Historical Cohort Of Patients Research Articles

Afterload mismatch is associated with gender mismatch and negatively affect long-term outcome after heart transplant

Abstract Background Cardiac physiology changes after heart transplant (HT), resulting in a restrictive physiology with an increase in both arterial elastance (Ea) and ventricular elastance (Ees). This leads to a higher susceptibility to develop afterload mismatch, although the early identification of this phenomenon has not yet been explored. The aim of this study is to identify the presence of afterload mismatch after HT, its determinants, and its impact on cardiac mortality. Methods We conducted an observational, single-centre study based on the historical cohort of patients who underwent HT from 1985 to 2015 at our institution. We included patients who had survived the first year after HT with left ventricular ejection fraction (LVEF) ≥ 50%, International Society of Heart and Lung Transplantation (ISHLT) cardiac allograft vasculopathy of grade 0-1, and ISHLT acute cellular rejection of grade 0-1R at 1 year after HT. Ea and Ees were calculated using a non-invasive method based on blood pressure and end-systolic volume and end-diastolic volume measured at transthoracic echocardiography. Patients were grouped in 3 categories according to the presence of increased afterload and afterload mismatch as follows: low afterload (LA - Ea lower the median), matched high afterload (MHA - Ea higher of equal than the median, Ees higher or equal than the median), afterload mismatch (AM - Ea higher or equal than the median, Ees lower than the median). The impact of AM on long-term outcome, defined as cardiac mortality, was investigated, as well as predictors of AM. Results The study cohort consisted of 345 HT patients. The median of Ea and Ees were 4.0mmHg/mL and 6.75mmHg/mL, respectively. 49 patients (13%) developed AM, while LA and MHA groups accounted for 49% and 36% of the cohort, respectively. Patients with AM were mostly male (91%), with ischemic heart disease (45%) and a higher percentage of left ventricular assisted device prior to HT (8%). LVEF was lower in AM (57% vs 63% and 64% for LA and MHA respectively, p < 0.0001), while stroke volume was lower than LA and similar to MHA (27ml vs 35mL and 26mL for LA and MHA respectively, p = 0.0001). Predictors of AM were male recipient from male donor (Mr/Md) (β 015, p = 0.0067) and Mr from female donor (Mr/Fd) (β 0.6, p = 0.0078). After a median of 11.3-year follow-up, 59 (17%) HT recipients died. Cardiac mortality was higher in AM than in the other groups (AM median survival 17.2y vs 27.8y and 24.1y for LA and MHA respectively, log-rank p = 0.005). After adjusting for confounding variables, AM was a predictor of cardiac mortality (HR: 2.26; 95%CI 1.18 – 4.35), such as Mr/Fd (HR 2.94; 95%CI 1.18 – 4.35, p = 0.0358). Conclusion AM, in the context of a normal LVEF, is associated with male donor and sex mismatch, and negatively affects long-term outcome after HT.KM curvesCox proportional hazard model

Telemedicine and Access to Elective Cholecystectomy for Socially Vulnerable Adults

Socially vulnerable patients with symptomatic cholelithiasis are more likely to face barriers to accessing surgical care. This barrier to access can lead to delays in treatment, the need for emergent cholecystectomy, and worse outcomes. To determine the effectiveness of telemedicine vs in-person surgical consultation on access to elective cholecystectomy in socially vulnerable populations and to evaluate the association of scheduling navigation with access to elective cholecystectomy in these populations. This pilot randomized clinical trial conducted in a single academic center enrolled 60 adults from February 1, 2023, to February 21, 2024, with 3-month follow-up of clinical outcomes. Data were also collected retrospectively on a comparison group of 32 patients referred from June 30 to December 29, 2022. Adults with social vulnerability, such as being non-White or Hispanic or having nonprivate insurance or low income, with a diagnosis of symptomatic cholelithiasis and referral for outpatient surgical consultation were included. All trial participants were randomized to the telemedicine or in-person surgical consultation group, and received professional scheduling navigation. The latter intervention was compared with a historical cohort without navigation assistance. The primary outcome was completion of outpatient surgical consultation. Secondary outcomes included receipt of treatment and operative urgency. The trial enrolled 60 participants (30 per arm). Their mean (SD) age was 48.2 (18.2) years, 50 (83.3%) were female, 2 (3.3%) were Asian, 39 (65.0%) were Black, 8 (13.3%) were Hispanic, 11 (18.3%) were White, and 41 (68.3%) had no private insurance. The historical patient cohort included 32 participants (mean [SD] age, 45.9 [3.2] years; 27 [84.4%] female; 3 [9.4%] Asian, 15 [46.9%] Black, 10 [31.3%] Hispanic, and 6 [18.8%] White; and 18 [56.3%] without private insurance). In total, 18 trial participants assigned to telemedicine (60.0%) completed surgical consultations compared with 23 trial participants assigned to in-person visits (76.7%; P = .17). For telemedicine participants who underwent cholecystectomy, 3 of 7 (42.9%) underwent emergent cholecystectomy compared with 0 of 14 (0%) participants with in-person consultations (P = .03). Of 30 trial participants who received scheduling navigation, 23 (76.7%) completed surgical consultations compared with 15 of 32 patients in the historical cohort who did not receive scheduling navigation (46.9%; P = .02). Of 14 trial participants who received scheduling navigation and cholecystectomy, no participants underwent emergent cholecystectomy compared with 4 of 16 (25.0%) participants in the historical cohort without scheduling navigation (P = .04). In this pilot randomized clinical trial of socially vulnerable adults with symptomatic cholelithiasis, telemedicine consultation compared with in-person visits did not improve access to elective outpatient surgical care. However, scheduling navigation services may improve access to elective outpatient surgical care. Future large-scale studies are needed to identify possible barriers to virtual health care and mechanisms to address inequities. ClincialTrials.gov Identifier: NCT05745077.

