DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF IVERMECTIN AND CLORSULON IN IVERCAM INJECTION

A precise, simple, accurate and selective method was developed and validate for estimation of Ivermectin and Clorsulon in Ivercam injection, Reversed phase high performance liquid chromatographic (RP-HPLC) method was developed for routine quantification of Ivermectin and Clorsulon in laboratory prepared mixtures as well as in combined dosage form. Chromatographic separation was achieved on a BDS hypersil C18 (5μ, 250 x 4.6 mm) utilizing mobile phase of filtered and degassed mixture of 60 phosphate buffer (pH 5.5 adjusted with 1% O-phosphoric acid) and Methanol (60:40 v/v) at a flow rate of 1 mL/min with UV detection at 234 nm. The method has been validated for linearity, accuracy and precision. In RP-HPLC method, the calibration graphs were linear in the concentration range of 2.5-7.5 μg/ml for Ivermectin and 25-75 μg/ml for Clorsulon with percentage recoveries of 100.34 % and 99.76% for Ivermectin and Clorsulon respectively. Conclusion: The results obtained by RP-HPLC methods are rapid, accurate and precise. Therefore proposed method can be used for routine analysis of Clorsulon and Ivermectin in injection

Overview of fetomaternal outcome in twin gestation

Background: Twin pregnancy, involving the presence of two fetuses in the uterus, has intrigued humanity across history. Key challenges presented by twin pregnancies include prematurity, low birth weight (LBW), intrauterine growth restriction (IUGR), birth trauma, asphyxia, and congenital anomalies. Preterm delivery poses the most significant risk, contributing to elevated perinatal mortality, neonatal morbidity, and long-term health issues for twins. Methods: Retrospective study at Smt NHL Municipal Medical College analyzed 80 twin pregnancies from July 2022 to January 2024. Data included patient demographics, complications, and neonatal outcomes, informing findings through data analysis. Results: In this study, the majority were under 30 years old (56%) and primigravida (68%), with 48% having a BMI over 30. Common complications included preterm labor (70%), pregnancy-induced hypertension (27.5%), and gestational diabetes (20%). Most twin pregnancies were dichorionic diamniotic (80%). Caesarean section rate was 47.5%. Deliveries mostly occurred between 33-36 weeks gestation, with cephalic-cephalic presentation being most common (40%). Neonatal complications were primarily prematurity (50%), resulting in high NICU admissions (62%) and a neonatal death rate of 13.76%. Conclusions: Multiple pregnancies require early diagnosis and vigilant care to reduce maternal and perinatal risks. Access to skilled healthcare providers and advanced facilities is crucial. Antenatal care must be strengthened for timely referrals. Ultrasonography aids early complication detection. Further advancements and awareness are essential for improved outcomes

Utility of first trimester ultrasound before 12 weeks of gestation at tertiary care centre in western India

Background: The first trimester begins on the first day of the last menstrual period (LMP) and lasts until the end of 12 weeks of gestation. Transvaginal ultrasound is modality of choice for establishing the presence of an intrauterine pregnancy in the first trimester. The focus of our study is routine early pregnancy ultrasound. The purpose of this study was to diagnose various conditions of pregnancy at an early stage by using ultrasound.Methods: We conducted retrospective data analysis of random 250 pregnant patients who had undergone first-trimester ultrasonography USG) (transvaginal/abdominal) in their first antenatal visit at S.V.P. Hospital, Ahmedabad, Gujarat, India from March 2021 to February 2022. The patient was selected by a simple randomized method. Maternal age, parity, gestational age, and special features regarding maternal gestational history were compared with USG findings. Patients were divided into 13 groups on the basis of ultrasonographic diagnosis.Results: We noted 76.8% of patients had single, viable, intrauterine pregnancies, while 23.2% had complicated pregnancies with uterine anomalies, ovarian cysts, leiomyoma, caesarean scar pregnancy or subchorionic hematomas.Conclusions: Ultrasound measurement of fetus in first trimester is most accurate method to confirm gestational age. It is less expensive and easily available modality. First-trimester ultrasound is useful to define embryonic landmarks in developmental stages with reference to gestational age, early diagnosis of miscarriage, ectopic pregnancy, molar pregnancy, multifetal pregnancy, major fetal malformation. And also, to diagnose pregnancy with leiomyoma, caesarean scar pregnancy, uterine anomaly and pre-eclampsia with the help of uterine artery PI

