Cox Proportional Hazards Analysis Research Articles

The therapeutic effect of radiotherapy combined with systemic therapy compared to radiotherapy alone in patients with simple brain metastasis after first-line treatment of limited-stage small cell lung cancer: a retrospective study

PurposeWe aimed to compare the therapeutic effect of radiotherapy (RT) plus systemic therapy (ST) with RT alone in patients with simple brain metastasis (BM) after first-line treatment of limited-stage small cell lung cancer (LS-SCLC).MethodsThe patients were treated at a single center from January 2011 to January 2022. BM only without metastases to other organs was defined as simple BM. The eligible patients were divided into RT alone (monotherapy arm) and RT plus ST (combined therapy arm). Univariate and multivariate Cox proportional hazards analyses were used to examine factors associated with increased risk of extracranial progression. After 1:1 propensity score matching analysis, two groups were compared for extracranial progression-free survival (ePFS), PFS, overall survival (OS), and intracranial PFS (iPFS).Results133 patients were identified and 100 were analyzed (monotherapy arm: n = 50, combined therapy arm: n = 50). The ePFS of the combined therapy was significantly longer than that of the monotherapy, with a median ePFS of 13.2 months (95% CI, 6.6–19.8) in combined therapy and 8.2 months (95% CI, 5.7–10.7) in monotherapy (P = 0.04). There were no statistically significant differences in PFS (P = 0.057), OS (P = 0.309), or iPFS (P = 0.448). Multifactorial analysis showed that combined therapy was independently associated with better ePFS compared with monotherapy (HR = 0.617, P = 0.034); more than 5 BMs were associated with worse ePFS compared with 1–5 BMs (HR = 1.808, P = 0.012).ConclusionsCompared with RT alone, combined therapy improves ePFS in patients with simple BM after first-line treatment of LS-SCLC. Combined therapy and 1–5 BMs reduce the risk of extracranial recurrence.

Rim Enhancement on Contrast-Enhanced CT as a Predictor of Prognosis in Patients with Pancreatic Ductal Adenocarcinoma.

This study investigated the utility of imaging features, such as rim enhancement on contrast-enhanced CT (CECT), in predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC). This retrospective study included 158 patients (84 men; mean age, 68 years) with pathologically confirmed PDAC. The following imaging features were evaluated on CECT by two radiologists: tumor size, tumor attenuation, and the presence of rim enhancement. Cox proportional hazards analysis was performed to identify the imaging and clinicopathological features for predicting disease-free survival (DFS) and overall survival (OS). Pathological features were compared with the presence of rim enhancement. Among the 158 patients, 106 (67%) underwent curative surgery (surgery group) and 52 (33%) received conservative treatment (non-surgery group). Rim enhancement was observed more frequently in the non-surgery group than in the surgery group (44% vs. 20%; p < 0.001). Rim enhancement showed significant associations with shorter DFS and OS in the surgery group (hazard ratios (HRs), 3.03 and 2.99; p < 0.001 and p = 0.003, respectively), whereas tumor size showed significant associations with shorter OS (HR per 1 mm increase, 1.08; p < 0.001). PDACs with rim enhancement showed significant associations with higher histological tumor grades (p < 0.001). PDAC with rim enhancement on CECT could predict poorer prognosis and more aggressive tumor grades.

Age is not a sole predictor of outcomes in octogenarians undergoing complex endovascular aortic repair

