Cox Proportional Hazard Ratios Research Articles

Enfortumab vedotin-related cutaneous toxicity correlates with overall survival in patients with urothelial cancer: a retrospective experience.

Enfortumab vedotin (EV) is an antibody drug conjugate approved for advanced urothelial cancer, consisting of a monomethyl auristatin E payload linked to a human monoclonal antibody targeting nectin-4. No validated biomarker predictive of or correlated with response exists for EV. Cutaneous toxicity is among the most common EV-related toxicities and typically emerges in early cycles. This retrospective experience of patients with urothelial cancer treated with EV monotherapy evaluated whether EV-related cutaneous toxicity correlated with improved outcomes including progression-free (PFS) and overall (OS) survival and overall response rate (ORR). Patients treated with EV monotherapy at Johns Hopkins were identified, and baseline characteristics, treatment, and toxicity details were extracted through chart review. Univariable Cox hazard ratios (HRs) were calculated for assessing the effect of baseline patient characteristics and cutaneous toxicity in PFS and OS. Based on the univariable analysis and known risk factors, all subsequent analyses were adjusted for: Eastern Cooperative Oncology Group performance status, visceral metastases at baseline, gender as well as EV dose, and weight to account for dosing differences. Multivariable Cox proportional HRs were used for comparing PFS and OS between patients with and without cutaneous toxicity, assessing toxicity and EV dose as a time-dependent variables. Adjusted p-values were calculated to compare ORR and disease control rate (DCR) between groups using the Poisson regression model. Of the 78 patients analyzed, 42 (53.8%) experienced EV-related cutaneous toxicity that appeared early during treatment (median time to occurrence 0.5 months from EV initiation). Cutaneous toxicity correlated with significantly improved OS [HR, 0.48; 95% confidence interval (CI), 0.25, 0.9; P = 0.0235], ORR (68.3% vs. 20.7%, P = 0.0033) and DCR (82.9% vs. 48.3%, P = 0.0122). Median PFS was numerically longer in the cutaneous toxicity group (6.3 vs. 1.7 months), although no significance was achieved in the multivariable analysis (HR, 0.62; 95% CI: 0.35, 0.108; P = 0.0925). In this retrospective study, EV-related cutaneous toxicity was associated with improved patient outcomes. Confirming this observation and understanding its mechanism could lead to discovery of a new clinical biomarker of EV response that can emerge in the first cycle.

Identification of patients with DCIS with low-risk clinicopathology who benefit from radiation therapy with and without endocrine therapy after breast-conserving surgery assessed with the 7-gene biosignature.

528 Background: Ductal carcinoma in situ (DCIS) accounts for 20% of breast cancers. For most patients with DCIS, the standard treatment involves breast-conserving surgery (BCS) followed by radiotherapy (RT). Adjuvant endocrine therapy (ET) is typically recommended for hormone receptor-positive disease. However, prospective trials have failed to identify a low-risk CP group not benefitting from RT with respect to ipsilateral breast recurrence (IBR), with no modern trials evaluating ET. We utilized the 7-gene predictive DCIS biosignature to assess the effects of RT and/or ET on 10yr IBR in women with low-risk CP DCIS. Methods: Women (n=926) from four DCIS cohorts treated with BCS had tissue samples analyzed at a CLIA lab (Laguna Hills, CA). Low-risk CP was defined with RTOG 9804-like criteria (margin negative by no-ink on tumor) or MSKCC-like criteria using nomogram-weighted factors (low-risk score<220, excluding number of re-excisions, using negative margin, and RT treatment). Women with either low-risk CP criteria were classified as molecular Low Risk (DS≤2.8, no Residual Risk subtype, RRt) or High Risk (DS>2.8 +/- RRt) using the 7-gene DCIS biosignature. Ten-year IBR Kaplan-Meier rates and Cox proportional hazard ratios (HR) were calculated for ET and RT. Results: Overall, 66% of 926 women were classified as low risk by one of the CP criteria. Patients with low-risk CP treated without ET (n=315) had 10yr IBR rates of 13% after BCS without RT and 7% with RT (HR=0.51, p=.10), while those treated with ET (n=291) had 10yr IBR rates of 9% after BCS without RT and 4% with RT (HR=0.39, p=.09). Overall, 37% of women were classified as low risk (n=338) by the biosignature and had a 10yr IBR rate of 5.6% after BCS with no significant ET (HR=0.66, p=.41) or RT benefit (HR=0.88, p=.78) in multivariable analysis. Of patients with low-risk CP, 48% of those treated without ET were classified as High Risk by the biosignature and had elevated 10yr IBR rates without RT (21%) and a substantial RT benefit (HR=0.31, p=.03, n=151), while 59% of those treated with ET after BCS were classified by the biosignature as High Risk and had elevated 10yr IBR rates without RT (14%) and a 9% absolute reduction from RT (HR=0.22, p=.02, n=173). Patients with concordant low-risk CP and biosignature Low Risk (n=269) had a 5.5% 10yr IBR rate after BCS and no significant RT (HR=1.10 95% CI 0.33 to 3.7, p=.87) or ET benefit (HR=0.44, 95%CI 0.1 to 1.6, p=.22) in multivariable analysis. Conclusions: The 7-gene biosignature provided better identification of patients with low 10yr IBR rates and no significant RT benefit compared to using CP low-risk criteria. Importantly, the biosignature classified over half of women with low-risk CP treated with ET as High Risk. This group received a substantial benefit from RT, while those with biosignature Low Risk did not.

