Term Safety Research Articles

Effects of Intermittent Fasting on Human Metabolism and Evaluation of Its Effectiveness in Weight Loss

Intermittent Fasting (IF), a dietary modification through time-restricted feeding, has gained significant attention in the past few years owing to its advantages in metabolic health and weight management. Available evidence suggests that IF can improve insulin sensitivity; lower the levels of blood glucose and fat; prevent body fat accumulation; and reduce the risk of obesity-related chronic disease by mitigating oxidative damage and affecting the activity of antioxidant enzymes. However, a number of gaps in knowledge remain regarding IF, especially its long-term safety and the generalisability of IF. This paper discussed the effects of IF on metabolism and body health through the mechanism of high-intensity, nutrient-strong IF. It mentioned that IF led to improved insulin sensitivity, lower blood lipid levels and inhibition of body fat accumulation, and was easier to stick to than daily calorie restriction. Other clinical studies with longer intervals and durations also reported significant effects of IF on weight loss and body health. Long term strict IF is unfavorable for some patients – in particular the elderly and the chronically ill – due to the potential for nutritional and metabolic problems. This study serves as an important reference for the use of IF in health and weight loss management, and offers potential directions for future research. Even though IF showed clear benefits, its safety in the long term and applicability across different populations still need to be validated. Future investigations may look into the long-term effects of IF in different populations, and its potential application in various health conditions.

Intracardiac leadless pacemaker: long term safety over traditional pacemakers. a systematic review and meta-analysis

Abstract Introduction Leadless pacemaker (LP) is a novel technology designed to reduce lead-related, including pocket infections, associated with traditional pacemakers. LP can be used in patients with high-degree AV block, sinus node dysfunction, and bradycardia with syncope. We conducted a systematic review and meta-analysis to examine the long-term safety of intra-cardiac leadless pacemakers compared with traditional pacemakers. Methods Our protocol was registered in advance on PROSPERO. Studies were eligible if they compared complications, revision, cardiac perforation, infections, and all-cause mortality between patients who received leadless pacemakers versus traditional pacemakers. The systematic search was conducted in five databases (MEDLINE, EMBASE, CENTRAL, Web of Science, Scopus) without restriction. The random-effect model was implemented to calculate pooled odds ratio (OR) with a 95% confidence interval (CI). Also, the Mantel-Haenszel method, Paule-Mandel estimator for tau^2, Q-Profile method for the confidence interval of tau^2 and tau, and Hartung-Knapp adjustment for random effects model methods were used for the prediction of data extracted directly from the curves. ROBINS-I tool was used for the risk of bias assessment, and the certainty of the evidence was evaluated with the GRADE approach. Results Of 6450 studies screened, we identified 21 observational studies of Nanostim and Micra leadless pacemakers. The pooled incidence of complications of leadless versus traditional pacemakers at 1, 6, 12-24 months show the odds are clinically and statistically different (OR=0.66, 95% CI: 0.42–1.02; OR=0.44, 95% CI: 0.22–0.86; OR=0.41, 95% CI: 0.32–0.53 respectively). The pooled incidence of infection rate at 6, 12-24 months is lower in patients with LP (OR=0.37, 95% CI: 0.31–0.44; OR=0.20, 95% CI: 0.00–97.31). The studies comparing all-cause mortality during 6, 12-24 months in leadless versus traditional pacemakers did not show statistically significant differences in these outcomes (OR=1.26, 95% CI: 0.88–1.81; OR=0.86, 95% CI: 0.25–2.92 respectively. Conclusion Our results show that complications and infections occur less frequently in patients with leadless pacemakers than in patients with conventional pacemakers with no difference in all-cause mortality. However, there is a need for high-quality randomized clinical trials and propensity score-matched studies focusing on this clinically relevant question.Complication Forest plotsInfection Forest plots