Analysis of progression-free and overall survival in ovarian cancer: Bevacizumab treatment outcomes using historical cohort.

Background: The incorporation of bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), has redefined therapeutic strategies for advanced ovarian cancer. This study evaluates the efficacy of bevacizumab combined with standard chemotherapy by comparing progression-free survival (PFS) and overall survival (OS) outcomes with a historical cohort of patients treated with standard chemotherapy alone. Methods: We conducted an analysis of 71 patients with advanced epithelial ovarian cancer treated at the University Clinical Center in Niš, Serbia, from April 2017 to March 2023. All patients received standard chemotherapy paired with bevacizumab and were monitored for progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier estimates. Subgroup analyses were performed based on age, ECOG performance status, presence of metastases, and pleural effusion. Additionally, a historical cohort of 30 patients treated with standard chemotherapy alone was used for comparison, and Cox regression analysis was conducted to identify factors influencing treatment outcomes. Results: The study findings indicate significant improvements in median PFS (20 months vs. 15 months) and OS (58 months vs. an undetermined upper limit) compared to the historical cohort. Subgroup analysis of the bevacizumab-treated group revealed that younger patients (<65 years) and those without metastases or pleural effusion exhibited notably better survival outcomes. The hazard ratio for PFS in patients younger than 65 was 0.65 (95% CI: 0.45-0.93), suggesting a substantial reduction in disease progression risk compared to older patients. Conclusion: Bevacizumab, when used alongside standard chemotherapy, significantly extends both PFS and OS in patients with advanced ovarian cancer. These benefits are particularly pronounced in younger patients. The results underscore the necessity of integrating bevacizumab into the treatment regimen for advanced ovarian cancer, advocating for tailored therapeutic strategies based on individual risk profiles and clinical characteristics. This study reinforces the pivotal role of bevacizumab in enhancing the current ovarian cancer treatment landscape and highlights the potential for further personalizing oncological care.

The real-world use and effectiveness of avacopan in routine practice for the treatment of ANCA vasculitis. First experiences in Spain.

ANCA-associated vasculitis (AAV) are chronic diseases with relapses that associate organic damage because of the disease and its treatment. Avacopan is a new treatment indicated for AAV. We present the first experiences with avacopan in Spain as part of an Early Access program. Patients with AAV who started avacopan between June 2022-September 2023 were included. For comparison, a historical cohort of patients diagnosed with AAV around the same time and treated without avacopan was also included. 29 patients treated with avacopan were analyzed. Twelve patients (41.4%) were male, median age was 56 years. Most of patients were ANCA MPO positive (21/29, 72.4%). The most frequently affected organ was the kidney (23/29, 79.31%), with a mean eGFR of 23.2 ml/minMedian follow-up was 456.8 ± 181.7 days with a remission rate of 86.2%. eGFR increased from 23.2 ± 11.2-38.38 ± 18.55 ml/min after 12 months of diagnosis.2 patients had Adverse Events related to avacopan as severe neutropenia and a gastrointestinal affectation , 13 infections were reported and 1 death.Patients treated with avacopan received a significantly lower cumulative dose of prednisone at 6 and 12 months (p-values of 0.02 and <0.01, respectively) compared with historical controls. The evolution of GFR at 1 year of follow-up and the incidence of relapse were similar in both groups. The combination of avacopan in clinical practice presents a good safety profile and provides added value by contributing to the control of AAV activity, increase GFR, and removal of steroids.

Cutoff Values of Aldosterone and the Aldosterone-Renin Ratio for Predicting Primary Aldosteronism in Patients with Resistant Hypertension: A Real-Life Study.

