Recent Randomized Clinical Trial Research Articles

High-Efficacy Therapy Discontinuation vs Continuation in Patients 50 Years and Older With Nonactive MS

A recent randomized clinical trial concluded that discontinuing medium-efficacy therapy might be a reasonable option for older patients with nonactive multiple sclerosis (MS), but there is a lack of data on discontinuing high-efficacy therapy (HET). In younger patients, the discontinuation of natalizumab and fingolimod is associated with a risk of rebound of disease activity. To determine whether discontinuing HET in patients 50 years and older with nonactive MS is associated with an increased risk of relapse compared with continuing HET. This observational cohort study used data from 38 referral centers from the French MS registry (Observatoire Français de la Sclérose en Plaques [OFSEP] database). Among 84704 patients in the database, data were extracted for 1857 patients 50 years and older with relapsing-remitting MS treated by HET and with no relapse or magnetic resonance imaging activity for at least 2 years. After verification of the medical records, 1620 patients were classified as having discontinued HET or having remained taking treatment and were matched 1:1 using a dynamic propensity score (including age, sex, disease phenotype, disability, treatment of interest, and time since last inflammatory activity). Patients were included from February 2008 to November 2021, with a mean (SD) follow-up of 5.1 (2.9) years. Data were extracted in June 2022. Natalizumab, fingolimod, rituximab, and ocrelizumab. Time to first relapse. Of 1620 included patients, 1175 (72.5%) were female, and the mean (SD) age was 54.7 (4.8) years. Among the 1452 in the HET continuation group and 168 in the HET discontinuation group, 154 patients in each group were matched using propensity scores (mean [SD] age, 57.7 [5.5] years; mean [SD] delay since the last inflammatory activity, 5.6 [3.8] years; mean [SD] follow-up duration after propensity score matching, 2.5 [2.1] years). Time to first relapse was significantly reduced in the HET discontinuation group compared with the HET continuation group (hazard ratio, 4.1; 95% CI, 2.0-8.5; P < .001) but differed between HETs, with a hazard ratio of 7.2 (95% CI, 2.1-24.5; P = .001) for natalizumab, 4.5 (95% CI, 1.3-15.5; P = .02) for fingolimod, and 1.1 (95% CI, 0.3-4.8; P = .85) for anti-CD20 therapy. As in younger patients, in patients 50 years and older with nonactive MS, the risk of relapse increased significantly after stopping HETs that impact immune cell trafficking (natalizumab and fingolimod). There was no significant increase in risk after stopping HETs that deplete B-cells (anti-CD20 therapy). This result may inform decisions about stopping HETs in clinical practice.

Aneuploidy in Oocytes From Women of Advanced Maternal Age: Analysis of the Causal Meiotic Errors and Impact on Embryo Development