ObjectiveTo examine the perioperative, postoperative, and long-term outcomes of fenestrated/branched endovascular aneurysm repair (F/BEVAR) in octogenarians compared with nonoctogenarians. MethodsA multicenter, retrospective cohort study was conducted using the Vascular Quality Improvement database, which prospectively captures information on patients who undergo vascular surgery across 1021 academic and community hospitals in North America. All patients who underwent F/BEVAR endovascular aortic repair from 2012 to 2022 were included. Patients were stratified into two groups: those aged <80 years and those aged ≥80 years at the time of the procedure. The preoperative, intraoperative, and postoperative factors were compared between the two groups. The primary outcome was long-term all-cause mortality; secondary outcomes included aortic-specific mortality and aortic-specific reintervention. ResultsA total of 6007 patients (aged <80 years, n = 4860; aged ≥80 years, n = 1147) who had undergone F/BEVAR procedures were included. No significant difference was found in technical success, postoperative length of stay, length of intensive care unit stay, postoperative bowel ischemia, and spinal cord ischemia. After adjustment for baseline covariates, octogenarians were more likely to suffer from a postoperative complication (odds ratio [OR]: 1.16; [95% confidence interval (CI): 0.98-1.37], P < .001) and be discharged to a rehabilitation center (OR: 1.60; [95% CI: 1.27-2.00], P < .001) or nursing home (OR: 2.23; [95% CI: 1.64-3.01], P < .001). Five-year survival was lower in octogenarians (83% vs 71%, hazard ratio [HR]: 1.70; [95% CI: 1.46-2.0], P < .0001). Multivariate Cox proportional hazard analysis demonstrated that age was associated with increased all-cause mortality (HR: 1.72, [95% CI: 1.39-2.12], P < .001) and aortic-specific mortality (HR: 1.92, [95% CI: 1.04-3.68], P = .038). Crawford extent II aortic disease was associated with an increase in all-cause mortality (HR 1.49; [95% CI: 1.01-2.19], P < .001), aortic-specific mortality (HR: 5.05; [95% CI: 1.35-18.9], P = .016), and aortic-specific reintervention (HR: 1.91; [95% CI: 1.24-2.93], P = .003). Functional dependence was associated with increased all-cause mortality (HR: 2.90; [95% CI: 1.87-4.51], P < .001) and aortic-specific mortality (HR: 4.93; [95% CI: 1.69-14.4], P = .004). ConclusionsOur findings suggest that octogenarians do have a mildly increased mortality rate and rate of adverse events after F/BEVAR procedures. Despite this, when adjusted for other risk factors, age is on par with other medical comorbidities and therefore should not be a strict exclusion criterion for F/BEVAR procedures, rather considered in the global context of patient’s aortic anatomy, health, and functional status.

Predicting outcome in disorders of consciousness: Amega-analysis.

Assessing recovery potential in patients with disorders of consciousness (DoC) is pivotal for guiding clinical and ethical decisions. We conducted a mega-analysis of individual patient data to understand (1) if a time threshold exists, beyond which regaining consciousness is almost impossible, and (2) how recovery varies based on factors such as diagnosis, etiology, age, sex, and neuropsychological status. A systematic literature search revealed a total of 3290 patients. In this sample, we performed a Cox proportional hazards analysis for interval censored data. We observed a late saturation of probability to regain consciousness in Kaplan-Meier curves, and the annual rate of recovery was remarkably stable, in that approximately 35% of patients regained consciousness per year. Patients in minimally conscious state (MCS) recovered more frequently than patients in unresponsive wakefulness syndrome (UWS). No significant difference was observed between the recovery dynamics of MCS subgroups: MCS+ and MCS-. Patients with hypoxic brain lesions showed worse recovery rate than patients with traumatic brain injury and patients with vascular brain lesions, while the latter two categories did not differ from each other. Male patients had moderately better chance to regain consciousness. While younger UWS patients recovered more frequently than older patients, it was not the case in MCS. Our findings highlight the necessity for neurologists to exercise caution when making negative predictions in individual cases, challenge traditional beliefs regarding recovery timelines, and underscore the importance of conducting detailed and prolonged assessments to better understand recovery prospects in DoC.

The effect of statins on the risk of anti-tuberculosis drug-induced liver injury among patients with active tuberculosis: A cohort study

BackgroundTuberculosis (TB) remains prevalent worldwide, and anti-TB drugs are associated with drug-induced liver injury (DILI). Statins have pleiotropic effects which may decrease inflammation and achieve immunomodulation. However, few studies have investigated the pleiotropic effects of statins on the risk of DILI. The purpose of this study was to investigate whether statins prevent anti-tuberculosis DILI among active TB patients on standard anti-TB drug therapy. MethodsWe conducted a hospital-based retrospective cohort study using claims data from the Integrated Medical Database of National Taiwan University Hospital (NTUH-iMD). Patients with a positive TB culture were included. The use of statins was defined as a daily equivalent dose >0.5 mg of pitavastatin. Deterioration in liver function was evaluated according to elevated liver enzyme levels. The primary and secondary endpoints were the DILI and the severe DILI. The prognostic value of statins was evaluated by Kaplan–Meier analysis, and Cox proportional hazards models. ResultsA total of 1312 patients with a diagnosis of TB and receiving anti-TB treatment were included. During the study period, 193 patients had the DILI and 140 patients had the severe DILI. Kaplan–Meier analysis showed a significant difference between the usual statin users and controls in the DILI. In multivariable Cox proportional hazards analysis, statins showed a protective effect against the primary and secondary endpoints. In addition, the protective effect of statins showed a dose–response relationship against the DILI. ConclusionStatin treatment had a protective effect against the risk of anti-TB DILI with a positive dose–response relationship.

