Conventional Standard Treatment Research Articles

Usefulness of Platelet-rich Fibrin in Open Fractures of Tibia: A Randomised Comparative Pilot Study

Background and Aims: Platelet-rich fibrin (PRF), rich in growth factors and cytokines, found useful for bone healing in animal studies, has paucity of literature on open fractures in humans. This randomised comparative interventional study aimed to find out the role of PRF in wound healing and fracture union in open fractures of tibia. Material and Methods: Random computerised allocation of 14 open tibial shaft fractures managed with an external fixator were done into PRF and non-PRF groups. Autologous PRF injected at fracture site, with PRF gel over open wounds in the PRF group, was compared with conventional standard treatment in the non-PRF group. Wound assessment on day 3, day 7 and weekly till complete wound healing and radiographs for fracture union at 3, 6, and 12 months were done in both groups. The statistical analysis was done using an unpaired t-test (wound size assessment) and chi-squared test (fracture union), using SPSS version 25. Results: Fractures union in PRF group 7/8 (87.5%) was better than 3/6 (50%) in non-PRF group. External fixators were removed 4 weeks earlier in PRF group. Wound healing time, though not statistically significant, was faster in PRF group (36.25±3.03 days) compared to non-PRF (42±7 days), even with larger wound size in PRF group (7.87±1.43 cm 2 ) than non-PRF group (7.5±1.5 cm 2 ). Conclusions: Results of injectable PRF at fracture site and PRF gel over the wound are encouraging, found to be safe, with faster wound healing and better fracture union in the small sample size of this pilot study.

Microbial Matryoshka: Addressing the Relationship between Pathogenic Flagellated Protozoans and Their RNA Viral Endosymbionts (Family Totiviridae).

Three genera of viruses of the family Totiviridae establish endosymbiotic associations with flagellated protozoa responsible for parasitic diseases of great impact in the context of One Health. Giardiavirus, Trichomonasvirus, and Leishmaniavirus infect the protozoa Giardia sp., Trichomonas vaginalis, and Leishmania sp., respectively. In the present work, we review the characteristics of the endosymbiotic relationships established, the advantages, and the consequences caused in mammalian hosts. Among the common characteristics of these double-stranded RNA viruses are that they do not integrate into the host genome, do not follow a lytic cycle, and do not cause cytopathic effects. However, in cases of endosymbiosis between Leishmaniavirus and Leishmania species from the Americas, and between Trichomonasvirus and Trichomonas vaginalis, it seems that it can alter their virulence (degree of pathogenicity). In a mammalian host, due to TLR3 activation of immune cells upon the recognition of viral RNA, uncontrolled inflammatory signaling responses are triggered, increasing pathological damage and the risk of failure of conventional standard treatment. Endosymbiosis with Giardiavirus can cause the loss of intestinal adherence of the protozoan, resulting in a benign disease. The current knowledge about viruses infecting flagellated protozoans is still fragmentary, and more research is required to unravel the intricacies of this three-way relationship. We need to develop early and effective diagnostic methods for further development in the field of translational medicine. Taking advantage of promising biotechnological advances, the aim is to develop ad hoc therapeutic strategies that focus not only on the disease-causing protozoan but also on the virus.

Characteristics of relapsed and refractory paediatric Hodgkin lymphoma; a 10-year retrospective study of an LMIC.

With conventional standard treatment modalities, children and adolescents with Hodgkin lymphoma (HL) have long-term overall survival rates of over 90%. However, primary refractory disease may occur in 5%-10% of HL patients, while relapse occurs in 5%-10% of patients with early stage disease and up to 30% in an advanced stage. This retrospective study evaluated patient characteristics in cases of HL relapse and refractory and their response to second-line treatment of standalone chemotherapy or in combination with radiotherapy. A retrospective study was conducted by Indus Hospital and Health Network to determine the outcomes of paediatric patients with first and second relapses of HL between 2013 and 2022. A total of 742 patients were diagnosed with HL at Indus Hospital & Health Network. Of these, 48 (6.5%) patients presented with relapse and 35 (4.7%) with refractory disease after initial chemotherapy. In HL relapse patients, 57% were stage IV at initial diagnosis with the most common pathology being nodular sclerosis constituting 42.9% of patients. The most common age group was 6-10 years, 45.8%. B symptoms were experienced by 25 (52%) patients. A time to relapse of >12 months following diagnosis was seen in 69% and 3-12 months was seen in 31%.After receiving second-line treatment, complete remission was achieved by 34 (70.8%) patients, partial remission (PR) was seen in 5 (10.4%), disease progression in 5 (10.4%), 3 (6.3%) patients left during treatment and 1 (2.1%) had a treatment-related mortality. Re-radiation in second-line treatment was only required for 2 patients. The second relapse was seen in 11 (28.2%) of 39 complete and PR patients. Major limitations in the treatment of HL relapse in a low-resource setting are the non-availability of immunotherapy and autologous stem cell transplantation due to extreme financial burden and lack of capacity in facilities. Dedicated efforts are required to provide these facilities free of cost in low-middle income countries (LMICs).

