Disease Outcome Research Articles

Neuromodulation for Neuropathic Pain Syndromes

ABSTRACT OBJECTIVE This article reviews the principles, applications, and emerging trends of neuromodulation as a therapeutic approach for managing painful neuropathic diseases. By parsing evidence for possible mechanisms of action and clinical trial outcomes for various diseases, this article focuses on five common therapy modalities: cutaneous, peripheral nerve, spinal cord, and brain stimulation, and intrathecal drug delivery. LATEST DEVELOPMENTS Recent advances in both invasive and noninvasive neuromodulation for pain have introduced personalized and closed-loop techniques, integrating real-time feedback mechanisms and combining therapies to improve physical and psychosocial function. Novel stimulation waveforms may influence distinct neural tissues to rectify pathologic pain signaling. ESSENTIAL POINTS With appropriate patient selection, peripheral nerve stimulation or epidural stimulation of the spinal cord can provide enduring relief for a variety of chronic pain syndromes. Newer technology using high frequencies, unique waveforms, or closed-loop stimulation may have selective advantages, but our current understanding of therapy mechanisms is very poor. For certain diagnoses and patients who meet clinical criteria, neuromodulation can provide profound, long-lasting relief that significantly improves quality of life. While many therapies are supported by data from large clinical trials, there is a risk of bias as most clinical studies were funded by device manufacturers or insurance companies, which increases the importance of real-world data analysis. Emerging methods like invasive or noninvasive brain stimulation may help us dissect basic mechanisms of pain processing and hold promise for personalized therapies for refractory pain syndromes. Finally, intrathecal delivery of drugs directly to segments of the spinal cord can also modify pain signaling to provide therapy for severe pain syndromes.

C57BL/6 Peritoneal Macrophage Exosomes Improve Antileishmanial Functions of the RAW264.7 Cells.

Leishmaniasis is considered one of the most critical health concerns in the world. Unfortunately, no protective vaccines exist and conventional treatments are relatively ineffective. Therefore, new strategies are necessary against leishmaniasis. In recent years, exosomes have shown promising therapeutic outcomes in various diseases, including infectious diseases. In this regard, we aimed to explore the effect of the exosome, pyrimethamine and their combination on the anti-parasitic function of RAW264.7 cells against Leishmania major. Exosomes were isolated from the C57BL/6 peritoneal macrophages. L. major infected and non-infected RAW264.7 cells treated with exosomes, pyrimethamine (PM), and exosomes along with PM. The effect of the treatments was analysed on phagocytosis, efferocytosis, the intracellular parasite count, arginase activity, nitric oxide (NO) and reactive oxygen species (ROS) production. Exosomes could significantly elevate the phagocytosis, efferocytosis, NO and ROS in both infected and non-infected groups (Pv < 0.05). The exosomes reduced the arginase activity in both groups (Pv < 0.05). The intracellular parasite count was significantly lower after treatment with exosomes (Pv < 0.05). These results demonstrate that MQ-derived exosomes can enhance in vitro anti-parasitic responses against L. major. This provides a potential pathway for more effective treatments and underscores the importance of further research in this area.

The outcome of coronavirus disease 2019 in hospitalized patients with diabetes mellitus at Assiut University Hospital

Rationale The chronic nature of diabetes renders it a risk factor for lower respiratory tract infections, adversely impacting patient prognosis. Objective This study aimed to investigate the influence of diabetes on the outcomes of coronavirus disease 2019 (COVID-19) patients. Patients and methods This prospective cohort study enrolled 160 patients admitted and diagnosed with COVID-19. Patients were categorized according to glycated hemoglobin level into two groups: diabetic and nondiabetics (80 patients each). The COVID-19 severity index was calculated for all patients. Follow-up of their in-hospital stay and incidence of complications was documented. Results It was found that diabetic patients had a significantly higher percentage of severe COVID-19 cases (83.8 vs. 61.3%) [odds ratio (OR)=1.89, 95% confidence interval (CI)=1.02–3.48]. The diabetic group had higher rates of ICU admission (OR=2.21, 95% CI=1.06–4.57), invasive mechanical ventilation (OR=3.75, 95% CI=1.321–10.803), and mortality (HR=1.69, 95% CI=1.132-2.514) compared with nondiabetic patients (33.8 vs. 18.8%, 20 vs. 6%, and 41.5 vs. 21.2%, respectively). From the nondiabetic group, 68.4% of prediabetic patients had hyperglycemia requiring insulin treatment during their hospital stay versus 31.6% of normoglycemic patients. Conclusion Diabetes mellitus is associated with more severe manifestations of the disease, increased complications, ICU admissions, ventilatory requirements, and mortality rates compared to nondiabetic individuals. COVID-19 is associated with poor glycemic control.

