Hospital-based Retrospective Cohort Research Articles

Breast Cancer Prognosis in Young BRCA1/BRCA2 Mutation Carriers: A Retrospective Hospital-based Cohort Study

AimStudies evaluating the prognostic impact of germline BRCA1/2 mutations (gBRCAm) in patients with breast cancer report conflicting results. Therefore, we aimed to investigate outcomes of patients with gBRCA mutations and early onset of breast cancer (<30 years) compared with those of noncarriers. Materials and methodsThis retrospective study included 149 patients recruited between 2005 and 2019. The outcomes were overall survival (OS) and disease-free survival (DFS), which were defined as the time from the first diagnosis to death from any cause and the first recurrence, second cancer, or death from any cause, respectively. Key patient data, Kaplan–Meier plots, and outcomes were described according to the BRCA mutation status. Hazard ratios (HR) were calculated using the Cox proportional hazards model. ResultsTwenty-eight patients (28/149; 18.8 %) were gBRCAm carriers. The OS median follow-up was 8.2 years. OS was 89.3% [70.4–96.4] in carriers vs 99.2% [95% CI: 94.3–99.9] in non-carrier patients at 2 years; 85.2% [65.2–94.2] vs 93.0% [86.5–96.5] at 5 years, and 76.5% [54.7–88.8] vs 85.2% [75.7–91.2] at 10 years. There was no difference in OS between groups in multivariable analysis (HR = 1.90 [0.69–5.23], p = 0.22). The DFS median follow-up was 6.6 years. Similar results were observed for DFS (HR = 1.39 [0.63–3.08], p = 0.42). ConclusionIn this large hospital-based cohort of patients with very early-onset breast cancer, we found no clear evidence that gBRCA1/2m significantly affects OS after adjusting for known prognostic factors.

Recent Trends in Diabetic and Nondiabetic Neuropathies: A Retrospective Hospital-based Nationwide Cohort Study

ObjectiveThe aim of this study was to evaluate the trends in the incidence of diabetic neuropathy (DN) and nondiabetic neuropathy (non-DN) in a hospital-based cohort between 2010 and 2019 in Romania. MethodsWe retrospectively analyzed cases with a primary or secondary discharge International Classification of Diseases, Tenth Revision, diagnosis code of neuropathy reported throughout Romania. ResultsA total of 1 725 729 hospitalizations with a diagnosis of neuropathy (DN, 769 324 - 44.6%, and non-DN, 956 405- 55.4%) were identified. Women accounted for more DN cases (40 0 936- 52.1%), and men accounted for more non-DN cases (63 7 968- 61.0%). The incidence rate showed an increasing trend during the index period, by a mean rate of 4.3%/year for non-DN and 1.4%/year for DN. Type 2 diabetes was responsible for the overall increase in the incidence rate of DN, whereas in type 1 diabetes, the incidence rate decreased; in both types of diabetes, diabetic polyneuropathy was predominant, whereas autonomic neuropathy had an incidence rate of 10 to 20 times lower than polyneuropathy. The incidence rates of non-DNs increased mainly due to inflammatory polyneuropathies (+3.8%) and uremic neuropathy (+10.3%). ConclusionUsing a nationally representative database of hospital-admitted cases, we found that the incidence rates of DN and non-DN increased from 2010 to 2019. The main contributors were type 2 diabetes, inflammatory polyneuropathy, and uremic neuropathy.

Changes in Bone Mineral Density in Patients With Non-dialysis-Dependent Chronic Kidney Disease Are Associated With Body Composition