Outcomes of Adjunctive Therapy with Open Arthrotomy for Patients with Septic Arthritis Due to Melioidosis: A Retrospective Study.

Melioidosis is a potentially fatal infection caused by the bacterium Burkholderia pseudomallei. Septic arthritis caused by this infection is uncommon and difficult to treat. The role of adjunctive open arthrotomy in this type of infection has not yet been elucidated. We conducted a retrospective study of patients with microbiologically confirmed melioidosis between January 2002 and December 2022. Patients with a clinical condition of septic arthritis and positive cultures for B. pseudomallei were included. Comparisons were made between patients who received adjunctive therapy with open arthrotomy with conventional standard treatment and those who did not in terms of clinical outcomes and hospital expenditures. Of the 478 patients diagnosed with melioidosis microbiological confirmation, 81 patients had septic arthritis, accounting for 17% of cases. Among these patients, only 36 (44%) underwent adjunctive therapy with open arthrotomy. The 14-day and 30-day in-hospital mortality and length of hospital stays of patients who underwent adjunctive therapy with open arthrotomy were more favorable than those of patients who did not receive adjunctive therapy with open arthrotomy; however, the difference was not statistically significant. Patients who underwent adjunctive therapy with open arthrotomy had lower hospital expenditures (antimicrobial and non-antimicrobial costs) than those who did not undergo open arthrotomy. Adjunctive therapy with open arthrotomy for patients with septic arthritis due to melioidosis was associated with favorable clinical outcomes and significantly lower hospital expenditures.

A phase II study of radiotherapy combined with docetaxel, cisplatin, and 5-fluorouracil for postoperative loco-regional recurrent esophageal cancer.

4029 Background: Recently, neoadjuvant chemotherapy or chemoradiotherapy followed by surgery for patients with esophageal cancer have resulted in favorable prognosis, but extended radical esophagectomy with two-field or three-field (neck, mediastinum, and abdomen) lymph node dissection remains a standard treatment. However, there is recurrence in 30-50% of patients who have undergone an operation and there is loco-regional recurrence in 40-55% of patients with postoperative recurrence. The efficacy and safety of chemoradiotherapy for postoperative loco-regional recurrent esophageal cancer have been reported, and the survival outcome has been improved; however, the median progression-free survival period according to past reports was 10 to 14 months, which was not enough. Recently, RT with docetaxel (DOC), cisplatin (CDDP) and 5-FU has shown better results than conventional standard treatment (CDDP+5-FU +radiotherapy) for primary esophageal cancer. The purpose of the phase II study was to evaluate the superior of definitive radiotherapy with DOC, CDDP and 5-FU to the standard treatment in patients with loco-regional recurrent esophageal cancer after curative resection. Methods: Between 2015 and 2023, this open-label, single-arm, phase II study of radiotherapy (60 Gy/30 fractions/6 weeks without prophylactic region) combined with chemotherapy consisting of 3 cycles of DOC (35 mg/m2), CDDP (40 mg/m2) and 5-FU (400 mg/m2/24 h for 5 days) for patients with postoperative loco-regional recurrent esophageal cancer was conducted at a single institution. The primary endpoint was progression-free survival rate. This trial was considered positive if median progression-free survival period was 24.0 months or more, which meaning superiority over conventional standard treatment. The secondary endpoints were overall survival rate and adverse events. This trial was registered with UMIN Clinical Trials Registry (UMIN000019269) and Japan Registry of Clinical Trials (jRCTs021200009). Results: A total of 29 patients were enrolled in this study. The regimen was completed in all the patients. The median observation period for survivors was 60 months (IQR, 30.0-75.5 months). The 5-year progression-free survival rate was 56.2% (95% CI = 37.4-75.0%) with a median progression-free survival period of 62.0 months (95% CI = 35.2-64.7 months). Only 2 patients showed grade 4 hematologic adverse events during chemoradiotherapy, and they had to be performed reduced chemotherapy; however, they also completed 3 cycles of concurrent chemotherapy. Grade 2 or higher late toxicity was not observed in any patients. Conclusions: The present protocol of radiotherapy combined with DOC, CDDP and 5-FU is a safe and effective salvage treatment for postoperative loco-regional recurrent esophageal cancer. It might be better than conventional treatment. Clinical trial information: UMIN000019269.