Primary aldosteronism (PA) is commonly associated with resistant hypertension. Biochemical tests can be clinically useful in the screening and diagnosis of primary aldosteronism. This study aimed to identify the cutoff values of aldosterone levels (A) and the aldosterone-renin ratio (ARR) for an accurate prediction of PA in patients with apparent resistant hypertension in a real-life scenario. This database-based study included a historical cohort of male and female patients with apparent resistant hypertension, aged 18 years or older and surveyed for PA in a specialized center from 2008 to 2018. Aldosterone and plasma renin activity (PRA) or the plasma renin concentration (PRC) were measured in the treated hypertensive patients. The patients with positive screening results were subsequently referred to the endocrinology department for confirmatory tests. The patients with confirmed PA were included in the case group, and the others remained as controls. Receiver-operating characteristic (ROC) curves were used to identify the cutoff points for aldosterone and the ARR, thereby analyzing their sensitivity and specificity for confirmed PA. Among the 3464 patients (59 ± 13 years old, 41% male) who had apparent resistance hypertension screened, PA was confirmed in 276 individuals (8%). A ≥ 16.95 ng/dL (95% CI: 0.908-0.933) had an odds ratio of 6.24 for PA, while A/PRA ≥ 29.88 (95% CI: 0.942-0.984) or an A/PRC ≥ 2.44 (95% CI: 0.978-0.990) had an odds ratio of 216.17 for PA diagnoses. Our findings suggest that a positive PA screening with aldosterone ≥ 17 ng/dL associated with A/PRA ≥ 29.88 or an A/PRC ratio of ≥2.44 should be sufficient to confirm the diagnosis of PA without confirmatory testing.

Abstract C074: Patient-provider communication and receipt of definitive prostate cancer treatment by race and rurality

Abstract Background: Patient-provider communication (PPC) is critical in treatment decisions for cancer care, and it is unknown if improved communication may mitigate disparities in prostate cancer (PCa) outcomes by race and rurality. We examined associations between PPC and treatment receipt among Black and White patients diagnosed with incident PCa in the North Carolina Louisiana Prostate Cancer Project. Methods: Near-equal numbers of Black (n=1130) and White (n=1128) participants were recruited by rapid case ascertainment from 2004-2009. PPC was assessed from the baseline survey, where participants rated their cancer provider using three subscales adapted from the Primary Care Assessment Survey for contextual knowledge of the patient (CK: knowledge of patient’s medical history, home/work responsibilities, their worries, and the patient as a person), and communication content (CMN: doctor’s thoroughness of questions, attention, explanations of health problems, instructions about symptoms, and advice/help in making care decisions), and interpersonal treatment (IT: amount of time spent, patience, friendliness, caring, concern, and respect for patient). First-course treatment was ascertained from medical records and defined as definitive (surgery or radiation) compared to non-definitive treatment (all other). We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for receipt of definitive treatment with logistic regression, adjusted for age at diagnosis, cancer aggressiveness, educational attainment, and marital status. Results: Black participants were diagnosed at younger ages (mean 62 vs. 64 years) with more aggressive disease (21% vs. 15%) and received surgery or radiation less often than White participants (73% vs. 77%). Median PPC subscales differed between Black and White participants (CK: 16 vs 15; CMN: 23 vs 24; IT: 22 vs 23), and between rural and urban participants (CK: 16 vs 16; CMN: 22 vs 24; IT: 21 vs 23). The odds of receiving definitive treatment was associated with positive communication content (1.12, 1.06-1.18), and interpersonal treatment (1.08, 1.02-1.14) among Black and White participants. Among urban participants, communication content (1.09, 1.05-1.15), and interpersonal treatment (1.09, 1.04-1.14) were associated with higher odds of definitive treatment. Among rural participants, higher communication content was associated with increased odds of receiving definitive treatment (OR 1.15, 95%CI: 1.04-1.28). We did not observe associations for contextual knowledge with the odds of receipt for definitive treatment subgroups. Conclusions: Positive patient-provider communication was associated with higher odds of receiving surgery/radiation in a historical cohort of PCa patients diagnosed between 2004-2009. Higher communication content and interpersonal treatment could promote uptake of contemporary guideline-based treatment recommendations for PCa. Future research will assess the validity and reliability of the communication subscales via annual follow-up questionnaires and associations with cancer-specific survival. Citation Format: Jeanny H Wang, Bria Carmichael, Shaun Jones, Hung-Jiu Tan, Deshira D. Wallace, Jennifer L. Lund, Lixin Song, Jeannette T. Bensen, Eboneé N. Butler. Patient-provider communication and receipt of definitive prostate cancer treatment by race and rurality [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C074.

Statin, aspirin and metformin use and risk of hepatocellular carcinoma related outcomes following liver transplantation: A retrospective study.