Chronic kidney disease (CKD) and low bone mineral density (BMD) are highly prevalent and can co-exist. Parameters of mineral metabolism are associated with BMD in CKD, but other contributing factors may contribute. The aim of this study was to assess changes in BMD and its determinants in patients with non-dialysis-dependent CKD (NDD-CKD). Body composition and biochemical profiles were assessed in a retrospective hospital-based cohort study of patients with NDD-CKD. BMD, lean soft tissue (LST), appendicular LST (ALST), and percentage fat mass were assessed by dual-energy X-ray absorptiometry (DXA). ALST index (ALSTI, ALST/height2) and load-capacity index (LCI, fat mass/LST) were calculated. Low BMD was defined as t-score ≤-1.0. Mean time between assessments was 2.8±1.3 years, 46 patients were included. A reduction in renal function was observed. Changes in body composition included reductions in ALST (p=0.031), ALSTI (p=0.021) and a trend for BMD (p=0.053); and an increase in percentage fat mass (p=0.044) and LCI (p=0.032). Females had a reduction in BMD (p=0.034), ALST (p=0.026), and ALSTI (p=0.037). Patients with low BMD at baseline had lower LST (p=0.013), ALST (p=0.023), and percentage fat mass (p=0.037) than those with normal BMD. Additionally, reductions in LST (p=0.041), ALST (p=0.006), and ALSTI (p=0.008) were observed in patients who had low BMD at baseline, while no significant changes in body composition were observed in those with normal BMD at baseline. The following body composition parameters at baseline were determinants of BMD status at follow-up: LST (OR:0.899, 95%CI:0.829-0.976, p=0.010), ALST (OR:0.825, 95%CI:0.704-0.967, p=0.017), and ALSTI (OR:0.586, 95%CI:0.354-0.968, p=0.037), independent of fat mass, and LCI. Detrimental body composition changes were observed without changes in body weight; these were more significant in females. Moreover, this is the first longitudinal study showing a protective effect of LST against BMD loss in patients with NDD-CKD.

Risk of circulatory diseases associated with proton-pump inhibitors: a retrospective cohort study using electronic medical records in Thailand.

Proton-pump inhibitors (PPIs) are prescribed to treat gastric acid-related diseases, while they may also have potential risks to population health. Recent studies suggested that a potential mechanism explaining the association between PPIs and cardiovascular diseases (CVD) includes the inhibition of the nitrate-nitrite-nitric oxide (NO) pathway. However, previous observational studies showed controversial results of the association. In addition, the inhibition of the NO pathway due to PPIs use may lead to peripheral vascular diseases (PVD); however, none of the studies explore the PPI-PVD association. Therefore, this study aimed to evaluate the association of PPIs with circulatory diseases (CVD, ischemic strokes or IS, and PVD). We conducted a retrospective hospital-based cohort study from Oct 2010 to Sep 2017 in Songkhla province, Thailand. PPIs and histamine 2-receptor antagonists (H2RAs) prescriptions were collected from electronic pharmacy records, while diagnostic outcomes were retrieved from electronic medical records at Songklanagarind hospital. Patients were followed up with an on-treatment approach. Cox proportional hazard models were applied to measure the association comparing PPIs vs H2RAs after 1:1 propensity-score-matching. Sub-group analysis, multi-bias E-values, and array-based sensitivity analysis for some covariates were used to assess the robustness of associations. A total of 3,928 new PPIs and 3,928 H2RAs users were included in the 1:1 propensity score-matched cohort. As compared with H2RAs, the association of PPIs with CVD, IS, and PVD, the hazard ratios were 1.76 95% CI = [1.40-2.20] for CVD, 3.53 95% CI = [2.21-5.64] for ischemic strokes, and 17.07 95% CI = [13.82-76.25] for PVD. The association between PPIs and each outcome was significant with medication persistent ratio of over 50%. In addition, the association between PPIs and circulatory diseases was robust to unmeasured confounders (i.e., smoking and alcohol). PPIs were associated with circulatory diseases, particularly ischemic strokes in this hospital-based cohort study, whereas, the strength of associations was robust to unmeasured confounders.

Age and Gender Difference among Elderly Stroke Patients in a Rehabilitation Center, Retrospective Study

Aims This study aims to report the patients’ associated factors related to the study cohort. Methods This is a retrospective hospital-based cohort study that recruited 503 elderly patients (>55 years) with stroke from a tertiary rehabilitation center. Data were collected through a pre-designed case report form, and stroke was classified according to Data on Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Results There was a female predominance at a rate of 52.9% and a significant co-morbidity related to diabetes, hyperlipidemia, and hypertension in addition to cardiac disease. The ischemic stroke affected 84.7% of the studied sample. The univariate analysis reported that male gender, diabetes, hypertension, and hyperlipidemia were not associated with an increased risk of non-ischemic stroke, while obesity showed a paradoxical reduction in the risk of stroke. Conclusion Stroke among old patients behaves differently and warrants initiating both primary and secondary prevention programs.

Vaccination Status and In-hospital Mortality Among Adults With COVID-19 in Jakarta, Indonesia: A Retrospective Hospital-based Cohort Study.