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Identifying genetic diversity of avirulence genes in Leptosphaeria maculans using whole genome sequencing

Next generation sequencing technology allows rapid re-sequencing of individuals, as well as the discovery of single nucleotide polymorphisms (SNPs), for genomic diversity and evolutionary analyses. By sequencing two isolates of the fungal plant pathogen Leptosphaeria maculans, the causal agent of blackleg disease in Brassica crops, we have generated a resource of over 76 million sequence reads aligned to the reference genome. We identified over 21,000 SNPs with an overall SNP frequency of one SNP every 2,065 bp. Sequence validation of a selection of these SNPs in additional isolates collected throughout Australia indicates a high degree of polymorphism in the Australian population. In preliminary phylogenetic analysis, isolates from Western Australia clustered together and those collected from Brassica juncea stubble were identical. These SNPs provide a novel marker resource to study the genetic diversity of this pathogen. We demonstrate that re-sequencing provides a method of validating previously characterised SNPs and analysing differences in important genes, such as the disease related avirulence genes of L. maculans. Understanding the genetic characteristics of this devastating pathogen is vital in developing long-term solutions to managing blackleg disease in Brassica crops

Resistance gene analogs in the brassicaceae: Identification, characterization, distribution, and evolution

The Brassicaceae consists of a wide range of species, including important Brassica crop species and the model plant Arabidopsis (Arabidopsis thaliana). Brassica spp. crop diseases impose significant yield losses annually. A major way to reduce susceptibility to disease is the selection in breeding for resistance gene analogs (RGAs). Nucleotide binding site-leucine rich repeats (NLRs), receptor-like kinases (RLKs), and receptor-like proteins (RLPs) are the main types of RGAs; they contain conserved domains and motifs and play specific roles in resistance to pathogens. Here, all classes of RGAs have been identified using annotation and assembly-based pipelines in all available genome annotations from the Brassicaceae, including multiple genome assemblies of the same species where available (total of 32 genomes). The number of RGAs, based on genome annotations, varies within and between species. In total 34,065 RGAs were identified, with the majority being RLKs (21,691), then NLRs (8,588) and RLPs (3,786). Analysis of the RGA protein sequences revealed a high level of sequence identity, whereby 99.43% of RGAs fell into several orthogroups. This study establishes a resource for the identification and characterization of RGAs in the Brassicaceae and provides a framework for further studies of RGAs for an ultimate goal of assisting breeders in improving resistance to plant disease

Induction of AHR Signaling in Response to the Indolimine Class of Microbial Stress Metabolites

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that plays an important role in gastrointestinal barrier function, tumorigenesis, and is an emerging drug target. The resident microbiota is capable of metabolizing tryptophan to metabolites that are AHR ligands (e.g., indole-3-acetate). Recently, a novel set of mutagenic tryptophan metabolites named indolimines have been identified that are produced by M. morganii in the gastrointestinal tract. Here, we determined that indolimine-200, -214, and -248 are direct AHR ligands that can induce Cyp1a1 transcription and subsequent CYP1A1 enzymatic activity capable of metabolizing the carcinogen benzo(a)pyrene in microsomal assays. In addition, indolimines enhance IL6 expression in a colonic tumor cell line in combination with cytokine treatment. The concentration of indolimine-248 that induces AHR transcriptional activity failed to increase DNA damage. These observations reveal an additional aspect of how indolimines may alter colonic tumorigenesis beyond mutagenic activity

VRd Versus KRd Safety Profiles in Newly Diagnosed Multiple Myeloma Patients Using Real-World Evidence Data from a Single Institution: VRd Has High Rates of Chronic Neuropathy, and KRd Has Low Rates of Cardiopulmonary or Renal Toxicities When Using Optimized IV Fluid Management Coupled with Baseline Cardiac Workup