ABSTRACT Many chromosome abnormalities are commonly observed and can lead to early pregnancy loss, miscarriage, or the birth of children with chromosomal defects. Such abnormalities are considered a major factor in the low pregnancy rate after assisted reproductive technology and natural conception. Preimplantation genetic testing for aneuploidy (PGT-A) aims to minimize the transfer of aneuploid embryos. Embryonic aneuploidies arising from errors in meiosis have an incidence of approximately 25% in embryos from women younger than 35 years, to more than half in embryos from women aged older than 35 years. Although these embryos are able to develop to the blastocyst stage, they tend to be of lower morphological quality. A recent multicenter randomized clinical trial (ESTEEM) analyzed polar bodies (PBs) from women after intracytoplasmic sperm injection aged between 36 and 40 years using microarrays in 205 cycles and found that the transfer of embryos from euploid oocytes did not lead to a higher live birth rate but was associated with a reduction in the number of embryo transfers and miscarriages. This study aimed to evaluate all PB results from this RCT and characterize the types of chromosomal abnormalities and the chromosomes most frequently affected. The ESTEEM trial obtained biopsy of first (PB1) and second (PB2) PB in the cohort receiving PGT-A and analyzed them using array comparative genomic hybridization (aCGH). A total of 693 PB pairs had full results available, including 676 confirmed fertilized oocytes. Chromosome segregations, including likely underlying mechanisms, from these pairs are reported here. To estimate the reliability of the aCGH procedure, 72 PB pairs from a single center were reanalyzed using next-generation sequencing (NGS). Embryos were classified into 4 categories based on morphology: good, fair, poor, and degenerated. A comparative analysis was performed to assess the association between chromosome status and embryo quality as well as study group (PGT-A vs control) and embryo quality. A total of 213/676 oocytes were euploid and 413/676 were aneuploid, whereas in the remaining 50 oocytes, an abnormality observed in PB1 was compensated by an abnormality in PB2. A total of 693 PB pairs reported chromatic numbers with results for 15,939 chromosomes. An abnormal segregation, in PB1 and/or PB2, was observed in 1162 chromosomes (7.3%) in 461 PB pairs. Chromosomes 22 (16.7%), 16 (16.6%), 19 (14.4%), 21 (13.7%), and 15 (12.4%) had the highest frequencies for abnormal segregations. The abnormal segregations were compatible with precocious separation of sister chromatids in meiosis 1 (M1) (n = 568; 48.9%), nondisjunction of chromatics in meiosis 2 (M2) or reverse segregation (n = 417; 35.9%), and nondisjunction in M1 (n = 65; 5.6%). However, 112 chromosomes had segregation patterns that could not be categorized into 1 of the 9 known mechanisms causing aneuploidy in oocytes. Concordance between aCGH and NGS was obtained for both PBs for 1650 of 1656 analyzed chromosomes (99.6%). Embryos predicted to be aneuploid had significantly worse quality scores on day 3 (adjusted odds ratio [aOR], 0.62; 95% confidence interval [CI], 0.43–0.90), day 4 (aOR, 0.15; 95% CI, 0.06–0.39), and day 5 (aOR, 0.28; 95% CI, 0.14–0.58). This study represents one of the largest analyses of chromosomal copy number in both PBs to date and highlights the frequent unexplained chromosome copy numbers underscoring the gap of knowledge into the mechanisms causing aneuploidy in oocytes.

Difference in one-year late lumen loss between high- and low-dose paclitaxel-coated balloons for femoropopliteal disease

The objective of the study is to investigate the difference in 1-year late lumen loss (LLL) between the high- (IN.PACT Admiral) and low-dose (Lutonix) paclitaxel-coated balloon (PCB). Although a recent randomized clinical trial demonstrated no difference in efficacy endpoint between high- and low-dose PCB, it remains unclear whether high-dose PCB was superior to low-dose PCB in actual clinical practice. We enrolled 64 patients with 67 de novo femoropopliteal lesions who underwent PCB angioplasty at Kokura Memorial Hospital from May 2014 to March 2020 and subsequent follow-up angiography after 1 year. The primary endpoint was 1-year LLL, whereas the secondary endpoints were binary restenosis and clinically driven target lesion revascularization (CD-TLR) after 1 year. The high- and low-dose PCB groups had 45 and 22 lesions, respectively. Although the low-dose PCB group had higher rates of coronary artery disease, hemodialysis, and chronic limb-threatening ischemia than the high-dose PCB group, the latter had a longer lesion length and more lesions with a TASC classification C or D than the former. The high-dose PCB group had a significantly lower LLL than the low-dose PCB group (0.40 ± 1.05 vs. 1.19 ± 1.03 mm; P = 0.003, respectively). Moreover, the high-dose PCB group had significantly lower rates of binary restenosis at 1 year than the low-dose PCB group (22.2% vs. 50.0%; P = 0.02, respectively). Moreover, negative LLL was only observed in the high-dose PCB group (33.3% vs. 0%, P = 0.005). The high-dose PCB group had a significantly lower LLL than the low-dose PCB group.

Missingness matters: a secondary analysis of thromboelastography measurements from a recent prehospital randomized tranexamic acid clinical trial

BackgroundTranexamic acid (TXA) has been hypothesized to mitigate coagulopathy in patients after traumatic injury. Despite previous prehospital clinical trials demonstrating a TXA survival benefit, none have demonstrated correlated changes in...