Cancer associated macrophages in blood correlates with poor outcomes in patients with clinically resectable disease in gastrointestinal cancers.

e15052 Background: Gastrointestinal (GI) cancers, i.e., pancreatic (PC), colorectal (CC), and esophageal (EC), are known to be both highly aggressive and clinically underdiagnosed, resulting in high rates of relapse after standard neoadjuvant therapy with curative intent resection. While cancer biomarkers (i.e. CEA, CA19-9) can aid in identifying early relapse post-resection, they lack accuracy and do not aid in identifying underdiagnosed patients. Recently, a circulating phagocytic macrophage engorged to ≥50 µm, i.e. cancer-associated macrophage-like cells (CAMLs), were identified in GI cancers and associated with highly aggressive cancer subtypes. However, monitoring CAMLs pre- and post-surgery and their clinical value in minimal residual disease remains unexplored. In this pilot study, we prospectively evaluated the blood of n = 133 patients with GI cancer pre- and post-surgery to assess CAMLs in resectable disease, and their association with progression free survival (PFS), relapse free survival (RFS), and overall survival (OS). Methods: In a single-blind multi-institutional prospective pilot study, we recruited n = 133 GI patients with newly diagnosed clinically resectable disease (n = 118), or with metastatic disease scheduled for curative resection post systemic therapy (n = 15). Whole peripheral blood (7.5mL) was drawn prior to neoadjuvant chemotherapy and/or radiation therapy at T1, and a post-surgery sample (T2) was obtained. CAMLs were filtered, stained with cytokeratin & CD45, and enumerated for CAML engorgement of ≥50 µm, as previously described. Cox proportional regression hazard ratios for PFS, RFS & OS using univariate and multivariate analyses were run over 96 months. Results: Of the patients with clinically resectable EC (n = 36/133), PC (n = 75/133) or CC (n = 22/133), 32% of patients (n = 43/133) did not undergo curative resection. T1 samples drawn pre-surgery were available from n = 105 patients and T2 samples drawn post-surgery were available from = 52 patients. Engorged ≥50 µm CAMLs were found in 51% (n = 53/105) of T1 patients and were significantly associated with worse PFS (HR = 3.4 CI95% 2.0-5.8, p < 0.001) and worse OS (HR = 63.5 CI95% 2.0-6.1, p < 0.001), compared to patients with < 50 µm CAMLs. Additionally, engorged ≥50 µm CAMLs were found in 60% (n = 31/52) of T2 patient samples and were associated with significantly worse RFS (HR = 5.7, CI95% 2.4-13.2, p < 0.001) and OS (HR = 5.3, CI95% 2.2-13.3, p < 0.001) compared to patients with < 50 µm CAMLs. Conclusions: These data suggest that GI cancer patients with CAMLs ≥50µm prior to curative intent resection have high rates of progression, and their presence post surgery may identify patients with residual disease that are likely to relapse. Given these results, more refined studies should evaluate CAMLs ability to identify such at risk patients who may benefit from alternative therapeutic approaches.

In-hospital mortality patterns and risk factors in patients with cancer with COVID-19.

e23070 Background: The current body of knowledge regarding outcomes of patients with cancer and COVID-19 is conflicting, with some studies suggesting worsened mortality in those with both diseases This study seeks to shed light on the distinctive factors influencing in-hospital mortality in these two cohorts, providing crucial insights that can guide targeted interventions and enhance healthcare strategies for individuals facing the dual burden of cancer and COVID-19. Methods: We conducted a retrospective review of all patients hospitalized with COVID-19 at our institution between January 1, 2021 and April 1, 2023. Patients were stratified into a cohort of those with cancer and coexisting COVID-19 infection and those with solely COVID-19. The cancer and COVID-19 cohort included patients over the age of 18 who had received treatment for cancer within the last 6 months. Information regarding patient demographic characteristics and comorbidities, as well as in-hospital treatment characteristics and outcomes. We performed descriptive analysis and conducted Chi-squared and t-tests to assess for differences in baseline characteristics between cohorts, then developed Cox proportional hazards models to evaluate risk factors for in-hospital mortality. Results: 456 patients with cancer and COVID-19 were compared with 12,566 patients with only COVID-19. In-hospital mortality was 8.2% in the cancer cohort compared with 9.0% in the COVID-19 only cohort. Patients in the cancer cohort were more likely to be male (55.7% vs 48.2%, p = 0.004), older (71 vs 64 years, p < 0.001) with histories of heart failure (27% vs 21%, p = 0.002), chronic kidney disease (50% vs 39%, p < 0.001), COPD (35% vs 24%, p < 0.001), and anemia (57% vs 24%, p < 0.001). The cancer cohort experienced significantly longer length of stay (9 vs 7 days, p < 0.001). Requirement of mechanical ventilation and ICU stay were similar between groups. Multivariate Cox proportional hazards ratios demonstrated similar mortality between cohorts (HR = 0.863, p = 0.361), with age (HR = 1.041, p < 0.001) and history of acute myocardial infarction (HR = 1.275, p = 0.01) being significant predictors of death. Conclusions: Our study demonstrates the complex relationship between cancer, COVID-19, and in-hospital mortality. Despite differences in baseline characteristics between the cohorts, our findings reveal that, after adjusting for confounding factors, there is no significant disparity in mortality rates between patients concurrently battling cancer and COVID-19 and those solely afflicted by COVID-19. The identification of age and a history of acute myocardial infarction as significant predictors of mortality underscores the need for targeted interventions and vigilant management strategies for individuals facing the dual burden of cancer and COVID-19, ensuring equitable and effective healthcare outcomes in this complicated patient population.