Abstract LB277: Exposure response and safety analysis of osimertinib in combination with pemetrexed and platinum-based chemotherapy for the first-line treatment of locally advanced or metastatic NSCLC patients with EGFRm (FLAURA2)

Abstract Osimertinib (Osi) is a potent, CNS-active irreversible inhibitor of epidermal growth factor receptor-mutate (EGFRm) and T790M mutations. It is currently approved as the standard of care in patients with locally advanced (Stage IIIB or IIIC) or metastatic (Stage IV) EGFR T790M mutation-positive NSCLC whose disease has progressed on or after EGFR-TKI therapy and as the first-line agent in patients with locally advanced or metastatic EGFRm NSCLC. FLAURA2 is a global, randomized, open-label, multi-center phase III clinical study to investigate the safety and efficacy of Osi 80 mg once daily in combination with platinum-pemetrexed chemotherapy compared to Osi monotherapy, as a first-line treatment in patients with locally advanced or metastatic EGFRm NSCLC. This study is ongoing and an sNDA has been submitted for approval. The objectives of this current analyses were to 1) assess the exposure-efficacy relationship between population PK model-derived Osi exposure metrics (AUCss, Cmaxss, Cminss), and PFS in patients from the investigational arm (Osi + chemotherapy arm, n=244) of FLAURA2 study and 2) assess the relationship between Osi exposure metrics and key safety endpoints. The exposure response (ER) relationship between Osi and progression free survival (PFS) in patients enrolled in the investigational arm of FLAURA2 was assessed. Kaplan Meier plots with patients stratified by quartile exposure of Osi in the investigational arm indicated no clear ER relationship, though there appears to be a trend of lower PFS with highest AUCss quartile. A stepwise Cox proportional hazard analysis indicated that the effect of Osi exposure metrics were not statistically significant associated with PFS; however, the number of pemetrexed cycles appeared to be a significant covariate on PFS. The relationship between Osi exposure metrics and AEs CTCAE Grade 3 and above causally related to Osi, as well as AESIs from the investigational arm of FLAURA2 study were explored. The graphical exploration and logistic regression analysis did not identify statistically significant relationship of Osi exposures on CTCAE ≥ Grade 3 adverse events (AEs) causally related to Osi, AEs leading to Osi dose interruptions/reductions/discontinuations, and AESIs including ≥ Grade 3 haematological AEs, cardiac effects, left ventricular ejection fraction decrease and ≥ Grade 1 interstitial lung disease causally related to Osi. In conclusions, no statistically significant relationships between exposure of Osi and response were observed, supporting the recommended dose of Osi of 80 mg daily in the FLAURA2 patient population. Overall, the recommended dose of Osi as monotherapy or in combination with chemotherapy is 80 mg once daily, with a dose reduction to 40 mg daily if unacceptable toxicity is observed. Citation Format: Jincheng Yang, Damilola Olabode, Aarti Sawant, Karthick Vishwanathan, Srinivas Bachina, Alexandar Todd, Dana Ghiorghiu, Yuri Rukazenkov, Alex Phipps, Diansong Zhou, Azar Shahraz. Exposure response and safety analysis of osimertinib in combination with pemetrexed and platinum-based chemotherapy for the first-line treatment of locally advanced or metastatic NSCLC patients with EGFRm (FLAURA2) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB277.

Bendopnea prevalence and prognostic value in older patients with heart failure: FRAGILE-HF-SONIC-HF post hoc analysis.

This study aimed to investigate the prevalence, clinical characteristics, and prognostic value of bendopnea in older patients hospitalized for heart failure. This post hoc analysis was performed using two prospective, multicentre, observational studies: the FRAGILE-HF (main cohort) and SONIC-HF (validation cohort) cohorts. Patients were categorized based on the presence of bendopnea, which was evaluated before discharge. The primary endpoint was 2-year all-cause mortality after discharge. Among the 1243 patients (median age, 81 years; 57.2% male) in the FRAGILE-HF cohort and 225 (median age, 79 years; 58.2% men) in the SONIC-HF cohort, bendopnea was observed in 31 (2.5%) and 10 (4.4%) patients, respectively. Over a 2-year follow-up period, all-cause death occurred in 20.8 and 21.9% of the patients in the FRAGILE-HF and SONIC-HF cohorts, respectively. Kaplan-Meier survival curves demonstrated significantly higher mortality rates in patients with bendopnea than in those without bendopnea in the FRAGILE-HF (log-rank P = 0.006) and SONIC-HF cohorts (log-rank P = 0.014). Cox proportional hazard analysis identified bendopnea as an independent prognostic factor for all-cause mortality in both the FRAGILE-HF [hazard ratio (HR) 2.11, 95% confidence interval (CI) 1.18-3.78, P = 0.012] and SONIC-HF cohorts (HR 4.20, 95% CI 1.63-10.79, P = 0.003), even after adjusting for conventional risk factors. Bendopnea was observed in a relatively small proportion of older patients hospitalized for heart failure before discharge. However, its presence was significantly associated with an increased risk of all-cause mortality.