PCSK9 inhibitors in HIV patients with dyslipidemia

Abstract Introduction Cardiovascular disease has become increasingly prevalent in the HIV (human immunodeficiency virus) population. Antiretroviral therapy and HIV itself independently increase the risk of dyslipidemia. While statins are currently the predominant therapy to treat dyslipidemia in HIV patients, drug-drug interactions and adverse drug events can limit their use. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a naturally occurring inhibitor of the LDL-receptor pathway. PCSK9 inhibitors offer an alternative in patients who cannot tolerate or need additional therapy in addition to statin for optimal dyslipidemia management. Purpose The purpose of this study is to compare major adverse cardiovascular events in HIV patients on a PCSK9 inhibitor (evolucumab, alirocumab, inclisiran) vs patients not on a PCSK9 inhibitor. Methods A retrospective cohort study was conducted using electronic medical records from a global federated health research network. The TriNetX network was searched on February 10, 2024, including records from 2020 to 2024. Patients were included based on a diagnosis of HIV status and concomitant dyslipidemia. Patients with HIV and dyslipidemia on a PCSK9 inhibitor were propensity-score matched for age, sex, race, and comorbidities with patients who were not on a PCSK9 inhibitor. The outcomes were mortality, myocardial infarction, heart failure and stroke. Results A total of 485 patients were included in the study. PCSK9 inhibitor use associated with 9% lower odds of all-cause mortality (odds radio, .29; 95% CI, 0.18-0.48; p<.0001). PCSK9 inhibitor use was also associated with 8% lower odds of heart failure (odds radio, .63; 95% CI, 0.47-0.85; p<.0023). No significant associations were noted for myocardial infarction (odds radio, .87; 95% CI, 0.63-1.21; p=0.406) or stroke (odds radio, .67; 95% CI, 0.45-1.01; p=0.052). Conclusion The role of dyslipidemia in HIV is challenging due the complex pathophysiology of HIV. There is an apparent increased risk of cardiovascular disease from the infection itself as well current antiretroviral therapies. While current guidelines recommend the use of statins as first line therapy for dyslipidemia in this population, the drug-drug interaction of statins with ARTs, as well as their side effects, limit their use at times. PCSK9 inhibitors are associated with lower odds of all-cause mortality and heart failure. No significant association was seen for myocardial infarction or stroke. They should be considered as an early intervention alongside statins in HIV patients with dyslipidemia. Further research should be done for the long term safety and tolerance of this therapy as well as cost-effectiveness and access to PCSK9 inhibitors in this population.

Targeted non-invasive Metformin-Curcumin co-loaded nanohyaluosomes halt osteoarthritis progression and improve articular cartilage structure: A preclinical study

Osteoarthritis (OA) is a degenerative disease that affects the quality of life in elderly and young populations. Current therapies using corticosteroids and non-steroidal anti-inflammatory drugs via parenteral or oral routes show limited ability to retard progression of the disease and achieve long term effectiveness and safety. Herein, the potential of MT-Cur combinatorial nano-formulations in OA management was explored for the first time. MT-Cur loaded nanohyaluosomes (MT-Cur-HL1) were designed for topical administration of the combined therapy in OA. The optimized MT-Cur-HL1 showed particle size 247.7 ± 3.7 nm, zeta potential −37.3 ± 0.4 mV; and entrapment efficiency (%EE) 70.22 %±0.303 and 76.7 %±0.077 for MT and Cur, respectively. MT-Cur-HL1 exhibited sustained drug release over 24 h and were stable over 3 months at 4 °C in terms of P.S., ZP and %EE. A detailed preclinical study, using MIA-induced osteoarthritis rat model, revealed the most significant anti-arthritic effect and halted OA progression of MT-Cur-HL1. This was proved to be mainly through the potentiation of p-AMPK signaling that ultimately led to suppression of its downstream TLR4/ NF-κB signaling pathway with subsequent reduction in MMP13 and ADAMTS5 induced chondrocytes degeneration. This study proved that this trajectory effectively promotes a significant improvement in the articular cartilage structure and reinforcement of joint mobility with an efficient antinociceptive effect. In conclusion, the novel MT-Cur coloaded nanohyaluosomes offer a promising non-invasive approach for the local management of OA.

Long term safety of controlled ovarian stimulation for fertility preservation prior to chemotherapy treatment in breast cancer patients