Potential role of solid lipid curcumin particle (SLCP) as estrogen replacement therapy in mitigating TDP-43-related neuropathy in the mouse model of ALS disease

BackgroundAmyotrophic lateral sclerosis (ALS) was first identified in 1869, but it wasn't until the 2014 Ice Bucket Challenge that widespread attention was drawn to the disease. Since then, substantial research has been dedicated to developing treatments for ALS. Despite this, only three drugs - riluzole, edaravone and AMX0035, have been approved for clinical use, and they can only temporarily alleviate mild symptoms without significant disease modification or cure. Therefore, there remains a critical unmet need to identify disease modifying or curative therapies for ALS. The higher incidence and more severe progression of ALS and FTLD (frontotemporal lobar degeneration) observed in men and postmenopausal woman compared to young women suggests that sex hormones may significantly influence disease onset and progression. In both animal models and human clinical studies, 17β estradiol (E2) has been shown to delay and improve the outcomes of many neurodegenerative diseases. Here, we examined the role of TDP-43 in the regulation of estrogen-related enzymes, CYP19A1 and CYP3A4. In addition, we examined the impact of curcumin on the regulation of estrogen E2 levels and TDP-43-associated neuropathy as a potential therapeutic strategy for the treatment of FTLD and ALS. MethodsPrp-TDP-43A315T mice was used as a model of ALS/FTLD to examine the expression patterns of E2 and its biosynthesis and degradation enzymes, CYP19A1 and CYP3A4. Moreover, the molecular mechanisms and the potency of solid lipid curcumin particles (SLCP) as an E2 replacement therapy for TDP-43 associated neuropathy was analyzed. We further examined the survival rates and the pathological TDP43 patterns in female and male Prp-TDP-43A315T mice administrated with or without SLCP. In addition, the changed expression levels of enzymes corresponding to E2 biosynthesis and degradation in the spinal cord of female and male Prp-TDP-43A315T mice with or without SLCP were determined. ResultsWe found that in addition to E2, the expression patterns of CYP19A1 and CYP3A4 proteins differed between Prp-TDP-43A315T mice compared to wild-type control, suggesting that toxic phosphorylated TDP43 oligomers may disrupt the balance between CYP19A1 and CYP3A4 expression, leading to reduced estrogen biosynthesis and accelerated degradation. In addition, we found that oral administration of SLCP prolonged the survival rates in female Prp-TDP-43A315T mice and significantly reduced the pathological insoluble phosphorylated TDP-43 species. Furthermore, SLCP attenuated disease progression associated with TDP-43-related neuropathies through modulating estrogen biosynthesis and the activity of CYP450 enzymes. ConclusionsOur results showed that Prp-TDP-43A315T mice exhibit altered estradiol levels. Moreover, we demonstrated the efficacy of SLCP as an estrogen replacement therapy in mitigating TDP-43-associated disease progression and pathogenesis. These findings suggest that SLCP could be a promising strategy to induce E2 expression for the treatment of ALS and FTLD.

S1497 Prevalence and Impact of Zinc Deficiency on Clinical Outcomes in Inflammatory Bowel Disease

S1497 Prevalence and Impact of Zinc Deficiency on Clinical Outcomes in Inflammatory Bowel Disease

Outcome of Peripheral Arterial Disease in Patients with ESKD on Hemodialysis

Outcome of Peripheral Arterial Disease in Patients with ESKD on Hemodialysis

TCT-774 Sex Differences in Prevalence, Clinical Presentation, Management Strategies and Clinical Outcomes of Valvular Heart Disease in Hospitalized Patients: Insights From a Single-Center Registry at a Tertiary Care Hospital in India

TCT-774 Sex Differences in Prevalence, Clinical Presentation, Management Strategies and Clinical Outcomes of Valvular Heart Disease in Hospitalized Patients: Insights From a Single-Center Registry at a Tertiary Care Hospital in India