Liver transplantation (LT) is a potentially curative therapy for patients with hepatocellular carcinoma (HCC). HCC-recurrence following LT is associated with reduced survival. There is increasing interest in chemoprophylaxis to improve HCC-related outcomes post-LT. To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC, and patient outcomes following LT. This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022, from a single Australian centre. Drug use was defined as statin, aspirin or metformin therapy for ≥ 29 days, within 24 months post-LT. A cox proportional-hazards model with time-dependent covariates was used for survival analysis. Outcome measures were the composite-endpoint of HCC-recurrence and all-cause mortality, HCC-recurrence and HCC-related mortality. Sensitivity analysis was performed to account for immortality time bias and statin dosing. Three hundred and five patients were included in this study, with 253 (82.95%) males with a median age of 58.90 years. Aetiologies of liver disease were 150 (49.18%) hepatitis C, 73 (23.93%) hepatitis B (HBV) and 33 (10.82%) non-alcoholic fatty liver disease (NAFLD). 56 (18.36%) took statins, 51 (16.72%) aspirin and 50 (16.39%) metformin. During a median follow-up time of 59.90 months, 34 (11.15%) developed HCC-recurrence, 48 (15.74%) died, 17 (5.57%) from HCC-related mortality. Statin, aspirin or metformin use was not associated with statistically significant differences in the composite endpoint of HCC-recurrence or all-cause mortality [hazard ratio (HR): 1.16, 95%CI: 0.58-2.30; HR: 1.21, 95%CI: 0.28-5.27; HR: 0.61, 95%CI: 0.27-1.36], HCC-recurrence (HR: 0.52, 95%CI: 0.20-1.35; HR: 0.51, 95%CI: 0.14-1.93; HR 1.00, 95%CI: 0.37-2.72), or HCC-related mortality (HR: 0.32, 95%CI: 0.033-3.09; HR: 0.71, 95%CI: 0.14-3.73; HR: 1.57, 95%CI: 0.61-4.04) respectively. Statin dosing was not associated with statistically significant differences in HCC-related outcomes. Statin, metformin or aspirin use was not associated with improved HCC-related outcomes post-LT, in a largely historical cohort of Australian patients with a low proportion of NAFLD. Further prospective, multicentre studies are required to clarify any potential benefit of these drugs to improve HCC-related outcomes.

Feasibility of ultrasound-guided axillary vein access for implantation of cardiac implantable electronic device leads

BackgroundThe axillary vein is preferred over the subclavian vein, and the cephalic vein for cardiac implantable electronic device (CIED) lead insertion. However, studies on ultrasound-guided axillary vein access (US-AVA) in Asia are scarce. This study aims to evaluate the feasibility of US-AVA for CIED lead implantation in Korean patients.MethodsFrom September 2021 to September 2023, we employed US-AVA for CIED lead implantation procedures. Patients’ demographic and procedural data were collected and analyzed retrospectively.ResultsUS-AVA was successful in 301 patients (97.7%). There were no occurrences of pneumothorax or severe hematoma due to inadvertent arterial puncture, nor were there any other significant vascular access-related acute complications. During the median 1.7 years of follow-up, no CIED infection or lead-related problems have occurred. Compared to a historical cohort of patients who underwent fluoroscopy-guided axillary vein access (FL-AVA), US-AVA significantly reduced procedure and fluoroscopy time and showed a trend toward reduced radiation doses.ConclusionUS-AVA is a safe and effective technique for CIED lead implantation in Korean patients, with advantages over FL-AVA in terms of procedural efficiency and patient safety.

Fine-Needle Aspiration versus the CytoCore® Motorized Rotating Needle Device for Thyroid Nodule Biopsies: A Retrospective Cohort Study

Introduction: Recently, an FDA cleared motorized fine-needle aspiration device (CytoCore®, Praxis Medical) has become available which is designed to reduce sample variability by enabling more consistent sampling due to the rotational drilling action of the device in combination with the standard in and out motion used to access the thyroid nodule with a needle. The rotation of the needle permits the ability to collect a higher quantity of intact cellular material, which is optimal for determining adequacy and, ultimately, for making a diagnosis. The present study compares the diagnostic performance of a motorized fine needle aspiration (FNA) device to a historical cohort of patients biopsied using ultrasound-guided fine needle aspiration (US-FNA). Methods: Data from 120 patients with thyroid nodules biopsied using a motorized FNA device was retrospectively analyzed. Patient demographics, lesion characteristics, number of passes, Bethesda category, and cellularity scores were compared to a historical control cohort of 100 patients who underwent US-FNA. Nondiagnostic and indeterminate samples rates for motorized FNA were separately compared to literature controls. Results: A significantly reduced median number of passes were required with motorized FNA compared to US-FNA (1.48 ± 0.62 vs. 2.64 ± 1.63, p < 0.001). Adequate samples were obtained after the first pass for 58% of biopsies with motorized FNA compared to 11% with US-FNA. The cumulative percentage of adequate samples increased to 98% after two passes for motorized FNA versus 58% for the US-FNA group. The mean cellularity score was also significantly greater for motorized FNA (3.42 ± 0.63 vs. 1.9 ± 0.59; p < 0.001). A determinant diagnosis was possible for a greater number of samples in the motorized FNA group compared to the control group (91.6% vs. 78%; p = 0.05). The motorized FNA also had a lower nondiagnostic rate compared to US-FNA (2.0% vs. 10%) and a lower indeterminate rate compared to published rates associated with the use of FNA (8.3% vs. 20.0%; p = 0.05). Conclusion: The motorized FNA device required less passes to obtain an adequate biopsy than US-FNA. Its use is also associated with obtaining samples with a higher cellularity and lower nondiagnostic and indeterminate sample rates.

Prehab, ERAS, Rehab: A patient care continuum around colo-rectal surgery: Prehabilitation combined with ERAS and rehabilitation to reduce morbidity and hospital stay.