Valuing innovative endoscopic techniques: hemostatic powder for the treatment of GI tumor bleeding

Access to new endoscopic treatment modalities often depends on price. To resolve this gap and therefore help to ensure that care delivery can occur on a clinical basis, we aimed to establish the value to insurers of novel hemostatic powder to treat GI tumor bleeding. A decision-analytic model developed to assess the impact of endoscopic intervention on the risk of 30-day readmission for GI bleeding from an insurer perspective was adapted to assess GI tumor bleeding with hemostatic powder or standard endoscopic therapy. Costs were derived from Medicare populations. Outcomes were derived from a recent multicenter randomized clinical trial. Costs ranged from $651 to $1613 to treat upper GI tumor bleeding and from $531 to $1014 to treat lower GI tumor bleeding based on risk reduction in 30-day hospital readmission for recurrent bleeding. These valuations should represent medical device and incremental facility costs in addition to incremental physician and staff time. Coverage for novel endoscopic hemostatic powder therapy seems cost-saving to insurers.

MODERN VIEW ON ANTI-INFLAMMATORY AND URAT-LOWERING THERAPY FOR GOUT

This article provides a thorough analysis of new and promising pharmaceuticals for the treatment of gout, encompassing anti-inflammatory and urate-lowering therapies. It covers drugs that have already received regulatory approval and are in active clinical use, as well as those in various stages of implementation and clinical research, showcasing their notable efficacy and safety. Additionally, the article discusses contemporary gout treatment approaches in alignment with international and domestic clinical guidelines. Emphasis is placed on the safety and efficacy of colchicine in gouty arthritis and its cardioprotective properties for patients with gout and comorbid cardiovascular disease. The article provides the information on the effectiveness of canakinumab, a new anti-inflammatory agent for the symptomatic therapy of gout. The effectiveness and safety of anakinra makes it possible to consider it as a promising alternative to the traditional approach to the anti-inflammatory therapy of gout. Rylonacept allows physicians to develop more effective treatment algorithms for those patients with gout who unsatisfactory respond to conventional therapy. The article provides a historical perspective on the use of adrenocorticotropic hormone as an anti-inflammatory agent for gout. It also highlights existing, new, and potential anti-inflammatory drugs, with a primary focus on the safety and effectiveness of febuxostat, supported by recent large randomized clinical trial results. Additionally, the article describes other medications aimed at reducing uric acid levels in the bloodstream, including uricosuric agents (such as probenecid, benzbromarone, sulfinpyrazone, lesinurad, verinurad, dotinurad, and archalofenate), xanthine oxidase inhibitors (allopurinol and topiroxostat), and pegylated uricase drugs, which may hold promise for future use in combination with primary urate-lowering therapies.

Clinical Characteristics, Treatment, and Outcomes of Provoked Acute Cerebral Sinovenous Thrombosis in Patients

Background Cerebral sinus venous thrombosis (CSVT) is a rare pediatric condition with an estimated incidence of 0.7 per 100,000 children. However, amongst pediatric venous thromboembolism (VTE), the proportion of CSVT is high, at about 10% of all pediatric VTE. Key risk factors include perinatal stressors in cases of neonatal CSVT and acute infections, especially head and neck infections, in older children. To date, few multinational trials of pediatric VTE treatment have reported findings specifically among CSVT patients. Aims We sought to describe the clinical characteristics, treatment strategies, and outcomes of the patients with provoked acute CSVT enrolled in the Kids-DOTT trial and to compare these features to those of Kids-DOTT participants with non-CSVT VTE. Methods Kids-DOTT was an NIH-sponsored multinational randomized clinical trial (RCT) comparing 6 weeks vs. 3 months of anticoagulation for provoked acute VTE treatment in patients &amp;lt;21 years, with two non-randomized cohort arms run in parallel to the RCT for patients with persistent antiphospholipid antibodies or complete veno-occlusion at 6 weeks post-diagnosis of the index VTE. The primary RCT findings were recently published. In the present analysis, descriptive statistics were used to summarize patient and thrombus characteristics, treatments, and outcomes, and variables were compared between CSVT and non-CSVT VTE groups using Mann-Whitney U test for continuous variables and Chi-squared or Fisher's exact test, as appropriate, for categorical variables. All statistical analyses were performed using R Core Team, 2021. A P-value of &amp;lt;0.05 was considered statistically significant. Results Among 532 patients enrolled in the Kids-DOTT trial, the index VTE was a CSVT in 75 (14%). Age distribution differed significantly ( P=0.002) between CSVT and non-CSVT VTE patients, with the CSVT more likely to occur in neonates and children, compared to non-CSVT VTE more likely to occur in adolescents. CSVT was less likely to be CVC-related compared to non-CSVT VTE. The frequency of any infection (56.9% vs 26%, p&amp;lt;0.001) and specifically infection of the head/neck (35.4% vs 2%; P&amp;lt;0.001) as a provoking factor was significantly higher for CSVT vs. non-CSVT VTE. Non-head and neck infections were less likely to be associated with CSVT compared to non-CSVT VTE. One-third of CSVT patients received 6 weeks, while two-thirds received &amp;gt; 3 months, of anticoagulation (Table 2). No patients developed ISTH-defined symptomatic recurrent VTE or clinically relevant bleeding. Conclusions These multinational trial findings substantiate those of retrospective studies implicating head/neck infection as an important provoking factor for CSVT in young patients. The absence of recurrent VTE or clinically relevant bleeding among CSVT patients managed with anticoagulation in Kids-DOTT serve to augment recent RCT findings of CSVT treatment in children involving direct oral anticoagulants, demonstrating the safety and efficacy of therapeutic anticoagulation for pediatric CSVT.