Prospective studies on vaccination status and mortality related to coronavirus disease 2019 (COVID-19) in low-resource settings are still limited. We assessed the association between vaccination status (full, partial, or none) and in-hospital mortality among COVID-19 patients at most hospitals in Jakarta, Indonesia during the Delta predomination wave. We conducted a retrospective cohort study among hospitalized COVID-19 patients who met the study criteria (>18 years old and admitted for inpatient treatment because of laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection). We linked individual-level data in the hospital admission database with vaccination records. Several socio-demographic and clinical characteristics were also analyzed. A Cox proportional hazards regression model was used to explore the association between vaccination status and in-hospital mortality in this patient group. In total, 40 827 patients were included in this study. Of these, 70% were unvaccinated (n=28 543) and 19.3% (n=7882) died during hospitalization. The mean age of the patients was 49 years (range, 35-59), 53.2% were female, 22.0% had hypertension, and 14.2% were treated in the intensive care unit, and the median hospital length of stay across the group was 9 days. Our study showed that the risk of in-hospital mortality among fully and partially vaccinated patients was lower than among unvaccinated adults (adjusted hazard ratio [aHR], 0.43; 95% confidence interval [CI], 0.40 to 0.47 and aHR, 0.70; 95% CI, 0.64 to 0.77, respectively). Vaccinated patients had fewer severe outcomes among hospitalized adults during the Delta wave in Jakarta. These features should be carefully considered by healthcare professionals in treating adults within this patient group.

Oxidative Stress-regulating Enzymes and Endometrial Cancer Survival in Relation to Metformin Intake in Diabetic Patients.

Metformin inhibits tumorigenesis in endometrial carcinoma and interferes with the expression of oxidative stress-regulating proteins, such as nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1). Although manganese superoxide dismutase (MnSOD) is vital for withstanding mitochondrial oxidative stress, it has also been linked with chemoresistance and poorer outcomes in several cancer types. However, data on endometrial cancers are limited. This study aimed to highlight the relationship between mitochondrial redox regulation and endometrial cancer survival in relation to metformin consumption in women with type 2 diabetes mellitus (T2DM). Our retrospective hospital-based cohort study included 121 patients diagnosed with endometrial carcinoma and T2DM between 2007 and 2014. Fifty-eight patients were using metformin at the time of diagnosis. Nrf2 and Keap1 expression levels in the tumor samples were assessed immunohistochemically, and MnSOD levels were measured both immunohistochemically and from the serum samples. High MnSOD tissue expression was associated with better overall survival among metformin users in the univariate analysis (p=0.03). When adjusted for histology and stage, high serum MnSOD was associated with better overall survival (HR=0.22, 95%CI=0.07-0.71, p=0.01). No association was found between MnSOD, Nrf2, or Keap1 and overall survival among metformin non-users. Higher expression of MnSOD in patients with endometrial cancer and T2DM is associated with better overall survival if the patient is consuming metformin.

Impact of Functional Status on Development of Clostridioides difficile Infection and Increase in Inhospital Mortality among Antibiotic Users

Introduction: Functional status is one of the surrogates of advanced age, an established risk factor for Clostridioides difficile infection (CDI). We aimed to investigate the usefulness of functional status in the clinical management of CDI. Methods: We enrolled all hospitalized adult patients receiving antibiotics from a retrospective hospital-based cohort in Japan between 2016 and 2020. Using the Barthel index (BI), which is an objective scale of functional status, we investigated the association of BI with developing CDI and its impact on inhospital mortality in patients with CDI. Results: We enrolled 17,131 patients with 100 cases of CDI. Multivariable analysis revealed that lower BI (≤25) was an independent risk factor for developing CDI (adjusted odds ratio, 4.11; 95% confidence interval, 2.62–6.46). Furthermore, a combination of BI and Charlson comorbidity index (CCI) showed an adjusted odds ratio of 36.40 (95% confidence interval, 17.30–76.60) in the highest risk group. A high-risk group according to the combination of BI and CCI was estimated to have significantly higher inhospital mortality in patients with CDI using the Kaplan-Meier method (p = 0.017). A combination of lower BI and higher CCI was an independent predictor of inhospital mortality even in the multivariable Cox regression model (adjusted hazard ratio, 3.00; 95% confidence interval, 1.01–8.88). Conclusions: Assessment of functional status, especially combined with comorbidities, was significantly associated with developing CDI and may also be useful in predicting inhospital mortality.

Perinatal outcome and long-term hospitalization of triplets according to birth order.