Clinical Observations on the Combined Use of Hyperbaric Oxygenation and Conventional Medications in the Management of Type 2 Diabetes Mellitus Concurrent With Sudden Deafness.

Objective: The aim of this study is to investigate the effectiveness of combining hyperbaric oxygen therapy (HBOT) with conventional pharmacological interventions in the management of type 2 diabetes mellitus concurrent with sudden deafness. Methods: A cohort of 96 patients diagnosed with sudden deafness was enrolled and subsequently randomized into 2 groups: a treatment group (n = 50) and a control group (n = 46). The control group received standard conventional treatment aimed at enhancing microcirculation and nutritional support for nerves, while the treatment group underwent conventional symptomatic treatment coupled with HBOT. The evaluation encompassed the monitoring of blood glucose and blood lipid levels, clinical efficacy, and absolute hearing threshold improvement in both groups. Results: Following the intervention, noteworthy reductions in blood glucose and blood lipid levels were observed in both groups compared to their respective pretreatment values. Furthermore, posttreatment values in the treatment group exhibited a statistically significant decrease in comparison to those in the control group (P < .05). On assessing clinical efficacy posttreatment, the treatment group demonstrated a significantly higher efficacy than the control group (P < .05). In addition, the absolute hearing thresholds in both groups exhibited a significant decrease posttreatment compared to baseline values. Notably, the treatment group displayed a statistically significant reduction in absolute hearing thresholds compared to the control group posttreatment (P < .05). Conclusion: The combined therapeutic approach utilizing hyperbaric oxygen exhibits effectiveness in mitigating auditory impairment among individuals manifesting sudden deafness concomitant with type 2 diabetes mellitus. Furthermore, this treatment approach is associated with a concurrent reduction in blood glucose and blood lipid levels.

A Combined Kundalini Yoga and Cognitive Behavioral Therapy Program for Posttraumatic Stress Disorder: A Pilot Study.

Cognitive behavioral therapy (CBT) is one of the standard conventional treatments for posttraumatic stress disorder (PTSD). However, recent studies have reported the benefits of yoga for reducing PTSD symptoms including a Kundalini Yoga (KY) intervention. The purpose of this study was to test the efficacy of a novel combined 8-week CBT and KY program for treating PTSD symptoms and improving sleep quality in a single group trial of 26 adults with PTSD. PTSD symptoms (PTSD checklist-5) and sleep quality (Pittsburgh Sleep Quality Index) were assessed at baseline, post intervention, and at 2-month follow-up. Both CBT and yoga homework compliance were also measured. Total PTSD symptom scores as well as the cluster symptoms (intrusion, avoidance, arousal/reactivity, and negative alterations in cognitions and mood) were significantly improved following the program, all p < .01. The improvements in total PTSD scores, intrusion, avoidance, arousal/reactivity were maintained at follow-up, with all values still less (p < .01) than baseline. The negative alterations in cognitions and mood symptom cluster continued to improve further at follow-up compared to post-intervention values (p < .05). Total sleep score (p < .05) and the subscales of sleep disturbance (p < .01), daytime dysfunction (p < .05), and sleep quality (p < .01) were significantly improved after the program and these improvements were maintained at follow-up compared to baseline. Sleep medication use was decreased (p < .05) and sleep latency was improved (p < .01) at follow-up only compared to baseline. There was a significant positive correlation (p < .05) between the completion of the yoga home practice and post change in total sleep scores. These results show that a combined KY and CBT intervention resulted in decreased PTSD symptoms and improved sleep quality and suggest this program may constitute an additional treatment option for PTSD.