Current Evidence for Combined Targeted Therapy for the Treatment of Inflammatory Bowel Disease.

Biologicals and small molecules have revolutionized the medical management of inflammatory bowel diseases (IBD), yet they are only effective in a proportion of patients, and their impact on changing the natural history of the disease is still debatable. Recently, the concept of combining targeted biologics and small-molecule therapies has been introduced to the treatment of IBD. Dual-targeted therapy (sequential and combined), which is the combination of two targeted therapies, might be a reasonable choice for patients to break through the therapeutic ceiling. A recent randomized clinical trial (VEGA) provided the first controlled evidence that the short-term combination of two biological agents may lead to superior disease control than either of the agents alone in patients with ulcerative colitis (UC) without jeopardizing safety. Multiple studies are underway in both Crohn's disease and UC. Additionally, real-world evidence is accumulating in IBD patients receiving combination therapies with concomitant IBD and extraintestinal manifestations or in patients with medically refractory IBD. Of note, the majority of these patients were exposed to multiple biological agents earlier and lost response to at least one of the agents in the combination. This review summarizes current knowledge regarding this attractive novel therapeutic option in IBD. Clearly, more controlled data are needed to evaluate optimal timing, efficacy, and mitigation of safety concerns.

The Montreal model: an integrative biomedical-psychedelic approach to ketamine for severe treatment-resistant depression.

Subanesthetic ketamine has accumulated meta-analytic evidence for rapid antidepressant effects in treatment-resistant depression (TRD), resulting in both excitement and debate. Many unanswered questions surround ketamine's mechanisms of action and its integration into real-world psychiatric care, resulting in diverse utilizations that variously resemble electroconvulsive therapy, conventional antidepressants, or serotonergic psychedelics. There is thus an unmet need for clinical approaches to ketamine that are tailored to its unique therapeutic properties. This article presents the Montreal model, a comprehensive biopsychosocial approach to ketamine for severe TRD refined over 6 years in public healthcare settings. To contextualize its development, we review the evidence for ketamine as a biomedical and as a psychedelic treatment of depression, emphasizing each perspectives' strengths, weaknesses, and distinct methods of utilization. We then describe the key clinical experiences and research findings that shaped the model's various components, which are presented in detail. The Montreal model, as implemented in a recent randomized clinical trial, aims to synergistically pair ketamine infusions with conventional and psychedelic biopsychosocial care. Ketamine is broadly conceptualized as a brief intervention that can produce windows of opportunity for enhanced psychiatric care, as well as powerful occasions for psychological growth. The model combines structured psychiatric care and concomitant psychotherapy with six ketamine infusions, administered with psychedelic-inspired nonpharmacological adjuncts including rolling preparative and integrative psychological support. Our integrative model aims to bridge the biomedical-psychedelic divide to offer a feasible, flexible, and standardized approach to ketamine for TRD. Our learnings from developing and implementing this psychedelic-inspired model for severe, real-world patients in two academic hospitals may offer valuable insights for the ongoing roll-out of a range of psychedelic therapies. Further research is needed to assess the Montreal model's effectiveness and hypothesized psychological mechanisms.

Absence of Proviral Human Immunodeficiency Virus (HIV) Type 1 Evolution in Early-Treated Individuals With HIV Switching to Dolutegravir Monotherapy During 48 Weeks.