The association between birth order and adverse perinatal outcomes has been well studied in twin pregnancies. However, little is known about the differences in immediate perinatal outcomes as well as long-term hospitalization of the offspring in triplet pregnancies according to their birth order. As such, we aimed to assess the differences in immediate perinatal outcomes and long-term hospitalizations among triplets by their birth order. In a retrospective hospital-based cohort study, immediate perinatal outcomes and long-term hospitalizations were compared among triplet siblings according to their birth order. Deliveries occurred between the years 1991 and 2021 in a tertiary medical center. The study groups were followed until 18 years of age for cardiovascular, respiratory, neurological, and infection-related hospitalizations. Generalized estimation equation (GEE) models were used to control for confounders. Kaplan-Meier survival curves were used to compare cumulative long-term hospitalization incidences and Cox proportional hazards models were performed to control for confounders. The study included 117 triplet deliveries. Rates of small for gestational age (SGA) infants increased linearly by birth order (6.0%, 7.7%, and 15.4% for the first, second, and third siblings, respectively; p-value for trends = 0.035). Using a GEE model controlling for maternal age, being born third in a triplet pregnancy was independently associated with SGA (third vs. first sibling, adjusted OR 3.0, 95% CI 1.38-6.59, p = 0.005). No significant differences in cardiovascular, respiratory, neurological, and infection-related hospitalizations were noted among the first, second, and third siblings. Likewise, using Kaplan-Meier survival analyses, no significant differences in the cumulative incidence of long-term pediatric hospitalizations were noted between the siblings. In Cox proportional hazards models, controlling for weight and gender, birth order in a triplet pregnancy did not exhibit an association with long-term hospitalizations of the offspring. Despite the association between birth order and SGA, birth order in triplets does not seem to have an impact on the risk for long-term offspring hospitalization.

Stroke incidence in Indigenous, minority populations: a review of methods for studying stroke in Aboriginal and Torres Strait Islander Australians

Declining worldwide or national stroke incidence rates are not always mirrored in disadvantaged, minority populations. Logistical barriers exist for effective measurement of incidence in minority populations; such data are required to identify targets for culturally appropriate interventions. In this comparative review, we aimed to examine whether “gold-standard” methodologies of stroke incidence studies are most effective for minority populations. We compared three studies of stroke incidence in Aboriginal Australians, each using different methodologies of case ascertainment. In Study 1, “gold-standard” population-based methods were used, while in Study 2, a retrospective hospital-based cohort design was utilized, and in Study 3, whole-of-population linked hospital and mortality data was employed. Study 1 captured both in-hospital and out-of-hospital stroke events but had a small sample size for Aboriginal patients. Study 2 provided a larger sample size while still allowing for clinical and radiological subtyping of stroke but was subject to selection bias and was limited to hospitalized cases. Study 3 had a large sample size and allowed for subgroup analysis, though lacked clinical adjudication and had large proportions of ‘undetermined stroke'. Despite diagnostic imprecision, we recommend a paradigm shift in measuring stroke incidence in Indigenous, minority populations, favoring the use of whole-of-population data linkage including non-hospitalized stroke deaths, over resource-intensive prospective methods, where more suitable for the target population.

Lessons to be learned from real life data from 98 gout patients using benzbromarone

Aim: This study aims to analyze the efficacy and safety of benzbromarone as uricosuric, in a real-life clinical setting of a retrospective hospital-based gout cohort. Methods: Data from gout patients were retrieved from the digital hospital dossiers. Demographics, clinical variables, and laboratory parameters were collected at baseline and 6 months. Efficacy was measured by reaching a serum uric acid (sUA) target &lt; 0.30 mmol/L at 6 months, and the fractional excretion of uric acid (FeUA) was used as a parameter with a potential predictor value. Results: Data from 98 gout patients were analyzed. Patients were 70 (± 12) years of age, and 90% were male. After 6 months of treatment, 68 out of 98 patients (69%) reached a sUA level &lt; 0.30 mmol/L (5 mg/dL). In patients with a FeUA &lt; 4.5%, so-called low excretors, the FeUA increase was most impressive from 3.2% (± 1.0%) to 12.1% (± 6.9%) after 6 months of benzbromarone treatment (mean increase +8.9% [95% confidence interval (CI): +6.5 to +11.5%], P &lt; 0.001). In non-low excretors, FeUA was on average 7.3% (± 5.1%) and increased to 9.7% (± 6.1%): a mean +2.1% change (95% CI: –2.2 to +6.6%). The increase differed insignificantly in low versus non-low excretors: P &gt; 0.05. Four patients stopped benzbromarone treatment because of a progressive decline in renal function, a condition that was already present before benzbromarone was initiated. Remarkably 38% of patients still using benzbromarone after 3.8 (± 3.4) years of treatment. Conclusions: Using the uricosuric benzbromarone in real-life gout patients proved effectivity in lowering sUA levels within 6 months by increasing FeUA significantly. Particularly low excretors benefit from benzbromarone treatment manipulating this mode of action. Determining FeUA in gout patients may further help to find the patient profile benefiting the most from benzbromarone treatment.