ObjectiveTo evaluate the long-term safety of controlled ovarian stimulation for fertility preservation prior to breast cancer chemotherapy treatment DesignRetrospective observational cohort Subjects213 women aged 18-43 years with newly diagnosed stage I-III breast cancer treated with systemic chemotherapy during 2015-2019. Of those, 74 underwent controlled ovarian stimulation for fertility preservation recipients and 141 did not (controls). ExposureControlled ovarian stimulation for fertility preservation Main outcome measuresInvasive disease-free survival, calculated from the time of surgery to the time of detection of breast cancer recurrence or death, whichever came first. ResultsAt diagnosis, fertility preservation recipients were significantly younger than controls (32.7 vs 38.5 years), were less likely to be partnered (44.4% vs 90.1%) or parous (38.9% vs 95%) and were more likely to harbor a BRCA germline mutation (36.5% vs 14.2%). Disease characteristics and treatment modalities were comparable between groups, apart from tumor staging, with maximal tumor diameter being over 5 cm in 22.2% of fertility preservation recipients as opposed to 5.7% of controls (P<0.05). Mean follow-up was 60.9 and 65.4 months for fertility preservation recipients and controls, respectively. 5-year-invasive disease free survival was 80% for fertility preservation recipients and 86% for controls (p=0.20). In a multivariate analysis adjusted for statistically significant covariates, invasive disease free survival remained similar between the groups (Hazards Ratio (HR), 0.86, 95CI 0.4-1.87, p = 0.71). Invasive disease free survival rates were not statistically different in clinically relevant subgroups including patients receiving neoadjuvant chemotherapy (HR 1.57, CI 95 0.62-3.99, p=0.34), and those co-treated with tamoxifen during stimulation due to an ER-positive disease (HR 1.66, 95CI 0.67-3.49, p=0.23). ConclusionsFertility preservation with controlled ovarian stimulation for patients with breast cancer was not found to impair long-term oncologic outcomes, including in emerging clinically relevant subgroups

ThP1.13 - Short term safety outcomes of immediate pre-pectoral implant based reconstruction

Abstract Aims In the UK up to 43% of women undergo immediate breast reconstruction (IBR) following mastectomy for breast cancer. Implant reconstruction is the commonest form of breast reconstruction and pre-pectoral techniques have been introduced with the aim of improving cosmetic outcome and avoiding animation. To assess the safety of pre-pectoral implant based breast reconstruction (PPBR), including infection rates, 30 day re-admission to hospital, need for unplanned surgery and implant loss at 3 months. Methods A retrospective study of 80 consecutive women who underwent PPBR for breast cancer or risk reduction between October 2020 and October 2023. Demographic, operative and complication data were collected. Results Eighty women (70 cancer, 8 risk reducing and 2 cancer/risk reducing) underwent 94 PPBR procedures (80 Skin sparing mastectomies and 14 Nipple and skin sparing mastectomies) with a mean age of 51.5 (range 28 to 79) years and a BMI of 25.2 kg/m2. 7 (8.8%) of women were smokers. The mean implant size used was 385cc (range 160cc to 650cc) with a mean breast weight of 448.6g (range 45g to 1700g). 10 (12.5%) women required oral antibiotics for wound infection with a further 2 (2.5%) women requiring re-admission within 30 days for IV antibiotics. 17 (21.3%) developed a seroma with 8 (47.1%) requiring drainage. No implant losses were recorded within 3 months of reconstruction. Conclusion We have demonstrated that PPBR is a good option for patients of a wide age range with a large variation in breast size with minimal complications and no implant losses.

Long term safety and outcomes after atrial shunting for heart failure with preserved or mildly reduced ejection fraction: 5-year and 3-year follow-up in the REDUCE LAP-HF I and II trials

BackgroundThere is a little evidence regarding long-term safety and efficacy for atrial shunt devices in heart failure (HF). MethodsThe REDUCE LAP-HF I (n=44) and II (n=621) trials (RCT-I and -II) were multicenter, randomized, sham-controlled trials of patients with HF and ejection fraction >40%. Outcome data were analyzed from RCT-I, a mechanistic trial with 5-year follow-up, and RCT-II, a pivotal trial identifying a responder group (n=313) defined by exercise PVR <1.74 WU and no cardiac rhythm management device with 3-year follow-up. ResultsAt 5 years in RCT I, there were no differences in cardiovascular (CV) mortality, HF events, embolic stroke, or new-onset atrial fibrillation between groups. After 3 years in RCT II, there was no difference in the primary outcome (hierarchical composite of CV mortality, stroke, HF events, and KCCQ) between shunt and sham in the overall trial. Compared to sham, those with responder characteristics in RCT-II had a better outcome with shunt (win ratio 1.6 [95% CI 1.2-2.2], P=0.006; 44% reduction in HF events [shunt 9 vs. control 16 per 100 patient-years], P=0.005; and greater improvement in KCCQ overall summary score [+17.9±20.0 vs. +7.6±20.4], P<0.001), while non-responders had significantly more HF events. Shunt treatment at 3 years was associated with a higher rate of ischemic stroke (3.2% vs. 0%, 95% CI 2% - 6.1%, p=0.032) and lower incidence of worsening kidney dysfunction (10.7% vs. 19.3%, p=0.041). ConclusionsWith up to 5 years of follow up, adverse events were low in patients receiving atrial shunts. In the responder group, atrial shunt treatment was associated with a significantly lower HF event rate and improved KCCQ compared to sham through 3 years of follow-up.Clinicaltrials.gov registration: NCT02600234, NCT03088033