Human immunodeficiency virus type 1 (HIV-1) infection is treated with antiretroviral therapy (ART), usually consisting of 2-3 different drugs, referred to as combination ART (cART). Our recent randomized clinical trial comparing a switch to dolutegravir monotherapy with continuation of cART in early-treated individuals demonstrated sustained virological suppression over 48 weeks. Here, we characterize the longitudinal landscape of the HIV-1 reservoir in these participants, with particular attention to potential differences between treatment groups regarding evidence of evolution as a proxy for low-level replication. Near full-length HIV-1 proviral polymerase chain reaction and next-generation sequencing was applied to longitudinal peripheral blood mononuclear cell samples to assess proviral evolution and the potential emergence of drug resistance mutations (DRMs). Neither an increase in genetic distance nor diversity over time was detected in participants of both treatment groups. Single proviral analysis showed high proportions of defective proviruses and low DRM numbers. No evidence for evolution during dolutegravir monotherapy was found in these early-treated individuals.

Attachment as a predictor of dropout in mentalization-based treatment.

Although treatments of patients with borderline personality disorder (BPD) were historically associated with relatively high dropout rates, dropout rates in contemporary evidence-based treatments for BPD are typically substantially lower. However, only a few studies have investigated dropout rates in mentalization-based treatment (MBT), and even fewer have investigated predictors of dropout in this type of treatment. In this study, we investigated dropout rates in two types of MBT (day hospital MBT [MBT-DH] and intensive outpatient MBT [MBT-IOP]) using data from a recent multicenter randomized clinical trial. Given the central importance of attachment considerations in MBT, we also investigated the relationship between dropout in these two treatments and attachment dimensions. Within a multicenter randomized clinical trial, 114 BPD patients were randomized to MBT-DH (n = 70) or MBT-IOP (n = 44). Dropout in both types of MBT was investigated using descriptive analyses, and its association with attachment anxiety and attachment avoidance, as measured by the Experiences in Close Relationships questionnaire at baseline, was investigated using regression analyses. Dropout rates were relatively low (10.5% across both types of MBT) and did not significantly differ between groups (11.4% in MBT-DH, 9.1% in MBT-IOP). Attachment avoidance and attachment anxiety did not impact dropout, nor did their interaction or the interaction with the type of MBT. Low dropout rates in both types of MBT indicate a high level of engagement of patients in both programmes. Attachment dimensions were not associated with dropout, consistent with the principle that MBT is tailored to each individual's needs. More research is needed, however, to investigate to what extent attachment is a dynamic context-bound adaptive process rather than a static personality feature.

Synthetic Osmotic Dilators for Pre-Induction Cervical Ripening - an Evidence-Based Review.

Mechanical methods have gained growing interest for pre-induction cervical ripening in women with an unripe cervix, since they have a better safety profile compared to prostaglandins. Balloon catheters have been the gold standard method for decades, while there was a lack of data on synthetic osmotic cervical dilators. Not until 2015, when Dilapan-S was approved by the Food and Drug Administration (FDA) for induction of labor, numerous studies have been published on the use of Dilapan-S in this field. The rate of vaginal deliveries associated with the use of Dilapan-S ranges from 61.6 to 81.7%, and no serious complications needing further interventions have been reported to this date. Dilapan-S was shown to be as effective as the Foley balloon catheter as well as the 10mg PGE 2 vaginal insert and orally applied misoprostol (25µg every 2 hours) in achieving vaginal delivery, but patient's satisfaction during the cervical ripening process was significantly higher compared to the other methods and the rate of uterine hyperstimulation was significantly lower compared to prostaglandins (PGs). Minor complications (e.g. vaginal bleeding) associated with the use of Dilapan-S were <2%, and maternal infectious morbidity was not higher compared to Foley balloon and vaginal PGE 2 or misoprostol. Due to these beneficial properties Dilapan-S might be an ideal option for outpatient cervical ripening, as shown in a recent randomized clinical trial comparing inpatient to outpatient cervical ripening. Furthermore, according to the manufacturers' product information, Dilapan-S is the only cervical ripening method that is not contraindicated for induction of labor in women with a previous cesarean section. Upcoming guidelines should consider synthetic osmotic cervical dilators as an effective and safe method for cervical ripening/induction of labor acknowledging that more evidence-based data are mandatory, particularly in patients with a previous cesarean section.

Refining the Stratification and Prognosis of Cardiogenic Shock Patients to Improve Their Outcome.