BackgroundPrehabilitation (Prehab) programs aim to optimize patients psycho-physical condition before surgery, to improve post-operative outcomes. Although functional benefits of Prehab are known, the clinical impact does not yet have concrete evidence. The objective of this study is to evaluate the efficacy of Prehab, associated with Enhanced Recovery After Surgery (ERAS) and surgical rehabilitation (Rehab), in frail colorectal oncological patients in terms of morbidity and hospitalization. Patients and methodsThe cohort of patients undergoing Prehab between January 2020 and December 2022 (Prehab group) is compared with the historical cohort of patients operated on in the period 01/2018-12/2019, not undergoing Prehab (no-Prehab group). Prehab scheme: multimodal (physiotherapy, clinical nutrition and psychological support). All patients followed an ERAS path. Only Prehab patients followed a surgical Rehab by a dedicated nurse case-manager. Propensity score matching (PSM) and weighting (PSW) analyses were used for statistical analysis. Primary objectives: complications at 30 days and hospital stay. Secondary objectives: functional outcomes. ResultsIn 3 years of preliminary enrollment, 36 patients completed the program: 22 in person, 16 in tele-prehab. The Prehab group experienced fewer complications than the no-Prehab group (PSM: 31 % vs 53 % p = 0.02; PSW: 31 % vs 51 % p = 0.02), less severe complications (CCI>20 PSM: 17 % vs 33 % p = 0.074; PSW: 17 % vs 53 % 0.026) and shorter hospital stay (4.5 vs 6 days; p = 0.02). Finally, prehabilitated patients improved their preoperative functional capacity and reduced anxiety levels. ConclusionThe strategy of combining Prehab with ERAS and Rehab has positively influenced post-operative clinical outcomes as well as functional parameters in our series.

An Assessment of the Efficacy of an Online Pain Management Programme During the Covid-19 Pandemic.

Following the outbreak of the Covid-19 pandemic and associated social distancing requirements, Pain Services were no longer able to deliver face-to-face Pain Management Programmes (PMP). As an alternative, the Bury Integrated Pain Service developed an interactive, online programme, delivered via Microsoft Teams videoconferencing technology. However, the efficacy of such programmes is unclear. The aim of this project was to assess whether comparable results were observed with online PMPs as with face-to-face PMPs. A non-inferiority study comparing patients attending an online PMP to a historical cohort of patients attending face-to-face PMPs. Analyses of variance were performed to assess between group differences and chi squared tests to compare the proportion of patients making clinically meaningful changes in pain, musculoskeletal health, anxiety, depression and self-efficacy. 24% of patients (n=9) deemed suitable for the online PMP were unable to participate due to technological difficulties. This resulted in 28 people attending the online PMP. Greater mean reductions in anxiety (GAD-7 mean difference=1.9; p<0.05) and depression (PHQ-9 mean difference 3.3; p<0.05) were observed with face-to-face PMP and a greater proportion of patients made clinically meaningful improvements in musculoskeletal health (face-to-face=13; online=5), anxiety (face-to-face=7; online=1), and depression (face-to-face=11; online=2). Some patients appear to obtain significant benefit from online PMPs, but this appeared to be to a lesser extent than face-to-face PMPs. It is possible that factors related to the experience of the pandemic influenced these results. However, online PMPs appear to show some promise and further research is warranted to explore the value of online PMPs.

Venetoclax-based non-intensive induction followed by allogenic stem-cell transplantation in elderly acute myeloid leukemia patients with adverse cytogenetics.

Elderly acute myeloid leukemia (AML) patients with poor-risk cytogenetics have a poor outcome with intensive chemotherapy (IC). While Venetoclax (VEN) has changed the outcomes of elderly unfit patients treatment, it is unknown whether it could be effective in poor-risk cytogenetics 60-75 years old patients. We included 60-75-year-old AML patients eligible to allogenic stem cell transplantation (allo-SCT) treated with VEN (combined with azacitidine or with Cladribin and Aracytine) at Institut Paoli Calmettes, between 2020 and 2023 and compared this cohort with patients treated by IC between 2010 and 2019. Twenty six patients were treated with VEN (17 in combination with azacitidine and 9 with Cladribin and Aracytine) and 90 were treated with IC. Thirteen patients (50%) had a TP53 mutation. The median time for leucocyte and platelet counts recovery was 26 days (range 0-103) and 26 days (range, 0-63). The median duration of the first hospitalization was 32 days (ranges, 7-79). The composite response rate was 69% (CR = 50%, CRi = 4%, MLFS = 15%). Allo-SCT could be performed in 42% of cases. Median overall survival (OS) was 7.9 months (20.9 months in the group of patients who transitioned to allo-SCT). We found no difference with the historical cohort of patients treated with IC except a trend toward less lower and upper tract gastro-intestinal (GI) tract infections in the VEN group (respectively 8% vs 26%, p = .06; and 0% vs. 13% p = .06). VEN-based treatment was found to be effective in high risk AML can be considered as an alternative to IC in patients aged 60-75 with adverse cytogenetics.