Impact of integrative care on cardiovascular disease risk in newly diagnosed type 2 diabetes mellitus patients: A BI-VitalLife Cohort study.

Type 2 diabetes mellitus (T2DM), a chronic metabolic disorder, significantly increases cardiovascular disease (CVD) risk. Integrative care (IC) offers a personalized health management approach, utilizing various interventions to mitigate this risk. However, the impact of IC on CVD risk in newly diagnosed T2Dm patients remains unclear. This study aims to assess the differences in CVD risk development within 120 months following a new diagnosis of T2DM, using real-world data from Bumrungrad International Hospital and Vitallife Scientific Wellness Center. This study utilized the BI-VitalLife Cohort dataset that contains de-identified demographics, vitals, diagnoses and clinical information, laboratory and radiological data, medications, and treatments of more than 2.8 million patients who visited Bumrungrad International Hospital and/or VitalLife Scientific Wellness Center from June 1, 1999, to May 31, 2022. This study focused on newly diagnosed T2DM patients, defined according to American Diabetes Association criteria. We compared CVD risk between the IC and conventional care (CC) groups using the Kaplan-Meier curve and Cox proportional hazard model, adjusted for age, sex, and laboratory values. Propensity score matching was employed to enhance comparability. Of the 5,687 patients included, 236 were in the IC group and 5,451 in the CC group. The IC group, characterized by a lower age at T2DM diagnosis, showed favorable hematological and metabolic profiles. The Cox proportional hazard ratios revealed a significantly lower CVD risk in the IC group within 120 months post-T2DM diagnosis compared to the CC group, consistent even after adjusting for confounding factors. Propensity score-matched analysis supported these findings. Personalized integrative care may offer a significant advantage in reducing CVD risk among newly diagnosed T2DM patients compared to conventional care, even when considering various confounding factors. This study sheds light on the potential of integrative care in informing treatment strategies for T2DM patients at risk of developing CVD.

The Influence of Pubertal Development on Autoantibody Appearance and Progression to Type 1 Diabetes in the TEDDY Study.

The 2 peaks of type 1 diabetes incidence occur during early childhood and puberty. We sought to better understand the relationship between puberty, islet autoimmunity, and type 1 diabetes. The relationships between puberty, islet autoimmunity, and progression to type 1 diabetes were investigated prospectively in children followed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Onset of puberty was determined by subject self-assessment of Tanner stages. Associations between speed of pubertal progression, pubertal growth, weight gain, homeostasis model assessment of insulin resistance (HOMA-IR), islet autoimmunity, and progression to type 1 diabetes were assessed. The influence of individual factors was analyzed using Cox proportional hazard ratios. Out of 5677 children who were still in the study at age 8 years, 95% reported at least 1 Tanner Stage score and were included in the study. Children at puberty (Tanner Stage ≥2) had a lower risk (HR 0.65, 95% CI 0.45-0.93; P = .019) for incident autoimmunity than prepubertal children (Tanner Stage 1). An increase of body mass index Z-score was associated with a higher risk (HR 2.88, 95% CI 1.61-5.15; P < .001) of incident insulin autoantibodies. In children with multiple autoantibodies, neither HOMA-IR nor rate of progression to Tanner Stage 4 were associated with progression to type 1 diabetes. Rapid weight gain during puberty is associated with development of islet autoimmunity. Puberty itself had no significant influence on the appearance of autoantibodies or type 1 diabetes. Further studies are needed to better understand the underlying mechanisms.

Quality of early stroke care and long-term mortality in patients with acute stroke: A nationwide follow-up study.

High quality of early stroke care is essential for optimizing the chance of a good patient outcome. The quality of care may be monitored by process performance measures (PPMs) and previous studies have found an association between fulfilment of PPMs and short-term mortality. However, the association with long-term mortality remains to be determined. We aimed to evaluate the association between fulfilment of PPMs and long-term mortality for patients with acute stroke in Denmark. We used data from Danish health care registers between 2008 and 2020 to identify all patients admitted with incident stroke (haemorrhagic (ICH) or ischaemic stroke). The quality of early stroke care was assessed using 10 PPMs. Mortality was compared using Cox proportional hazard ratios, risk ratios computed using Poisson regression, and standardized relative survival. We included 102,742 patients; 9804 cases of ICH, 88,591 cases of ischaemic stroke, and 4347 cases of unspecified strokes. The cumulative 10-year mortality risk was 56.8%. Fulfilment of the individual PPMs was associated with adjusted hazard rate ratios of death between 0.76 and 0.96. Patients with 100% fulfilment of all PPMs had a lower 10-year post-stroke mortality (adjusted risk ratio 0.90) compared to the patients with 0%-49% fulfilment and a standardized relative survival of 81.3%, compared to the general population. High quality of early stroke care was associated with lower long-term mortality following both ICH and ischaemic stroke, which emphasizes the importance of continued attention on the ability of stroke care providers to deliver high quality of early care.

