High Efficacy Rates Research Articles

Machine learning and sensitivity analysis for predicting nasal drug delivery for targeted deposition

Targeted nasal drug delivery can provide improved efficacy for drug formulations to be delivered at high efficacy rates. Some parameters that influence drug delivery have a dependency on the patient’s technique of administration and the spray device itself. When the different parameters, each having a specific range of values are combined, the combinatory permutations for studying its effects on particle deposition become large.In this study, we combine six input spray parameters (the spray half-cone angle, the mean spray exit velocity, the breakup length from the nozzle exit, the diameter of the nozzle spray device, the particle size, and the sagittal angle of the spray) with a range of values to produce 384 combinations of spray characteristics. This was repeated for three inhalation flow rates of 20, 40, and 60 L/min.To reduce the computational costs of a full transient Large Eddy Simulation flow field, we create a time-averaged frozen field and perform the time integration of particle trajectories through the flow field to determine the particle deposition in four anatomical regions of the nasal cavity (anterior, middle, olfactory and posterior) for each of the 384 spray field.A sensitivity analysis determined the significance of each input variable on the deposition. It was found the particle size distribution significantly affected deposition in the olfactory and posterior regions, while the spray device insertion angle was significant for deposition in the anterior and middle regions.Five machine learning models were evaluated based on 384 cases and it was found that despite the small sample dataset the simulation data was sufficient to provide accurate machine-learning predictions.

Long-term efficacy of the single-incision mini-sling procedure using surgeon-tailored mesh

ObjectivesTo evaluate the long-term efficacy of a surgeon-tailored single-incision mini-sling procedure (SIMS) for the surgical treatment of stress urinary incontinence (SUI) in terms of objective cure rates, quality of life, and cost-effectiveness. Study designThis retrospective study included 93 women with pure SUI who underwent surgeon-tailored SIMS. All patients were evaluated with a stress cough test and quality of life questionnaire (Incontinence Impact Questionnaire [IIQ-7]) at 1 month, 6 months, 1 year, and last follow-up visit (4–7 years). Early and late (after 1 month) complication rates and the reoperation rate were also evaluated. ResultsMean operative time and follow-up duration were 12 ± 2.5 min and 5.7 years (4–7 years), respectively. Objective cure rates determined by the stress cough test were 83.8%, 94.6%, 93.5%, and 91.3% at 1 month, 6 months, 1 year, and last follow-up, respectively. IIQ-7 scores improved at every visit compared to the preoperative value. There were no cases of hematuria, bladder perforation, or major bleeding requires a blood transfusion. ConclusionOur results suggest that the surgeon-tailored SIMS procedure has high efficacy and low complication rates and offers a practical and inexpensive alternative to commercial high-cost SIMS systems.

Description and Treatment Progress of Postpartum Body Pain in Chinese Medicine

Postpartum body pain is one of the common postpartum diseases, the damage to the patient’s physical and mental health can not be ignored. The recognition and treatment of postpartum body pain in traditional Chinese medicine mainly take qi and blood, Zang-fu organs and ying wei as the main points of syndrome differentiation. Its main etiology and pathogenesis are postpartum deficiency of qi and blood, wind-cold and dampness evil invading human body, the dysfunction of each viscera and the disharmony of camp and health. According to the cause, the treatment can be summarized as supplementing qi and blood, harmonizing Yingwei, dispelling wind and dispersing cold, activating collages and relieving pain, regulating zang fu organs and so on. TCM treatment focuses on the holistic view, and its systematic treatment through early intervention, multiple means and multiple approaches has the advantages of high safety, significant efficacy and low recurrence rate. Clinical syndrome differentiation is not limited to one of the above types, but this article can provide treatment ideas for this disease.