Prognostic impact of selection criteria of current adjuvant endocrine therapy trials NATALEE and monarchE in postmenopausal HRpos/HER2neg breast cancer patients treated with upfront letrozole

BackgroundThe monarchE and NATALEE trials demonstrated the benefit of CDK4/6 inhibitor (CDK4/6i) therapy in adjuvant breast cancer (BC) treatment. Patient selection, based on clinical characteristics, delineated those at high (monarchE) and high/intermediate recurrence risk (NATALEE). This study employed a historical patient cohort to describe the proportion and prognosis of patients eligible for adjuvant CDK4/6i trials. MethodsBetween 2009 and 2011, 3529 patients were enrolled in the adjuvant PreFace clinical trial (NCT01908556). Eligibility criteria included postmenopausal patients with hormone receptor-positive (HRpos) BC for whom a five-year upfront therapy with letrozole was indicated. Patients were categorized into prognostic groups according to monarchE and NATALEE inclusion criteria, and their invasive disease-free survival (iDFS) and overall survival (OS) were assessed. ResultsAmong 2891 HRpos patients, 384 (13.3 %) met the primary monarchE inclusion criteria. The majority (n = 261) qualified due to having ≥ 4 positive lymph nodes. For NATALEE, 915 out of 2886 patients (31.7 %) met the eligibility criteria, with 126 patients (13.7 %) being node-negative. Patients from monarchE with ≥ 4 positive lymph nodes and NATALEE with stage III BC exhibited the poorest prognosis (3-year iDFS rate 0.87). Patients ineligible for the trials demonstrated prognoses similar to the most favorable patient groups within the eligibility criteria. ConclusionPatient populations eligible for monarchE and NATALEE trials differed. Nearly a third of the postmenopausal HRpos population, previously under upfront letrozole treatment, met the NATALEE prognostic eligibility criteria. As certain eligible groups had a prognosis similar to non-eligible patients, it might be interesting to explore additional patient groups for CDK4/6i therapy.

Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: A large real-life worldwide population

BackgroundThe TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combination's real-world efficacy and tolerability, we conducted a global multicenter retrospective analysis of its first-line treatment outcomes. MethodsWe included patients with unresectable, locally advanced, or metastatic BTC treated with durvalumab, gemcitabine, and cisplatin at 39 sites in 11 countries (Europe, the United States, and Asia). The primary endpoint was overall survival (OS). Results666 patients were enrolled. Median OS was 15.1 months and median PFS was 8.2 months. The investigator-assessed overall response rate was 32.7 %, with stable disease in 45.2 % of patients. High baseline CEA levels, ECOG PS > 0, metastatic disease, and NLR > 3 were associated with poor survival. Any grade adverse events (AEs) occurred in 92.9 % of patients (grade >2: 46.6 %). Immune-related AEs (irAEs) occurred in 20.0 % (grade >2: 2.5 %). Three deaths (0.5 %) were deemed treatment-related, none linked to immunotherapy. Common irAEs were rash (8.2 % all grades; 0.3 % grade >2), itching (10.3 % all grades; 0.2 % grade >2), and hypothyroidism (5.1 % all grades; 0.3 % grade >2). Durvalumab discontinuation rate due to AEs was 1.5 %.ESMO-recommended genes were analyzed and no outcome differences were found. A comparative analysis with a historical cohort of patients treated with chemotherapy alone confirmed the positive survival impact of durvalumab in combination with cisplatin/gemcitabine. ConclusionThis first global real-world analysis largely confirmed the TOPAZ-1 findings, supporting gemcitabine, cisplatin, and durvalumab as a first-line standard of care for patients with advanced BTC.

Retrospective analysis of pediatric patients with Burkitt lymphoma treated in Tanzania following the implementation of the 2016 National Treatment Guidelines: Poor outcomes to current standard-of-care therapy.

Despite the excellent outcomes achieved in the treatment of pediatric Burkitt lymphoma (BL) in high-income countries (HICs), outcomes remain poor in low- and middle-income countries (LMICs). Efforts to improve BL outcomes in Tanzania included the creation of National Treatment Guidelines in 2016. However, disease outcomes in Tanzania following the creation of these guidelines have not been reported to date. Historical records from 2016 to 2021 for patients 0-18years of age with a diagnosis of BL and seen at Bugando Medical Centre (BMC), in Mwanza, Tanzania, were curated into an electronic database and analyzed descriptively. Patients in this cohort were treated per the Tanzanian National Treatment Guidelines, which include six cycles of cyclophosphamide, vincristine, and methotrexate (COM) chemotherapy with intrathecal methotrexate and cytarabine. In total, 92 BL patients' records were eligible for analysis. Patients in this cohort were most commonly Murphy stage II (28%) or stage III (34%). Nearly all, 91%, met International Network for Cancer Treatment and Research (INCTR) high-risk criteria at presentation. Forty-two percent of patients did not receive a biopsy and were treated with a presumed diagnosis of BL alone. A 1-year event-free survival of 29.6% (95% confidence interval [CI]: 20.3%-39.5%) and a 1-year overall survival of 38.5% (95% CI: 28%-48.9%) were observed. A high rate of treatment abandonment (34%) was also observed. In a historical cohort of pediatric patients with BL treated per the 2016 Tanzanian National Treatment Guidelines, we observed poor outcomes and a high rate of abandonment. These outcomes appear inferior to those achieved in the INCTR clinical trial that informed the guidelines' creation, and highlights the importance of "real-world" outcomes data in LMICs. These data reinforce the idea that continued clinical research and capacity building efforts are necessary to improve BL outcomes in LMICs.