Abstract PO1-11-05: Diet quality and cardiovascular disease risk among breast cancer survivors in the Pathways Study

Abstract Background: While studies have shown that breast cancer survivors with healthier diets have a lower risk of non-breast cancer-specific and all-cause mortality after a breast cancer diagnosis, the relationship between diet quality and cardiovascular disease (CVD) among breast cancer survivors is not well characterized. We examined the association between diet quality at the time of breast cancer diagnosis and CVD-related outcomes in the Pathways Study, a prospective cohort of 3,415 women diagnosed with invasive breast cancer. Methods: This analysis included four diet quality indices (DQIs) consistent with healthy eating: 1. Dietary Approaches to Stop Hypertension (DASH), 2. healthy plant-based dietary index (hPDI), 3. 2015 Healthy Eating Index (HEI), 4. American Cancer Society nutrition guidelines (ACS). Each DQI was calculated from food frequency questionnaires (FFQ) at or around the time of breast cancer diagnosis, between 2005 and 2013, with a higher score representing a more healthful dietary pattern. DQI scores were categorized into quartiles with the most concordant diets in the highest quartile and the least concordant diets in the lowest quartile, for each DQI. CVD outcomes were ascertained through December 31, 2021 and included ischemic heart disease, heart failure, cardiomyopathy, stroke/transient ischemic attack, arrhythmia, cardiac arrest, valvular disease, venous thromboembolic disease and CVD-related death. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated from proportional hazards regression accounting for clinical and demographic factors. Results: FFQs were completed an average 2.2 (range=0.3-7.6) months after a breast cancer diagnosis, and a total 623 (18.2%) incident CVD events and 340 (10.0%) CVD-related deaths were ascertained over 39,263 person-years of follow-up. Participants in the highest quartile of the DASH DQI had substantially reduced risks of heart failure (HR=0.50, 95% CI 0.31-0.81), arrhythmia (HR=0.76, 95% CI 0.62-0.93), cardiac arrest (HR=0.75, 95% CI 0.60-0.93), valvular disease (HR=0.77, 95% CI 0.62-0.96), venous thromboembolic disease (HR=0.74, 95% CI 0.59-0.92), and a 33% reduced risk of CVD-related death (HR=0.67, 95% CI 0.48-0.95) relative to those in the lowest quartile. Tests for trend across quartiles of the DASH DQI were also statistically significant at a p-value &amp;lt; 0.03. The only notable association found in the other three DQIs was between hPDI and lower risk of heart failure (HR=0.61, 95% CI 0.39-0.95) in women in the highest quartile compared to the lowest quartile (Table 1). Summary: These findings suggest that diets concordant with DASH and hPDI dietary patterns, may be beneficial for preventing CVD and CVD-related death after a breast cancer diagnosis. Table 1. Cox proportional hazard ratios and 95% confidence intervals for quartiles of diet quality indices and CVD events and CVD-related death Citation Format: Isaac Ergas, Janise Roh, Lawrence Kushi, Carlos Iribarren, Mai Nguyen-Huynh, Jamal Rana, Eileen Rillamas-Sun, Cecile Laurant, Valerie Lee, Richard Cheng, Heather Greenlee, Marilyn Kwan. Diet quality and cardiovascular disease risk among breast cancer survivors in the Pathways Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-11-05.

Collared Cementless Femoral Components Reduce the Revision Rates in Primary Total Hip Arthroplasty Using the Direct Anterior Approach: An Australian Orthopaedic Association National Joint Replacement Registry Study

BackgroundAn increased risk of periprosthetic fracture and aseptic loosening is reported when the direct anterior approach (DAA) is used for total hip arthroplasty (THA), especially with cementless implants. We assessed the rate of revision comparing collared and collarless femoral stems when using the DAA for THA. MethodsWe used data from the Australian Orthopaedic Association National Joint Replacement Registry for primary THA for osteoarthritis inserted with the DAA between January 2015 and December 2022. There were 48,567 THAs that used the DAA (26,690 collarless cementless, 10,161 collared cementless, and 11,716 cemented). Cumulative percent revision was calculated for all-cause revision, revision for periprosthetic femoral fractures, and aseptic femoral stem loosening. Cox proportional hazard ratios [HRs] were used to compare the revision of collared and collarless cementless stems. We also compared collared cementless stems and cemented stems. ResultsA higher rate of all-cause revision within 3 months of surgery was observed with collarless compared to collared cementless implants (HR: 1.99 [95% confidence interval (CI), 1.56 to 2.54]; P < .001). Similarly, collarless cementless implants were associated with a greater rate of revision for fracture in the first 6 months (HR: 2.90 [95% CI, 1.89 to 4.45]; P < .001) and after 6 months (HR 10.04 [95% CI 1.38 to 73.21]; P = .02), as well as an increased rate of revision for aseptic loosening after 2 years (HR: 5.76 [95% CI, 1.81 to 18.28], P = .003). Collared cementless and cemented stems performed similarly. ConclusionCollared stems were associated with a reduced rate of all-cause revision for cementless THA performed via the DAA. The reduction in risk may be due to protection from periprosthetic femoral fracture and aseptic loosening.