Cardiogenic shock (CS) remains associated with substantial morbidity and short-term mortality that often exceeds 40% despite contemporary therapy, and no recent randomized clinical trial has demonstrated an incremental improvement in outcomes.1 There is a wide spectrum of risk within CS populations, with severalfold variation in the likelihood of short-term survival between groups. Risk-tailored treatment has been proposed in other acute cardiovascular conditions, such as acute myocardial infarction (AMI).

Abstract HER2-11: HER2-11 Epidemiology and Prognosis of HER2-Low Breast Cancer (BC) in the National Cancer Data Base (NCDB)

Abstract Title: Epidemiology and Prognosis of HER2-Low Breast Cancer (BC) in the National Cancer Data Base (NCDB) Background: Characterization of HER2 status has focused on HER2 overexpressing BC, which are uniquely sensitive to HER2-directed therapy. However, approximately 60% of BC traditionally characterized as HER2-negative express low levels of HER2 on immunohistochemistry (IHC). Although these ‘HER2-low’ cancers are insensitive to traditional HER2 blockade, a recent randomized clinical trial showed that antibody drug conjugates such as trastuzumab deruxtecan (T-DXd) are effective in this population. Given the heterogenity of low level HER2 expression and the impact of T-DXd on outcomes in this population, further data on the epidemiology and prognosis of HER2-low BC is needed. Methods: We conducted a retrospective cohort study of patients (pts) in the NCDB diagnosed from 2010 to 2019 with invasive BC classified as HER2-negative, and with HER2 IHC results available. We compared demographics and other clinical characteristics of HER2 0 vs HER2-low (defined as IHC score of 1+ or 2+) cases in this cohort. A logistic regression was used to quantify the independent association of demographic and clinical factors with HER2-low status, and odds ratios (OR) and 95% confidence intervals (CI) were reported. Overall survival (OS) was compared for HER2 0 vs HER2-low by receptor subtype and stage, and a multivariable Cox model was fit to also control for age, race/ethnicity, comorbidity score, treatment facility type, grade, and histologic type. In pts who received neoadjuvant chemotherapy (NAC), a logistic regression was used to determine if pathological complete response (pCR) rate was different between HER2-low and HER2 0 pts. Results: We identified 1,191,389 pts, including 394,937 HER2 0 and 796,452 HER2-low; median follow-up was 54 months with 84.1% of pts surviving. Hispanic and Black pts and pts with higher grade, non-ductal, triple-negative breast cancer (TNBC) and affect minority Hispanic and Black women (table 1). On multivariable analysis, TNBC (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.47 – 0.49), lobular (OR 0.74, 95% CI 0.73 – 0.75) and other non-ductal histology (OR 0.66, 95% CI 0.64 – 0.67) had lower likelihood of HER2-low status. Hispanic ethnicity remained associated with lower likelihood of HER2-low (OR 0.89, 95% CI 0.87 – 0.91), whereas Black race was associated with a slight increased likelihood of HER2-low status (OR 1.06, 95% CI 1.04 – 1.08). In multivariable survival analysis of TNBC patients, HER2-low BC was associated with improved OS for stage 2 (hazard ratio [HR] 0.93, 95% CI 0.90 – 0.96), stage 3 (HR 0.92, 95% CI 0.88 – 0.96) and stage 4 (HR 0.92, 95% CI 0.87 – 0.97) cancer. By contrast, survival analysis of hormone receptor positive cancer showed that HER2-low BC was associated with improved OS only for stage 4 disease (HR 0.96, 95% CI 0.92 – 0.99). In 62,667 pts receiving NAC, HER2-low status was associated with a lower likelihood of pCR (OR 0.88, 95% CI 0.84 – 0.92). Conclusions: HER2-low BC is most frequently HR+ with a ductal histology, and is associated with a lower likelihood of response to chemotherapy but an improved OS, especially for metastatic cases. This lower pCR in the HER2-low population could be explained by a higher proportion of these tumors being HR+. There are racial/ethnic differences in the incidence of HER2-low BC, largely mediated by differences in rates of TNBC, and fewer Black and Hispanic pts will be candidates for therapies targeting low level HER2 expression. Citation Format: Daniel Peiffer, Frederick M. Howard, Nan Chen, Olwen M. Hahn, Rita Nanda, Olufunmilayo I. Olopade, Dezheng Huo. HER2-11 Epidemiology and Prognosis of HER2-Low Breast Cancer (BC) in the National Cancer Data Base (NCDB) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr HER2-11.