A leadless ventricular pacemaker providing atrioventricular synchronous pacing in the real-world setting: 12-Month results from the Micra AV post-approval registry

BackgroundAdvances in leadless pacemaker technology have enabled accelerometer-based atrioventricular (AV) synchronous pacing by sensing atrial mechanical contraction. ObjectiveThe purpose of this study was to report the performance of the Micra AV leadless pacemaker from the worldwide Micra AV post-approval registry (PAR) through 12 months. MethodsThe Micra AV PAR is a prospective, single-arm, observational registry designed to assess the safety and effectiveness of Micra AV in a real-world setting. For the present interim analysis, major complications and system revisions through 12 months were summarized and compared to a historical cohort of 2667 patients implanted with a transvenous dual-chamber pacing system. ResultsThe device was successfully implanted in 796 of 801 patients (99.4%) at 97 centers in 19 countries. Micra AV patients were older (74.1 years vs 71.1 years; P < .0001) with a higher incidence of renal disease (22.3% vs 9.8%; P < .0001) compared with transvenous dual-chamber patients. Through 12 months, the major complication rate was 3.7% in Micra AV patients compared with 8.8% in transvenous dual-chamber patients (hazard ratio 0.42; 95% confidence interval 0.28–0.61; P < .001). The system revision rate was 1.5% in Micra AV patients compared with 5.5% for transvenous dual-chamber patients (hazard ratio 0.25; 95% confidence interval 0.13–0.47; P < .001); this reduction was largely driven by the absence of lead dislodgments requiring revision. The median AV synchrony index was 79.4% (interquartile range 65.2%–86.4%) in patients paced >90%. ConclusionThe Micra AV leadless pacemaker was implanted with a high rate of success in patients with multiple comorbidities, with a significantly lower rate of complications and system revisions through 12 months compared to a historical cohort of patients with transvenous dual-chamber pacemakers.

Implementation of and Systems-Level Barriers to Guideline-Driven Germline Genetic Evaluation in the Care of Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia.

Knowledge of an inherited predisposition to myelodysplastic syndrome (MDS) and AML has important clinical implications for treatment decisions, surveillance, and care of at-risk relatives. National Comprehensive Cancer Network (NCCN) guidelines recently incorporated recommendations for germline genetic evaluation of patients with MDS/AML on the basis of personal and family history features, but the practicality of implementing these recommendations has not been studied. A hereditary hematology quality improvement (QI) committee was formed to implement these guidelines in a prospective cohort of patients diagnosed with MDS/AML. Referral for germline genetic testing was recommended for patients meeting NCCN guideline criteria. Referral patterns and genetic evaluation outcomes were compared with a historical cohort of patients with MDS/AML. Barriers to evaluation were identified. Of the 90 patients with MDS/AML evaluated by the QI committee, 59 (66%) met criteria for germline evaluation. Implementation of the QI committee led to more referrals for germline evaluation in accordance with NCCN guidelines (31% v 14%, P = .03). However, the majority of those meeting criteria were never referred due to high medical acuity or being deceased or in hospice at the time of QI committee recommendations. Despite this, two (17%) of the 12 patients undergoing genetic testing were diagnosed with a hereditary myeloid malignancy syndrome. Current NCCN guidelines resulted in two thirds of patients with MDS/AML meeting criteria for germline evaluation. A hereditary hematology-focused QI committee aided initial implementation and modestly improved NCCN guideline adherence. However, the high morbidity and mortality and prolonged inpatient stays associated with MDS/AML challenged traditional outpatient genetic counseling models. Further improvements in guideline adherence require innovating new models of genetic counseling and testing for this patient population.

Profile of breast cancer in patients with Li-Fraumeni syndrome: An institutional experience.