Treatment with trimetazidine dihydrochloride and lung cancer survival: Implications on metabolic re-programming

BackgroundMetabolic re-wiring with preferential fatty acid oxidation has been observed in lung cancer cells. Whether the use of trimetazidine, an anti-anginal agent that inhibits fatty acid oxidation, alters clinical outcomes in ischemic heart disease (IHD) patients with lung cancers is unknown. MethodsWe carried out this territory-wide, retrospective cohort study of 279,894 IHD patients prescribed with trimetazidine or long-acting oral nitrates in Hong Kong (population coverage of 7.5 millions, January 1999 − December 2020). A total of 6561 patients with pre-existing or de novo lung cancers were identified. Clinical outcomes of all-cause mortality were longitudinally compared between lung cancer patients who received trimetazidine (n = 547) versus non-users (control, n = 6014). ResultsOver 902.9 ± 1410.6 days, lower incidence of deaths occurred in the trimetazidine group (79.0 %, n = 432/547) compared to controls (90.5 %, n = 5442/6014, P < 0.001). Kaplan-Meier analyses showed that trimetazidine use was associated with significantly higher survival from all-cause mortality in IHD patients (trimetazidine: mean survival = 1840.6 [95 %CI 1596.0–2085.3], versus control: 1056.7 [95 %CI 1011.3–1102.0] days, Log Rank = 69.4, P < 0.001). Cox regression showed that trimetazidine use was significantly associated with reduced risk of all-cause mortality in crude (HR = 0.60 [95 %CI: 0.53 to 0.68], P < 0.001) and multivariable models (HR = 0.65 [95 % CI: 0.57 to 0.74], P < 0.001). Pre-specified analyses amongst patients with pre-existing lung cancers yielded similar findings (HR = 0.49 [95 %CI: 0.35 to 0.67], P < 0.001). Survival benefits related to trimetazidine use was predominantly restricted to non-cardiovascular mortality (P < 0.001). ConclusionsTrimetazidine use is associated with higher overall survival in IHD patients with lung cancers, particularly from non-cardiovascular death. These findings need to be confirmed by randomized controlled trials.

Genetic Polymorphisms of Prokineticins and Prokineticin Receptors Associated with Human Disease

Prokineticins (PKs) are low molecular weight proteins that exert their effects by binding to two seven-transmembrane G-protein-coupled receptors (prokineticin receptors, PKRs). The prokineticin system is an important player in the development of various diseases. Several polymorphisms that are associated with infertility, neuroendocrine disorders, Hirschsprung’s syndrome (HSCR), idiopathic central precocious puberty (CPP) and congenital disorders such as Kallmann syndrome (KS) have been described for both the PKs and PKR genes. The aim of this study is to summarize and describe the impact of PK/PKR polymorphisms on the pathogenesis and outcome of the above diseases, highlighting the PK system as a therapeutic target and diagnostic biomarker in pathological conditions.

S1811 Acute Decompensated Congestive Heart Failure Outcomes in Chronic Liver Disease: Analysis Using the National In-Patient Sample

S1811 Acute Decompensated Congestive Heart Failure Outcomes in Chronic Liver Disease: Analysis Using the National In-Patient Sample

Protective effects of phenylethanol glycosides from Cistanche tubulosa against ALD through modulating gut microbiota homeostasis

