Efficacy Of Treatment Research Articles

Feasibility and preliminary efficacy of an online nutrition education intervention for those with a sleeve gastrectomy: A pilot randomised control trial.

A sleeve gastrectomy (SG) is a lifelong treatment that improves health and better outcomes are associated with follow-up. However, there is lack of access or high attrition to aftercare. This potentially contributes to sub-optimal dietary intake and a lack of evidence for nutrition interventions. The present study assessed the feasibility and preliminary efficacy of a nutrition intervention to improve diet quality in Australian adults living with a SG. Adults (n = 96) post-SG were recruited into a cross-sectional diet quality study, with 68 eligible for randomisation to an intervention or wait-list control group. Over 10 weeks, a Facebook group was used to post daily nutrition education. Feasibility outcomes included participant recruitment, engagement, retention and acceptability. Preliminary efficacy was assessed using change in Australian Recommended Food Score (ARFS). Linear mixed models were used to measure differences in mean outcome between the experimental groups over time. Sixty-eight participants (97% female) aged 48.2 ± 9.8 years, body mass index 33.1 ± 5.8 kg/m2, and mean ± SD ARFS 39 ± 9 points were randomised to the intervention, with 66% retention at 10 weeks. At follow-up, diet quality increased for the intervention group (mean ARFS, 95% confidence interval = 0.2 [-1.5 to 1.9]) and decreased for the control group (mean ARFS, 95% confidence interval= -2.0 [-5.2 to 1.2]) with no between group difference (p = 0.2). Participants (n = 30) rated the intervention positively. Recruiting and retaining adults post-SG into a nutrition intervention is feasible. Low-cost recruitment attracted strong interest from women to identify greater support to know what to eat following SG. A future fully powered trial to assess intervention efficacy is warranted.

Salmonella spp. in Domestic Ruminants, Evaluation of Antimicrobial Resistance Based on the One Health Approach—A Systematic Review and Meta-Analysis

Salmonella spp. pose a global threat as a leading cause of foodborne illnesses, particularly prevalent in the European Union (EU), where it remains the second cause of foodborne outbreaks. The emergence of antimicrobial resistance (AMR) in Salmonella spp. has become a critical concern, complicating treatment strategies and escalating the risk of severe infections. The study focuses on large and small ruminants, identifying a prevalence of Salmonella spp. in slaughterhouses and revealing varied AMR rates across antimicrobial families throughout a meta-analysis. Also, comparison with AMR in human medicine was carried out by a systematic review. The results of the present meta-analysis displayed a prevalence of Salmonella spp. in large and small ruminants at slaughterhouses of 8.01% (8.31%, cattle; 7.04%, goats; 6.12%, sheep). According to the AMR of Salmonella spp., 20, 14, and 13 out of 62 antimicrobials studied were classified as low (<5%), high (>5% but <10%), and very high (>10%), respectively. Salmonella spp. did not display AMR against aztreonam, mezlocillin, ertapenem, meropenem, cefoxitin, ceftazidime, levofloxacin, tilmicosin, linezolid, fosfomycin, furazolidone, quinupristin, trimethoprim and spectinomycin. In contrast, a prevalence of 100% of AMR has been described against ofloxacin, lincomycin, and cloxacillin. In the context of the main antibiotics used in the treatment of human salmonellosis, azithromycin was shown to have the highest resistance among Salmonella spp. isolates from humans. Regarding cephalosporins, which are also used for the treatment of salmonellosis in humans, the prevalence of Salmonella spp. resistance to this class of antibiotics was similar in both human and animal samples. Concerning quinolones, despite a heightened resistance profile in Salmonella spp. isolates from ruminant samples, there appears to be no discernible compromise to the efficacy of salmonellosis treatment in humans since lower prevalences of AMR in Salmonella spp. isolated from human specimens were observed. Although the resistance of Salmonella spp. indicates some degree of concern, most antibiotics are not used in veterinary medicine. Thus, the contribution of cattle, sheep and goats to the rise of antibiotic resistance of Salmonella spp. and its potential impact on public health appears to be relatively insignificant, due to their low prevalence in carcasses and organs. Nevertheless, the observed low prevalence of Salmonella spp. in ruminants at slaughterhouse and the correspondingly low AMR rates of Salmonella spp. to key antibiotics employed in human medicine do not indicate that ruminant livestock poses a substantial public health risk concerning the transmission of AMR. Thus, the results observed in both the meta-analysis and systematic review suggests that AMR is not solely attributed to veterinary antibiotic use but is also influenced by factors such as animal health management (i.e., biosecurity measures, prophylactic schemes) and human medicine.