Patterns of Statin Therapy Use and Associated Outcomes in Older Veterans Across Kidney Function

BackgroundDespite significant morbidity and mortality related to atherosclerotic cardiovascular disease, to date, most major clinical trials studying the effects of statin therapy have excluded older adults. The objective of this analysis was to evaluate the effect of initiating statin therapy on incident dementia and mortality among individuals 75 years of age or older across the complete spectrum of kidney function. MethodsWe conducted a retrospective cohort study of 640,191 VA health system patients who turned 75 years of age between 2000 and 2018. Patients on statin therapy received the medication for an average of 6.3 years (standard deviation 4.6 years). The primary outcome of interest included incident dementia diagnosis during the study period. The secondary outcome was all-cause mortality. Cox proportional hazard analysis was used to evaluate the adjusted association of statin initiation with these outcomes. ResultsThere was a higher rate of incident dementia in the No Statin group (4.7%) vs the Statin group (3.2%). Additionally, we observed a 22% all-cause mortality benefit associated with statin therapy. We did not observe a treatment effect with respect to primary or secondary outcomes across varying levels of kidney function. ConclusionThis large cohort study did not reveal an association between the initiation of statin therapy and incident dementia. A survival benefit was seen in statin users compared with nonusers. Prospective studies in more diverse populations including older adults will be needed to verify these findings.

Late Outcomes of Porcine and Pericardial Bioprostheses After Mitral Valve Replacement in 1162 Patients

BackgroundDebate continues regarding the superiority of porcine vs pericardial bioprostheses, and data relevant to this comparison are scant. This study compared late survival and structural valve deterioration of porcine and pericardial mitral valve prostheses. MethodsAdults undergoing mitral valve replacement with 1 first-generation porcine valve model and 1 pericardial valve line were reviewed from a prospectively maintained institutional database between 1976 and 2020. Multivariable regression and Cox proportional hazards analysis were used to compare late outcomes. ResultsOf 1162 consecutive patients, 612 (53%) received porcine valves and 550 (47%) received pericardial valves. At 10 years, patient survival (porcine, 36% ± 2%; pericardial, 38% ± 3%; P = .5) and cumulative incidence of mitral valve structural deterioration (porcine, 18% ± 2%; pericardial, 19% ± 3%; P = .3) were similar. The structural failure mode was more likely severe mitral stenosis in pericardial valves (35 of 50 [70%] vs 38 of 106 [36%]; P < .001), and it was more likely severe mitral regurgitation in porcine valves (80 of 106 [75%] vs 19 of 50 [38%]; P < .0001). After adjustment, structural deterioration was associated with younger patient age (P < .001) but not valve type. At 10 years, porcine valves demonstrated a higher cumulative incidence of mitral reoperation (19% ± 2% vs 9% ± 2%; P < .001) and reoperation for structural deterioration (15% ± 1% vs 6% ± 2%; P = .007). ConclusionsThis study demonstrated similar rates of 10-year survival and structural deterioration with porcine and pericardial bioprostheses in mitral valve replacement. The study suggests a lack of major improvement in durability of mitral bioprosthetic valves over time. The failure mode may have a greater influence on surgeon decision making regarding valve choice.

385 Genomic Alterations Associated With Postoperative Nodular Leptomeningeal Disease After Resection of Brain Metastases

INTRODUCTION: The relationship between brain metastasis resection and risk of nodular leptomeningeal disease (nLMD) is unclear. Prior studies have not explored genomic alterations associated with postoperative nLMD. METHODS: A retrospective, single-center study was conducted with patients who underwent resection of a BM with available clinical and genomic data available. Postoperative nLMD was the primary endpoint of interest. Targeted next-generation sequencing of over 500 oncogenes using a CLIA certified assay was performed in brain metastases. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with nLMD. RESULTS: One hundred and one patients composed the cohort with tumors originating from multiple cancer types. There were 15 cases of nLMD (14.9% of the cohort) with a median time from surgery to nLMD diagnosis of 8.2 months. Two supervised machine learning algorithms consistently identified CDKN2A/B co-deletion and ERBB2 amplification as the top predictors associated with postoperative nLMD across all cancer types. In a multivariate Cox proportional hazard analysis including clinical factors and genomic alterations observed in the cohort, tumor volume (HR 8.8, 95% CI 1.1-69, p = 0.04), CDKN2A/B co-deletion (HR 5.3, 95% CI 1.7-16.9, p = 0.004), and ERBB2 amplification (HR 3.9, 95% CI 1.1-14.4, p = 0.04) were associated with decreased time to postoperative nLMD. CONCLUSIONS: In addition to increased resected tumor volume, ERBB2 amplification and CDKN2A/B deletion were independently associated with an increased risk of postoperative nLMD across multiple cancer types. Additional work is needed to determine if targeted therapy decreases this risk in the postoperative setting.