Long-term Efficacy and Safety of Sodium Oxybate in Treating Alcohol Use Disorder: A Systematic Review and Meta-Analysis.

Worldwide, three million deaths each year are reported due to the harmful use of alcohol. To date, only a few drugs have been approved for the treatment of Alcohol Use Disorder (AUD). This systematic review and meta-analysis aim to assess the long-term efficacy and safety of sodium oxybate (SMO) treatment in patients with AUD. We followed the PRISMA statement guidelines and searched PubMed and ISI Web of Science to retrieve the studies of interest. In total, 13 studies on long-term (>12 weeks) SMO administra- tion in patients with AUD were included in this systematic review, and 7 were included in the meta- analysis. Overall, the abstinence rate after 12 weeks of treatment was similar in the SMO and placebo groups, while it was significantly in favour of SMO compared to Naltrexone (NTX). The completion rate was similar in all three conditions. Mean corpuscular volume (MCV) levels favoured SMO over NTX, while Alcohol Craving Scale (ACS) scores did not favour SMO. The incidence of adverse reactions varied widely between studies. SMO in the chronic treatment of patients with AUD showed no superiority to placebo in our analysis of published RCTs, although many observational studies reported its beneficial effect in the long term. On the contrary, SMO was superior to NTX treatment on abstinence. The rate of study completion was similar in the three groups. Safety was not an issue in any of the studies included. Further studies are needed to better assess SMO efficacy and safety in the long term.</p>.

123 Long Term Safety and Efficacy of Radiosurgery for High-Risk Brain Cavernomas

123 Long Term Safety and Efficacy of Radiosurgery for High-Risk Brain Cavernomas

290. EVALUATION OF THE POST-OPERATIVE GERD AND RESIDUAL CHEST PAIN AFTER POEM

Abstract Background Per-oral endoscopic myotomy (POEM) for esophageal achalasia has increasingly become a mainstream procedure worldwide, and its short and middle term efficacy and safety are more and more recognized. However, the long-term outcomes are still unclear and we sometimes experience the cases with severe post-operative GERD and residual chest pain. Methods We retrospectively reviewed 241 cases who were performed POEM in our center from Apr 2015 to Feb 2022 and evaluate their post-operative GERD and residual chest pain. Results Before POEM, 126 cases (54.8%) had chest pain. Residual chest pain 2 months after POEM was observed in 28 patients (23.1%). 78.2% had complete remission of chest pain after 1 year. Severe GERD (LA Grade C or D) 2 months and 1 year after POEM was observed in 5.1%, 8.2%, respectively. All of them except one patient were improved by PPIs. On univariable analysis, younger patients and pre-treatment were at risk for residual chest pain (p=0.02, p=0.04, respectively). Higher BMI was risk for severe GERD after 2 months (p=0.02), however it was not associate with that after 1 year (p=0.04). Conclusion Younger age and pre-treatment were at risk for residual chest pain after POEM and post-operative severe GERD was related to higher BMI, however almost all of them was controlled by PPIs. The number of cases was small, so it is necessary to accumulate more cases.

Safety and Efficacy of Bimekizumab in Patients with Psoriatic Arthritis: 2-Year Results from Two Phase 3 Studies.