Pharmacogenomics: A Genetic Approach to Drug Development and Therapy

The majority of the well-known pharmacogenomics research used in the medical sciences contributes to our understanding of medication interactions. It has a significant impact on treatment and drug development. The broad use of pharmacogenomics is required for the progress of therapy. The main focus is on how genes and an intricate gene system affect the body’s reaction to medications. Novel biomarkers that help identify a patient group that is more or less likely to respond to a certain medication have been discovered as a result of recent developments in the field of clinical therapeutics. It aims to improve customized therapy by giving the appropriate drug at the right dose at the right time and making sure that the right prescriptions are issued. A combination of genetic, environmental, and patient variables that impact the pharmacokinetics and/or pharmacodynamics of medications results in interindividual variance in drug response. Drug development, illness susceptibility, and treatment efficacy are all impacted by pharmacogenomics. The purpose of this work is to give a review that might serve as a foundation for the creation of new pharmacogenomics applications, techniques, or strategies.

Cancer mutationscape: revealing the link between modular restructuring and intervention efficacy among mutations

There is increasing evidence that biological systems are modular in both structure and function. Complex biological signaling networks such as gene regulatory networks (GRNs) are proving to be composed of subcategories that are interconnected and hierarchically ranked. These networks contain highly dynamic processes that ultimately dictate cellular function over time, as well as influence phenotypic fate transitions. In this work, we use a stochastic multicellular signaling network of pancreatic cancer (PC) to show that the variance in topological rankings of the most phenotypically influential modules implies a strong relationship between structure and function. We further show that induction of mutations alters the modular structure, which analogously influences the aggression and controllability of the disease in silico. We finally present evidence that the impact and location of mutations with respect to PC modular structure directly corresponds to the efficacy of single agent treatments in silico, because topologically deep mutations require deep targets for control.

Efficacy of forskolin as a promising therapy for chronic olfactory dysfunction post COVID-19.

Olfactory dysfunction is increasingly common among COVID-19 patients, impacting their well-being. Reports have demonstrated decreased levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate among patients with chronic olfactory dysfunction. A prospective randomized clinical trial was developed to demonstrate the efficacy of an oral forskolin regimen treatment, an adenylyl cyclase activator that raises intracellular levels of cyclic adenosine monophosphate, for the treatment of olfactory dysfunction following COVID-19, compared to placebo regimen. The study enrolled 285 participants with persistent olfactory dysfunction post COVID-19 infection, randomly assigning them to receive either placebo capsules (n = 120) or oral forskolin capsules (n = 165). Follow-up was conducted to track progress, with 18 participants from the placebo group and 12 from the forskolin group lost during this period. Olfactory function was assessed using the "Sniffin' Sticks" test, measuring threshold, discrimination and identification scores before and after treatment. Subjects administered forskolin capsules demonstrated a significant enhancement in their composite TDI (threshold, discrimination and identification) score, suggesting a notable amelioration in olfactory functionality. Moreover, the discrimination and identification scores notably improved within the forskolin group. Conversely, no significant alterations were observed in the threshold scores. This study suggests that forskolin can contribute potentially to improve chronic olfactory dysfunction post COVID-19. DFM-IRB00012367-23-10-001.