Correlation of older age with better progression-free survival despite less aggressive resection in nonfunctioning pituitary adenomas.

Nonfunctioning pituitary adenomas (NFPAs) present at a wide range of ages; it is possible that variable outcomes are based on patient age at presentation. This study aimed to explore long-term outcomes of patients with NFPAs following endonasal transsphenoidal surgery (ETS), considering age stratification. This retrospective study included 228 patients with NFPAs who underwent ETS, with a median follow-up period of 63 months. The outcomes included progression-free survival (PFS) rates and neurological and endocrinological outcomes. Age-stratified Kaplan-Meier and Cox proportional hazards analyses were performed. Patients were classified into four age groups: ≤ 49, 50-59, 60-69, and ≥ 70 years. Age-stratified analysis showed a significant correlation between age and PFS in NFPAs (5-year PFS rates: 63.0% in those ≤ 49 years, 76.7% in those 50-59 years, 85.0% in those 60-69 years, and 88.1% in those ≥ 70 years; p = 0.001, log-rank test). Bivariate (HR 1.03, 95% CI 1.01-1.05; p = 0.001) and multivariable (HR 1.03, 95% CI 1.02-1.05; p = 0.001) analyses demonstrated that older age was significantly associated with longer PFS. Multivariable analysis also demonstrated that smaller maximum tumor diameter (HR 0.77, 95% CI 0.60-0.99; p = 0.036) and gross-total resection (HR 8.55, 95% CI 3.90-18.75; p = 0.001) were significantly associated with longer PFS. Multivariable logistic regression analysis demonstrated that only younger age was associated with postoperative improvement of male hypogonadism (HR 0.91, 95% CI 0.84-0.99; p = 0.019). Other postoperative neurological and endocrinological outcomes were not significantly associated with age. Older patients with NFPAs treated with ETS demonstrated a longer PFS. Of endocrinological outcomes studied, only male hypogonadism improvement was associated with younger patient age.

Impact of lymph node dissection on cancer-specific survival in non-small cell lung cancer patients: a SEER database analysis.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide, and lymph node dissection (LND) is a significant surgical procedure employed in its management. Although some studies suggest benefits of LND, the extent of its impact on survival, the optimal range of lymph nodes to be examined, and the specific patient groups that benefit most remain areas of active debate and investigation. A population-based analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER) database. Patients diagnosed with NSCLC between 2004 and 2017, undergoing primary tumor resection, were included. Descriptive, univariate, and multivariate analyses assessed the effect of LND on survival, and a restricted cubic spline method determined the optimal range for lymph node examination. This study of 37,323 NSCLC patients delved into the impact of LND on lung cancer-specific survival. Key findings revealed a median survival of 19.58 months, with 85% mortality. Baseline characteristics included a majority of White patients (81%), distant stage diagnoses (63%), and 64% with Grade IV tumors. LND emerged as a crucial predictor, influencing survival across age, gender, race, and tumor characteristics. Univariate analysis highlighted its significance, with higher T, N, and M categories, advanced stage, and poorer grade associating with elevated hazard ratios. Multivariate Cox proportional hazards (PH) analysis reinforced LND's impact, showcasing lower hazard ratios post-removal. Hazard ratios for biopsy/aspiration and removal of regional lymph nodes were 0.85 [95% confidence interval (CI): 0.81-0.89; P<0.001] and 0.43 (95% CI: 0.39-0.46; P<0.001), underscoring the protective effect. Visualizations and a U-shaped curve analysis identified an optimal range (24-32 nodes) for examination, emphasizing the nuanced benefits across NSCLC stages. The study findings suggest that LND plays a critical role in improving cancer-specific survival in NSCLC patients, particularly when tailored to the early stages of the disease. The optimal range of lymph nodes examined, between 24 and 32, offers crucial insights for personalized NSCLC treatment strategies and may enhance overall survival. These results underscore the need for refined surgical guidelines that incorporate the extent of LND, supporting the utility of a more personalized approach in NSCLC management.