Background The use of immunomodulatory agents and proteasome inhibitors in newly diagnosed multiple myeloma (NDMM) patients has improved outcomes and led to their widespread use as induction regimens independent of transplant eligibility. Although the overall toxicity profiles of these regimens are considered favorable, their prolonged use warrants a heightened vigilance for toxicities during therapy, and treating physicians need to carefully balance efficacy and toxicity profiles for each patient. Given that patients enrolled on clinical trials, per eligibility criteria, are less frail and/or have fewer comorbidities than patients in the general population, we were motivated to conduct a large study designed to define the safety profiles of the most commonly used induction regimens in the US, based on real-world evidence data. Methods We identified 185 consecutive NDMM patients treated with bortezomib, lenalidomide, and dexamethasone (VRd) vs. carfilzomib, lenalidomide, and dexamethasone (KRd) at MSKCC between 2015 and 2019. By reviewing all available data for these patients, we defined the incidence of cardiopulmonary toxicities, hypertension, renal complications, and peripheral motor or sensory neuropathy. Results A total of 81 and 104 patients were treated with VRd and KRd induction, respectively (Table 1). The VRd (compared to KRd) group had a smaller proportion of patients with high-risk cytogenetics (36% vs. 55%, P=0.01); yet, the >CR rate was lower in the VRd (compared to KRd) group (28% vs. 45%, P=0.02) (Table 2). Table 3 summarizes select toxicities. The incidence of cardiopulmonary AEs was similar in both groups: 12% (N=9) and 10% (N=11) in the VRd and KRd groups, respectively, with the majority limited to grade 1 and 2 (P=1.00); observed cardiac toxicity was reversible in 8 of 9 (89%) vs. 9 of 11 (82%) patients. Renal toxicity was rare in both groups (2% vs. 4% for VRd vs. KRd, P=0.70). New onset or worsening of pre-existing (at baseline) neuropathy was significantly (P2), and 26/45 (58%) patients developed chronic neuropathy after completion of induction therapy. These patients required various interventions, including opiates (N=7), pregabalin/gabapentin/duloxetine (N=17), rehabilitation/physical therapy (N=2), assistive devices such as canes, walkers, and wheelchairs (N=3). None of the patients treated with KRd had new onset neuropathy requiring pain medication. In the VRd group, neuropathy resulted in treatment discontinuation for 6 (7%) patients. Overall, 9% and 4% of patients treated with VRd and KRd, respectively, had treatment discontinuation due to AEs (P=0.22). There were no deaths in the two groups. Conclusion Using real-world evidence data, we defined the safety profiles of VRd and KRd. In sharp contrast to clinical trials mandating recurrent IV fluids before/after administration of carfilzomib, we use optimized IV fluid management (250 ml saline before dose 1 of cycle 1, thereafter no IV fluids) coupled with baseline work-up, including EKG and echocardiogram, for all patients treated with KRd. Therefore, we did not observe excess rates of cardiopulmonary or renal AEs with KRd, and the majority were reversible. In the VRd group, 45 (56%) patients developed new onset or worsening neuropathy, and a third of these developed sensory alteration or paresthesia interfering with function and/or symptomatic weakness interfering with function, or more severe forms of neuropathy. Overall, about 30% of all VRd treated patients developed chronic neuropathy after induction therapy, including disabling neuropathy in some patients and often with need for continued pain treatment. Neuropathy resulted in treatment discontinuation for 7% of patients treated with VRd. These real-world evidence data demonstrate the general tolerability and efficacy of KRd induction, with less severe neuropathy compared to VRd. Disclosures Hultcrantz: Daiichi Sankyo: Research Funding; Amgen: Research Funding; Intellisphere LLC: Consultancy; GSK: Research Funding. Korde:Amgen: Research Funding; Astra Zeneca: Other: Advisory Board. Lesokhin:GenMab: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Serametrix Inc.: Patents & Royalties; Juno: Consultancy, Honoraria; Janssen: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Genentech: Research Funding. Mailankody:Allogene Therapeutics: Research Funding; Physician Education Resource: Honoraria; PleXus Communications: Honoraria; Takeda Oncology: Research Funding; Juno Therapeutics, a Bristol-Myers Squibb Company: Research Funding; Janssen Oncology: Research Funding. Hassoun:Takeda: Research Funding; Novartis: Consultancy; Celgene: Research Funding. Shah:Physicians Education Resource: Honoraria; Celgene/BMS: Research Funding. Scordo:Kite - A Gilead Company: Other: Ad-hoc advisory board; Omeros Corporation: Consultancy; Angiocrine Bioscience, Inc.: Consultancy, Research Funding; McKinsey & Company: Consultancy. Chung:Genentech: Research Funding. Shah:Amgen Inc.: Research Funding; Janssen: Research Funding. Lahoud:MorphoSys: Other: Advisory Board. Giralt:Actinuum: Research Funding; Amgen: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Quintiles: Research Funding; Pfizer: Research Funding; CSL Behring: Research Funding; Jazz: Research Funding; Kite: Research Funding; Sanofi: Research Funding; Adienne: Research Funding. Landgren:Adaptive: Consultancy, Honoraria; Seattle Genetics: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Merck: Other; Pfizer: Consultancy, Honoraria; Juno: Consultancy, Honoraria; Cellectis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Binding Site: Consultancy, Honoraria; Karyopharma: Research Funding; Merck: Other; Pfizer: Consultancy, Honoraria; Seattle Genetics: Research Funding; Juno: Consultancy, Honoraria; Glenmark: Consultancy, Honoraria, Research Funding; Cellectis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Binding Site: Consultancy, Honoraria; Karyopharma: Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Glenmark: Consultancy, Honoraria, Research Funding; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Celgene: Consultancy, Honoraria, Research Funding

