1st Follow-up Research Articles

P702 Clinical and biomarker remission is maintained after switch from monthly dosed intravenous to subcutaneous maintenance treatment with vedolizumab in Inflammatory Bowel Disease

Abstract Background Background: Subcutaneous (SC) formulation of vedolizumab (VDZ), a gut selective integrin antagonist used for treatment of inflammatory bowel disease (IBD), has proven effective and safe in clinical trials after intravenous (IV) induction. However, it is not clear if patients can be effectively switched from IV maintenance treatment to SC. We aimed to assess real-world efficacy of switch from IV to SC formulation and to investigate if baseline maintenance regimen (every 8 weeks (q8) versus every 4 weeks(q4)) impacts outcome after switch. Methods Methods: In this observational study at a tertiary referral centre, we enrolled 126 prospectively followed consecutive adult patients with IBD who were switched to SC VDZ maintenance treatment. We included patients after IV induction (2 or 3 infusions) and patients who switched from IV maintenance treatment q8 and q4. SC VDZ dosing was 108 mg every 2 weeks regardless of the previous IV regimen. Clinical (Harvey Bradshaw index (HBI) for Crohn’s disease (CD) and partial Mayo score (pMayo) for ulcerative colitis (UC)) and biochemical disease activity (CRP, fecal calprotectin (FC)) were assessed at the time of switch and at first and second follow-up. HBI<5 and pMayo<2 were considered clinical remission. CRP <5mg/L and FC<150mg/kg were considered biomarker remission. Results Results: In total 126 patients (40% CD, 60% UC) were switched to SC vedolizumab. Demographics and baseline characteristics are presented in Table 1. Median time to 1st follow up (FU) was 14,5 weeks (IQR 12-26) and median time to 2nd FU was 40 (IQR 36-52) weeks. From all patients, 8/126 (6%) discontinued SC VDZ treatment, 5 of them due to endoscopically active disease (2 in IV induction group, 3 in q4 group), 1 had dysplasia and required surgery (IV induction group), two others (both q8 group) discontinued on their wish. In patients who continued SC treatment clinical and biomarker remission appears to be maintained at 1st and 2nd FU. Clinical and biomarker outcomes are presented in Table 1. Vedolizumab concentrations were 16.9, 24.6 and 13.0 at baseline, 27.0, 25.3 and 25.2 at 1st FU and 25.5, 34.6 and 22.1 at 2nd FU in the q8, q4 and IV induction group, respectively. Conclusion Conclusion: The results of this real-world study suggest maintenance of clinical and biomarker remission in patients switched from IV to SC vedolizumab. Baseline vedolizumab dosing regimen (every 4 weeks versus every 8 weeks) did not have an impact on outcomes.

Outcome of two knots tension band wiring (TBW) in Mayo type-IIA olecranon fracture

Olecranon fracture is relatively common and accounts for approximately 40% of elbow joint fractures. It is an intra-articular fracture, so the aim of treatment is anatomic reduction, stable fixation and early mobilization. Tension band wiring (TBW) may be a popular and widely practiced method using either single knot or two knots techniques. Now two knots TBW are widely accepted by AO foundation as well as various countries. But single knot technique is commonly practiced in Bangladesh. The present study was done to see the clinical, radiologi- cal and functional outcome of two knots Tension band wiring (TBW) in Mayo type IIA olecranon fracture. This observational study was carried out by the National Institute of Traumatology and Orthopaedic Rehabilitation (NITOR), Dhaka, Bangladesh. A total of 32 patients with Mayo type IIA olecranon fractures were treated with two knots TBW, out of which 30 cases had completed at least 24 weeks of follow-up and analyzed for final functional outcome with Mayo Elbow Performance Score (MEPS). The mean age was 32.58±14.21 years and the male to female ratio was 2.6:1. The mean radiological union time was 8.15±2.25 weeks. In 6 (18.75%) cases, it took 6 weeks, in 18 (56.25%) cases, it took 8 weeks and in 8 (25.0%), it took 12 weeks. Complications were found in 21.9% of patients. At first follow-up after the operation showed that 21 (70.0%) had moderate pain and the final follow-up showed 21 (70.0%) had no pain. The mean arc of elbow motion at first follow-up and final follow-up were 61.090±16.2340 and 122.820±15.2870, respectively. The mean functional score at 1st follow-up was 6.75±5.63 and the last follow-up was 24.76±1.69. The mean total Mayo Elbow Performance Score (MEPS) scores at first and last follow-up were 40.65±14.48 and 94.13±8.35, respectively. Excellent and good outcomes were found among 21 (70.0%) and 9 (30.0%) patients, respectively. Two knots TBW technique is safe regarding overall complication rate, pain status and excellent outcome. BSMMU J 2022; 15(2): 90-95

The effect of the 2019 ESC/EAS dyslipidaemia guidelines on low-density lipoprotein cholesterol goal achievement in patients with acute coronary syndromes: The ACS EuroPath IV project