COMPUTER VISION IN PRECISION AGRICULTURE FOR WEED CONTROL: A SYSTEMATIC LITERATURE REVIEW

The paper aims to carry out a systematic literature review to determine what computer vision techniques are prevalent in the field of precision agriculture, specifically for weed control. The review also noted what situations the techniques were best suited to and compared their various efficacy rates. The review covered a period between the years 2011 to 2022. The study findings indicate that computer vision in conjunction with machine learning and particularly Convolutional Neural Networks were the preferred options for most researchers. The techniques were generally applicable to all situations farmers may face themselves with a few exceptions, and they showed high efficacy rates across the board when it came to weed detection and control.

(284) A Systematic Review of Loco-sedative Anesthesia for Penile and Scrotal Surgery

Abstract Introduction The current standard of care for patients undergoing the majority of scrotal and penile procedures is to administer general or spinal anesthesia. The use of general or spinal anesthesia can lead to several complications, long wait times and is not feasible in many rural and remote areas. Objective The objective of this study is to perform a systematic review of the characteristics and outcomes of conscious sedation and local anesthesia for penile and scrotal urologic procedures. Methods A systematic search was conducted on PubMed, and Scopus databases following PRISMA criteria from inception to August 2021. Articles were included if they were prospective, randomized or non-randomized controlled trials that used local anesthetic or conscious sedation for penile or scrotal interventions. Additionally, included studies provided primary data on the use loco-sedative anesthesia and the efficacy and complications from the procedures. Results Nine articles with 4511 patients were included in the study. Procedures examined included vasectomies, adult circumcisions, varicocelectomies, urethrocutaneous fistula repair, microepididymal sperm aspiration and testicular sperm extraction. Of the studies that reported age, the mean patient age was 29.3 years old. The most common anesthetic and analgesic relief was the use of local anesthetic with 1% lidocaine. Only one study used conscious sedation whereas the rest used local anesthetics. However, there was significant heterogeneity in the type of local or conscious sedation method and whether there was a combination was used. 44.4% of the studies used the visual analog scale (VAS) for their primary endpoint. All the studies reported 100% successful procedures with no sedative complications. Conclusions Given the high efficacy rates, loco-sedative anesthesia is a promising technique for penile and scrotal urologic interventions. However, the current body of literature has limited data on a wider array of procedures. Further controlled studies examining the use of loco-sedative anesthesia for a larger variety of penile and scrotal interventions are recommended. This review also demonstrates the significant heterogeneity on how sedation may be assessed and the variety of local anesthetics that can be used to substitute for general or spinal anesthesia. Disclosure No

Clinical Efficacy and Safety of Flumatinib in Newly Diagnosed Chronic Myelogenous Leukemia.

The present study aimed to investigate the efficacy and safety of flumatinib in patients newly diagnosed with chronic myeloid leukemia in the chronic phase (CML-CP). A retrospective study was conducted using five patients newly diagnosed with CML-CP who received flumatinib (600 mg/day). Results of the present study demonstrated that all five patients with CML-CP that were treated with flumatinib achieved the optimal molecular response within three months. In addition, two patients experienced major molecular response (MMR), and one patient acquired undetectable molecular residual disease, which was maintained for more than one year. Moreover, one patient exhibited grade 3 hematological toxicity, two patients exhibited transient diarrhea, one patient exhibited vomiting and one patient exhibited a rash with pruritus. No second-generation tyrosine kinase inhibitor-specific adverse cardiovascular events occurred in any patients. In conclusion, flumatinib exhibits high efficacy and high early molecular response rate in patients newly diagnosed with CML-CP. The majority of patients obtained MMR within three months, and the adverse reactions experienced were mild and tolerable.

Sustained Remission Off-Treatment (SROT) of TPO-RAs: The Burgos Ten-Step Eltrombopag Tapering Scheme.