Effect of modified Buyang huanwu decoction on hemorheology, myocardial remodeling, serum soluble CD40 ligand and serum soluble P-selectin in patients with acute myocardial infarctionafter percutaneous coronary intervention

Purpose: To investigate the effect of modified Buyang Huanwu decoction on hemorheology and myocardial remodeling in patients with acute myocardial infarction (AMI) after conventional percutaneous coronary intervention (PCI), and its relationship with serum levels of soluble CD40 ligand (sCD40L) and soluble P-selectin (sP-sel). &#x0D; Methods: After PCI, 80 patients seen from February 2021 to February 2022 in Shijiazhuang Fourth Hospital, China with AMI were enrolled in the study. Subjects were assigned to study and control groups. Control group received standard conventional medical treatments, while study group received modified Buyang Huanwu decoction, in addition to the same standard treatment, orally twice a day (morning and night) for 3 months). The effect of modified Buyang Huanwu decoction was determined by comparing the post-treatment clinical outcomes and levels of hemorheology indices and myocardial remodeling-associated indices (myocardial injury markers) in both groups of patients. &#x0D; Results: The clinical outcome in study group was significantly better, and the hemorheology indices were significantly improved when compared to control subjects (p &lt; 0.05). Serum levels of myocardial injury markers (cardiac troponin (cTnI), cardiac markers (CRP), and brain natriuretic peptide (BNP)), and inflammatory markers (sCD40L and sP-sel) in study group were significantly decreased to varying degrees, relative to control group (p &lt; 0.05). &#x0D; Conclusion: Modified Buyang Huanwu decoction reduces inflammatory marker levels, cardiac inflammatory response and myocardial remodeling, and improves the prognosis of AMI in patients after PCI. Therefore, it may be beneficial to develop other methods for treating acute myocardial infarction after percutaneous coronary intervention.

Optimization of the complex treatment of chronic pancreatitis in elderly patients using systemic enzyme therapy

In the last few years, the number of young people with pancreatic pathology has increased. However, exacerbation of chronic pancreatitis (CP) in “favorable conditions” occurs at any age, leading to extremely unfavorable consequences.&#x0D; The aim is to study clinical and etiological factors of CP in elderly patients and optimize the complex treatment of this category of patients by including a systemic enzyme therapy agent.&#x0D; Materials and methods. The study included 98 CP patients, with a mean age of 71.3±1.4 years, who were randomized into two groups. All patients received the standard conventional treatment complex (CTC): pantoprazole 40 mg on an empty stomach on demand; prolonged enzyme replacement therapy with pure pancreatin at an adequate dose with each meal; prokinetics and/or antispasmodics as needed for 6 weeks. The study group was randomized into two groups: group I (CTC) — 20 patients got only CTC; group II (CTC+W) — 78 patients received Wobenzym in addition to CTC, 5 tablets three times per day.&#x0D; Results and discussion. It has been proven that CP in elderly patients occurs against the background of mixed etiopathogenetic factors: ischemic (87.7%), gastroduodenal (84.7%), and dyslipid (70.4%). Clinically, asthenic and dyspeptic syndromes predominate (92.8% and 77.5%, respectively). According to the anthropometric examination, body weight deficiency is observed in 64.3% of the examined, with endocrine pancreatic insufficiency in 29.6% in terms of fasting glucose and exocrine pancreatic insufficiency in 70.4% in terms of FαE. The use of CTC contributed to the reduction of dyspeptic and painful abdominal syndromes (p˂0.05), a decrease in body weight deficit by 4.3% in terms of body mass index, and a tendency to normalize pancreatic function.&#x0D; Conclusions. The addition of CTC with Wobenzym resulted in a decrease in the clinical manifestations of the disease (p&lt;0.03–p&lt;0.05), an improvement in carbohydrate imbalance in terms of postprandial glycemia (p&lt;0.05), and a trend towards a decrease in the level of glycated hemoglobin by an average of 0.2%. The administration of Wobenzym in the complex treatment of CP in elderly patients contributed to an increase in the level of FαE by 42.6% compared to this index before treatment (p&lt;0.001) and a decrease in nutrient deficiency due to the elevated body mass index of this category of patients by 7.0%.

Add on effect of Indian Breed A2 Cow milk colostrum Tablet (Gopiyush) in management of Covid 19: An Observational study (Case Series)

Background Novel coronavirus acts by binding to angiotensin converting 2 enzymes(ACE2), heparan sulfate proteoglycans(HSPGs). Cow milk colostrum) is effective in binding ACE2, HSPGs. Gopiyush Tablet role also observed for preventing cytokine storm in COVID 19. As cow milk derived exosomes downregulate the inflammatory cytokine Methods It is a prospective observational study was conducted on patients hospitalized in Ambernath covid care hospital, Mumbai, India for mild and moderate symptoms of COVID 19. Patients received Gopiyush Tablet 400mg twice in a day along with conventional modern medicine. Standard conventional treatment included Vitamin C, Azithromycin, Paracetamol, Cough Syrup, hydroxychloroquine, Pantoprazole, Vitamin D, doxycycline according to symptoms of patients. Primary outcome was reduction in symptoms, duration of symptomatic phase and requirement of critical care unit. Findings Observations were recorded on 112 patients; no any adverse effect was observed after add on treatment Gopiyush Tablet 400mg with standard therapy. 7 days’ treatment of Gopiyush Tablets showed significant reduction in COVID 19 symptoms and negative COVID RTPCR report after 7 days of hospitalization as compared to published data on Standalone conventional standard treatment in COVID 19. Conclusion In this case series it is observed that addition of Gopiyush Tablet along with standard therapy in COVID 19 patients decreases the length of hospitalization and reduces the need for respiratory support. Rapid recovery of symptoms as compared to only standard therapy is also observed. Gopiyush tablets are effective as a add on treatment in mild to moderate covid 19 to bring faster symptomatic recovery

