.008). In multivariate Cox proportional hazard models analysis, SII during treatment was an independent prognostic factor for 5-year PFS (p < 0.001) and 5-year OS (p < 0.001). All results were found in the training cohort and confirmed in the validation cohort.ConclusionsThe SII during treatment is a promising indicator of predicting the survival in NPC patients, especially the risk of uncontrolled occurrence. By monitoring the SII during treatment, it is possible to better evaluate the treatment effect and formulate personalized treatment.

The modification of individual factors on association between serum 25(OH)D and incident type 2 diabetes: Results from a prospective cohort study.

Several epidemiological studies have suggested an association between low vitamin D status and increased risk for type 2 diabetes (T2D). This study aimed to explore the dose-response relationship of serum 25-hydroxyvitamin D [25(OH)D] concentrations with incident T2D and the interaction between serum 25(OH)D with individual factors on T2D risk. A total of 1,926 adults without diabetes (mean age: 52.08 ± 13.82 years; 42% men) were prospectively followed for 36 months. Cox proportional hazards model and restricted cubic spline analysis were performed to assess the association and dose-response relationship between serum 25(OH)D and T2D incidence. Both additive and multiplicative interactions were calculated between serum 25(OH)D and individual factors. The net reclassification index (NRI) was used to evaluate the improvement of risk prediction of T2D by adding serum 25(OH)D to traditional risk factors. There were 114 new T2D cases over a mean follow-up of 36 months. Serum 25(OH)D was not associated with T2D incidence, and no significant dose-response relationship was found in the total population. However, stratified analyses suggested a non-linear inverse relationship among individuals with baseline fasting plasma glucose (FPG) <5.6 mmol/L (P overall = 0.061, P non-linear = 0.048). And a significant multiplicative interaction was observed between serum 25(OH)D and FPG on T2D risk (P = 0.005). In addition, we found a significant additive interaction of low serum 25(OH)D with older age (RERI = 0.897, 95% CI: 0.080-1.714; AP = 0.468, 95% CI: 0.054-0.881), male (AP = 0.441, 95% CI: 0.010-0.871), and insufficient physical activity (RERI = 0.875, 95% CI: 0.204-1.545; AP = 0.575, 95% CI: 0.039-1.111) on T2D risk. Significant additive interactions were also observed between vitamin D deficiency/insufficiency with male, overweight/obesity, and insufficient physical activity on T2D risk. Moreover, adding low serum 25(OH)D to a model containing established risk factors yielded significant improvements in the risk reclassification of T2D (NRI = 0.205, 95% CI: 0.019-0.391). Our results indicated a non-linear relationship of serum 25(OH)D concentrations with T2D risk among individuals with normal FPG and additive interactions of serum 25(OH)D with gender, overweight/obesity, and physical activity on T2D risk, suggesting the importance of outdoor exercise.

Should patients on levothyroxine therapy be screened for pancreatic cancer?

Pancreatic ductal adenocarcinoma is an aggressive disease with increasing incidence. Thyroid hormones play different roles in development and physiological processes of the entire digestive system, including pancreas. Therefore, many have hypothesized that thyroid hormone supplementation for hypothyroidism disorders might increase the risk of malignancy. We conducted retrospective observational mono-centre study. The aim was to examine the prevalence of thyroid disorders among patients with pancreatic cancer. Moreover, we investigated the impact of thyroid hormone supplementation in pancreatic cancer patients' outcome and the correlation with various clinicopathologic parameters. A total of 92 consecutive pancreatic cancer patients were retrospectively reviewed: 18.5% patients had a history of hypothyroidism and all received a replacement hormone therapy with levothyroxine, in particular 20% in metastatic group and 11% in radically resected PDAC patients' group. Nor in radically resected neither in metastatic group, we did not observe any statistically significant difference in outcome between the group with or without thyroid disorders. On multivariate analyses, cox proportional hazards model analysis showed that only the presence of perineural invasion was associated with a significantly higher hazard ratio for overall survival in metastatic PDAC patients (HR=2.7; 95%CI=1.029-6.925; p=0.009). We observed higher prevalence of thyroid disorders in PDAC patients. Further studies are warranted to explore the impact of levothyroxine therapy on outcome in PDAC patients.

Association between lack of sexual interest and all-cause mortality in a Japanese general population: The Yamagata prospective observational study.