Background and Objectives: TPO-RAs (romiplostim/eltrombopag/avatrombopag) have broadly demonstrated high efficacy rates (59-88%), durable responses (up to three years) and a satisfactory safety profile in clinical trials. The effect of TPO-RAs is classically considered to be transient because platelet numbers usually dropped rapidly to baseline unless therapy was maintained. However, several groups have reported the possibility of successfully discontinuing TPO-RAs in some patients without further need for concomitant treatments. This concept is usually referred as sustained remission off-treatment (SROT). Materials and Methods: Unfortunately, we still lack predictors of the response to discontinuation even after the numerous biological, clinical and in vitro studies performed to study this phenomenon. The frequency of successful discontinuation is matter of controversy, although a percentage in the range of 25-40% may probably be considered a consensus. Here, we describe all major routine clinical practice studies and reviews that report the current position on this topic and compare them with our own results in Burgos. Results: We report our Burgos ten-step eltrombopag tapering scheme with which we have achieved an elevated percentage rate of success (70.3%) in discontinuing treatment. Conclusions: We hope this protocol may help successfully taper and discontinue TPO-RAs in daily clinical practice.

Effectiveness and Safety of Bictegravir/Emtricitabine/Tenofovir Alafenamide in Patients With HIV-1 Infection and Ongoing Substance Use Disorder: The BASE Study.

People with human immunodeficiency virus (HIV) and substance use disorder (PWH/SUD) are at higher risk of nonadherence to antiretroviral therapy. Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) exhibits high rates of efficacy with a favorable adverse event profile. The BASE study (NCT03998176) is a phase 4, single-arm study evaluating the effectiveness and safety of B/F/TAF among PWH/SUD. Viremic (HIV RNA >1000 copies/mL) PWH/SUD initiated B/F/TAF once daily for 48 weeks (W). The primary endpoint was proportion of participants with HIV RNA <50 copies/mL at W24. Secondary endpoints were proportion of participants with HIV-1 RNA <50 copies/mL at W48, safety, B/F/TAF adherence (dried blood spot [DBS] concentrations of emtricitabine triphosphate and tenofovir diphosphate [TFV-DP]), substance use (NIDA-ASSIST), and quality of life (SF-12). Forty-three participants were enrolled; 95% reported methamphetamine use. Median age was 38 (range, 21-62) years; 21% were female, 81% White, 14% Black, and 16% Hispanic. Thirty-two (74%) and 21 (49%) participants had HIV RNA <50 copies/mL (intention-to-treat) at W24 and W48, respectively. Seven participants (16%) experienced confirmed virologic failure through W48; 1 developed emergent drug resistance (M184V). Fifteen participants (35%) experienced grade ≥3 adverse events. Five participants (12%) reported suicidal ideation; none resulted in discontinuation. Median DBS concentrations were representative of 5-6 doses/week (TFV-DP, 1603 fmol/punches). NIDA-ASSIST scores declined from baseline to W48 with methamphetamine use decreasing most (-7.9 points; -29%), and SF-12 physical/mental scores increased 1.2 and 7.6 points, respectively. B/F/TAF among a high-risk population of PWH/SUD resulted in an initial 72% viral suppression rate at W24 before dropping to 49% at W48 as retention declined. One participant developed emergent drug resistance (M184V).

The Effects of Vaccine Efficacy Information on Vaccination Intentions Through Perceived Response Efficacy and Hope

Response efficacy information indicating the effectiveness of a recommended behavior in risk reduction is an important component of health communication. For example, many messages regarding COVID-19 vaccines featured numerical vaccine efficacy rates in preventing infections, hospitalizations, and deaths. While the relationship between disease risk perceptions and fear has been well established, we know less about the psychological factors involved in communicating vaccine efficacy information, such as response efficacy perceptions and hope. This study examines the effects of numerical vaccine efficacy information and message framing on vaccination intentions and their relationship to perceived response efficacy and hope, using a fictitious infectious disease similar to COVID-19. Findings suggest that communicating a high efficacy rate of the vaccine in preventing severe illness increased perceived response efficacy, which in turn boosted vaccination intention directly and indirectly through increasing hope. Also, fear about the virus was positively associated with hope about the vaccine. Implications of using response efficacy information and hope appeals in health communication and vaccination promotion are discussed.