Novel Vpx virus-like particles to improve cytarabine treatment response against acute myeloid leukemia

Knowledge of the molecular pathogenesis of acute myeloid leukemia has advanced in recent years. Despite novel treatment options, acute myeloid leukemia remains a survival challenge for elderly patients. We have recently shown that the triphosphohydrolase SAMHD1 is one of the factors determining resistance to Ara-C treatment. Here, we designed and tested novel and simpler virus-like particles incorporating the lentiviral protein Vpx to efficiently and transiently degrade SAMHD1 and increase the efficacy of Ara-C treatment. The addition of minute amounts of lentiviral Rev protein during production enhanced the generation of virus-like particles. In addition, we found that our 2nd generation of virus-like particles efficiently targeted and degraded SAMHD1 in AML cell lines with high levels of SAMHD1, thereby increasing Ara-CTP levels and response to Ara-C treatment. Primary AML blasts were generally less responsive to VLP treatment. In summary, we have been able to generate novel and simpler virus-like particles that can efficiently deliver Vpx to target cells.

Elemental Diet as a Therapeutic Modality: A Comprehensive Review.

Elemental diets have been employed for the management of various diseases for over 50years, with several mechanisms mediating their beneficial effects. Yet, they are underutilized due to poor palatability, access, cost, and lack of awareness regarding their clinical efficacy. Therefore, in this review, we aimed to systematically search and review the literature to summarize the formulation variability, mechanisms of action, clinical applications, and tolerability of the elemental diets in gastrointestinal diseases. While large prospective trials are lacking, elemental diets appear to exhibit objective and subjective clinical benefit in several diseases, including eosinophilic esophagitis, eosinophilic gastroenteritis, inflammatory bowel diseases, small intestinal bacterial overgrowth,intestinal methanogen overgrowth, chemoradiotherapy-associated mucositis, and celiac disease. Although some data support the long-term use of elemental diets as an add-on supplement for chronic pancreatitis and Crohn's disease, most of the literature on exclusive elemental diets focuses on inducing remission. Therefore, subsequent treatment strategies for maintaining remission need to be adopted in chronic/relapsing diseases. Several mechanistic pathways were identified to mediate the effects of elemental diets, including food additive and allergen-free content, high passive absorption rate, and anti-inflammatory properties. High rates of intolerance up to 40% are seen in the trials where exclusive elemental diets were administered orally due to poor organoleptic acceptability; however, when tolerated, adverse events were rare. Other limitations of elemental diets are cost, access, and lifestyle/social restrictions. Moreover, judicious use is advised in presence of a concomitant restrictive food intake disorders. Elemental diets offer a potentially highly efficacious dietary intervention with minor side effects. Palatability, cost, access, and social restrictions are common barriers of use. Prospective clinical trials are needed to elucidate the role of elemental formulas in the management of individual diseases.

Establishing Minimal Clinically Important Differences (MCIDs) for the Pemphigus Disease Area Index (PDAI).

Pemphigus is a rare autoimmune blistering disease (AIBD) with potentially life-threatening consequences. Establishing minimal clinically important differences (MCIDs) for disease severity scores like the Pemphigus Disease Area Index (PDAI) is crucial for assessing treatment efficacy. To calculate MCIDs for both improvement and deterioration in PDAI scores in patients with pemphigus vulgaris (PV) and pemphigus foliaceous (PF) using the anchor-based method. A total of 41 pemphigus patients were recruited, with 35 meeting the MCID analysis criteria. The anchor-based method was employed to calculate MCIDs for PDAI scores against the 15-point Likert scale and the Physician Global Assessment Visual Analogue Scale (PGA-VAS) anchors. Receiver operating characteristic (ROC) curves were employed to determine optimal MCID cutpoints with the highest Youden Index (J). The 15-point Likert scale scores the change in disease severity spanning from -7 to +7, designed to quantify the extent of disease improvement/deterioration since the preceding visit. The MCID for improvement in PDAI activity scores was 2.65 points using the 15-point Likert scale (78.7% correct classification; sensitivity 75.9%; specificity 73.5%) and 2.5 points using the PGA-VAS as the anchor (78.0% correct classification; sensitivity 84.4%; specificity 68.2%). Given the slightly higher correct classification rate using the 15-point Likert scale anchor, the MCID of 2.65 points was selected for PDAI activity score improvement. In contrast, MCID for deterioration consistently remained at 2.5 points for the 15-point Likert scale anchor (81.0% correct classification; sensitivity 72.7%; specificity 81.0%) and 2.5 points for the PGA-VAS anchor (70.9% correct classification; sensitivity 69.6%; specificity 76.9%). This study marks the inaugural attempt at MCID determination for PDAI scores in pemphigus, filling a critical knowledge gap. The study's calculated MCIDs provide essential benchmarks for clinical trials, treatment evaluation, and research design optimisation. Future studies should explore international collaborations to examine potential cross-cultural variations in MCIDs.