Psoriatic arthritis (PsA) is a chronic inflammatory disease requiring long-term treatment. Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated tolerability and sustained clinical efficacy for up to 1year for patients with PsA. Here, we report the longer-‍term safety and efficacy of bimekizumab up to 2years. BE OPTIMAL (biologic disease-modifying antirheumatic drug [bDMARD]-naïve) and BE COMPLETE (prior inadequate response/intolerance to tumor necrosis factor inhibitors [TNFi-IR]) assessed subcutaneous bimekizumab 160mg every 4weeks in patients with PsA. BE OPTIMAL included a reference arm (adalimumab 40mg every 2weeks); patients switched to bimekizumab at week 52 with no washout between treatments. BE OPTIMAL week 52 and BE COMPLETE week 16 completers were eligible for the BE VITAL open-label extension. Efficacy outcomes are reported to week 104/100 (BE OPTIMAL/BE COMPLETE). A total of 710/852 (83.3%) bDMARD-naïve and 322/400 (80.5%) TNFi-IR patients completed week 104/100. Up to 104weeks, patients treated with bimekizumab in BE OPTIMAL and BE COMPLETE had treatment-emergent adverse event incidence rates (exposure-adjusted incidence rate/100 patient-years) of 179.9 (95% CI 166.9, 193.7) and 100.3 (89.2, ‍112.4), respectively. The proportion of patients achieving efficacy outcomes (≥ 50% improvement from baseline in American College of Rheumatology [ACR] response criteria, 100% improvement from baseline in Psorisis Area and Severity Index [PASI], minimal disease activity [MDA]) was sustained in all patients from week 52 to week 104/100. Bimekizumab was well tolerated for up to 2years of treatment and no new safety signals were observed. Sustained clinical efficacy was observed up to 2years in bDMARD-naïve and TNFi-IR patients with active PsA. Patients switching from adalimumab to bimekizumab demonstrated further improvement in skin and nail symptoms, and sustained efficacy in joint symptoms. BE OPTIMAL (NCT03895203), BE COMPLETE (NCT03896581), BE VITAL (NCT04009499).

Long term efficacy and safety of lerodalcibep in patients with atherosclerotic cardiovascular disease (liberate-CVD)

Long term efficacy and safety of lerodalcibep in patients with atherosclerotic cardiovascular disease (liberate-CVD)

Long term efficacy and safety of saroglitazar in metabolic-dysfunction associated steatotic liver disease including patients with advanced fibrosis: real world data of 96 week therapy

Long term efficacy and safety of saroglitazar in metabolic-dysfunction associated steatotic liver disease including patients with advanced fibrosis: real world data of 96 week therapy

Long Term Safety, Feasibility and Efficacy of Left Bundle Branch Area Pacing in a Large Single Centre Study

Long Term Safety, Feasibility and Efficacy of Left Bundle Branch Area Pacing in a Large Single Centre Study

Long term safety, continuation rates and subjective and objective success of Posterior Tibial Nerve Stimulation for Overactive Bladder

Introduction:Posterior tibial nerve stimulation (PTNS) is currently offered to patients with refractory overactive bladder (OAB). We aim to evaluate the efficacy, safety and long-term continuation of PTNS over 11 years. Methods:We conducted a retrospective cohort study on all patients who underwent PTNS from 2012 to 2023. The primary outcomes were change in urinary frequency over 24 hours, maximum voided volume (MVV), number of episodes of urgency urinary incontinence (UUI) and patient perception of intensity of urgency scale (PPIUS). Results:We identified 81 patients. 83% of patients completed 12 treatments of PTNS, and 54% of those that did not complete their full course of treatment stated that this was due to inefficacy. 33% of patients underwent PTNS ‘top ups’ as needed. Only 1 patient reported an adverse effect of musculoskeletal leg pain.28% of patients reported a subjective improvement of their symptoms by 50% or more. There was an average reduction in daytime frequency by 0.6 episodes (p = 0.033), an increase in MVV by 13mls (p = 0.927), a reduction in UUI episodes each day by 0.7 (p = 0.008) and a reduction in average PPIUS by 0.4 (p = 0.024). Conclusion:PTNS remains a safe treatment option for patients with refractory OAB with evidence of both subjective and objective improvement to most symptoms. The majority of our patients completed a 12-week cycle but only 1 in 3 chose to have further PTNS ‘top ups’ and only 1 in 5 are continuing with PTNS for long term management of their OAB.

Long term surgical results and safety profile of the novel CM T Flex scleral fixated intraocular lens.

