Citations

AbstractINTRODUCTIONFemale‐specific reproductive factors and exogeneous estrogen use are associated with cognition in later life. However, the underlying mechanisms are not understood. The present study aimed to investigate the effect of reproductive factors on neuroimaging biomarkers of Alzheimer's disease (AD) and cerebrovascular pathologies.METHODSWe evaluated 389 females (median age of 71.7 years) enrolled in the Mayo Clinic Study of Aging with reproductive history data and longitudinal magnetic resonance imaging (MRI) scans. We used linear mixed effect models to examine the associations between reproductive factors and changes in neuroimaging measures.RESULTSEver hormonal contraception (HC) use was longitudinally associated with higher fractional anisotropy across the corpus callosum, lower white matter hyperintensity (WMH) volume, and greater cortical thickness in an AD meta‐region of interest (ROI). The initiation of menopausal hormone therapy (MHT) > 5 years post menopause was associated with higher WMH volume.DISCUSSIONHC use and initiation of MHT >5 years post menopause were generally associated with neuroimaging biomarkers of cerebrovascular pathologies.Highlights Hormonal contraception use was associated with better brain white matter (WM) integrity. Initiation of menopausal hormone therapy >5 years post menopause was associated with worsening brain WM integrity. Hormonal contraception use was associated with greater cortical thickness. Ages at menarche and menopause and number of pregnancies were not associated with imaging measures. There were few associations between reproductive factors or exogenous estrogens and amyloid or tau PET.

Abstract Aim Recent evidence challenges the current standard of offering surgery to patients with ileocaecal Crohn's disease (CD) only when they present complications of the disease. The aim of this study was to compare short‐term results of patients who underwent primary ileocaecal resection for either inflammatory (luminal disease, earlier in the disease course) or complicated phenotypes, hypothesizing that the latter would be associated with worse postoperative outcomes. Method A retrospective, multicentre comparative analysis was performed including patients operated on for primary ileocaecal CD at 12 referral centres. Patients were divided into two groups according to indication of surgery for inflammatory (ICD) or complicated (CCD) phenotype. Short‐term results were compared. Results A total of 2013 patients were included, with 291 (14.5%) in the ICD group. No differences were found between the groups in time from diagnosis to surgery. CCD patients had higher rates of low body mass index, anaemia (40.9% vs. 27%, p < 0.001) and low albumin (11.3% vs. 2.6%, p < 0.001). CCD patients had longer operations, lower rates of laparoscopic approach (84.3% vs. 93.1%, p = 0.001) and higher conversion rates (9.3% vs. 1.9%, p < 0.001). CCD patients had a longer hospital stay and higher postoperative complication rates (26.1% vs. 21.3%, p = 0.083). Anastomotic leakage and reoperations were also more frequent in this group. More patients in the CCD group required an extended bowel resection (14.1% vs. 8.3%, p : 0.017). In multivariate analysis, CCD was associated with prolonged surgery (OR 3.44, p = 0.001) and the requirement for multiple intraoperative procedures (OR 8.39, p = 0.030). Conclusion Indication for surgery in patients who present with an inflammatory phenotype of CD was associated with better outcomes compared with patients operated on for complications of the disease. There was no difference between groups in time from diagnosis to surgery.

Abstract Randomized trials have not been performed, and may never be, to determine if osteoporosis treatment prevents hip fracture in men. Addressing that evidence gap, we analyzed data from an observational study of new hip fractures in a large integrated healthcare system to compare the reduction in hip fractures associated with standard-of-care osteoporosis treatment in men versus women. Sampling from 271,389 patients aged ≥ 65 who had a hip-containing CT scan during care between 2005 and 2018, we selected all who subsequently had a first hip fracture (cases) after the CT scan (start of observation) and a sex-matched equal number of randomly selected patients. From those, we analyzed all who tested positive for osteoporosis (DXA-equivalent hip BMD T-score ≤ −2.5, measured from the CT scan using VirtuOst). We defined “treated” as at least six months of any osteoporosis medication by prescription fill data during follow-up; “not-treated” was no prescription fill. Sex-specific odds ratios of hip fracture for treated vs not-treated patients were calculated by logistic regression; adjustments included age, BMD T-score, BMD-treatment interaction, BMD, race/ethnicity, and seven baseline clinical risk factors. At two-year follow-up, 33.9% of the women (750/2,211 patients) and 24.0% of the men (175/728 patients) were treated primarily with alendronate; 51.3% and 66.3%, respectively, were not-treated; and 721 and 269, respectively, had a first hip fracture since the CT scan. Odds ratio of hip fracture for treated vs not-treated was 0.26 (95% confidence interval: 0.21–0.33) for women and 0.21 (0.13–0.34) for men; the ratio of these odds ratios (men:women) was 0.81 (0.47–1.37), indicating no significant sex effect. Various sensitivity and stratified analyses confirmed these trends, including results at five-year follow-up. Given these results and considering the relevant literature, we conclude that osteoporosis treatment prevents hip fracture similarly in both sexes.