Targeting the CDK7-MDK axis to suppresses irinotecan resistance in colorectal cancer

AimsColorectal cancer (CRC) remains a major global health issue, with metastatic cases presenting poor prognosis despite advances in chemotherapy and targeted therapy. Irinotecan, a key drug for advanced CRC treatment, faces challenges owing to the development of resistance. This study aimed to understand the mechanisms underlying irinotecan resistance in colorectal cancer. Main methodsWe created a cell line resistant to irinotecan using HT29 cells. These resistant cells were utilized to investigate the role of the CDK7-MDK axis. We employed bulk RNA sequencing, conducted in vivo experiments with mice, and analyzed patient tissues to examine the effects of the CDK7-MDK axis on the cellular response to irinotecan. Key findingsOur findings revealed that HT29 cells resistant to irinotecan, a crucial colorectal cancer medication, exhibited significant phenotypic and molecular alterations compared to their parental counterparts, including elevated stem cell characteristics and increased levels of cytokines and drug resistance proteins. Notably, CDK7 expression was substantially higher in these resistant cells, and targeting CDK7 effectively decreased their survival and tumor growth, enhancing irinotecan sensitivity. RNA-seq analysis indicated that suppression of CDK7 in irinotecan-resistant HT29 cells significantly reduced Midkine (MDK) expression. Decreased CDK7 and MDK levels, achieved through siRNA and the CDK7 inhibitor THZ1, enhanced the sensitivity of resistant HT29 cells to irinotecan. SignificanceOur study sheds light on how CDK7 and MDK influence irinotecan resistance in colorectal and highlights the potential of MDK-targeted therapies. We hypothesized that irinotecan sensitivity and overall treatment efficacy would improve by inhibiting MDK. This finding encourages a careful yet proactive investigation of MDK as a therapeutic target to enhance outcomes in colorectal cancer patients.

Clinical Outcomes and Treatment Efficacy in Cervical Cancer Patients in the UAE: A Retrospective Cohort Study

Clinical Outcomes and Treatment Efficacy in Cervical Cancer Patients in the UAE: A Retrospective Cohort Study

Endovascular treatment for 2 types of subclavian artery injury: A case report.

Subclavian artery (SCA) injuries, though rare, carry significant morbidity and mortality risks due to significant blood loss causing hypovolemic shock. Early diagnosis and adequate treatment are crucial to minimize bleeding and associated morbidity. Recent advances in endovascular techniques offer faster and more accurate treatment options compared to traditional open surgical repair. This study demonstrates the efficacy of endovascular treatment in 2 cases of SCA injury and reviews its indications, limitations, and precautions. A 69-year-old man presented with a penetrating SCA injury from a steel bar, and a 38-year-old woman presented with a blunt SCA injury caused by a fall. Both patients were hemodynamically unstable upon presentation. Both patients were diagnosed with SCA injuries. The man had a penetrating injury, while the woman had a blunt injury, both resulting in hemodynamic instability and significant risk of hypovolemic shock. Endovascular techniques, including the use of covered stent grafts, were employed to manage the injuries. These techniques allowed for rapid and efficient treatment, reducing the need for open surgical intervention. Both patients were successfully treated using endovascular methods and were discharged without any complications. The endovascular approach minimized blood loss, transfusion needs, and hospital stay. This study demonstrates the effectiveness of endovascular techniques in rapidly diagnosing, bridging, and definitively treating SCA injuries, suggesting their use as a first-line therapy.

Microsurgical clipping versus endovascular therapy for treating patients with middle cerebral artery aneurysms presenting with neurological ischemic symptoms.