Association of aortic valve calcium with dementia and stroke: The Multi-Ethnic Study of Atherosclerosis

Background and aimsCalcific aortic valve disease is associated with increased thrombin formation, platelet activation, decreased fibrinolysis, and subclinical brain infarcts. We examined the long-term association of aortic valve calcification (AVC) with newly diagnosed dementia and incident stroke in the Multi-Ethnic Study of Atherosclerosis (MESA). MethodsAVC was measured using non-contrast cardiac CT at Visit 1. We examined AVC as a continuous (log-transformed) and categorical variable (0, 1-99, 100-299, ≥300). Newly diagnosed dementia was adjudicated using International Classification of Disease codes. Stroke was adjudicated from medical records. We calculated absolute event rates (per 1,000 person-years) and multivariable adjusted Cox proportional hazards ratios (HR). ResultsOverall, 6,812 participants had AVC quantified with a mean age of 62.1 years old, 52.9% were women, and the median 10-year estimated atherosclerotic cardiovascular disease (ASCVD) risk was 13.5%. Participants with AVC >0 were older and less likely to be women compared to those with AVC=0. Over a median 16-year follow-up, there were 535 cases of dementia and 376 cases of stroke. The absolute risk of newly diagnosed dementia increased in a stepwise pattern with higher AVC scores, and stroke increased in logarithmic pattern. In multivariable analyses, AVC was significantly associated with newly diagnosed dementia as a log-transformed continuous variable (HR 1.09; 95% CI 1.04-1.14) and persons with AVC ≥300 had nearly a two-fold higher risk (HR 1.77; 95% CI 1.14-2.76) compared to those with AVC=0. AVC was associated with an increased risk of stroke after adjustment for age, sex, and race/ethnicity, but not after adjustment for ASCVD risk factors. ConclusionsAfter multivariable adjustment, AVC >0 was significantly associated with an increased risk of newly diagnosed dementia, but not incident stroke. This suggests that AVC may be an important risk factor for the long-term risk of dementia beyond traditional ASCVD risk factors.

High prevalence of "non-pathogenic" POLE mutation with poor prognosis in a cohort of endometrial cancer from South India.

The Cancer Genome Atlas (TCGA) project identified favorable prognosis regarding the ultra-mutated endometrial cancer (EC) subtype linked to polymerase epsilon gene (POLE) mutations. This study investigated POLE mutations in EC of Indian patients. This retrospective analytical study was conducted between January 2016 and January 2023 at the Government Medical College, Kozhikode, and the MVR Cancer Center, Kozhikode, Kerala. Sanger sequencing of POLE gene exons 9 and 13 in 151 EC patients was carried out to analyze the relationship between mutations and epidemiological factors, clinicopathologic features, and treatment outcomes. Among 151 cases enrolled, 39 were unique POLE-mutated cases. Significant associations were high-grade tumors, myometrial invasion >50%, and Lymph-vascular space invasion (LVSI). The median follow-up was 40 months (95% confidence interval [CI], 34-46). A lower mean disease-specific survival (DSS) of 51.7 months (95% CI, 43.7-59.6) was noted in the POLE-mutated group compared with 72.11 months (95% CI, 67.60-76.62) for the POLE wild-type. A statistically significant hazard ratio (HR) of 2.683 for DSS in the POLE-mutated group was noted. In advanced stages (FIGO stages II-IV), a nine-fold HR for DSS and overall survival (OS) compared with POLE wild-type was identified. After controlling for treatment effects using Cox proportional HR, advanced-stage POLE-mutated tumors had a significantly higher HR of 8.67 for DSS compared with POLE-wild-type tumors of the same stage. This study identified a unique set of POLE mutations in Indian EC patients associated with poor prognosis, which were particularly pronounced in advanced stages. Advanced stage of presentation, type of POLE mutations, and possibly ethnicity are predictors of adverse outcomes in POLE-mutated EC. The present study highlights ethnicity as a determinant of phenotypic expression of genetic change.

A prospective study of dietary patterns and the incidence of endometriosis diagnosis

BackgroundAlthough endometriosis is a common condition—affecting ∼10% of premenopausal individuals—its etiology is unknown. Diet receives large patient attention, but studies of the role of diet are limited. Examining dietary patterns is essential to provide new insight. ObjectiveWe sought to determine whether dietary patterns are associated with laparoscopically-confirmed endometriosis diagnosis. Study DesignWe conducted a prospective cohort study among 81,997 premenopausal participants of the Nurses’ Health Study II, who were followed from 1991-2015. Diet was assessed with validated food frequency questionnaires every four years. We examined six dietary patterns: Western, Prudent, Alternative Healthy Eating Index (AHEI-2010), Dietary Approaches to Stop Hypertension (DASH), an estrogen-associated pattern, and a pro-inflammatory pattern. Cox proportional hazard ratios (HR) and 95% confidence intervals (CI) were used to quantify the association between each of these patterns and laparoscopically-confirmed endometriosis diagnosis. Results3,810 incident cases of endometriosis were diagnosed during 24 years of follow-up. Adherence to the AHEI-2010, reflecting a healthier dietary pattern, was associated with a 13% lower risk of endometriosis diagnosis (5th vs 1st quintile 95% CI=0.78-0.96; ptrend=0.02). Participants in the highest quintile of the Western dietary pattern, characterized by high intake of red meat, processed meat, refined grains, and desserts, had a 27% higher risk of endometriosis diagnosis compared to those in the lowest quintile (95% CI=1.09–1.47; ptrend=0.004). The Prudent, DASH, and estrogen-associated dietary patterns did not demonstrate clear associations with endometriosis risk, and there was the suggestion of higher risk of endometriosis diagnosis among those with a higher pro-inflammatory diet score (HR for 5th vs 1st quintile=1.10; 95% CI=0.99-1.23; ptrend=0.01). ConclusionOur results suggest that consuming a dietary pattern that adheres to the AHEI-2010 recommendations lowers the risk of endometriosis diagnosis, potentially through a beneficial impact on pelvic pain. In addition, consuming a less healthy diet high in red/processed meats and refined grains may have a detrimental impact on endometriosis symptoms.