A Nomogram for Predicting the Recurrence of Acute Non-Cardioembolic Ischemic Stroke: A Retrospective Hospital-Based Cohort Analysis.

Non-cardioembolic ischemic stroke (IS) is the predominant subtype of IS. This study aimed to construct a nomogram for recurrence risks in patients with non-cardioembolic IS in order to maximize clinical benefits. From April 2015 to December 2019, data from consecutive patients who were diagnosed with non-cardioembolic IS were collected from Lanzhou University Second Hospital. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to optimize variable selection. Multivariable Cox regression analyses were used to identify the independent risk factors. A nomogram model was constructed using the "rms" package in R software via multifactor Cox regression. The accuracy of the model was evaluated using the receiver operating characteristic (ROC), calibration curve, and decision curve analyses (DCA). A total of 729 non-cardioembolic IS patients were enrolled, including 498 (68.3%) male patients and 231 (31.7%) female patients. Among them, there were 137 patients (18.8%) with recurrence. The patients were randomly divided into training and testing sets. The Kaplan-Meier survival analysis of the training and testing sets consistently revealed that the recurrence rates in the high-risk group were significantly higher than those in the low-risk group (p < 0.01). Moreover, the receiver operating characteristic curve analysis of the risk score demonstrated that the area under the curve was 0.778 and 0.760 in the training and testing sets, respectively. The nomogram comprised independent risk factors, including age, diabetes, platelet-lymphocyte ratio, leukoencephalopathy, neutrophil, monocytes, total protein, platelet, albumin, indirect bilirubin, and high-density lipoprotein. The C-index of the nomogram was 0.752 (95% CI: 0.705~0.799) in the training set and 0.749 (95% CI: 0.663~0.835) in the testing set. The nomogram model can be used as an effective tool for carrying out individualized recurrence predictions for non-cardioembolic IS.

1089-P: Gestational Glucose Intolerance and Risk of Childhood Overweight and Obesity

Infants of individuals with gestational glucose intolerance (GGI, abnormal glucose loading test [GLT] without gestational diabetes [GDM]) have increased risk of large for gestational age birthweight, but an association between GGI and childhood adiposity has not been consistently observed. We studied the risk of overweight and obesity in 2-5-year-old children exposed to varying degrees of maternal glycemia in utero in a retrospective hospital-based cohort. We defined normal glucose tolerance (NGT) as a GLT &amp;lt;140 mg/dl, GGI as GLT ≥ 140 mg/dl and zero (GGI-0) or 1 (GGI-1) abnormal values on a 3-hour 100-gram oral glucose tolerance test (OGTT), and gestational diabetes (GDM) as ≥2 abnormal values. We used logistic regression to investigate the risk of obesity, defined as body mass index (BMI) &amp;gt; 95th percentile, in children born to individuals with GGI and GDM as compared to NGT. In model 1, we adjusted for maternal age, gestational weight gain, parity, insurance, race/ethnicity, marital status, gestational age at delivery and infant sex; in model 2, we further adjusted for maternal 1st trimester BMI. Of n=12728 children, 48.5% were female, the mean (SD) gestational age at delivery was 39.4 (1.7) weeks, and the mean birthweight was 3341 (519) grams. A total of 10567 children were exposed to NGT in utero, 1156 to GGI-0, 428 to GGI-1, and 577 to GDM. Obesity was present in 12.9% of children exposed to NGT, 12.5% exposed to GGI-0, 16.6% exposed to GGI-1, and 18.5% exposed to GDM, respectively. In model 1, there was an increased odds of obesity in those exposed to GGI-1 (1.37 [1.04, 1.78], P=0.02) and GDM (1.61 [1.28, 2.02] P&amp;lt;0.001). After maternal BMI adjustment, we did not find a significant increased risk of obesity in any group compared to NGT (GGI-1: 1.15 [0.86, 1.51] P=0.33; GDM 1.24 (0.97, 1.57), P=0.08). After accounting for maternal BMI, children exposed to GGI and GDM in utero have a similar risk of obesity in early childhood to those born to NGT pregnancies. Disclosure J.Maya: None. S.Hsu: None. C.C.M.Schulte: None. K.James: None. T.Thaweethai: None. M.Hivert: None. C.E.Powe: Consultant; Mediflix, Inc., Other Relationship; Wolters Kluwer Health. Funding National Institutes of Health (T32DK007028-47S1)