Studies comparing different treatment methods in patients with middle cerebral artery (MCA) aneurysms in different subgroups of onset symptoms are lacking. It is necessary to explore the safety and efficacy of open surgical treatment and endovascular therapy in patients with MCA aneurysms in a specific population. This study aimed to compare microsurgical clipping versus endovascular therapy regarding complication rates and outcomes in patients with MCA aneurysms presenting with neurological ischemic symptoms. This was a retrospective cohort study in which 9656 patients with intracranial aneurysms were screened between January 2014 and July 2022. Further, 130 eligible patients were enrolled. The primary outcome was the incidence of serious adverse events (SAEs) within 30days of treatment, whereas secondary outcomes included postprocedural target vessel-related stroke, disabling stroke or death, mortality, and aneurysm occlusion rate. Among the 130 included patients, 45 were treated with endovascular therapy and 85 with microsurgical clipping. The primary outcome of the incidence of SAEs within 30days of treatment was significantly higher in the clipping group [clipping: 23.5%(20/85) vs endovascular: 8.9%(4/45), adjusted OR:4.05, 95% CI:1.20-13.70; P = 0.024]. The incidence of any neurological complications related to the treatment was significantly higher in the clipping group [clipping:32.9%(28/85) vs endovascular:15.6%(7/45); adjusted OR:3.49, 95%CI:1.18-10.26; P = 0.023]. Postprocedural target vessel-related stroke, disabling stroke or death, mortality rate, and complete occlusion rate did not differ significantly between the two groups. Endovascular therapy seemed to be safer in treating patients with MCA aneurysms presenting with neurological ischemic symptoms compared with microsurgical clipping, with a significantly lower incidence of SAEs within 30days of treatment and any neurological complications related to the treatment during follow-up.

Efficacy and safety of gemcitabine/nab-paclitaxel combined with anlotinib and PD-1 inhibitors as a first-line treatment for advanced pancreatic cancer

ObjectiveTo investigate the clinical efficacy and adverse reactions of gemcitabine/nab-paclitaxel (AG regimen) combined with anlotinib and PD-1 inhibitors as a first-line treatment for advanced pancreatic cancer (PC). MethodsData of 52 patients with advanced PC who were treated in the Affiliated Hospital of Xuzhou Medical University (Xuzhou, China) between August 2019 and March 2023 were retrospectively analyzed. According to the treatment regimen, patients were divided into two groups, including 27 patients in the chemotherapy group (AG regimen) and 25 patients in the combined treatment group (AG regimen combined with anlotinib and PD-1 inhibitors). Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse reactions were compared between the two groups. The survival curves of the two groups were drawn using the Kaplan-Meier method, and the differences in PFS and OS between the two groups were compared by the log-rank test. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors influencing prognosis. ResultsThe median OS and PFS in the combined treatment group were significantly longer than those in the chemotherapy group (OS, 12.8 vs. 7.9 months, P = 0.005; PFS, 5.6 vs. 4.4 months, P = 0.003). There was no significant difference in ORR between the two groups (32.0 % vs. 25.9 %, P = 0.629), and DCR in the combined treatment group was significantly better than that in the chemotherapy group (84.0 % vs. 59.3 %, P = 0.049). Grade 1–2 adverse reactions were predominant in both groups, and no adverse reaction-related deaths occurred. ConclusionCompared with chemotherapy alone, AG regimen combined with anlotinib and PD-1 inhibitors exhibited to have a higher efficacy for the first-line treatment of advanced PC, and the adverse reactions were also controllable.

Spatial landscape of malignant pleural and peritoneal mesothelioma tumor immune microenvironment.

Immunotherapies have demonstrated limited clinical efficacy in malignant mesothelioma treatment. We conducted multiplex immunofluorescence (mIF) analyses on tissue microarrays (n=3) from malignant peritoneal (MPeM, n=25) and pleural (MPM, n=88) mesothelioma patients. Our study aimed to elucidate spatial distributions of key immune cell populations and their association with LAG3, BAP1, NF2, and MTAP, with MTAP serving as a CDKN2A/B surrogate marker. Additionally, we examined the relationship between the spatial distribution of major immune cell types with MM patient prognosis and clinical characteristics. We observed a higher degree of interaction between immune cells and tumor cells in MPM compared to MPeM. Notably, within MPM tumors, we detected a significantly increased interaction between tumor cells and CD8+ T cells in tumors with low BAP1 expression compared to those with high BAP1 expression. To support the broader research community, we have developed The Human Spatial Atlas of Malignant Mesothelioma (https://mesotheliomaspatialatlas.streamlit.app/), containing mIF and hematoxylin and eosin (H&E) images.

