Sjögren’s syndrome is a chronic and insidious auto-immune disease characterized by lymphocyte infiltration of exocrine glands. The patients typically present with ocular surface diseases related to dry eye and other systemic manifestations. However, due to the high prevalence of dry eye disease and the lack of objective and clinically reliable diagnostic tools, discriminating Sjögren’s syndrome dry eye (SSDE) from non-Sjögren’s syndrome dry eye (NSSDE) remains a challenge for clinicians. Diagnosing SS is important to improve the quality of life of patients through timely referral for systemic workups, as SS is associated with serious systemic complications such as lymphoma and other autoimmune diseases. The purpose of this article is to describe the current molecular understanding of Sjögren’s syndrome and its implications for novel diagnostic modalities on the horizon. A literature review of the pre-clinical and clinical studies published between 2016 and 2022 was conducted. The SSDE pathophysiology and immunology pathways have become better understood in recent years. Novel diagnostic modalities, such as tear and saliva proteomics as well as exosomal biomarkers, provide hope on the horizon.

Background: Metastatic prostate cancers frequently harbour pathogenic aberrations in Homologous Recombination Repair (HRR) genes that confer sensitivity to PARP inhibitors (PARPi). Therefore, accurate identification of all eligible patients is needed. The development of a circulating tumour DNA (ctDNA) testing alternative is promising as genomic testing of archived tissue leads to a failure rate of up to 30–40% in prostate cancer. Methods: This was a bi-institutional retrospective cohort study of patients with metastatic prostate cancer treated at the Jewish General Hospital or the McGill University Health Center, Montreal, Canada, between 2021 and 2023. Molecular data and treatment information were abstracted from a chart review. Chi-square, Fisher’s exact test, and Mann–Whitney tests were used to assess differences between groups. Results: We identified 484 metastatic prostate cancer patients. Somatic and germline testing for HRR was performed in 55.4% (n = 268) and 20% (n = 97) patients, respectively. Somatic testing was performed on tissue (n = 192, 71.6%) or ctDNA from liquid biopsies (n = 18, 6.7%) or both (n = 58, 21.7%). Pathogenic somatic HRR alterations were detected in 48 patients (17.9%). BRCA2 was the most frequent (n = 17), followed by ATM (n = 11), then CHEK2 (n = 5). Amongst patients with germline testing, 13/97 (13.4%) had pathogenic alterations predicted to lead to deficient HRR, mostly BRCA2 (n = 9), and three had detectable BRCA2 in tissue. Dual testing modality (tissue+ctDNA) significantly enhanced the detection rate of HRR alterations 19/58 (32.7%) vs. 29/210 (13.8%) for single testing modality (tissue or ctDNA), p = 0.008. The rate of inconclusive results was significantly lower in dual testing modality 0/58 (0%) vs. 25/210 in single testing modality (11.9%), p = 0.003. Amongst the 14 patients who had discordant results between liquid and tissue tests, HRR abnormalities were more frequently identified in ctDNA (n = 11) vs. tissue (n = 3). Patients who had HRR deficiency detected only in ctDNA had older tissue samples (median 5.6 years) compared to those who had deficient HRR detected only in tissue (median 0.2 years; p = 0.14). Conclusions: These data highlight a potential role in implementing liquid biopsy—especially in patients who only have older archival tissue available or failed tissue testing—to improve the detection rate of deficient HRR. Our ongoing prospective study will further validate whether the addition of liquid biopsy can identify more patients who are eligible to receive precision therapies by increasing the rate of detection of HRR deficiency compared to routine tissue testing alone.