P671 Ustekinumab in paediatric patients with moderately to severely active Crohn's disease: Results from the UniStar study long-term extension

Abstract Background Ustekinumab (UST) is an approved biologic for the treatment of adults with Crohn’s disease (CD). Through 16 weeks (wks), UST demonstrated high rates of efficacy, low rates of immunogenicity, and safety in paediatric patients (pts) similar to that observed in adults.1 Here, we evaluated UST in paediatric CD pts through 268 wks. Methods UniStar was a phase 1, multicentre, double-blind study in paediatric pts (2-18 years old; body weight ≥10kg) with moderately to severely active CD. Pts (n=45) were randomised 1:1 and stratified by body weight (&amp;lt;40kg or ≥40kg) to low (3 mg/kg [&amp;lt;40kg]; 130 mg [≥40kg]) or high (9 mg/kg [&amp;lt;40kg]; 390 mg [≥40kg]) dose intravenous UST. At wk 8, pts received 1 subcutaneous maintenance dose (2 mg/kg [&amp;lt;40kg]; 90 mg [≥40kg]). Pts responding to UST at wk 16 were eligible to enter the long-term extension (LTE) and continued UST maintenance dosing every 8 wks up to wk 268. This study reports efficacy, safety, pharmacokinetics (PK), and immunogenicity evaluated at wks 16, 24, 48, 224, and through 240 wks, as applicable. The primary visit was wk 48, representing outcomes after ~1 year of UST treatment. Results Of the 44 pts treated with UST, 34 (77%) responded and entered the LTE; the number of pts receiving treatment at wks 48, 104, 152, and 208 was 26 (77%), 16 (47%), 12 (35%), and 8 (24%), respectively. Among pts in the LTE (n=34), baseline median age (range) was 13.0 (6.0-17.0) years, 62% were female, 47% weighed &amp;lt;40kg, 18% weighed &amp;lt;30kg, and 94% previously failed anti-tumor necrosis factor therapy. At wk 48, 41% (14/34) of pts achieved clinical remission, and 59% (20/34) achieved clinical response. The proportion of pts with abnormal C-reactive protein (CRP) levels at baseline was 71% (24/34), and 59% (16/27) of pts achieved normalization of CRP (&amp;lt;3mg/L) at wk 48. By the final safety visit at wk 240, 91% of pts reported ≥1 adverse event (AE), and 15% discontinued due to AEs, with CD worsening as the most frequent reason. Infections occurred in 74% of pts, and 32% had serious AEs. The majority of serious AEs were gastrointestinal disorders associated with CD. No injection-site reactions, serious infections, malignancies, or deaths were reported. Median serum UST concentrations tended to be lower in pts weighing &amp;lt;40kg compared with pts weighing ≥40kg, but were generally consistent from wks 16 to 268 and remained detectable through wk 200 (Figure). Incidence of UST antibodies was low (1/34; 3%). Conclusion In the UniStar LTE, the efficacy, safety, PK, and immunogenicity of UST in paediatric pts with CD was generally consistent with adult pts for as long as 4 years of treatment. Reference: 1. Rosh JR et al. J Crohns Colitis. 2021;15(11):1931.

Smartphone app-delivered gut-directed hypnotherapy improves symptoms of self-reported irritable bowel syndrome: A retrospective evaluation.