Limited English Proficiency and Graves’ Disease at an Urban Safety Net Hospital

IntroductionDecision-making regarding definitive therapy for Graves’ disease requires effective patient-provider communication. We investigated whether patients with limited English proficiency have differences in thyroidectomy outcomes or perioperative management when compared to English proficient (EP) patients at a safety net hospital with high-volume endocrine surgery practice. MethodsRetrospective study of patients who underwent thyroidectomy (2012-2021) for Graves’ disease within a tertiary referral system. Demographics, preoperative factors, and postoperative outcomes were abstracted via chart review and compared between EP and limited English proficient (LEP) patients in univariate analyses. Odds of postoperative complications were assessed via multivariable logistic regression. Time metrics such as time from endocrinology consultation to surgery were compared via Kaplan–Meier analysis and adjusted Cox proportional regression models. ResultsOf 236 patients, 85 (36%) had LEP. Low and equivalent complication rates occurred across language groups (<1% permanent). LEP patients had similar odds of thyroidectomy-specific complications (odds ratio = 1.2; 95% confidence interval 0.6-2.4). Adjusted Cox proportional hazards ratios showed that LEP patients experienced significantly shorter time from endocrinology consultation to surgery compared to EP patients [hazard ratio = 0.7; 95% confidence interval 0.5-0.9]. ConclusionsThyroidectomy-specific complication rate for patients with Graves’ disease was low, and we detected no independent association between complications and English language proficiency. Non-English primary language was independently associated with reduced time from endocrinology consultation to surgery. This finding must be interpreted with nuance and is likely multifactorial. It may reflect a well-organized, efficient system for under-resourced patients, or it may derive from communication barriers that limit robust shared decision-making, thus accelerating time to surgery.

Prognostic impact of positive microscopic margins (R1 resection) in patients with GIST (gastrointestinal stromal tumours): Results of a multicenter European study

BackgroundAlthough several prognostic factors in GIST have been well studied such as tumour size, mitotic rate, or localization, the influence of microscopic margins or R1 resection remains controversial. The aim of this study was to evaluate the influence of R1 resection on the prognosis of GIST in a large multicentre retrospective series of patients. MethodsFrom 2001 to 2013, 1413 patients who underwent surgery for any site of GIST were identified from 61 European centers. 1098 patients were included, excluding synchronous metastases, concurrent malignancies, R2 resection or GIST recurrence. Tumour rupture (TR) was reclassified according to the Oslo sarcoma classification. Cox proportional hazards ratio and Kaplan-Meier survival estimates were used to analyse 5-year recurrence-free survival (RFS). ResultsOf 1098 patients, 38 (3%) underwent R1 resection with a risk of TR of 11%. The 5-year RFS was 89.6% with a median follow-up of 81 months [range: 31.2–152 months]. On univariate analysis, lower RFS was significantly associated with R1 resection [HR = 2.13; p = 0.04], high risk score according to the modified NIH classification, administration of adjuvant therapy [HR = 2.24; p < 0.001] and intraoperative complications [HR = 2.82; p < 0.001]. Only intraoperative complications [HR = 1.79; p = 0.02] and high risk according to the modified NIH classification including the updated definition of TR [HR = 3.43; p = 0.04] remained significant on multivariate analysis. ConclusionThis study shows that positive microscopic margins are not an independent predictive factor for RFS in GIST when taking into account the up-dated classification of TR. R1 resection may be considered a reasonable alternative to avoid major functional sequelae and should not lead to reoperation.

Abstract 3680: Prognostic value of serum biomarkers in pancreatic adenocarcinoma: Results from a Swiss single center cohort analysis