To report the long term visual outcomes and complications with use of the novel CM-T Flex scleral fixated intraocular lens (CMT-SFIOL). 116 eyes that underwent CMT-SFIOL were reviewed and 57 eyes with CMT-SFIOL that completed a 2-year follow-up were included. Main outcome measures noted were best-corrected visual acuity (BCVA) and complications. Postoperatively, follow-ups were done at 1week (1w), 1month (1m), 1year (1y) and 2-year (2y) intervals. 40 (70.17%) of 57 eyes received CMT-SFIOL for surgical aphakia. Mean follow up was 39.77 ± 8.44months. BCVA for distance & near improved from 1.26 ± 0.84 to 0.76 ± 0.77, 0.50 ± 0.72 and 0.51 ± 0.73 & 1.28 ± 0.58 to 0.98 ± 0.49, 0.92 ± 0.44 and 0.89 ± 0.40 at 1m, 1y and 2y respectively (p < 0.001 for all). At 1w, 10 eyes (17.54%) had corneal edema (CE) and 8 eyes (14.03%) had anterior chamber (AC) reaction. Two eyes (3.50%) had IOP > 30mm Hg and 1 eye (1.75%) had vitreous hemorrhage (VH). At 1m, 3 eyes (5.26%) had CE and 5 eyes (8.77%) had AC reaction. Two eyes (3.50%) had IOP > 30mm Hg and 1 eye (1.75%) had VH. Cystoid macular edema was noted in 3 eyes (5.26%). At 1y and 2y, 2 eyes (3.5%) and 1 eye (1.75%), had CE. No decentration, dislocation, haptic exposure or retinal detachment was noted. No eyes required resurgery. CM-T Flex SFIOL is an effective method to correct aphakia, with reliable and safe long-term results.

Stem cell therapy in diabetic men with erectile dysfunction: a 24-month follow-up of safety and efficacy of two intracavernous autologous bone marrow derived mesenchymal stem cells injections, an open label phase 2 clinical trial

BackgroundRecently we reported results of phase 1 pilot clinical trial of 2 consecutive intracavernous (IC) injection of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) for the first time in the treatment of diabetic patients with erectile dysfunction (DM-ED). In phase 2 of this study our aim is to evaluate long term safety and efficacy of IC injections of BM-MSC on additional eight patients with DM-ED.ResultsEach patient received 2 consecutive IC injections of BM-MSC and evaluated at 1, 3, 6, 12, and 24-month time points. Primary outcome was the tolerability and safety of stem cells therapy (SCT), while the secondary outcome was improvement of erectile function (EF) as assessed using the International Index of Erectile Function-5 (IIEF-5), Erection Hardness Score (EHS) questionnaires, and Color Duplex Doppler Ultrasound (CDDU). IC injections of BM-MSCs was safe and well-tolerated. Minor local and short-term adverse events related to the bone marrow aspiration and IC injections were observed and treated conservatively. There were significant improvement in mean IIEF-5, EHS, all over the follow-up time points in comparison to the baseline. At 24-month follow up there were significant decline in the mean IIEF-5, and EHS compared to the baseline. The mean basal and 20-min peak systolic velocity was significantly higher at 3-month after the IC injections compared to baseline.ConclusionsThis phase 2 clinical trial confirmed that IC injections of BM-MSC are safe and improve EF. The decline in EF over time suggests a need for assessing repeated injections.Clinical trial registrationNCT02945462

Sjogren's Antibodies and Neonatal Lupus: A Scoping Review.

Sjogren's syndrome (SS) is an autoimmune disease characterized by inflammation of exocrine glands. The disorder predominantly affects middle-aged women. Autoantibodies, includinganti-SS-A/Ro and anti-SS-B/La antibodies, are present in most cases of SS. These antibodies can cross the placenta and likely play a role in pregnancy complications as well as the development of neonatal lupus, resulting in congenital heart block (CHB). It is essential to monitor the fetus for CHB during pregnancy. In particular, screening with echocardiography and monitoring heart rate at home are recommended practices. Regarding medical management, hydroxychloroquineand glucocorticoids have shown promise in reducing cardiac manifestations, but further research is needed to elucidate their longer term efficacy and safety. This scoping review analyzes literature from 2001 to 2024, focusing on pregnancy outcomes among women with SS, clinical manifestations of neonatal lupus, the role of anti-SS-A/Ro and anti-SS-B/La antibodies in the development of neonatal lupus and CHB, and emphasizes the need for future research efforts to refine treatment protocols and enhance clinical care strategies for pregnant women with SS.