e13042 Background: Li Fraumeni syndrome (LFS) is a rare autosomal dominant syndrome, associated with multisystem cancer predisposition. Considering the rarity of this syndrome, studies are very sparse on survival outcomes of breast cancer with germline TP53 mutation and there exists discrepancy amongst the results. Methods: This retrospective observational study included 17 patients with germline TP53 mutated breast cancer registered at All India Institute of Medical Sciences (AIIMS), New Delhi, India between the period of 1st April 2016 to 31st Dec 2023. Among the 577 high-risk breast cancer patients, who underwent germline mutation testing, 231 (40.03%) cases had pathogenic mutation [145(25.12%) were BRCA mutated,15 (2.59%) were TP53 mutated, and the rest were others pathogenic variant]. All the TP53 mutations were crosschecked via the ClinVar mutation database to be classified as pathogenic. Results: The median age of 15 patients was 31 years (23-55) and 12 (80%) cases were premenopausal. All the patients had breast cancer as the index malignancy. The Stage distribution (AJCC-7th edition) Stage I, 1(6.6%); Stage II, 7 (46.6 %); Stage III, 4 (26.6 %); and Stage IV, 3 (20 %). Eight cases (53.3%) were HER2 positive, 4 (26.6%) were hormone receptor-positive, and 3 (20%) were Triple-negative breast carcinoma (TNBC). Ten (10) patients received neoadjuvant chemotherapy and 6 (60%) had a complete pathological response. Eight cases (53.3%) cases had a significant family history with 9 (60%) of them having at least one first-degree relative with cancer and two had more than one first-degree relative with cancer. One patient had a family history of LFS. The most common familial cancer was breast, followed by lung, GI malignancies, brain tumor, and sarcoma. Synchronous breast cancer was seen in 2 patients, synchronous malignancies were seen in 4 cases (one patient: each with lung adenocarcinoma, periampullary carcinoma, carcinoma colon, and synovial sarcoma, along with breast cancer), Four patients (26.6%) had metachronous cancers: lung cancer, ovarian carcinoma, contralateral breast cancer, and high-grade sarcoma respectively. The most common mutations were point mutations ( n = 11, 73.3%) followed by frameshift mutations ( n = 4, 26.6%). The subtypes of point mutations included missense mutations ( n = 9) and nonsense mutations ( n = 2) with the most common aberration being a replacement of arginine with glycine (c.743G&gt;A, p. Arg248Gln) and locus being exon 7. The median disease-free survival was 41 months and progression-free survival was 15 months. Conclusions: The prevalence of TP53 mutation in our breast cancer patients is 2.5%. With standard treatment protocols, the overall survival of LFS-associated breast cancer is similar to the historic cohort of patients without any germline mutation. Active surveillance of the patient and family screening is imperative, for all positive cases.

Validation of the Safety and Efficacy of Apixaban as Postoperative Thromboembolism Prophylaxis for Patients with Gynecologic Malignancies.

Venous thromboembolism is a preventable complication of gynecologic cancer surgery that leads to postoperative morbidity and mortality. This study compared apixaban with enoxaparin to identify whether apixaban had the same safety and efficacy for patients undergoing gynecologic cancer surgery. The study identified patients with a gynecologic malignancy who underwent surgery and were prescribed apixaban at discharge between June 2020 and April 2023. International Classification of Diseases 10 codes were used to identify patients who had a thromboembolism within 90 days or a bleeding event within 60 days after surgery. The rates of events for patients prescribed apixaban were compared with those for a historical cohort of patients who received enoxaparin. Fisher's exact tests were used to compare categorical variables, and t tests were used to compare continuous variables. A logistic regression was performed to compare the odds of thromboembolism between the two groups. Baseline patient characteristics differed in terms of body mass index (BMI), race, route of surgery, and type of cancer. Of the 490 patients in the apixaban cohort, 12 (2.4%) had a thromboembolism compared with 3 (2.1%) of the 138 patients in the enoxaparin group (adjusted odds ratio [aOR], 1.02; 95% confidence interval [CI] 0.30-4.70; p > 0.999). The odds ratio was adjusted for BMI, age, and route of surgery. A bleeding event occurred for 1 (0.2%) of the 490 patients in the apixaban group and for 1 (0.7%) of the 138 patients in the enoxaparin group. This validation study showed that apixaban is a safe and effective method of postoperative venous thromboembolism prophylaxis. The data provide support to previous data and guideline updates recommending the use of apixaban for postoperative prophylaxis.

HbA1c changes in a deprived population who followed or not a diabetes self-management programme, organised in a multi-professional primary care practice: a historical cohort study on 207 patients between 2017 and 2019

BackgroundDiabetes self-management (DSM) helps people with diabetes to become actors in their disease. Deprived populations are particularly affected by diabetes and are less likely to have access to these programmes. DSM implementation in primary care, particularly in a multi-professional primary care practice (MPCP), is a valuable strategy to promote care access for these populations. In Rennes (Western France), a DSM programme was designed by a MPCP in a socio-economically deprived area. The study objective was to compare diabetes control in people who followed or not this DSM programme.MethodThe historical cohort of patients who participated in the DSM programme at the MPCP between 2017 and 2019 (n = 69) was compared with patients who did not participate in the programme, matched on sex, age, diabetes type and place of the general practitioner’s practice (n = 138). The primary outcome was glycated haemoglobin (HbA1c) change between 12 months before and 12 months after the DSM programme. Secondary outcomes included modifications in diabetes treatment, body mass index, blood pressure, dyslipidaemia, presence of microalbuminuria, and diabetes retinopathy screening participation.ResultsHbA1c was significantly improved in the exposed group after the programme (p < 0.01). The analysis did not find any significant between-group difference in socio-demographic data, medical history, comorbidities, and treatment adaptation.ConclusionsThese results, consistent with the international literature, promote the development of DSM programmes in primary care settings in deprived areas. The results of this real-life study need to be confirmed on the long-term and in different contexts (rural area, healthcare organisation).