Sexual interest is essential for maintaining positive sexual relationships and sexual function, which have recently been recognized as important indicators of good health and quality of life. Here, we prospectively investigated associations between sexual interest and mortality in a community-based population. This study enrolled 20,969 subjects (8,558 males and 12,411 females) aged ≥ 40 years who participated in annual health check-ups in Yamagata Prefecture. Sexual interest was assessed by a self-report questionnaire. Associations between sexual interest and increased all-cause mortality, cardiovascular disease mortality, and cancer mortality were investigated by Cox proportional hazards modeling. During follow-up (median: 7.1 years), 503 subjects died; 67 deaths were due to cardiovascular disease, and 162 were due to cancer. Kaplan-Meier analysis showed that all-cause mortality and cancer mortality were significantly elevated among men who lacked sexual interest (log-rank P<0.0001, P<0.05). Cox proportional hazards model analysis with adjustment for age, hypertension, diabetes, dyslipidemia, smoking, alcohol drinking status, BMI, education, marital status, frequency of laughter, and psychological distress showed that the risk of all-cause mortality was significantly higher among men who lacked sexual interest than men who had sexual interest (hazard ratio [HR] 1.69; 95% confidence interval [CI], 1.17-2.44). Lack of sexual interest is suggested to be a risk factor for all-cause mortality in Japanese males over 40 years old. This finding has implications for the importance of sexual interest in increasing longevity in this population.

Restratifying the prognosis of acute myeloid leukemia patients with CEBPA double mutations based on CSF3R mutations and measurable residual disease

Objective: This investigation aims to assess the impact of CSF3R mutations and the presence of measurable residual disease (MRD) on the prognosis of patients with CEBPA double mutations who have acute myeloid leukemia (AML) . Methods: The prognostic significance of these two factors was examined in the present study, which included 66 patients with complete genetic mutations and sequential MRD information. Results: Following the second course of chemotherapy, the MRD status and CSF3R mutations of these patients were linked to their long-term prognosis. CSF3R mutated patients showed inferior relapse-free survival (RFS) (5-year RFS: 15.2% vs 38.7% , P=0.006) and overall survival (OS) (5-year OS: 18.2% vs 60.6% , P=0.038) compared with those with wild-type CSF3R. After the second course of chemotherapy, patients with negative MRD had an RFS of 64 months and an OS of not reaching, which was significantly longer than that of patients with positive MRD (15 and 48 months, and the P value were 0.004 and 0.050, respectively) . CSF3R mutations (HR=0.317, 95% CI 0.129-0.779, P=0.012) , WT1 mutations (HR=0.304, 95% CI 0.115-0.804, P=0.016) , and NRAS mutations (HR=0.153, 95% CI 0.061-0.385, P<0.001) were all independently associated with a poor prognosis for RFS, and CSF3R mutations and positive MRD tended to be independently associated with a poor prognosis for OS, according to the results of a Cox proportional-hazards model analysis (P values were 0.071 and 0.088, respectively) . The patients were divided into three groups based on their CSF3R mutation status and MRD status following treatment: wide-type CSF3R and negative MRD, mutated CSF3R or positive MRD, and mutated CSF3R and positive MRD, which showed significantly different RFS (P<0.001) and OS (P=0.006) . Conclusion: Both CSF3R mutations and positive MRD were associated with poor outcome in AML patients with CEBPA double mutations. An integrity model based on these two factors may be beneficial for accurately evaluating the prognosis of these patients.

Pathological multifocality is not a prognosis factor of papillary thyroid carcinoma: a single-center, retrospective study

IntroductionNon-total thyroidectomy (non-TTx) is a widely accepted operative procedure for low-risk papillary thyroid carcinoma (PTC). PTC patients preoperatively diagnosed with unifocal disease are often revealed as having multifocal foci by microscopy. The present study determined whether or not patients with clinically unifocal, but pathologically multifocal non-high-risk PTC treated with non-TTx have an increased risk of a poor prognosis compared to those with pathologically unifocal PTC.Materials and methodsPTC patients diagnosed as unifocal preoperatively who underwent non-TTx were multifocal in 61 and unifocal in 266 patients microscopically. Oncologic event rates were compared between pathologically multifocal and unifocal PTC patients.ResultsPathological multifocality was associated with positive clinical lymph node metastasis (cN1) (odds ratio [OR] 4.01, 95% confidence interval [CI]: 1.91–8.04) and positive pathological lymph node metastasis (pN1) in > 5 nodes (OR 3.68, 95% CI: 1.60–8.49). No patients died from PTC. There was no significant difference in the disease-free survival rate, remnant thyroid disease-free survival rate, lymph node disease-free survival rate, or distant disease-free survival rate between the two groups. Recurrence in pathologically multifocal PTC patients was locoregional in all cases and able to be salvaged by reoperation. Cox proportional hazard model analyses showed no significant difference in recurrence rates with regard to pathological multifocality and cN or number of pNs.ConclusionThe prognosis of PTC with pathological multifocality treated by non-TTx was not inferior to that of unifocal PTC. Immediate completion thyroidectomy is not necessary when microscopic foci are proven.