Ethnopharmacological relevanceCistanche tubulosa (Schenk) Wight, a Chinese herbal medicine (Rou Cong Rong) with Xinjiang characteristics, was recorded in many medical books in ancient China and often used as a tonic medicine. Supported by the traditional Chinese medicine theory of “homology of liver and kidney,” C. tubulosa (Schenk) Wight has many clinical applications in tonifying the kidney and protecting the liver. Modern pharmacological studies have also found that the protective effects of phenylethanol glycosides from C. tubulosa (Schenk) Wight (CPhGs) play an important role in ameliorating alcoholic liver injury. Aim of the studyWe aimed to investigate whether CPhGs can enhance the therapeutic outcome of alcoholic liver disease (ALD) by targeting the “gut–liver axis,” thus contributing to the knowledge of how Chinese herbs alleviate disease by influencing the gut microbiota. Materials and methodsAn ALD mouse model was established using the Lieber–DeCarli alcohol liquid diet, and the effects of CPhGs on the intestinal barrier and gut microbiota of ALD mice were investigated in a pseudo-sterile mouse model and fecal microbiota transplantation (FMT) mouse model. We fed female C57BL/6N mice with Lieber-DeCarli ethanol liquid diet, according to the NIAAA model. Animal experiment of long-term, ethanol diet intervention for 6W, and short-term for 11d. The FMT experiments were also performed. ResultsCPhGs significantly improved ALD manifestations. ALD mice demonstrated significant gut microbiota dysbiosis and significantly abnormal proliferation of Allobaculum compared with the control diet group in long-term NIAAA mouse model (L-Pair). In mice that received the long-term intervention, the improvement in gut barrier function in the CPhGs-treated group was accompanied by a significant decrease in the abundance of Allobaculum and a significant increase in the abundance of Akkermansia. Furthermore, compared with the mouse were gavaged fecal microbiota from the long-term NIAAA mouse donors (FMT-EtOH), the number of goblet cells, abundance of Akkermansia, and the intestinal short-chain fatty acid concentrations were significantly increased in the mouse were gavaged fecal microbiota from high (700 mg/kg) doses of CPhGs orally in long-term NIAAA model donors (FMT-EtOH-H). Network analysis and species distribution results demonstrated that Akkermansia and Allobaculum were the genera with the highest abundances in the gut microbiota and that their interaction was related to propionic acid metabolism. ConclusionsThe results suggest that CPhGs exert a protective effect against ALD by modulating the abundance and composition of Akkermansia and Allobaculum in the intestine, maintaining the intestinal mucus balance, and safeguarding intestinal barrier integrity.

S590 Comparative Outcomes of Gastroesophageal Reflux Disease, Nonerosive Reflux Disease, and Erosive Esophagitis in Patients Undergoing Roux-en-Y Gastric Bypass versus Sleeve Gastrectomy for Weight Loss

S590 Comparative Outcomes of Gastroesophageal Reflux Disease, Nonerosive Reflux Disease, and Erosive Esophagitis in Patients Undergoing Roux-en-Y Gastric Bypass versus Sleeve Gastrectomy for Weight Loss

Clinicopathological Characteristics and Outcomes of Nondiabetic Kidney Disease in Patients with Type 2 Diabetes

Clinicopathological Characteristics and Outcomes of Nondiabetic Kidney Disease in Patients with Type 2 Diabetes

The Relationship of Vitamin A and Neonatal Respiratory Diseases: A Meta-Analysis.

This study systematically analyzes the relationship of vitamin A on the neonatal respiratory diseases. An extensive literature search for relevant studies was conducted on PubMed, Web of Science, and so on. After screening in strict accordance with the inclusion and exclusion criteria, 12 articles on vitamin A deficiency and 12 articles on vitamin A supplementation were included. Stata 17.0 software was used to perform meta-analysis, heterogeneity test, and sensitivity analysis, and the corresponding mathematical model was used to merge the data. The meta-analysis results of the relationship between vitamin A deficiency and neonatal respiratory diseases indicated that compared with the neonates with normal vitamin A, the neonates with vitamin A deficiency had adverse health outcomes of neonatal respiratory diseases (OR = 4.86, 95% CI: 2.68-8.84), of which neonatal respiratory distress syndrome (NRDS) (OR = 4.10, 95% CI: 2.32-7.23) and neonatal pneumonia (OR = 3.22, 95% CI: 2.18-4.77) were analyzed by subgroup analysis. The meta-analysis of the relationship between vitamin A supplementation therapy and neonatal respiratory diseases showed that vitamin A supplementation was an effective therapeutic measure for neonatal respiratory diseases (RR = 1.06, 95% CI: 1.04-1.07): NRDS (RR = 1.03, 95% CI: 1.02-1.05) and NBPD (RR = 1.08, 95% CI: 1.01-1.15). The funnel chart method results show that there was publication bias in studies on vitamin A deficiency induced to and vitamin A supplementation therapy for neonatal respiratory diseases. The sensitivity analysis results showed that excluding some special article had some effect on the final pooled effect. But generally speaking, the result of meta-analysis was stable. There is a statistical correlation of vitamin A on the neonatal respiratory diseases from two aspects of etiological exploration and effect evaluation of treatment.