Gut-directed hypnotherapy (GDH) has high rates of durable efficacy for treating irritable bowel syndrome (IBS) but its widespread use is limited due to high costs and poor access. A smartphone app delivering GDH was developed to fill gaps in accessibility but has not been assessed in IBS patients. The current retrospective evaluation aims to assess the efficacy of app-delivered GDH in managing IBS symptoms and to investigate associating factors that predict response. Irritable bowel syndrome patients who downloaded the app between June 2019 and April 2020 were retrospectively evaluated. The first seven sessions were free. Daily GDH, psycho-education, and breathing exercises were included. Overall and individual gastrointestinal symptoms were assessed at baseline and completion using a 100-mm visual analogue scale. Clinical data were extracted. 2843 patients with self-reported IBS commenced the free sessions, 1428 (50%) purchased the app and 253 (9%) completed all 42 sessions. Outcome data were available for 190 users who completed all 42 sessions. 64% of patients who completed the GDH and provided outcome data responded (defined as >30% reduction in abdominal pain). Abdominal pain reduced from 60mm (50-73mm) at baseline to 26mm (13-50mm) on study completion (p<0.001 Wilcoxon). Similar results were seen for overall and individual symptoms. On multivariable analysis, symptom response was positively associated with being ≥ 40 years (estimated OR 0.398, p=0.025) and negatively associated with trying probiotics (0.323, p=0.042). Adherence to app-delivered gut-directed hypnotherapy was low but users who completed the program saw notable improvements in their IBS symptoms. Patients ≥40 years, with symptoms for ≥5 years, may respond better. A controlled trial comparing face-to-face to app-delivered GDH is indicated.

Lower risk of hepatocellular carcinoma with tenofovir than entecavir in antiviral treatment-naïve chronic hepatitis B patients: a systematic review and meta-analysis involving 90,897 participants.

Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are equally recommended as first-line treatments for antiviral treatment-naïve (ART-naïve) chronic hepatitis B (CHB) patients by practice guidelines because of their similarly high antiviral efficacy and low resistance rate. However, whether one is superior to the other in terms of hepatocellular carcinoma (HCC) prevention is currently largely controversial. We aimed to identify and synthesize these existing studies regarding the HCC risk of these two highly potent antivirals in treatment-naïve CHB patients. PubMed, EMBASE, and Cochrane Library were searched for studies between January 1, 2012 and June 25, 2022. These studies used ETV monotherapy and/or TDF monotherapy to treat ART-naïve CHB patients and reported the incidence of HCC. The extracted data were analyzed using a DerSimonian-Laird random-effects models. The HCC incidence difference was expressed as hazard ratio (HR) and 95% confidence interval (95% CI). A total of 17 studies with 90,897 ART-naïve CHB patients (ETV = 60,980 vs TDF = 29,917) were included in this meta-analysis. Compared with ETV, TDF was associated with a significant lower cumulative incidence of HCC (HR 0.66; 95% CI 0.56-0.76). No significant heterogeneity or publication bias was found among the included studies (I2 = 48.1%, Begg's p = 0.363 and Egger's p = 0.748). TDF is associated with a lower risk of HCC compared with entecavir in ART-naïve CHB patients. The results suggest that TDF may be a better option for ART-naïve CHB patients with high HCC risks.

Intravascular lithotripsy in the treatment of coronary artery calcification in a high-risk real world population.

The DISRUPT-CAD study series demonstrated feasibility and safety of intravascular lithotripsy (IVL) in selected patients, but applicability across a broad range of clinical scenarios remains unclear. This study aims to evaluate the procedural and clinical outcomes of IVL in a high-risk real-world cohort, compared to a regulatory approval cohort. Consecutive patients treated with IVL and percutaneous coronary interventionat our center from May 2016 to April 2020 were included. Comparison was made between those enrolled in the DISRUPT-CAD series of studies to those with calcified lesions but an exclusion criteria. Among 177 patients treated with IVL, 142 were excluded from regulatory trials due to acute coronary syndrome presentation (47.2%), left ventricular ejection fraction <40% (22.5%), chronic renal failure (12.0%), or use of mechanical circulatory support (8.5%). This clinical cohort had a higher SYNTAX score (22.6 ± 12.1 vs. 17.4 ± 9.9, p = 0.019), and more treated ACC/AHA C lesions (56.3% vs. 37.1%, p = 0.042). Rates of device success (93.7% vs. 100.0%, p = 0.208), procedural success (96.5% vs. 100.0%, p = 0.585), and minimal lumen areagain (221.2 ± 93.7% vs. 198.6 ± 152.0%, p = 0.807) were similar in both groups. The DISRUPT-CAD cohort had no in-hospital mortality, 30-day major adverse cardiac events (MACE), or 30-day target vessel revascularization (TVR). The clinical cohort had an in-hospital mortality of 4.2%, 30-day MACE of 7.8%, and 30-day TVR of 1.5%. There was no difference in 12-month TVR (2.9% vs. 2.2%; p = 0.825). Twelve-month MACE was higher in the clinical cohort (21.1% vs. 8.6%, p = 0.03). IVL use remains associated with high clinical efficacy, procedural success, and low complication rates in a real-world population previously excluded from regulatory approving trials.