SummaryHigh-resolution esophageal manometry [HRM] has become the gold standard for the evaluation of esophageal motility disorders. It is unclear whether there are HRM differences in diagnostic outcome based on regional or geographic distribution. The diagnostic outcome of HRM in a diverse geographical population of Mexico was compared and determined if there is variability in diagnostic results among referral centers. Consecutive patients referred for HRM during 2016–2020 were included. Four major referral centers in Mexico participated in the study: northeastern, southeastern, and central (Mexico City, two centers). All studies were interpreted by experienced investigators using Chicago Classification 3 and the same technology. A total of 2293 consecutive patients were included. More abnormal studies were found in the center (61.3%) versus south (45.8%) or north (45.2%) P &lt; 0.001. Higher prevalence of achalasia was noted in the south (21.5%) versus center (12.4%) versus north (9.5%) P &lt; 0.001. Hypercontractile disorders were more common in the north (11.0%) versus the south (5.2%) or the center (3.6%) P.001. A higher frequency of weak peristalsis occurred in the center (76.8%) versus the north (74.2%) or the south (69.2%) P &lt; 0.033. Gastroesophageal junction obstruction was diagnosed in (7.2%) in the center versus the (5.3%) in the north and (4.2%) in the south p.141 (ns). This is the first study to address the diagnostic outcome of HRM in diverse geographical regions of Mexico. We identified several significant diagnostic differences across geographical centers. Our study provides the basis for further analysis of the causes contributing to these differences.

Summary: Despite concerns from 1980s case reports, oral isotretinoin, a derivative of vitamin A, has largely proven to be safe in surgical procedures, with the exception of deep skin resurfacing. Isotretinoin modulates thinning skin and internal scarring in select rhinoplasty patients who may otherwise have poor definition and excessive scarring. A review of patients undergoing surgical interventions, including rhinoplasty, in the setting of concomitant isotretinoin use was performed to examine safety and therapeutic potential. A total of 49 studies were reviewed. Isotretinoin use appears to be safe in a wide variety of surgical procedures relying on internal scar formation. In rhinoplasty, oral isotretinoin was used to thin skin and improve appearance, and resulted in patient and surgeon satisfaction. As such, the clinical potential for using oral isotretinoin in select rhinoplasty candidates—such as those with thick, glaborous, sebaceous skin; male sex; certain races or ethnicities; or revision cases—could mitigate internal scarring processes. Further studies examining the optimal dosing regimen and long-term benefits are warranted.

Abstract Alpha-gal syndrome (AGS) is an immunoglobulin E–mediated hypersensitivity to galatcose-alpha-1,3-galactose (alpha-gal), a carbohydrate compound present in nonprimate mammalian products. Initial exposure to alpha-gal most often occurs through a tick bite, most commonly the lone star tick in the United States. Repeated exposure to alpha-gal may elicit severe allergic reactions, including anaphylaxis. The allergy restricts dietary intake and may significantly impact perioperative risk, as many medications, anesthetics, and intraoperative surgical products utilize bovine or porcine-derived agents, including those containing magnesium stearate, glycerol, and gelatin. Here, we review the perineurosurgical care of two individuals with AGS and highlight pertinent clinical practices and perioperative management of these patients.

TPS7575 Background: Light chain (AL) amyloidosis is a plasma cell malignancy characterized by the production of amyloidgenic clonal light chains that deposit in various tissues. The addition of daratumumab to bortezomib, cyclophosphamide and dexamethasone (Dara-VCD) has improved depth of hematologic and organ responses. However, this approach has not yet demonstrated an overall survival (OS) benefit with short follow-up. Autologous stem cell transplant (ASCT) consolidation remains safe and is associated with deep and durable hematologic responses with an 83% 2-year progression free survival (PFS) and up to 72% of patients achieving a VGPR or better, comparable to Dara-VCD (79%). In multiple myeloma, ASCT improved PFS even in patients who are MRD negative at the end of standard induction therapy. It is thus reasonable to consider that ASCT might provide similar benefits in AL patients. No randomized data exist to inform the optimal use of ASCT in the era of Dara-VCD. Methods: This randomized phase 3 SWOG led intergroup trial will accrue a total of 143 participants per arm and compare MOD-PFS (major organ deterioration progression free survival: defined as time from randomization to death, cardiac/renal progression, or hematologic progression) between participants receiving an ASCT with those receiving Dara-VCD consolidation following uniform Dara-VCD induction. A median MOD-PFS of 31 months is anticipated in the non-ASCT arm. This study has 90% power and a two-sided significance level of 0.05 to detect a hazard ratio of 0.62 corresponding to a MOD-PFS of 50 months in the ASCT arm. Important additional endpoints include OS, hematological PFS, cardiac and renal responses and progression, MRD negativity both by peripheral blood mass spectrometry and bone marrow next generation flow cytometry, delayed utilization of ASCT, and quality of life. This trial was activated on 12/1/2023. Funding: NIH/NCI/NCTN grants and in part by Janssen Pharmaceuticals. Clinical trial information: NCT06022939 . [Table: see text]