Colorectal Carcinoma Peritoneal Metastases-derived Organoids as a new Tool to Determine Patient response at HIPEC regimens

Background: Peritoneal metastases (PM) from colorectal carcinoma (CRC) are still related to bad prognosis and poor survival, despite the improvements brought by cytoreductive (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Moreover, a recent randomized clinical trial showed controversies about HIPEC efficacy in employing oxaliplatin. To improve HIPEC efficacy, a representative in vitro CRCPM model is required. Patient derived cancer organoids (PDO) provide the opportunity to use more specific and relevant human cancer models in a comprehensive bench-to-bedside strategy. We established a preclinical platform based on CRCPM-PDO to rationalize HIPEC protocols, develop patient-tailored HIPEC regimens, and predict therapeutic responses in a personalized manner based on drug sensitivity tests.

Parasympathetic control of gastrointestinal motility and cross-branch actions of parasympathetic neuromodulation.

Parasympathetic control of gastrointestinal motility and cross-branch actions of parasympathetic neuromodulation.

What's New in Adult Reconstructive Knee Surgery.

What's New in Adult Reconstructive Knee Surgery.

Review of Prospective Trials for Degenerative Cervical Myelopathy.

Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord dysfunction in adults. DCM refers to a collection of degenerative conditions that cause the narrowing of the cervical canal resulting in neurological dysfunction. A lack of high-quality studies and a recent increase in public health awareness has led to numerous prospective studies evaluating DCM. Studies evaluating the efficacy of surgical intervention for DCM can be characterized by the presence (comparative) or absence (noncomparative) of a nonoperative control group. Noncomparative studies predominate due to concerns regarding treatment equipoise. Comparative studies have been limited by methodological issues and have not produced consistent findings. More recent noncomparative studies have established the safety and efficacy of surgical intervention for DCM, including mild myelopathy. The optimal surgical intervention for DCM remains controversial. A recent randomized clinical trial comparing dorsal and ventral techniques found similar improvements in patient-reported physical function at early follow-up. Recent prospective studies have enriched our understanding of DCM and helped guide current treatment recommendations.

INVESTIGATING HETEROGENEITY OF TREATMENT EFFECT FOR CONVALESCENT PLASMA IN SEVERE COVID-19: SECONDARY ANALYSIS OF A RANDOMIZED CONTROLLED TRIAL

INVESTIGATING HETEROGENEITY OF TREATMENT EFFECT FOR CONVALESCENT PLASMA IN SEVERE COVID-19: SECONDARY ANALYSIS OF A RANDOMIZED CONTROLLED TRIAL

The use of blue-light cystoscopy in the detection and surveillance of nonmuscle invasive bladder cancer.

Nonmuscle invasive bladder cancer is associated with a high risk of recurrence as well as progression to muscle-invasive disease. Therefore, adequate visualization and identification of malignant lesions as well as complete resection are critical. Traditional white-light cystoscopy is limited in its ability to detect bladder cancer, specifically carcinoma in situ. Blue-light cystoscopy makes use of the intravesical instillation of a heme precursor to differentiate areas of malignancy from normal tissue. A narrative review of the literature on the use of blue-light cystoscopy in bladder cancer was conducted. Blue-light cystoscopy has been shown in several randomized clinical trials to increase detection of Ta, T1, and carcinoma in situ, as well as reduce risk of recurrence at 12 months as compared with traditional white-light cystoscopy. Research into the effects of blue-light cystoscopy on risk of disease progression has produced mixed results, in part due to changing definitions of progression. However, more recent research suggests a correlation with decreased risk of progression. Whereas the use of blue-light was initially limited to rigid cystoscopy in the operating room, results from a recent randomized clinical trial showing enhanced detection of recurrent disease using blue-light in-office surveillance flexible cystoscopy have led to expanded Food and Drug Administration approval. Overall, blue-light cystoscopy offers promise as an enhancement to white-light cystoscopy for the detection of nonmuscle invasive bladder cancer and may yield additional benefits in reducing disease recurrence and progression. Further prospective research is needed to evaluate the true benefit of blue-light cystoscopy in terms of disease progression as well as the cost-effectiveness of this technique.