Atrial Fibrillation Burden Specifically Determines Human Ventricular CellularRemodeling.

Atrial fibrillation (AF) can either be a consequence or an underlying mechanism of left ventricular systolic dysfunction. Patients included in the CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) trial who suffered from AF and left ventricular systolic dysfunction benefited from an AF burden<50% after catheter ablation compared with those patients with an AF burden >50%. This analysis tried to explain the clinical findings of the CASTLE-AF trial regarding AF burden in a "back-to-bench" approach. To study the ventricular effects of different AF burdens, experiments were performed using human ventricular induced pluripotent stem cell-derived cardiomyocytes undergoing invitro AF simulation. Epifluorescence microscopy, action potential measurements, and measurements of sarcomere regularity were conducted. Induced pluripotent stem cell-derived cardiomyocytes stimulated with AF burden of 60% or higher displayed typical hallmarks of heart failure. Ca2+ transient amplitude was significantly reduced indicating negative inotropic effects. Action potential duration was significantly prolonged, which represents a potential trigger for arrhythmias. A significant decrease of sarcomere regularity could explain impaired cardiac contractility in patients with high AF burden. These effects were more pronounced after 7days of AF simulation compared with 48 hours. Significant functional and structural alterations occurred at the cellular level at a threshold of ∼50% AF burden as it was observed to be harmful in the CASTLE-AF trial. Therefore, these translational results may help to understand the findings of the CASTLE-AF trial.

CD44+/CD24- Expression as predictors of ovarian cancer chemoresistance: immunohistochemistry and flow cytometry study

BackgroundThe conventional standard treatment for ovarian cancer is not very effective, and the disease is fatal for women. Cancer Stem Cells (CSCs) that express CD44+/CD24- can contribute to chemoresistance and a poor prognosis. We seek to investigate the expression of CSCs (CD44+/CD24-) in ovarian cancer and their predictive significance.MethodsThe ambispective cohort was performed on 64 patients (32 patients in each group) at four hospitals (Cipto Mangunkusumo, Tarakan, Fatmawati, and Dharmais Hospital). Debulking surgery was performed on the patients, followed by histopathological analysis. The patients had six rounds of chemotherapy and were under monitoring for six months. The therapeutic responses were evaluated using the RECIST criteria (Response Criteria in Solid Tumors) and categorized as chemoresistant or chemosensitive. Using immunohistochemistry, we directly assess the CSCs from ovarian cancer tissue and using flow cytometry to assess the CSCs from the blood.ResultsHigh CSCs expression and ovarian cancer chemoresistance were significantly related in both trials (p 0.05). A better outcome was obtained using CD44+/CD24- immunohistochemistry.ConclusionsWe conclude that there is a substantial association between high CSCs expression and chemoresistance in ovarian cancer and that CSCs immunohistochemistry has a higher predictive value.

2 Receptor Specific Ligand Conjugated Nanocarriers: An Effective Strategy for Targeted Therapy of Tuberculosis.

Tuberculosis (TB) is an ancient chronic disease caused by the bacillus Mycobacterium tuberculosis, which has affected mankind for more than 4,000 years. Compliance with the standard conventional treatment can assure recovery from tuberculosis, but the emergence of drug-resistant strains poses a great challenge for the effective management of tuberculosis. The process of discovery and development of new therapeutic entities with better specificity and efficacy is unpredictable and time-consuming. Hence, delivery of pre-existing drugs with improved targetability is the need of the hour. Enhanced delivery and targetability can ascertain improved bioavailability, reduced toxicity, decreased frequency of dosing and therefore better patient compliance. Nanoformulations are being explored for effective delivery of therapeutic agents, however, optimum specificity is not guaranteed. In order to achieve specificity, ligands specific to receptors or cellular components of macrophage and Mycobacteria can be conjugated to nanocarriers. This approach can improve localization of existing drug molecules at the intramacrophageal site where the parasites reside, improve targeting to the unique cell wall structure of Mycobacterium or improve adhesion to the epithelial surface of intestine or alveolar tissue (lectins). The present review focuses on the investigation of various ligands like Mannose, Mycolic acid, Lectin, Aptamers, etc., installed nanocarriers that are being envisaged for targeting antitubercular drugs.