Thrombogenesis-associated genetic determinants as predictors of thromboembolism and prognosis in cervical cancer

Venous thromboembolism (VTE) is a leading cause of death among cancer patients. Khorana score (KS) is the most studied tool to predict cancer-related VTE, however, it exerts poor sensitivity. Several single-nucleotide polymorphisms (SNPs) have been associated with VTE risk in the general population, but whether they are predictors of cancer-related VTE is a matter of discussion. Compared to other solid tumours, little is known about VTE in the setting of cervical cancer (CC) and whether thrombogenesis-related polymorphisms could be valuable biomarkers in patients with this neoplasia. This study aims to analyse the effect of VTE occurrence on the prognosis of CC patients, explore the predictive capability of KS and the impact of thrombogenesis-related polymorphisms on CC-related VTE incidence and patients’ prognosis regardless of VTE. A profile of eight SNPs was evaluated. A retrospective hospital-based cohort study was conducted with 400 CC patients under chemoradiotherapy. SNP genotyping was carried on by using TaqMan® Allelic Discrimination methodology. Time to VTE occurrence and overall survival were the two measures of clinical outcome evaluated. The results indicated that VTE occurrence (8.5%) had a significant impact on the patient’s survival (log-rank test, P < 0.001). KS showed poor performance (KS ≥ 3, χ2, P = 0.191). PROCR rs10747514 and RGS7 rs2502448 were significantly associated with the risk of CC-related VTE development (P = 0.021 and P = 0.006, respectively) and represented valuable prognostic biomarkers regardless of VTE (P = 0.004 and P = 0.010, respectively). Thus, thrombogenesis-related genetic polymorphisms may constitute valuable biomarkers among CC patients allowing a more personalized clinical intervention.

Impacts of androgen pathway manipulation on patients with lung cancer.

e21010 Background: Sex hormone may play a role in lung cancer pathophysiology. We aimed to evaluate if androgen pathway manipulation (APM) is associated with better survival in patients with lung cancer, and how finasteride, a 5-alpha reductase inhibitor, impacts androgen receptor (AR) activation and growth of lung cancer cells. Methods: In this retrospective hospital-based cohort study, we screened all men with lung cancer diagnosed during the period from January 2006 to December 2021. APM exposure was defined as using antiandrogens, 5-alpha reductase inhibitors, or gonadotropin-releasing hormone agonists for &gt; 30 days after lung cancer diagnosis. The in vitro study was conducted on A549 lung cancer cells; while the tumor xenograft model was conducted on BALB/c nude mice. Results: Among 4744 men with lung cancer, 98 (2.1%) were identified as having APM exposure. The majority of patients (73.5%) received 5-alpha reductase inhibitors. The patients with APM exposure were older (71.5 vs. 67.0, p &lt; 0.001), had a higher proportion of having prostate cancer (27.6% vs. 1.4%, p &lt; 0.001), and had a smaller proportion of having metastatic lung cancer (41.8% vs. 54.0%, p = 0.003), compared to those without APM exposure. In multivariable Cox proportional hazards analysis, patients with APM exposure experienced better OS compared to those without exposure (Hazard ratio 0.57; 95% CI, 0.44–0.73, p &lt; 0.001). In in vitro study, we illustrated that AR protein stimulated the cell proliferation of A549 cells. Finasteride reduced the AR protein expression and inhibited A549 cell growth. Finasteride promoted ubiquitination and degradation of AR protein and therefore interfered the stability of AR protein. Furthermore, finasteride inhibited cell cycle progression and promoted apoptosis of A549 cells. The in vivo results also supported the inhibition effect of finasteride on lung cancer growth. Conclusions: APM was associated with better OS in male patients with lung cancer. Finasteride interfered with the stability of AR and inhibited A549 lung cancer cell growth. Our findings indicated an oncogenic role of AR on lung cancer which may provide potential therapeutic and targets for lung cancer. The inhibition effect of finasteride on lung cancer might be of benefit for future treatment strategies, prevention and control.[Table: see text]

Comparative Safety and Changes in Immunologic and Virologic Parameters of Dolutegravir versus Efavirenz-Based Antiretroviral Therapies Among HIV Patients: A Retrospective Cohort Study.