Fortelyzin® in the treatment of ischemic stroke. Case report

Given the current high incidence of cerebral circulatory disorders and the challenging treatment of such patients, developing therapies and medications for these conditions is urgent. The proportion of patients undergoing various reperfusion techniques is increasing, and so is the medical community's need for novel agents with high efficacy and low complication rate.

The role of ketamine as an antidepressant agent

The role of ketamine as an antidepressant agent

1258. B/F/TAF in HIV-Infected Adults with Substance Use Disorders: BASE Week 48 Results

Abstract Background People with HIV (PWH) and substance use disorders (SUD) are at higher risk of non-adherence. Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) exhibits high rates of efficacy with a favorable adverse event profile. The BASE study (NCT03998176) is a Phase 4, single-arm study evaluating the effectiveness and safety of B/F/TAF among PWH and SUD. Methods Viremic (HIV RNA &amp;gt;1000 copies [c]/mL) treatment-naïve or -experienced PWH and ongoing SUD initiated B/F/TAF once daily for 48 weeks (W). The primary endpoint was HIV RNA &amp;lt; 50 c/mL (FDA Snapshot Algorithm) at W48. Secondary endpoints were safety, adherence (dried blood spot [DBS] levels of emtricitabine-triphosphate [FTC-TP] and tenofovir-diphosphate [TVF-DP]), substance use (NIDA ASSIST) and quality of life (SF-12). Results Forty-three participants enrolled; 95% reported methamphetamine use. Median age was 38 years (range: 21-62); 19% female, 81% White, 14% Black, 16% Latinx. At W48, 21 participants (49%) had HIV RNA &amp;lt; 50 c/mL (ITT, Figure 1). Four participants (9%) experienced confirmed virologic failure; none developed treatment-emergent resistance. Seventeen participants (40%) experienced grade ≥3 adverse events; none attributed to B/F/TAF. Five participants reported suicidal ideation; none resulted in discontinuation. Observed mean FTC-TP and TVF-DP concentrations in DBS corresponded to 5-6 doses/week (FTC-TP: &amp;gt;3.6 pmol/7mm punches; TVF-DP: &amp;gt;1733 fmol/7 mm punches; Figure 2). NIDA ASSIST scores declined from baseline, with methamphetamine use decreasing most (-7.9 points; -29%). SF-12 physical/mental scores increased 1.2 and 7.6 points, respectively, but remained below mean US scores. Longitudinal virologic outcomes, intent-to-treat analysis Mean observed intracellular emtricitabine triphosphate (FTC-TP) and tenofovir diphosphate (TFV-DP) in dried blood spots at weeks 6, 24, and 48 Thresholds for 2-3 doses/week (Solid Line) and 4-5 doses/week (Dashed Line) are noted for both FTC-TP and TFV-DP based on TAF-DBS data [Yager J, et al. JAIDS, 2020]. Notes: Y-axis represents femtomoles/punches Conclusion B/F/TAF among a high-risk population of PWH and ongoing SUD resulted in a 49% viral suppression rate at W48. No emergent resistance was noted supporting the high barrier to resistance provided by B/F/TAF. Disclosures Sara H. Bares, MD, Gilead Sciences: Expert Testimony|GSK ViiV Healthcare: Grant/Research Support|Janssen: Grant/Research Support Kimberly Scarsi, PharmD, Organon: Grant/Research Support.