Hailey-Hailey Disease Treated with Individualised Homoeopathy—An Evidence-Based Case Report

AbstractHailey-Hailey disease (HHD) is a rare autosomal dominant skin disorder presented as blistering dermatosis with recurrent erythematous plaques, leading to erosions, fissures and vegetations seen in the skin folds. Prevalence of this disease occurs in 1 to 4 per 100,000 affected between third and fourth decade, mostly either under-reported or misdiagnosed. Under standard conventional treatment, recurrence and remissions are typical. Therefore, it affects the quality of life compared with other skin disorders. However, with the individualised homoeopathic medicine, Psorinum, this rare case was treated without topicals; no recurrence of the complaints and adverse effects were observed in 1 year of follow-up. Furthermore, changes in the dermatology life quality of life questionnaire score from 20 (at baseline) to zero have been noticed; the modified Naranjo criteria for homeopathy total score was +9 out of +13, providing evidence attributed by the intervention. This case report reinforces that individualised homoeopathic intervention is beneficial in rare skin disorders like HHD, and pooling such data will develop future research concepts in this area.

Abstract 1371: Rho-GEF hampers CD8+T cells-mediated immunosurveillance by reducing antigen presentation

Abstract Immune response is a critical anti-tumor response to overcome tumorigenesis. In line with this, immune checkpoint blockade shows tremendous anti-tumor efficacy by enhancing cytotoxicity of CD8+ cytotoxic T lymphocytes (CTLs). However, cancer cells develop different mechanisms of immune evasion, among which suppression of immune recognition of somatic mutations via tumor antigen is prevalent. In fact, 65% to 90% of the cancers show reduced MHC-I antigen presentation. There is, nonetheless, little achievement toward the therapeutic approaches to restore antigen presentation on tumor cells. Colorectal cancer (CRC), the second deadliest cancer in U.S., shows increasing incidence and mortality rates over the past years. Standard conventional CRC treatments, surgery, chemotherapy and radiotherapy, often lead to many side effects due to their non-specificity and cytotoxicity. While immunotherapy is very promising, only a small population of CRC patients respond to the current immune checkpoint inhibitors. In this study, our objective was to harness a novel immunological approach to target CRC tumors. We developed a bioinformatics tool to create a pool of genes whose expression negatively correlates with cytotoxicity of CD8+ CTLs in the tumor microenvironment of CRC patients. Given the central role of antigen presentation in activating CD8+ CTLs, we further screened these genes based on the scope of their effects on antigen presentation. To this end, we developed stable clones of OVA expressing MC38 cells (MC38OVA) where OVA-derived peptide, SIINFEKL, will be bound to MHC-I complex for cell surface presentation. 4 genes with highest capacity to alter MHC-I cell surface levels were identified. Our consequent in vivo experiments and in vitro cytotoxicity assays identified that “Rho-GEF” gene was the top actionable target with striking suppressive effects on tumor growth. TCGA database analysis showed Rho-GEF is upregulated in 22% of CRC patients accompanied by a poor prognosis. Rho-GEF knockdown (KD) significantly inhibited tumor growth in immunocompetent mice whereas it only showed minor effects on immunocompromised mice, suggesting that the Rho-GEF may modulate tumor growth by regulating the interaction of tumor cells with non-tumor cells such as immune cells. Consistent with the major contribution of antigen presentation in promoting CD8+ CTLs activity, TNFα, IFNγ, and GZMB levels in CD8+ T cells isolated from Rho-GEF KD MC38-derived tumors showed a significant increase compared to the wild type tumors. Taken together, we introduced Rho-GEF as a potential clinical target involved in CRC immune evasion by modulating antigen presentation and CD8+ CTLs anti-tumor responses. Citation Format: Haniyeh Eyvani, Xinna Zhang. Rho-GEF hampers CD8+T cells-mediated immunosurveillance by reducing antigen presentation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1371.