Panic disorder (PD) is a neurological disorder associated with an abnormally high hypercapnic ventilatory response. In humans and rodents, early life stress is a significant risk factor for PD. Based on recent data indicating that CO ₂ /H ⁺ sensing by microglia is an important mechanism in the translation of hypercapnic stimulation into physiological responses, we tested the hypothesis that depletion of microglia by pharmacological treatment can decrease the hypercapnic ventilatory response. We also proposed that this effect is greater in stressed rats than controls. The prevalence of PD being ~2 times greater in women than men, experiments were performed on female rats. Following birth, rats were either raised under control conditions or subjected to neonatal maternal separation (NMS; 3h/day, postnatal days 3 to 12). At 8 weeks, females were fed a palatable treat containing either vehicle (DMSO) or PLX3397 (40mg/kg). Treatment was performed daily for 10 consecutive days. 1 day after completion of the treatment, rats were placed in a plethysmography chamber to measure ventilatory activity at rest (room air) followed by hypercapnic exposure (FiCO ₂ = 0.05; 10 min). Iba‐1 immunohistochemistry was used to quantify microglial density; measurements performed in hypothalamic structures containing orexin neurons showed that PLX3397 treatment educed microglial density by 31%; this effect did not differ between the structures quantified. Furthermore, our preliminary results suggest that oestrus cycle influences the impact of microglial depletion on the CO ₂ response. During the estrus phase, PLX3397 attenuated the hypercapnic ventilatory response of controls but augmented the response of NMS females. These data suggest that microglia contribute to the abnormal effects that ovarian hormones exert on the neural networks regulating CO ₂ /H ⁺ chemoreflex respiratory regulation in NMS rats. These data provide the basis for the exploration of new treatment for respiratory manifestations of PD. Support or Funding Information Supported by the Canadian Institutes of Health Research (RK & FB). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Introduction: Biliary tract cancers (BTCs) are associated with a poor prognosis and a lack of standardized management guidelines in Canada, resulting in variable care influenced by age, ethnicity, and region. This study analyzes BTC demographics, diagnostics, treatment modalities, and survival outcomes at the Centre Hospitalier Universitaire de Sherbrooke (CHUS), Quebec. Methods: A retrospective study from 2009 to 2021 included patients aged 18 and older diagnosed with carcinoma-type BTCs and treated at the CHUS. Results: A total of 218 patients were included in our study. The median age at diagnosis was 70.7 years, with 48.6% being male and 51.4% being female. In our population, extrahepatic cholangiocarcinomas were the most frequently diagnosed (31.7%), followed by intrahepatic cholangiocarcinomas (29.8%), gallbladder carcinomas (19.7%), and Ampulla of Vater cancers (16.1%). Identifiable risk factors were very rare. Computed tomography (CT) scans were the primary diagnostic tool (98.1%). Surgical resection was performed in 35.3% of patients, and 40.4% received chemotherapy. The median overall survival was 10.2 months, with a 1-year survival rate of 46%. Patients with Ampulla of Vater cancer had the longest median survival at 55 months. Surgical resection improved overall survival for all biliary tract cancer subtypes, reaching 52 months. Conclusions: BTC patients at CHUS show diverse demographics and cancer types, mirroring national trends. Early detection and surgical treatment enhance survival. Ongoing research is essential to improve BTC management and explore its complex causes.