Evaluation of Direct-acting Antiviral Drugs for Hepatitis C patients below 30 years age in Sialkot, Pakistan

Background: Infection of Hepatitis C virus (HCV) is major contributor in liver problems, affecting nearly more than 70 million people all over the world. Top ten countries which are affected by Hepatitis, also include Pakistan. Medical science has entered a new era of HCV therapy in elimination of infection and disease is a real possibility. In Asia, Genotype 3 is chronic hepatitis C genotype as compared to other genotypes. Direct-acting antiviral drugs are famous for their high efficacy rate, but less work has done in Asia. Methods: A follow up research was performed to evaluate 3 months treatment outcome of some direct acting antiviral drugs in 35 patients (26 patients of HCV genotype 3) below 30 years of age using some relevant biological parameters. Results: A total of 30 patients yielded a pooled SVR of more than 85% after twelve weeks outcome of commonly used antiviral drugs evaluation. Conclusion: Commonly used antiviral drugs in Sialkot, Pakistan showed effectiveness in HCV patients having genotypes 1, 2, 3 and 5. Keywords: Hepatitis C virus, genotype 3, direct acting antiviral drugs, liver function tests, renal function tests

Fixed Duration Daratumumab, Ixazomib, Lenalidomide, and Dexamethasone Quadruplet for Newly Diagnosed Multiple Myeloma - MRD Negativity and Survival Outcomes

Background: The combination of a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and dexamethasone is the current standard induction therapy for myeloma. Daratumumab (Dara), a monoclonal antibody directed against CD38, is highly effective in treating myeloma and improves response rates and progression free survival (PFS) when added to a PI or IMiD. Recent studies have shown high efficacy rates with quadruplet regimens that contain these three drug classes, potentially allowing for limited duration therapy as well as reduction in the steroid doses. We designed this trial to examine the efficacy of the quadruplet regimen containing daratumumab, ixazomib (an oral proteasome inhibitor), lenalidomide and dexamethasone (Dara-IRd) given for fixed duration, and to evaluate impact of early discontinuation of steroids. Patients and Methods: Patients with previously untreated MM who had measurable disease and adequate organ function were enrolled, irrespective of their autologous stem cell transplant eligibility (NCT03012880). The primary objective was to determine the rate of complete response to Dara-IRD combination. Treatment involved 28-day cycles consisting of ixazomib 4 mg days 1, 8, 15; lenalidomide 25 mg days 1-21, dexamethasone 40 mg, weekly and Dara 16 mg/kg, weekly for two cycles, every other week during cycles 3-6 and then every 4 weeks thereafter during induction (12-cycles) followed by Dara-ixazomib maintenance (maximum 24 cycles). Patients were enrolled into two sequential cohorts: Cohorts A (n=38) and B (N=40), with dexamethasone discontinued after two cycles in Cohort B. Transplant eligible patients were allowed to collect stem cells for future transplant anytime after 4 cycles. Serum immunofixation was assessed with mass spectrometry (MASS-FIX) and marrow MRD negativity by Euro flow (sensitivity of 1 in 105). Results: Seventy-eight patients were enrolled; median age was 63.5 (range 33, 81), 55% were male. A third of the patients were high risk by mSMART criteria and ISS stage 1, 2, and 3 had 41%, 35%, and 24% of patients respectively. All patients have completed the treatment phase and those who have not gone off study continue on observation. Among the 40 patients who have gone off study, the reasons for discontinuation among patients in Cohorts A and B, respectively were: progression, 9 and 12; alternate therapy (most often transplant), 11 and 8. The best overall response on therapy was 96% including 31% CR, 39% VGPR. For the entire cohort, time to response was fast, median time to VGPR, CR or minimal residual disease negative (MRD) negativity was 4 cycles. Responses deepened over the duration of treatment as shown in the figure; 31% of patients achieved a marrow MRD negative status (28% CR and MRDneg). After a median follow up was 37.8 months, median PFS or OS has not been reached. Five patients enrolled on the study have died. A grade 3 or higher adverse event at least possibly attributed to the study drugs was seen in 56% of patients. The most common toxicities included fatigue, neutropenia, lymphopenia, peripheral neuropathy, diarrhea, and nausea. Stem cells were collected in 60 patients; median (range) of CD34 cells/kg 7.8 (2.8, 15.9) x 106, with plerixafor used in 88% of patients as per our standard of care "on-demand” approach based on blood CD34 count. Conclusion: Dara-IRd is an active regimen in newly diagnosed MM, with high overall rates of response and deep and durable responses with nearly a third of the patients being MRDneg (Mass Spec based blood testing and flow based MRD), that improved over time with therapy. The toxicities were manageable, with dose modifications. All patients were able to collect stem cells when required, though the majority needed plerixafor. This study demonstrates excellent outcomes with limited duration quadruplet regimen without planned upfront autologous stem cell transplant and no maintenance till progression. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Patient-Reported Outcomes for Fully Vaccinated COVID-19 Patients Over 6Weeks: The Experiences of Clinical Breakthrough Cases.