S1177 Outcomes in Inflammatory Bowel Disease in Patients Undergoing Coronary Artery Bypass Grafting: A Nationwide Analysis

S1177 Outcomes in Inflammatory Bowel Disease in Patients Undergoing Coronary Artery Bypass Grafting: A Nationwide Analysis

A-142 Cutaneous T-cell lymphoma in pregnancy: disease activity and outcomes

A-142 Cutaneous T-cell lymphoma in pregnancy: disease activity and outcomes

Maternal Kidney Disease and Offspring Neurodevelopmental Outcomes: A Nationwide Population-Based Study

Maternal Kidney Disease and Offspring Neurodevelopmental Outcomes: A Nationwide Population-Based Study

Allogeneic Hematopoietic Cell Transplantation in Elderly Patients with Myelodysplastic Syndromes: Considerations and Challenges

Myelodysplastic syndromes/neoplasms (MDS) and related diseases are highly heterogeneous myeloid stem cell cancers that predominantly affect the elderly. The only curative treatment is allogeneic hematopoietic cell transplantation (HCT). Given the prevalence of age-related comorbidities, HCT in patients aged 65 years or older requires a highly personalized approach. This review summarizes disease risk stratification, treatment modalities, and outcomes for patients with MDS and related disorders, and discusses specific considerations and challenges for elderly patients undergoing HCT, including geriatric assessment, timing, conditioning treatment, donor and graft selection, and graft-versus-host disease prophylaxis.

Gender differences in the management and outcomes of acute coronary syndrome in indians: A systematic review and meta-analysis

BackgroundGender differences in acute coronary syndrome (ACS) outcomes have been noted in global data, which however did not analyse Indian data. No prior systematic review and meta-analysis (SRM) has addressed this important aspect of gender bias in Indian women with ACS. Hence this SRM aimed to address this knowledge gap. MethodsElectronic databases were searched for studies in ACS comparing cardiovascular disease presentation, treatment received and outcomes in women and men from India. Primary outcomes were to evaluate gender-differences in 30-day death and major adverse cardiovascular events (MACE). Secondary outcomes were to evaluate gender-differences in presentation, management and mortality. The SRM is registered with PROSPERO (CRD42023477286). ResultsFrom initially screened 3753 articles, data from 9 studies (61,185 patients) were analysed. Women with ACS had higher prevalence of diabetes [Odds ratio (OR) 1.65(95%CI:1.33–2.04); p < 0.001; I2 = 95 %] and hypertension [OR2.06(95%CI:1.88–2.25); p < 0.001; I2 = 42 %]. Smoking was significantly lower in women [OR 0.05(95%CI:0.03–0.07); p < 0.001; I2 = 87 %]. Non-ST elevation myocardial infarction (NSTEMI) was significantly higher in women [OR 1.92(95%CI:1.66–2.21); p < 0.001; I2 = 0 %]. Diagnostic angiography [OR 0.64(95%CI:0.56–0.74); p < 0.001; I2 = 46 %] and percutaneous coronary interventions [OR0.71(95%CI:0.55–0.92); p = 0.01; I2 = 92 %] were significantly lower in women. Women had significantly higher 30-day mortality [Hazard ratio (HR)2.26(95%CI:2.01–2.55); p < 0.001; I2 = 6 %], 1-year mortality [HR2.41(95%CI:1.89–3.07); p < 0.001; I2 = 53 %], in-hospital death [HR1.88(95%CI:1.19–2.96); p = 0.007; I2 = 92 %], stroke [HR 1.84 (95%CI:1.34–2.52); p < 0.001; I2 = 0 %] and MACE outcomes [OR 2.05 (95%CI:1.78–2.35); p < 0.001]. Use of aspirin, clopidogrel, beta-blockers and nitrates were significantly lower in women. ConclusionOur study highlights worse outcomes in Indian women with ACS. Higher burden of diabetes and hypertension, decreased used of PCI and lesser aggressive pharmacotherapy may be some of the contributing factors.

Association of Neutrophil-to-Lymphocyte Ratio with Atherosclerotic Cardiovascular Disease and Kidney Outcomes in CKD

Association of Neutrophil-to-Lymphocyte Ratio with Atherosclerotic Cardiovascular Disease and Kidney Outcomes in CKD