Clinical Outcomes after Surgical Aortic Valve Replacement in 681 Octogenarians: A Single-Center Real-World Experience Comparing the Old Patients with the Very Old Patients

Aortic valve disease is a lethal condition, once it becomes symptomatic. Surgical aortic valve replacement (SAVR) has, for a long time, been the only treatment option. In patients aged 85 and older, the consequences of SAVR have rarely been investigated. A total of 681 octogenarian patients were subdivided into a group with patients between 80 and 84 years (n = 527) and a group with patients aged 85 or older (n = 154). For each group, the temporal referral pattern, preoperative comorbid profile, operative data, postoperative need for resources, and adverse postoperative events including 30-day mortality and long-term survival were determined using the chi-squared test, Student’s t-test, and log-rank test. For both age groups, the predictors for mortality were identified using a logistic regression analysis. In the oldest patient group, there were significantly more prior episodes of heart failure (75/154 vs. 148/527) and a greater need for urgent SAVR (45/150 vs. 109/515). The operative data and the need for postoperative resources were comparable, but the 30-day mortality was almost twice as high (24/154 vs. 45/527). The need for urgent SAVR was twice as high in the oldest group (odds ratio of 3.12 vs. 6.64). A logistic regression analysis for all 681 patients showed that age over 85 ranked fourth of six predictors for 30-day mortality. Five-year survival was favorable for both groups (67.8 ± 2.1% vs. 60.0 ± 4.3%). A Cox proportional hazard analysis failed to identify an age over 85 as a predictor for long-term mortality. Aortic valve disease and its effect on the left ventricle seemed to be more advanced in the highest age group. The mortality rate was almost double the need for urgent SAVR. This can be avoided by obtaining an earlier referral.

The influence of prior percutaneous rhizotomy on outcomes following microvascular decompression for trigeminal neuralgia.

Microvascular decompression (MVD) is an effective intervention in patients with trigeminal neuralgia (TN). How prior rhizotomy can impact long-term pain outcomes following MVD is not well understood. In this study, the authors sought to compare pain outcomes in patients who had undergone primary MVD versus those who had undergone secondary MVD after a single or multiple rhizotomies. The authors retrospectively reviewed the data on all patients who had undergone MVD at their institution from 2007 to 2020. Patients were included in the study if they had undergone primary MVD or if their surgical history was notable for past rhizotomy. Barrow Neurological Institute (BNI) pain scores were assigned at preoperative and final follow-up appointments. Perioperative complications were noted for each patient, and evidence of pain recurrence was recorded as well. A history of rhizotomy as well as other variables that might influence TN pain recurrence were evaluated using a Cox proportional hazards model. The impact of prior rhizotomy on TN pain recurrence following MVD was further assessed using Kaplan-Meier survival analysis. Of 1044 patients reviewed, 947 met the study inclusion criteria. Of these, 796 patients had undergone primary MVD, 84 had a history of a single rhizotomy before MVD, and 67 had a history of ≥ 2 rhizotomies prior to MVD. Patients in the single rhizotomy and multiple rhizotomies cohorts exhibited a greater frequency of preoperative numbness (p < 0.001), higher preoperative BNI pain scores (p < 0.005), and higher rates of postoperative numbness (p = 0.04). However, final follow-up BNI pain scores were not significantly different between the primary MVD and prior rhizotomy groups (p = 0.34). Cox proportional hazards analysis revealed that younger age, multiple sclerosis, and female sex independently predicted an increased risk of pain recurrence following MVD. Neither a history of a single prior rhizotomy nor a history of multiple prior rhizotomies independently increased the risk of pain recurrence. Furthermore, Kaplan-Meier analysis of pain-free survival among the 3 groups revealed no relationship between a history of prior rhizotomy and pain recurrence following MVD (p = 0.57). Percutaneous rhizotomy does not complicate outcomes following subsequent MVD for TN pain. However, patients undergoing rhizotomy before MVD may have an increased risk of postoperative facial numbness compared to that in patients undergoing primary MVD.

A signature based on circadian rhythm-associated genes for the evaluation of prognosis and the tumour microenvironment in HNSCC

The morbidity and mortality rates of head and neck squamous cell carcinoma (HNSCC) remain high worldwide. Therefore, there is an urgent need to identify a new prognostic biomarker to guide the personalized treatment of HNSCC patients. Increasing evidence suggests that circadian rhythm genes play an important role in the development and progression of cancer. We aimed to explore the value of circadian rhythm genes in predicting prognosis and guiding the treatment of HNSCC. We first obtained a list of circadian rhythm genes from previous research. The sequencing data were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Finally, univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox proportional hazard analysis were performed to develop a prognostic signature (Circadian Rhythm-Related Gene Prognostic Index, CRRGPI) consisting of nine circadian rhythm genes. The signature exhibited good performance in predicting overall survival. Patients with low CRRGPI scores had lower metabolic activities and an active antitumour immunity ability. Additionally, a clinical cohort was used to further evaluate the ability of the CRRGPI to predict the efficacy of immune checkpoint inhibitors. In conclusion, the novel circadian rhythm-related gene signature can provide a precise prognostic evaluation with the potential capacity to guide individualized treatment regimens for HNSCC patients.