In combination with other two antiretroviral drugs, an efavirenz (EFV) or dolutegravir (DTG)-based regimen is the treatment of choice for human immunodeficiency virus (HIV) infection. This study aimed to determine the safety and changes in immunologic and virologic parameters of DTG compared with EFV-based ART as first-line HIV treatment among HIV patients. A retrospective hospital-based cohort study was carried out from September 1, 2019 to August 30, 2020 at HIV clinics of three selected hospitals in North-West-East Ethiopia, Amhara Region. All HIV patients ≥3 years old, who had been on either DTG or EFV-based combination anti-retroviral therapy (cART), and had detectable viral load (VL) were included. Descriptive and multivariate Cox regression analyses were used. Overall, 990 HIV patients were included in the analysis (DTG n=694, EFV n=296). A VL of <50 copies/mL was observed in 69% of patients in the DTG group and 66% in the EFV group (crude hazard ratio [CHR] =1.28, 95% CI: 1.08-1.51; p=0.004). Out of the total, 289 (42%) of the patients in the DTG group reported adverse drug events (ADEs) compared with 147 (50%) in the EFV group (p=0.020). Younger age, opportunistic infections (OIs), bed-ridden condition, no prophylaxis for OIs, low baseline cluster of differentiation 4 (CD4) count, high baseline VL, poor adherence, and ADEs were predictors of poor survival, and younger age, OIs, low baseline CD4, DTG-based initial regimen, poor adherence with cART, naïve treatment history, and student job type were predictors of poor safety outcomes. The DTG-based regimen demonstrates an improved viral suppressionand CD4 cell recovery, and better safety profile compared with the EFV-based regimen for the treatment of HIV-infected patients. A baseline CD4+ T-cell count <200 cells/mm3, OIs, and poor adherence with therapy were factors associated with poor survival and safety outcomes. HIV patients with these risk factors should be treated and monitored regularly.

Vonoprazan poses no additional risk of developing Clostridioides difficile infection compared to proton pump inhibitors.

The use of proton pump inhibitors (PPIs) has been repeatedly reported as a trigger of Clostridioides difficile infection (CDI), a leading cause of nosocomial diarrhea. However, only a few studies have reported on the association between vonoprazan, a novel potassium-competitive acid blocker providing potent acid suppression, and CDI, with no studies having been conducted in a clinical setting. We therefore evaluated the association between various classes of acid suppressants and CDI with special attention paid to differences in the magnitudes of association between PPIs and vonoprazan. A retrospective hospital-based cohort from a secondary-care hospital in Japan (n=25821) was collected, wherein eligible CDI cases were defined as hospital-onset cases (n=91). A multivariable adjusted logistic regression analysis for the entire cohort and propensity analyses for subgroups consisting of PPI and/or vonoprazan users at various doses (n=10306) were performed. The overall CDI incidence rate was 1.42/10000 patient-days, which was comparable with previous reports. A multivariable analysis showed that both PPIs and vonoprazan were positively associated with CDI (odds ratios [95% confidence intervals]: 3.15 [1.67-5.96] and 2.63 [1.01-6.88], respectively). In addition, matched subgroup analyses showed that PPIs and vonoprazan had equivalent magnitudes of association with CDI. We found that both PPIs and vonoprazan were associated with CDI, and the magnitude of the association was comparable. Because vonoprazan is widely available in Asian countries, further studies on the association of its usage with CDI are warranted.

A retrospective cohort study on the cardiotoxicity incidence rates of immune checkpoint inhibitors for oncology patients.

This present study investigated the incidence rates of cardiotoxicity among cancer patients treated with immune checkpoint inhibitors (ICIs) plus other anticancer drugs. This was a retrospective hospital-based cohort study using the medical records and the Cancer Registry records from the Taipei Veterans General Hospital. We enrolled patients diagnosed with cancer between 2011 and 2017, who were over 20 years old and had received ICI therapy, including pembrolizumab, nivolumab, atezolizumab, and ipilimumab. Cardiotoxicity was defined by the diagnosis of myocarditis, pericarditis, arrhythmia, heart failure, and Takotsubo syndrome. We identified 407 patients who were eligible to participate in this study. We defined the three treatment groups as follows: ICI therapy, ICI combined with chemotherapy, and ICI combined with targeted therapy. Using ICI therapy as a reference group, the cardiotoxicity risk was not significantly higher compared to the ICI combined with chemotherapy group (adjusted hazard ratio 2.1, 95% confidence interval 0.2-21.1, p = 0.528] or to the ICI combined with targeted therapy group (adjusted hazard ratio 1.2, 95% confidence interval 0.1-9.2, p = 0.883). The total incidence rate of cardiotoxicity was 3.6 of 100 person-years, indicating an average incidence time of 1.0 ± 1.3 years (median: 0.5 years; range: 0.1-4.7 years) for 18 cardiotoxicity patients. The incidence rate of ICI-related cardiotoxicity is low. Combination of ICI with either chemotherapy or targeted therapy might not significantly increase the risk of cardiotoxicities among cancer patients. Nevertheless, it is recommend being careful in patients treated high-risk cardiotoxicity medications to avoid drug-related cardiotoxicity with a combination of ICI therapy.