Abstract Introduction: Inflammatory and nutritional biomarkers, such as neutrophil to lymphocyte ratio (NLR), C-Reactive Protein (CRP), lactate dehydrogenase (LDH) and albumin, are valuable prognostic indicators, refining stratification strategies in oncological patients. This study aims to delineate the impact of these markers on overall survival in patients with pancreatic adenocarcinoma, in order to aid in clinical risk stratification. Methods: We conducted a retrospective analysis on patients with adenocarcinoma of the pancreas, treated at the Cantonal Hospital Baselland (January 2018 - February 2022). Clinical data, including diagnosis, treatment, and blood markers, were extracted from electronic records. The analysis incorporated the computation of median values for each blood marker, followed by survival analysis and determination of Cox proportional hazard ratios with a 95% confidence interval. Results: Our cohort included 43 patients, 53% women, 44% men, median age 73 years (IQR 14.75) with adenocarcinoma of the pancreas. Most patients (56%) had advanced distant disease and 25% of these did not receive any oncological therapy. At least one cycle of chemotherapy was administered in 85% of patients. NLR&amp;lt;4 was reported in 63% of cases, normal albumin levels in 72%, normal LDH levels in 79%, and normal CRP levels in 47%. In the multivariate Cox regression analysis, there was a significant higher risk for death with metastatic disease (HR 6.216 CI 2.00-19.28, p=0.002), age ≥75 (HR 4.88, CI 1.65-14.39, p=0.004) and CRP&amp;gt;10 (HR 3.38, CI 1.18-9.66, p=0.023) and lower risk with addition of chemotherapy (HR 0.076, CI 0.02-0.29, p&amp;lt;0.001). NLR, LDH and albumin levels did not significantly correlate with higher HR for death. At a median follow-up period of 8.5 months (IQR 14), the median overall survival was 9 months (IQR 14.5) with a worsening prognostic for increased CRP (p=0.00027), NLR&amp;gt;4 (p=0.051), albumin &amp;lt;35g/l (p=0.0024), LDH &amp;gt;250 U/l (p=0.037). Better survival rates were seen in patients receiving chemotherapy 75% vs 20 for those without chemotherapy (p&amp;lt;0.0001) and in those with local disease 80% vs 60% for metastatic disease p=0.034). Age ≥75 years carried a significant poorer prognostic (p=0.0017), while gender was not relevant. However, due to small sample size, age adjusted survival was not carried out and age was considered not relevant for the survival analysis. Conclusion: Beyond the expected factors like stage of disease and therapy, an increased CRP appears to carry significant correlation with hazard ratio for death among patients with adenocarcinoma of the pancreas. In our cohort, abnormal CRP, NLR, albumin and LDH levels demonstrated significant association with shorter survival period, underscoring the potential utility of these biomarkers in prognostic stratification and their incorporation into routine oncological assessments. Citation Format: Elena D. Chiru, Marie Knufike, Martina Sonderegger-Stalder, Raphael Mosimann, Antonia Sgries, Robert Rosenberg, Emanuel Burri, Sandra Mitrovic, Michèle Voegeli, Kristen Mertz, Alessandra Angelini, Marcus Vetter. Prognostic value of serum biomarkers in pancreatic adenocarcinoma: Results from a Swiss single center cohort analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3680.

Factors associated with the worsening of COVID-19 symptoms among cohorts in community- or home-isolation care in southern Thailand.

This study aimed to investigate factors associated with time-to-referral due to worsening symptoms in patients with laboratory-confirmed COVID-19 in southern Thailand. While underlying diseases have been evaluated to assess COVID-19 severity, the influence of vaccinations and treatments is also crucial. A cohort of 8,638 patients quarantined in home or community isolation with laboratory-confirmed COVID-19 was analyzed. Survival analysis and the Cox proportional hazard ratio were employed to assess factors influencing time-toreferral. Age ≥ 60 years, neurologic disorders, cardiovascular disease, and human immunodeficiency virus infection were identified as significant risk factors for severe COVID-19 referral. Patients who received full- or booster-dose vaccinations had a lower risk of experiencing severe symptoms compared to unvaccinated patients. Notably, individuals vaccinated during the Omicron-dominant period had a substantially lower time-to-referral than those unvaccinated during the Delta-dominant period. Moreover, patients vaccinated between 1 and 6 months prior to infection had a significantly lower risk of time-to-referral than the reference group. These findings demonstrate early intervention in high-risk COVID-19 patients and the importance of vaccination efficacy to reduce symptom severity. The study provides valuable insights for guiding future epidemic management strategies and optimising patient care during infectious disease outbreaks.

Clinicopathologic characteristics and treatment outcomes of pancreatic cancer patients at a tertiary referral hospital in Kenya.

The global incidence of pancreatic cancer (PC) continues to steadily increase whereas its prognosis remains poor. Previous studies have suggested worse outcomes among individuals of African descent. The characteristics of patients with PC in Kenya, and their contemporary management and survival outcomes remain largely unknown. This study aimed to describe the clinical and pathologic characteristics, management, and outcomes of patients diagnosed with PC at Kenyatta National Hospital (KNH), a tertiary referral hospital in Kenya. Records of 242 patients diagnosed with PC at KNH between 1st January 2014 and 30th September 2021 were assessed in this retrospective cohort study. Data on their clinical, histopathologic, and treatment characteristics was presented as mean (± standard deviation) and/or median (interquartile range) for continuous variables and frequency (percentage) for categorical variables. Kaplan-Meier and Cox proportional hazard ratios were used for survival analysis. PC occurred in a young population, the median age being 58.5 years (inter-quartile range 35-88). The majority of tumours (54%) were metastatic at diagnosis, while 28% and 14% were stage III and stage I/II, respectively. Surgical resections with curative intent were performed on 7% overall and 44% of stage I/II cases. The majority of patients with stage I/II disease (52.9%) received chemotherapy whereas the majority with stage III and IV disease received the best supportive care only (62.7% and 64.9%, respectively). Patients who underwent surgical resection (HR for mortality 0.20, 95% CI 0.05-0.83, p = 0.021) and chemotherapy (HR for mortality 0.15, 95% CI 0.08-0.29, p < 0.001) had significantly improved survival, reflecting a more favourable stage of the disease more amenable to aggressive therapies. The median survival time was 3 months and the 1-year survival rate was 32%.