Nisha-Amalaki in Uncontrolled Type 2 Diabetes Mellitus- A Case Report

During the last few years India has maximum increase of Type 2 diabetes mellitus. Type 2 diabetes is characterized by high blood sugar, insulin resistance, and relative lack of insulin. There are approximate 72.96 million cases of diabetes mellitus in adult population of India. In modern era single anti-diabetic drug is not sufficient for glucose control. These days multidrug therapy is building its popularity for maintaining glycaemic levels. A 59-year-old female presented with known case of Type 2 diabetes with evidence of polyuria, itching over extremities, and fatigue was poorly controlled despite a drug regimen consisting of oral metformin and glimepiride. Her Blood Sugar level was constantly around 200 mg/dl in spite of having modern medicine with adjusted doses. She has administered Nisha-Amalaki Churna with warm water early in the morning along with standard conventional treatment for 8 weeks. The effect of therapy was evaluated at the interval of 4 weeks for 8 weeks which is done on the basis of objective parameters. Objective parameters were fasting and post prandial Blood Sugar Level. Nisha-Amalaki churna has reduced Blood Sugar Level to normal. It also reduced the dose of conventional drug which may cause side effects with long term use. There is a need for combined multidisciplinary treatment to maintain suggested glycaemic control. Thus, the present case study is to understand the significant effect of Nisha-Amalaki as an adjuvant to standard conventional treatment in chronic uncontrolled type 2 Diabetes Mellitus.

Clinical implementation and feasibility of long-course fractionated MR-guided chemoradiotherapy for patients with esophageal cancer: An R-IDEAL stage 1b/2a evaluation of technical innovation

PurposeThis R-Ideal stage 1b/2a study describes the workflow and feasibility of long-course fractionated online adaptive MR-guided chemoradiotherapy with reduced CTV-to-PTV margins on the 1.5T MR-Linac for patients with esophageal cancer. MethodsPatients with esophageal cancer scheduled to undergo chemoradiation were treated on a 1.5T MR-Linac. Daily MR-images were acquired for online contour adaptation and replanning. Contours were manually adapted to match the daily anatomy and an isotropic CTV-to-PTV margin of 6 mm was applied. Time was recorded for all individual steps in the workflow. Feasibility and patient tolerability were defined as on-table time of ≤60 min and completion of >95% of the fractions on the MR-Linac, respectively. Positioning verification and post-treatment MRIs were retrospectively analyzed and dosimetric parameters were compared to standard non-adaptive conventional treatment plans. ResultsNine patients with esophageal cancer were treated with chemoradiation; eight patients received 41.4 Gy in 23 fractions and one received 50.4 Gy in 28 fractions. Four patients received all planned fractions on the MR-Linac, whereas for two patients >5% of fractions were rescheduled to a conventional linac for reasons of discomfort. A total of 183 (86%) of 212 scheduled fractions were successfully delivered on the MR-Linac. Three fractions ended prematurely due to technical issues and 26 fractions were rescheduled on a conventional linac due to MR-Linac downtime (n = 10), logistical reasons (n = 3) or discomfort (n = 13).The median time per fraction was 53 min (IQR = 3 min). Daily adapted MR-Linac plans had similar target coverage, whereas dose to the organs-at-risk was significantly reduced compared to conventional treatment (26% and 12% reduction in mean lung and heart dose, respectively). ConclusionDaily online adaptive fractionated chemoradiotherapy with reduced PTV margins is moderately feasible for esophageal cancer and results in better sparing of heart and lungs. Future studies should focus on further optimization and acceleration of the current workflow.

STUDY OF EFFECTIVENESS OF MASSAGE THERAPY AS A THERAPEUTIC ADJUVANT IN THE MANAGEMENT OF PRESSURE ULCER

Pressure ulcer (PU) is a common cause of morbidity and mortality in spine injuries. We now know that pressure is the single most important etiological factor. The compression of soft tissues results in ischemia and if not relieved, will progress to cause necrosis and ulceration; the basic cause is pressure followed by ischemia and necrosis. PU can develop in Traumatic Brain injured, paraplegic and nonparaplegic patients. Patients with spinal cord injury have reported prevalence of 25 – 40%. Management of pressure ulcer is multicentric. This study was conducted on paraplegic patients admitted in the ward with PU to determine the effectiveness of massage therapy in the management of PU as a therapeutic adjuvant to standard treatment protocol. 36 cases of paraplegic inpatients with stage II and III PU were selected, properly randomized and divided into two groups, A &amp; B. The dimensions of ulcer were recorded. Both groups received standard conventional treatment. Group A received, in addition, massage therapy around the ulcer area using commercially available vibrator for ve minutes continuously, two times daily. Group B patients served as controls. Ulcer diameter and area were measured every week and documented. The group which received massage showed better ulcer heali RESULTS: ng. CONCLUSION. Massage therapy is a cost effective method for management of pressure ulcer and can be easily delivered to the patient by a reliable care giver once it is taught to them.