S166 - Randomized Controlled Trial Testing the Efficacy of a Remote Caffeine Reduction Intervention

S166 - Randomized Controlled Trial Testing the Efficacy of a Remote Caffeine Reduction Intervention

Update in the diagnosis and treatment of actinic keratosis

Actinic keratosis (AK) is among the most common conditions in dermatology in an increasingly aging population. However, the presence of severe field cancerization with large treatment fields showing multiple lesions with distinct features often poses atherapeutic challenge. The most accurate possible characterization of the treatment field, risk assessment concerning the occurrence of cutaneous squamous cell carcinoma, and knowledge of the efficacy and local side effects of the available interventions are of paramount importance for effective management and preventive efforts. This article summarizes current developments in the diagnosis and treatment of AK and discusses their application in everyday clinical practice. In particular, the focus is on the increasing value of non-invasive diagnostic techniques like "line-field" confocal optical coherence tomography, and the recently approved topical agents tirbanibulin 1% ointment and 5‑fluorouracil 4% cream, as well as current developments of photodynamic therapy and prevention.

Pharmacological interventions for preventing upper gastrointestinal bleeding in people admitted to intensive care units: a network meta-analysis

ObjectivesTo assess the efficacy and safety of pharmacological interventions for preventing upper gastrointestinal (GI) bleeding in people admitted to intensive care units (ICUs).Design and settingSystematic review and frequentist network meta-analysis...

Comparative efficacy and safety of non-pharmacological interventions as adjunctive treatment for vascular dementia: a systematic review and network meta-analysis

Comparative efficacy and safety of non-pharmacological interventions as adjunctive treatment for vascular dementia: a systematic review and network meta-analysis

Long- and Short-Term Glucosphingosine (lyso-Gb1) Dynamics in Gaucher Patients Undergoing Enzyme Replacement Therapy

Background: Gaucher disease (GD) is a lysosomal storage disorder caused by mutations in the GBA1 gene, leading to β-glucocerebrosidase deficiency and glucosylceramide accumulation. Methods: We analyzed short- and long-term dynamics of lyso-glucosylceramide (lyso-Gb1) in a large cohort of GD patients undergoing enzyme replacement therapy (ERT). Results: Eight-years analysis of lyso-Gb1 revealed statistically insignificant variability in the biomarker across the years and relatively high individual variability in patients’ results. GD type 1 (GD1) patients exhibited higher variability compared to GD type 3 (GD3) patients (coefficients of variation: 34% and 23%, respectively; p-value = 0.0003). We also investigated the short-term response of the biomarker to enzyme replacement therapy (ERT), measuring lyso-Gb1 right before and 30 min after treatment administration. We tested 20 GD patients (16 GD1, 4 GD3) and observed a rapid and significant reduction in lyso-Gb1 levels (average decrease of 17%; p-value < 0.0001). This immediate response reaffirms the efficacy of ERT in reducing substrate accumulation in GD patients but, on the other hand, suggests the biomarker’s instability between the infusions. Conclusions: These findings underscore lyso-Gb1’s potential as a reliable biomarker for monitoring efficacy of treatment. However, individual variability and dry blood spot (DBS) testing limitations urge a further refinement in clinical application. Our study contributes valuable insights into GD patient management, emphasizing the evolving role of biomarkers in personalized medicine.

Plasma metabolome analysis for predicting antiviral treatment efficacy in chronic hepatitis B: diagnostic biomarkers and therapeutic insights

Plasma metabolome analysis for predicting antiviral treatment efficacy in chronic hepatitis B: diagnostic biomarkers and therapeutic insights