Tuberculosis and Nontuberculous Mycobacterial Infections in Patients with Spondyloarthritis: A Population-Based Study.

Background and Objectives: Tuberculosis is caused by Mycobacterium tuberculosis (MTB), while nontuberculous mycobacteria (NTM) encompass a group of mycobacterial species that are distinct from the MTB complex and leprae. Spondyloarthritis (SpA) is a group of chronic inflammatory diseases with shared clinical characteristics and is treated with biological agents; however, their use may elevate the risk of MTB and NTM infections. This study aimed to compare the incidence and risk of MTB and NTM infections in patients with SpA, including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), using a population-based approach. Materials and Methods: This study included 2333 patients with SpA and 9332 age- and sex-matched controls from the Korea National Health Insurance Service-National Sample Cohort database from 2002 to 2019. The patients were identified using the International Classification of Diseases-10 codes for AS, PsA, MTB, and NTM. Results: The results showed that a negligible percentage of patients with SpA developed NTM (0.002%) and MTB (0.016%), with no significant difference in the incidence rate ratio (IRR) compared to controls. Among patients with SpA treated with biologics, the IRRs for NTM and MTB were 5.66 and 3.069, respectively; however, these were not statistically significant. No cases of NTM or MTB infection were reported in female patients with SpA treated with biologics. In both the SpA patient group and the control group, the incidence of MTB was higher in individuals over 60 years old compared to those under 60 years old. Cox proportional hazard analysis revealed a significant adjusted hazard ratio of 1.479 for MTB in patients with SpA after adjusting for age, sex, smoking history, insurance level, and comorbidities. However, this significance was not maintained when biological therapy was further adjusted. Conclusions: Our study indicated that the risks of NTM and MTB infection are not elevated in patients with SpA. Although biological use may potentially increase the risk of MTB infection, it does not lead to a significant increase in incidence rates. Proactive screening for latent tuberculosis and adequate prophylaxis using biologics can effectively manage the risk of NTM and MTB infections.

Prognostic significance of systemic immune-inflammation index in patients with nonfunction pancreatic neuroendocrine tumor undergoing surgical resection.

The purpose of our study was to investigate the clinical significance and prognostic role of the systemic immune-inflammation index (SII) in patients who underwent surgical resection for nonfunctioning pancreatic neuroendocrine tumors (pNETs). We conducted a retrospective analysis of 364 patients with nonfunctioning pNETs. The association between the SII level and clinical parameters was investigated. The receiver operating characteristic (ROC) curve was used to calculate the optimal SII value. Cox proportional hazard analysis was performed to evaluate the prognostic factors. Our study included 364 patients with nonfunctioning pNETs who underwent surgery. The median age was 51.0 (43.0, 59.3), and 164 (45.1%) were male. The optimal threshold of SII determined by ROC analysis was 523.95. Higher SII levels were significantly associated with older age (p = 0.001), sex (p = 0.011), tumor size (p = 0.032), and tumor grade (p = 0.002). Recurrence was observed in 70 (19.2%) patients following a median follow-up of 98 months. Univariate analysis showed that higher SII (p < 0.0001), tumor size >4 cm (p = 0.015), and G2/G3 grade (p = 0.002) were significantly associated with disease-free survival (DFS). Multivariate analysis revealed that higher SII (HR: 7.35; 95% CI: 3.44, 15.70; p < 0.0001) and G2/G3 grade (HR: 3.11; 95% CI: 1.42, 6.82; p = 0.005) remained significantly associated with tumor recurrence. Furthermore, 46 (12.6%) patients died during the follow-up. Higher SII (HR: 8.43; 95% CI: 3.19, 22.72; p < 0.0001) and G2/G3 grade (HR: 3.16; 95% CI: 1.01, 9.86; p = 0.048) were independent predictors of overall survival (OS) by multivariate analysis. In conclusion, our study revealed that a higher SII level was associated with tumor-related features (larger tumor size and advanced grade) and subsequent shorter DFS and OS in patients with nonfunctioning pNETs. These results indicated that the SII could serve as an efficient prognostic biomarker for nonfunctioning pNETs.