Abstract P6-02-16: Breast cancer prognosis of germline BRCA1/BRCA2 mutation carriers of young women: a retrospective hospital-based cohort

Abstract Background Studies evaluating prognostic impact of germline BRCA1/2 mutations (gBRCAm) on breast cancer patients reported controversial results. The primary aim of this study was to investigate outcomes of young gBRCAm patients with very early onset of breast cancer (&amp;lt; 30 years) compared with noncarriers. Methods In this retrospective study, 149 patients 30 years aged or younger at early breast cancer diagnosis between 2005 and 2019 were included in Oscar Lambret Center. Outcomes were overall survival (OS) and disease-free survival (DFS), defined as time from first diagnosis to first recurrence, second cancer or death from any cause, at 2 years, 5 years, and 10 years. Key patient data, kaplan-meier plots and outcomes were described by BRCA mutation status. Hazard ratios (HR) were calculated using Cox proportional-hazards models. Results Twenty-eight (18.8%) patients were gBRCAm carriers. The median follow-up was 6.5 years (IQR 0.25-16.5). Twenty-three deaths, 41 recurrences and 2 second cancers were reported. OS was 89.3% [70.4–96.4] in gBRCAm patients vs 99.1% [95% CI 93.9–99.9] in non-carriers patients at 2 years; 85.0% [64.7–94.1] vs 92.3% [85.1–96.1] at 5 years and 75.3% [52.5–88.3] vs 80.2% [66.6–88.7] at 10 years. There was no difference in OS between groups in multivariable analysis (HR=1.63 [0.55–4.77], p=0.37). Similar results were noted when comparing disease-free survival (HR=1.42 [0.64–3.11], p=0.38). Conclusions In this cohort of 149 patients with very early onset breast cancer, outcomes of gBRCAm mutation carriers did not differ from non-carriers when adjusted for others prognostic factors. Citation Format: Florent HEGO, Maël BARTHOULOT, Charles PIERARD, Audrey Mailliez. Breast cancer prognosis of germline BRCA1/BRCA2 mutation carriers of young women: a retrospective hospital-based cohort [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-02-16.

Polycythemia vera disease profile in an African population-experience from a tertiary facility in Ghana.

The study describes the clinical and laboratory profile of the patients with polycythemia vera at Komfo Anokye Teaching Hospital in Kumasi, Ghana. This was a retrospective hospital-based cohort study conducted from September 2020 to August 2022. Hematology clinic entry book was used to identify the patient's unique hospital code. Using these unique codes, retrospective data were collected using an Excel spreadsheet from the Hospital Lightwave health information management system (LHIMS) database. A total of 20 participants were recruited over the period of 2 years. The overall mean age was 51.53 ± 16.39 years. The hematological profile of the male participants revealed a mean hemoglobin of 18.25 ± 1.373 g/dl, mean hematocrit of 52 ± 3.47%, and a mean platelet of 345.5 ± 180.82. Comparatively, the mean hemoglobin, hematocrit, and platelet for the female participants were higher with figures of 19.26 ± 1.43 g/dl, 53 ± 3.61%, and 816 ± 935.32, respectively. Headache, tiredness, numbness, splenomegaly, and abnormal labs were the most common reasons why participants sought medical attention. Majority (60%) of the study participants had Janus Kinase 2 mutation. New-onset hypertension was identified in 45% of the study participants during follow-up. Thromboembolism was seen in 10% of the study population. Polycythemia vera is an uncommon disease in Ghana mostly found in older males above 50 years. It is important to recognize it early to initiate therapy aimed at preventing common complications such as hypertension and thromboembolism. Polycythemia vera should be considered a differential diagnosis for patients with secondary hypertension.