315 Background: Perioperative systemic therapy is standard in localized upper gastrointestinal (UGI) cancers, yet real-world outcomes are inferior to trials, with many patients unable to complete both neoadjuvant and adjuvant phases. While tumor grade and regression response are recognized prognostic factors, the relative contributions of systemic therapy completion versus intrinsic tumor biology, and the determinants of treatment completion, remain poorly defined. Methods: We retrospectively analyzed 248 patients with localized UGI adenocarcinoma treated with curative intent across multiple institutions (2006–2025). Demographic, clinical, pathologic, and treatment variables were abstracted. Logistic regression models evaluated predictors of recurrence and early mortality (≤24 months). Covariates included systemic therapy exposure (neoadjuvant ± adjuvant), tumor grade, regression (TRG), and patient factors (age, ECOG, albumin, LDH, neutrophil-to-lymphocyte ratio [NLR]). Separate models assessed predictors of completing ≥4 cycles of neoadjuvant therapy, ≥4 cycles of adjuvant therapy, and receipt of both neoadjuvant+adjuvant (Neo+Adj). Results: Median age was 64; 85% were male, and most presented with cT3N1 disease. 98% received neoadjuvant therapy, 67% received adjuvant therapy, and 66% completed both phases. Recurrence occurred in 46%. Median overall survival (OS) was 50.3 months, and 34 months for those who recurred. In multivariable analysis, completion of both systemic therapy phases was the strongest predictor of improved OS and reduced recurrence, independent of age, ECOG, stage, grade, and TRG (OR for death ≤24 months 0.28, p=0.004). While high grade and poor TRG retained adverse impact (OR ~2–4), their effect size was smaller than systemic therapy exposure. Importantly, the specific chemotherapy regimen (DCF, FLOT, DCF+IO, others) did not independently influence recurrence or OS once completion was considered. Predictors of treatment completion were not tumor-related: stage, grade, and TRG were not significant. Instead, patient factors dominated: higher albumin favored neoadjuvant completion (OR 1.09 per g/L, p=0.017); elevated NLR predicted failure to complete both phases (OR 0.88 per unit, p=0.035); ECOG ≥1 consistently reduced odds of completion. Conclusions: In localized UGI cancer, completing planned systemic therapy—not regimen choice—most strongly predicts recurrence and survival, outweighing tumor grade and regression. The main determinants of therapy completion are host factors rather than tumor characteristics. These findings suggest that future research and quality improvement should prioritize optimizing patient resilience (nutrition, inflammation, functional status) to enable therapy delivery, rather than focusing solely on intensifying or substituting regimens.

125 Background: Perioperative chemotherapy improves survival in resectable gastric and gastroesophageal junction (GEJ) adenocarcinoma; however, many patients fail to initiate postoperative therapy in routine practice. Host-related determinants of adjuvant treatment feasibility and survival remain incompletely defined. Methods: We conducted a retrospective cohort study of patients with localized gastric or GEJ adenocarcinoma treated with perioperative chemotherapy and curative-intent resection at the McGill University Health Centre (2006-2025). The primary outcome was adjuvant chemotherapy initiation. Overall survival (OS) was analyzed using Kaplan-Meier and Cox proportional hazards models; prespecified 3-month landmark analyses were performed to mitigate immortal time bias. Sequential multivariable logistic models evaluated tumor variables, host factors (age, ECOG, serum albumin), and postoperative inflammatory recovery (ΔlogNLR), with incremental discrimination assessed by AUC. Results: Among 248 patients (median age 64; 85% male), 168 (67.7%) initiated adjuvant chemotherapy, which was associated with improved OS (HR 0.45; 95% CI, 0.33–0.62), including in landmark analyses. Pathology-only modeling showed modest discrimination (AUC 0.66). Addition of host factors improved discrimination (AUC 0.75); increasing age was independently associated with lower odds of initiating adjuvant therapy (OR 0.94 per year; 95% CI, 0.89–0.98), whereas higher serum albumin was independently associated with greater odds of initiation (OR 1.09 per g/L; 95% CI, 1.01–1.18). In a prespecified nested analysis among 69 patients with available longitudinal inflammatory data, model discrimination improved sequentially from AUC 0.65 to 0.77 to 0.80 with addition of host factors and ΔlogNLR. Tumor factors and chemotherapy regimen were not independently associated with adjuvant initiation after adjustment. Conclusions: In localized upper gastrointestinal adenocarcinoma, postoperative chemotherapy feasibility and survival are more strongly associated with host factors and recovery than with tumor pathology or regimen selection. These findings support perioperative optimization strategies, including nutritional support, prehabilitation, and interventions targeting systemic inflammation, to improve treatment delivery. Incorporating host vulnerability into risk stratification may refine treatment planning beyond pathological response alone. Prospective validation of dynamic inflammatory biomarkers and targeted host-directed interventions is warranted to determine whether improving treatment feasibility translates into survival benefit.