Effects of preterm birth, maternal ART and breastfeeding on 24-month infant HIV-free survival in a randomized trial.

IMPAACT 1077BF/FF (PROMISE) compared the safety/efficacy of two HIV antiretroviral therapy (ART) regimens to zidovudine (ZDV) alone during pregnancy for HIV prevention. PROMISE found an increased risk of preterm delivery (<37 weeks) with antepartum triple ART (TDF/FTC/LPV+r or ZDV/3TC/LPV+r) compared with ZDV alone. We assessed the impact of preterm birth, breastfeeding, and antepartum ART regimen on 24-month infant survival. We compared HIV-free and overall survival at 24 months for liveborn infants by gestational age, time-varying breastfeeding status, and antepartum ART arm at 14 sites in Africa and India. Kaplan-Meier survival probabilities and Cox proportional hazards ratios were estimated. Three thousand four hundred and eighty-two live-born infants [568 (16.3%) preterm and 2914 (83.7%) term] were included. Preterm birth was significantly associated with lower HIV-free survival [0.85; 95% confidence interval (CI) 0.82-0.88] and lower overall survival (0.89; 95% CI 0.86-0.91) versus term birth (0.96; 95% CI 0.95-0.96). Very preterm birth (<34 weeks) was associated with low HIV-free survival (0.65; 95% CI 0.54-0.73) and low overall survival (0.66; 95% CI 0.56-0.74). Risk of HIV infection or death at 24 months was higher with TDF-ART than ZDV-ART (adjusted hazard ratio 2.37; 95% CI 1.21-4.64). Breastfeeding initiated near birth decreased risk of infection or death at 24 months (adjusted hazard ratio 0.05; 95% CI 0.03-0.08) compared with not breastfeeding. Preterm birth and antepartum TDF-ART were associated with lower 24-month HIV-free survival compared with term birth and ZDV-ART. Any breastfeeding strongly promoted HIV-free survival, especially if initiated close to birth. Reducing preterm birth and promoting infant feeding with breastmilk among HIV/antiretroviral drug-exposed infants remain global health priorities.

No Difference in Revision Rates up to 10 years Following Total Hip Arthroplasty in Patients Who Had Prior Bariatric Surgery When Compared to Patients Who Had Class III Obesity: A Propensity Matched Analysis

BackgroundThere is no clear research showcasing bariatric surgery’s (BS’s) impact on long-term surgical complications following total hip arthroplasty (THA). Therefore, this study compared the 10-year cumulative incidence and risk of revision following THA in patients who underwent BS when compared to the general population and class III obesity patients who did not undergo BS. MethodsPatients who underwent elective THA from 2010 to 2021 were identified using an all-payer claims database. Patients who underwent BS prior to THA were separately matched to a control of the general population and those who had class III obesity (body mass index ≥40) by age, sex, Charlson Comorbidity Index, and diabetes using a 1:4 ratio. Kaplan-Meier analyses generated 10-year cumulative incidence rates, and a Cox proportional hazard ratio (HR) model generated HRs and 95% confidence intervals (CIs). ResultsWhen compared to the general control, patients who have a history of BS had an elevated 10-year risk of all-cause revision (HR 1.31, 95% CI: 1.16 to 1.47, P < .001), prosthetic joint infection (HR: 1.62, CI: 1.30 to 2.04; P < .001), mechanical loosening (HR: 1.20, CI: 1.01 to 1.44; P = .040), and dislocation/instability (HR: 1.35, CI: 1.09 to 1.68; P = .007). There was no difference in the 10-year risk of all-cause revision or other indications for revision in the BS cohort compared to the matched class III obesity cohort (P = .142). ConclusionsThose who underwent BS before THA had comparable 10-year revision rates when compared to those who had class III obesity and higher rates compared to the general population. This suggests BS may not reduce the 10-year surgical risks associated with obesity when compared to a class III obese surgical population.

Clinicopathological and cellular senescence biomarkers in chronic stalled wounds.

Chronic wounds have been associated with an elevated burden of cellular senescence, a state of essentially irreversible cell cycle arrest, resistance to apoptosis, and a secretory phenotype. However, whether senescent cells contribute to wound chronicity in humans remains unclear. The objective of this article is to assess the role of clinicopathological characteristics and cellular senescence in the time-to-healing of chronic wounds. A cohort of 79 patients with chronic wounds was evaluated in a single-center academic practice from February 1, 2005, to February 28, 2015, and followed for up to 36 months. Clinical characteristics and wound biopsies were obtained at baseline, and time-to-healing was assessed. Wound biopsies were analyzed histologically for pathological characteristics and molecularly for markers of cellular senescence. In addition, biopsy slides were stained for p16INK4a expression. No clinical or pathological characteristics were found to have significant associations with time-to-healing. A Cox proportional hazard ratio model revealed increased CDKN1A (p21CIP1/WAF1 ) expression to predict longer time-to-healing, and a model adjusted for gender and epidermal hyperplasia revealed increased CDKN1A expression and decreased PAPPA expression to predict longer time-to-healing. Increased p16INK4a staining was observed in diabetic wounds compared to non-diabetic wounds, and the same association was observed in the context of high dermal fibrosis. The findings of this pilot study suggest that senescent cells contribute to wound chronicity in humans, especially in diabetic wounds.