Association of Patient Activity Bioprofiles with Hrqol and Clinical Responses: A Prospective Novel Trial Using Mobile Wearables in Newly Diagnosed Multiple Myeloma Patients

Introduction The current standard to assess chemotherapy tolerability and health related quality of life (HRQOL) relies on patient (PT) self-reporting. Continuous passive monitoring using mobile wearable devices can objectively aggregate and monitor "activity" over long periods of time without potential reporting bias. Due to the nature of the disease, multiple myeloma (MM) PTs are often ridden with bone disease and pain, thereby limiting activity while impacting HRQOL. In this prospective clinical study, we enrolled 40 newly diagnosed MM PTs and remotely monitored their activity (steps/24 hrs) while administering electronic PT reported outcome (ePRO) surveys at baseline (BL) and through induction therapy. The study aim was to assess whether wearables can establish patterns of physical activity while receiving therapy and how these activity bioprofiles correlate with HRQOL outcomes. Methods PTs were eligible for the study if they had newly diagnosed MM, not having received any systemic therapy, and if they owned a device (iOS or Android) compatible with Garmin Vivofit® (GV) device. Regimens were determined by treating physicians. PTs were given GV® devices and asked to download a GV® application and Medidata ePRO app. PTs were assigned to either Cohort A - PTs VGPR Responders (Res) vs. < PR Sub-responders (Sub-Res). Associations between physical activity measurements, QLQC30 and MY20 scores, and time from the start of treatment were estimated using a linear mixed model with a random intercept. A Wald-test was used to compute p-values for the significance of association. Results Between Feb 2017 and Sep 2019, 40 PTs (21 M and 19 F) were enrolled with 20 in cohort A (mean 54 yrs, 41-64) and 20 in cohort B (mean 71 yrs, 65-82). Treatment regimens included KRd 14(35%), RVd 12(30%), Dara-KRd 8(20%), VCd 5(12.5%), and Rd 1(2.5%). Activity bioprofiles were compiled among 24/40(60%) PTs: 14 full sets (7/7 cycle periods) and 10 partial sets [1 PT - 2/7(28.5%) cycle periods; 2 PTs - 3/7(42.8%); 1 PT - 4/7(57.1%); 2 PTs- 5/7(71.4%); 4 PTs 6/7(85.7%)]. PT activity increased over time by 179 steps/24 hrs per cycle (p=0.001, 95% CI: 68-289) for the entire study. Mean activity pre- vs. post- for cohort A was 6,041 vs. 7,266 steps/24 hrs, respectively with an increase of 116 steps/24 hrs per cycle (p=0.2, 95% CI: -60-293), and for cohort B 2,984 steps/24 hrs vs. 5,007 steps/24 hrs with an increase of 260 steps/24 hrs per cycle (p<0.001, 95% CI: 154-366) (fig 1). There was improvement in activity levels in both Res 169 steps/24 hrs per cycle (p= 0.02, 95% CI: -31-305) and Sub-Res 212 steps/24 hrs per cycle (p= 0.01, 95% CI: 53-371) groups. PTs reported improvement in ePRO MY20 disease burden symptoms over time, -1.6 score/cycle (p=0.001, 95% CI -2.6- -0.6). There was no observed change in time over self-body image (p=0.5), while PTs reported worsening of future perspective, -2.8 score/cycle (p<0.001, 95% CI -2.6- -0.6). Similarly, there was an observed improvement