Rac1/pSTAT3 expression: A pharmacodynamic marker panel as a first step toward optimization of thiopurine therapy in inflammatory bowel disease patients.

Thiopurine derivatives, such as azathioprine and mercaptopurine, are standard conventional treatment options in inflammatory bowel disease (IBD). Unfortunately, approximately half of patients discontinue thiopurine therapy within 2 years. To improve the prediction of clinical effectiveness, thiopurine therapy is currently optimized using therapeutic drug monitoring. Ras-related C3 botulinum toxin substrate 1 (Rac1) has been suggested as a potential pharmacodynamic marker of the thiopurine effect in lymphocytes. The active thiopurine metabolite 6-thioguanine triphosphate (6-Thio-GTP) causes T cell apoptosis via Rac1 and the downstream transcription factor signal transducer and activator of transcription 3 (STAT3). The aim of this study was to develop and validate a functional pharmacodynamic multiparameter flow cytometric assay to determine Rac1/pSTAT3 expression in the various leukocyte subpopulations in peripheral blood in order to predict therapeutic response in IBD patients in the future. Peripheral blood samples of healthy subjects (no fever or clinical complaints of active disease, C-reactive protein < 10mg/L) were used for immunocytochemical labeling, applying an optimized fixation and permeabilization strategy. A gating procedure was performed to separate all leukocyte subpopulations. Quantitative data were obtained by measuring presence and median fluorescent intensity. In vitro, Rac1 presence and expression were detectable in all leukocyte subpopulations. After IL-6 stimulation, used as proxy for inflammation, a distinct pSTAT3 signal could be detected in T lymphocytes of healthy subjects. In vivo, an upregulated pSTAT3 signal was detected in nearly all IBD patients with active disease and differed substantially from the signal found in IBD patients in remission on thiopurines and healthy subjects. We developed and validated a functional flow cytometric assay to assess Rac1 and pSTAT3 presence and expression. This opens a venue for a pharmacodynamic assay to predict thiopurine effectiveness in IBD patients.

Comparative Efficacy and Safety of Diacerein in Patients with Knee Osteoarthritis: A Pilot Study

Background Osteoarthritis (OA) is the most common chronic rheumatic disease. The prevalence of OA is skyrocketing with time. Providing a proper treatment regimen for OA is also growing as a major public health challenge. Conventional pharmacological treatments are mainly for alleviating pain and have some severe adverse effects. Diacerein is a new oral anti-inflammatory drug especially developed for the management of OA having only mild to moderate adverse effects. However, the evidence of efficacy and safety of Diacerein in OA is not well documented and yet to be explored.&#x0D; Objective To compare the efficacy and safety of Diacerein in knee OA with conventional nonsteroidal anti-inflammatory drugs (NSAIDs).&#x0D; Method A comparative study was conducted among knee OA patients attending Out- Patient Orthopedic department in Dhulikhel Hospital, Nepal from December 2019 to September 2020, using self-structured and standard questionnaire. The patients were randomized to receive either a conventional standard treatment (Treatment Group I: NSAIDs) or alternative treatment regimen (Treatment Group II: NSAIDS+ Diacerein). Patients were followed-up after two months and data were analyzed using SPSS 21.0.&#x0D; Result Among 72 patients enrolled in this study, majority (44.44%) were between 51-60 years of age in which 81.94% of the patients were female. Post treatment data was collected from 15 participants. The mean KOOS-PS score of the participants in Treatment Group I decreased from 35.56 ± 14.33 to 35.14 ± 12.65 while that of the Treatment Group II participants reduced from 63.31 ± 12.08 to 49.99 ± 13.10 in two months. Similarly, the mean WOMAC score decreased from 46.87 ± 17.80 to 34.37 ± 16.83 in Treatment Group I and from 54.23 ± 14.66 to 46.22 ± 12.16 in Treatment Group II. The mean Lysholm score in Treatment Group I increased from 55.57 ± 8.16 to 60.86 ± 15.01 and in Treatment Group II, it increased from 46.62 ± 13.01 to 60.25 ± 17.598.&#x0D; Conclusion Diacerein treatment group had better functional outcome compared to the patients in the treatment group with conventionally used drugs. Also, the adverse effects faced by the patients were minor. The current study are suggestive of better efficacy and safety of Diacerein compared to other drugs.