Impact of semaglutide and tirzepatide administration on weight in women with stage I-III breast cancer.

e24140 Background: Weight gain and obesity are significant problems for women receiving adjuvant therapy for breast cancer and obesity is associated with adverse breast cancer outcomes. In addition, obesity is associated with negative impact on overall physical and mental health. The GLP-1 agonists, semaglutide (S) and tirzepatide (T), are effective in achieving weight loss and have been associated with decreased incidence of diabetes, stroke and overall mortality in the non-diabetic as well as diabetic populations. There are limited data on the efficacy and safety of GLP1 agonists in women with breast cancer. Methods: We performed a retrospective analysis of the association of S and T use with weight loss in patients with stage I-III breast cancer diagnosed and treated at the Yale Cancer Center/Yale New Haven Health Network between 2017 and 2022. After institutional review board approval, a database including 7149 patients including 92,989 office visits was constructed. Maximal weight loss after S/T prescription as well as mean weight loss were calculated. S and T treated patient’s stage distribution and rates of recurrence were compared to untreated patients. For patients without metastatic disease, repeated measures regression analysis was utilized to evaluate changes in weight and BMI. Results: Of the 5430 evaluable patients with non-metastatic disease, 70 (1.3%) were prescribed S or T. Mean age was 58 (41-78). 74% received endocrine therapy. Mean pretreatment weight was 95.8 kg and BMI was 35.9 kg/m2. Mean weight loss for S/T treated patients was 3.03 kg (3.9-2.13, p &lt; .0001) corresponding to reduction in BMI of 1.1 kg/m2 (0.7-1.5 p &lt; .0001). We also calculated maximal weight loss after S/T prescription. Mean maximal weight loss was 8.89 kg (6.71-10.98 P &lt; .0001) corresponding to a mean maximal reduction in BMI of 3.2 kg/m2 (2.3-4.2 P &lt; .0001). Rates of local, locoregional, and distant breast cancer recurrence were 1.5%, 0%, 1.5% in the S/T treated patients and 1.3%, 4.7% and 3.3% in the untreated patients. None of these differences were statistically significant. Conclusions: In this retrospective analysis, GLP-1 agonist are associated with clinically meaningful weight loss in overweight and obese women with early breast cancer. Recurrence risk did not appear to be preliminarily impacted by treatment. Additional research is needed on long term safety as well as weight loss maintenance with these drugs in breast cancer survivors.

Metabolic changes due to dexamethasone premedication in patients with breast cancer.

e24127 Background: The treatment for patients diagnosed with breast cancer is based, in the curative intent scenario, on chemotherapy (CT) such as anthracyclines and taxanes. We are aware that some drugs are widely used and necessary before CT administration to avoid unwanted side effects. Dexamethasone is part of the arsenal of these medications, however, pathological conditions resulting from high doses of administration of this corticosteroid are clinically evident in these patients. In this study we aim to evaluate whether omitting a dose of corticosteroid therapy as a premedication after the second week of treatment with taxane can prevent or reduce the incidence of metabolic changes, and its impact on a patient's quality of life (QoL). Methods: A prospective, randomized, open label study. Breast cancer patients with indication for adjuvant or neoadjuvant treatment with doxorubicin, cyclophosphamide and paclitaxel + trastuzumab (AC-T+ TTZ) chemotherapy were randomized to standard arm, with dexamethasone 10 mg IV administered pre-paclitaxel in all cycles and experimental arm, where dexamethasone was omitted from the premedication from the third to the last taxane application. Results: 86 patients were included, 43 patients in each arm. Premedication was administered every cycle and/ or week before the administration of chemotherapy drugs. Patients had lab analysis and QoL EORTC QLQ-C30 before the beginning of the CT, before the third application of Paclitaxel and 24 hours after the last administration. We observed an increase in ACTH in the experimental group, which is predictable since high doses of corticosteroids suppress the hormone pathway; a drop of insulin levels in its levels in the experimental group and stability in its serum levels in the control group; a stability of GH and IGF-1 in the control group and a more pronounced drop in circulating levels of this hormone in the experimental group. The control group had a greater increase in the excretion of aldosterone, probably due water retention caused by the use of dexamethasone. There were no adverse events reported in the experimental group and also hypersensitivity or anaphylactic reactions were not observed. The EORTC-QLQ-C30 scores related to diarrhea, constipation, inappetence and insomnia were better in the experimental group, as well the average score for global health. Conclusions: The omission of dexamethasone in patients in the experimental group improved QOL scores related to common AEs during CT, mainly GI and also insomnia. Insulin levels were also lower in this group. The potential reduction of the incidence of metabolic syndrome seems palusible but would require larger sample size. The short term safety and tolerability of this regimen warrants its use in larger populations. Clinical trial information: NCT04350229 .