e19534 Background: Immunomodulatory drugs, proteasome inhibitors plus dexamethasone are the standard triplet induction regimen for TENDMM. We analyzed the efficacy of adding either anti-CD38 monoclonal antibodies (mAbs) or anti-SLAMF7 antibody to the triplet therapy. Methods: Ovid MEDLINE, EMBASE and published abstracts were systematically searched from each database’s inception through 01-31-2024 to identify II/III trials assessing quadruplet therapy versus triplet therapy in TENDMM patients. Hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS), odds ratios (OR) for overall response rates (ORR), measurable residual disease (MRD) negativity rate (with sensitivity of 10 -5) and grade 3 or higher treatment-related adverse events (G≥3 TRAE) were summarized using random effects meta-analysis via inverse variance approach. Additional subgroup analyses based on the cytogenetic risk were performed. P-value of interaction (Pint ) < 0.1 was pre-specified as statistically significant for the difference between the two groups. Results: 3806 studies were screened and seven trials were included with a total of 3546 patients. Four trials (2303 patients) assessed the addition of anti-CD-38 mAbs and three (1243 patients) assessed anti-SLAMF7 mAb, elotuzumab to the triplet regimen. Quadruplet therapy significantly improved PFS as compared to triplet (HR: 0.63; 95% CI: 0.43-0.92), and the PFS benefit was also observed in standard risk group (HR 0.5; 95% CI 0.2-0.9); however, results were insignificant for high-risk group (HR 0.8; 95% CI 0.62-1.93). No significant OS benefit was observed (HR: 0.79; 95% CI 0.49–1.26); however, data for three trials (CASSIOPEIA, DSMM XVII, PERSEUS) is immature, with longer-term follow-up ongoing. Quadruplet therapy showed significant results for very good partial response or better (OR: 1.7; 95% CI 1.2-2.36), stringent complete response (OR: 1.74; 95% CI 1.27-2.07) and complete response or better (OR: 1.91; 95% CI 1.19-3.06). MRD rate shows benefit with quadruplet therapy (OR: 2.59; 95% CI 2.22-3.01). Improved MRD rate was also observed for high-risk (OR 2.13; 95% CI 1.4-3.2) and standard-risk group (OR 2.58; 95% CI 1.68-3.94). Secondary analysis for efficacy of anti-CD38 mAbs showed benefit for PFS (HR: 0.44; 95% CI: 0.35-0.56), ORR (OR: 1.77;95% CI: 1.02-3.06), and MRD (OR: 2.98; 95% CI 1.8-4.8). G ≥3 TRAE did not significantly differ between the groups (OR: 1.05; 95% CI 0.97-1.12). However, quadruplet therapy showed significant risk of infection (OR: 1.2; 95% 1.05-1.35) and thrombocytopenia (OR: 1.41; 95% CI 1.24-1.59). Conclusions: Quadruplet therapy improved PFS, ORR, and MRD rates compared to triplet regimen and has demonstrated promising benefits to be considered the new standard of care for TENDMM patients.

7558 Background: Survival in patients with multiple myeloma (MM) continues to improve with the newer therapies, but there is no clear evidence of a cure and patients continue to relapse. However, most patients have the most extended period without progression with their first-line therapy, and subsequent therapies often provide a shorter duration of response due to the use of drugs with overlapping mechanisms of action and, more importantly, a shorter first remission, pointing toward more aggressive disease biology. With newer immunotherapies being used at 1st relapse, this may change. We designed this study to explore the natural history of MM after the 1st relapse and define the predictors of outcome after the initial relapse. Methods: We identified all patients in the Mayo Clinic database diagnosed between Jan 2004-June 2019 who had had initial disease progression. The study cohort included 2005 patients. We explored the overall survival (OS) from the time of documented disease progression or the start of second-line treatment in patients who had not met IMWG criteria before second-line therapy. Front-line therapy was grouped into those with either an IMiD or PI, both IMiD and PI, daratumumab with IMiD and PI, and none of these agents. The IMiD and PI were always used with dexamethasone with or without an alkylator. Results: The median age was 63 (range 24-95) years and 60% were male. The median estimated follow-up from diagnosis for all patients was 86 mos. (95% CI; 82, 88) and the median time to progression from the start of therapy was 25 mos. (95% CI; 24, 26). The median OS from the first progression was 45 mos. (95% CI; 42, 50), 36 mos. for those diagnosed before 2009, and 52-53 mos. for those diagnosed later. On univariate analysis, age <70 at 1st relapse, RISS I, novel agents in initial therapy, CR in the first line, diagnosis after 2009, initial remission >18 mos, and initiation of therapy before IMWG progression were all associated with improved OS after 1st relapse (Table). On multivariate analysis, age <70, RISS I, initial remission >18 mos, and initiation of therapy before IMWG progression were all associated with improved OS after 1st relapse. Conclusions: The study provides an estimate of the outcomes and significant predictors of outcomes after 1st relapse in patients with MM. These factors should be taken into consideration when designing clinical trials in this patient population. In particular, these factors identify a high-risk group of patients not always identified by baseline characteristics and should be the focus of future trials. [Table: see text]