of QLQC30 global health status, + 1.7 score/cycle (p=0.02, 95% CI: 0.3-3.1) and physical functioning over time +2.1 score/cycle (p<0.001, 95% CI: 1.2-3.0). An association between increased PT activity (steps/24 hrs) and decreased symptom burden was observed (p=0.04). Increased PT activity was also associated with improved global health status (p=0.02) and physical functioning (p<0.001) scores. Conclusion Our study demonstrates that passive wearable monitoring can successfully capture PT activity in newly diagnosed MM, and that PT activity bioprofiles correlate well with traditional HRQOL measurements. Of clinical relevance, our study shows that activity bioprofiles improve with therapy, regardless of depth of response. Significant gains in activity were attributable to the older cohort, suggesting a greater functional impact at BL in this population. Future studies are needed to elucidate how mobile wearables may aid the clinician in passive monitoring of therapy tolerability in the outpatient setting. Figure 1 Disclosures Korde: Amgen: Research Funding; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees. Mailankody:PleXus Communications: Honoraria; Juno Therapeutics, a Bristol-Myers Squibb Company: Research Funding; Allogene Therapeutics: Research Funding; Janssen Oncology: Research Funding; Takeda Oncology: Research Funding; Physician Education Resource: Honoraria. Hassoun:Novartis: Consultancy; Celgene: Research Funding; Takeda: Research Funding. Lesokhin:Takeda: Consultancy, Honoraria; GenMab: Consultancy, Honoraria; Serametrix Inc.: Patents & Royalties; BMS: Consultancy, Honoraria, Research Funding; Janssen: Research Funding; Juno: Consultancy, Honoraria; Genentech: Research Funding. Lendvai:Janssen: Current Employment. Smith:Bristol Myers Squibb: Consultancy, Patents & Royalties, Research Funding; Fate Therapeutics: Consultancy; Precision Biosciences: Consultancy. Hultcrantz:Daiichi Sankyo: Research Funding; GSK: Research Funding; Intellisphere LLC: Consultancy; Amgen: Research Funding. Shah:Physicians Education Resource: Honoraria; Celgene/BMS: Research Funding. Shah:Amgen: Research Funding; Janssen Pharmaceutica: Research Funding. Giralt:Jazz: Research Funding; Kite: Research Funding; Actinuum: Research Funding; CSL Behring: Research Funding; Pfizer: Research Funding; Quintiles: Research Funding; Janssen: Research Funding; Amgen: Research Funding; Sanofi: Research Funding; Celgene: Research Funding; Adienne: Research Funding. Landgren:Adaptive: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Glenmark: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Karyopharma: Research Funding; Binding Site: Consultancy, Honoraria; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; BMS: Consultancy, Honoraria; Cellectis: Consultancy, Honoraria; Glenmark: Consultancy, Honoraria, Research Funding; Juno: Consultancy, Honoraria; Seattle Genetics: Research Funding; Pfizer: Consultancy, Honoraria; Merck: Other; Karyopharma: Research Funding; Binding Site: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Cellectis: Consultancy, Honoraria; Juno: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Merck: Other