While coronavirus disease 2019 (COVID-19) vaccines have high rates of efficacy, fully vaccinated individuals can become infected with COVID-19. Among this population, symptoms tend to be less severe and shorter lasting. Less is known about how vaccinated individuals who contract COVID-19 experience the disease through patient-reported outcomes (PROs) and how this changes over time. The aim of this study was to describe the physical, mental, and social health PROs for fully vaccinated individuals who contracted COVID-19 over a 6-week period. Prospective design using the Patient-Reported Outcomes Measurement Information System short-form (PROMIS-10) collected through a mobile application-based platform. 1114 fully vaccinated patients who tested positive for COVID-19 at a large US health system and engaged with the study on or after 1 March 2021 and reported onset of illness prior to 1 November 2021. Global physical and mental health PROMIS-10 T-scores for the 6-week period, component PROMIS-10 questions for the 6-week period, and component PROMIS-10 questions restricted to a subset of participants for the first month to measure individual recovery were analyzed. Mean global physical and mental health T-scores increased over time and remained within one standard deviation of the population mean. At baseline, at least 40% of participants reported good health for all component questions except Fatigue (25%), and the proportion reporting good health increased over time for all questions, with the largest improvements in Fatigue (25.5 to 67.5%), Pain (59.1 to 82.8%), and Emotional Problems (42.3 to 62.5%). Over the first month, the greatest positive changes in individual recovery were observed for Fatigue (65.0%), Pain (53.0%), and Emotional Problems (41.1%); at least 30% of respondents reported no change in at least one category, and the greatest decreases were for Usual Social Activities (23.9%), Social Satisfaction (23.2%), and Mental Health (21.8%). This study provides an important step towards better understanding the impact of 'breakthrough' COVID-19 infections on clinically engaged, fully vaccinated patients' physical and mental health to improve support for their treatment and recovery.

Chylous ascites following mesenteric cyst resection. Case report and literature review

Introduction: chylous ascites (CA) is defined as the extravasation of milky fluid rich in triglycerides into the peritoneal cavity. Clinical case: 69-year-old patient with a history of having undergone surgery for a mesenteric cyst two months before presenting on this occasion with marked ascites observed by ultrasound and clinical examination. Diagnostic paracentesis was performed and showed abundant ascitic fluid (2500 ml) with a milky yellow appearance. A sample was taken for biochemical analysis of the fluid, which was positive, which together with the history of recent surgery confirmed the diagnosis of AQ. Conclusions: the usual cause in the adult population is obstruction due to abdominal neoplasms. Other causes include: abdominal trauma or secondary to abdominal surgery (associated with extensive retroperitoneal lymphadenectomies or with aortic surgery). a complete anamnesis and physical examination are essential for the diagnosis of AQ. Therefore, in case of suspicion, emphasis should be placed on the causes, especially if its appearance is subsequent to interventional therapies. Optimal management would be aimed at conservative treatment based on nutritional therapy (of choice due to its high efficacy rate)