Joint Association of Low Nadir Serum Sodium and Potassium with Worse Outcomes after Ischemic Stroke

Background. Potassium and sodium are inextricably linked to the maintenance of cell potential and electrolyte homeostasis. Few studies have examined their joint relationship with outcomes after stroke. The objective of this study is to ascertain whether combined low nadir serum sodium and potassium levels are correlated with an unfavorable outcome in ischemic stroke. Methods. Retrospective cohort study of 2,920 consecutive patients with first-ever ischemic stroke. Serum sodium and potassium levels were measured at 10 consecutive time points over 10 days poststroke. The Youden Index was performed to identify patients with low nadir sodium (&lt;140 mmol/L) and potassium (&lt;3.65 mmol/L) levels, defined as a NaK score of 2. Multivariable logistic regression and Cox proportional hazard analysis were used to evaluate the independent relationship of sodium and potassium levels with clinical outcomes at three months. Results. A total of 2,920 patients with ischemic stroke were analyzed (mean age 62.14±14.13 years; 60.19% male), of whom 740 (25.3%) with both low nadir sodium and potassium levels had a quintuple 3-month case fatality compared to other patients (10.6% vs. 2.1%). Multivariable analyses identified NaK=2 as an independent predictor of 3-month death (adjusted odds ratio (OR) 2.23; 95% confidence interval (CI) 1.17-4.53; p=0.019) and an unfavorable shift in the distribution of scores on the modified Rankin scale (adjusted OR 1.51, 95% CI 1.12-2.04; p=0.007). Conclusions. Low sodium and potassium levels are common after ischemic stroke and are independent predictors of subsequent death.

Validation and comparison of prognostic scoring systems in patients with head and neck squamous cell carcinoma treated with nivolumab.

Several scoring systems have been developed to predict prognosis in patients with refractory cancer. We aimed to validate eight scoring systems and determine the best method for predicting the prognosis of head and neck squamous cell carcinoma treated with nivolumab. This multicentre retrospective study involved 154 patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with nivolumab between 2017 and 2020. Oncological outcomes were assessed according to the scoring systems, including MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio and Hammersmith scores. Objective response, overall survival and progression-free survival were evaluated using logistic regression and Cox proportional hazards analyses. Receiver operating curve analysis was used to calculate the area under the curve and estimate the efficacy of each score. No significant associations were found between the responses and any score. Seven of the eight scoring systems were associated with disease control (odds ratio, 0.26-0.70). Amongst the eight scoring systems, MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio showed the highest area under the curve for predicting response and disease control. Seven scoring systems were prognostic factors for progression-free survival (hazard ratio, 1.22-1.95). All eight scoring systems were prognostic factors for overall survival (hazard ratio, 1.62-3.83). According to the time-dependent receiver operating characteristics analysis for overall survival, the Hammersmith scoring system had the best predictive ability at 3months, and the MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio scoring system had the highest area under the curve between 6 and 24months. MD Anderson Cancer Center + neutrophil-to-lymphocyte ratio and Hammersmith scoring systems were better predictors of prognosis in patients with head and neck squamous cell carcinoma treated with nivolumab.

Impact of atrial fibrillation phenotype and left atrial volume on outcome after pulmonary vein isolation.

Pulmonary vein isolation (PVI) is increasingly performed in patients with atrial fibrillation (AF). Both AF phenotype and left atrial (LA) volume have been shown to influence ablation outcome. The inter-relationship of the two is incompletely understood. We aimed to investigate the impact of AF phenotype vs. LA volume on outcome after PVI. In a retrospective analysis of a prospective registry of patients undergoing a first PVI, the association of AF phenotype and LA volume index (LAVI) was assessed as well as their impact on AF recurrence during follow-up. Overall, 476 patients were enrolled (median age 63 years, 29% females, 65.8% paroxysmal AF). Obesity, hypertension, chronic kidney disease, and heart failure were all significantly more frequent in persistent AF. After 1 year, single-procedure, freedom from arrhythmia recurrence was 61.5%. Patients with paroxysmal AF had better outcomes compared with patients with persistent AF (65.6 vs. 52.7%, P = 0.003), as had patients with no/mild vs. moderate/severe LA dilation (LAVI <42 mL/m2 67.1% vs. LAVI ≥42 mL/m2 53%, P < 0.001). The combination of both parameters refined prediction of 1-year recurrence (P < 0.001). After adjustment for additional clinical risk factors in multivariable Cox proportional hazard analysis, both AF phenotype and LAVI ≥42 mL/m2 contributed significantly towards the prediction of 1-year recurrence. Atrial fibrillation phenotype and LA volume are independent predictors of outcome after PVI. Persistent AF with no/mild LA dilation has a similar risk of recurrence as paroxysmal AF with a moderate/severe LA dilation and should be given similar priority for ablation.