AimsTo evaluate the effect of the ESC/EAS 2019 dyslipidaemia guidelines on patient management of lipid-lowering therapy in patients with acute coronary syndrome (ACS), through a survey designed to compare post-ACS patient management in 2022 with that in 2018. MethodsOnline questionnaires focused on lipid profile and medications were used to gather data from 2650 ACS patients in 6 European countries, treated between March–June 2022 (ACS EuroPath IV survey). These data were compared with data collected from 2650 patients who participated in the ACS EuroPath I survey (conducted in 2018). ResultsLipid testing was performed in 90% of patients and was done sooner after admission in 2022 versus 2018 (mean 1.4 vs 1.7 days). Increased testing for non-HDL-C, lipoprotein(a), and ApoB was observed over time. At discharge, most patients (≥90%) were receiving lipid-lowering therapy. Prescribing patterns differed, with a higher proportion of patients receiving statin plus ezetimibe combination therapy in 2022 versus 2018 (34% vs 13%). LDL-C levels were lower in 2022 versus 2018 at admission and at 1st, 2nd and 3rd post-discharge follow-up points. More patients achieved low-density lipoprotein cholesterol (LDL-C) goals in 2022 versus 2018 at the first follow-up (average 14 vs 16 weeks since discharge; <70 mg/dL [1.8 mmol/L]: 34% vs 20%; <55 mg/dL [1.4 mmol/L]: 18% vs 10%) and at subsequent follow-up points. ConclusionLDL-C goal achievement has improved since the release of the 2019 guidelines, but lipid management in post-ACS patients remains suboptimal.

An Image-Based Scoring System as an Alternative to Face-to-Face Examination for Acne Vulgaris to Deliver Follow-Up Care: A Comparative Study

Background: AV is a chronic disease with flares and remissions requiring regular follow-ups. Image-based lesion counting (LC) is useful when in-person consultations are not possible, like the COVID-19 pandemic. Objective: The aim of this study is to validate the proposed scoring system for teledermatology consultation and compare it with face to face. Materials and Methods: The face was divided into three zones which was further divided by drawing the imaginary lines from fixed points. AV (Grade 1 and 2) lesions were counted by co-investigator in person at baseline, first, and second follow-up visits. The images of the same were evaluated and scored by the principal investigator. Acne scores obtained were compared and statistically analyzed. Results: Two hundred cases were enrolled. Mean acne scores for in-person were 945.37, 647.57, and 550.81 and for teledermatology 1044.99, 718.79, and 654.36 for baseline, 1st, and 2nd follow-up, respectively. The mean decrease from baseline, 1st and 2nd follow-up, independent sample t-test and correlation analysis was significant in both groups (P = 0.001). Limitations: AV grade 3 and 4 are not included. Conclusion: During the 1st follow-up, a decrease in acne scores was observed, along with consistency in the scores between the evaluators. Image-based lesion counting is a promising approach. The proposed scoring system can be used for both modes of consultation-face-to-face and teledermatology.

EFFECTS of COGNITIVE BEHAVIORAL THERAPY on BODY MASS INDEX, EMOTIONAL EATING and MINDFUL EATING of POST-BARIATRIC SURGERY PATIENTS: A RANDOMIZED CONTROLLED TRIAL

Purpose: Bariatric surgery is one of the most effective treatments of obesity, but some patients regain weight post-operatively. Continuum of disordered eating behaviors and emotional eating are among the main predictors of weight regain. The purpose of this study was to investigate the effects of cognitive behavioral therapy (CBT) on Body Mass Index (BMI), emotional eating and mindful eating of post-bariatric surgery patients. We also aimed to find out the best time for post-surgical application of CBT. Study design: The study was designed as a randomized control trial. A total of 60 post-bariatric surgery patients were randomized into two groups: (1) 30 patients received only nutritional education (ONE group); (2) 30 patients received CBT + Nutritional education (CBT + NE group). Acute treatment phase consisted of 5 one in two week sessions, maintenance phase consisted of 3 monthly sessions, and a follow-up session was made at the end of 1 year. Patients were further divided into 3 subgroups: (1) The patients who had surgery more than 2 years ago, (2) The patients who had surgery 1-2 years ago, (3) The patients who had surgery 6 months-1 year ago. All patients were evaluated for BMI, and the Emotional Eating Scale (EES) and Mindful Eating Questionnaire (MEQ) were applied at baseline (1st session), after the acute phase (5th session), at the last session of the maintenance phase (8th session), and at the 1-year follow-up. Results: BMI of both groups decreased significantly at the end of the acute and maintenance phase, but mean BMI of ONE group increased at the end of the 1st year follow-up while the CBT group preserved the weight loss. EES decreased significantly for both groups at the end of the maintenance phase, but increased for ONE-1 group at the end of the 1 year follow-up while all sub-groups of CBT preserved the decrease of mean EES scores at the 1st year follow-up. For ONE group, there was an increase in MEQ scores and this increase began as early as the 5th session, especially for ONE-3 sub-group (mean scores of MEQ increase from 97.5 to 121.25, p= 0.022), but this increase was not statistically significant for ONE group at the 8th session and 1 year follow-up (p=0.072). For NE + CBT group, the increase in MEQ scores began as early as at the 5th session for NE + CBT-1 (mean scores of MEQ increase from 93.3 to 107.1) and NE + CBT-3 (mean scores of MEQ increase from 86 to 97.14), and remained statistically significant even at the 1-year follow-up (p=0.000). Conclusion: CBT is effective for continuum of weight loss, decrease of emotional eating and increase of mindful eating of post-bariatric patients, and these beneficial effects of CBT are preserved at the end of 1 year.

A Case Series of Trichotillomania; Impact of Therapeutic Intervention: Clinical Out-turn

Trichotillomania (TTM) is a less addressed cause of alopecia. Refusal to accept this condition as a psychiatric illness causes marked delay in seeking help. This article aims to evaluate the treatment response of TTM patients. This is a case series study on 5 patients (4 females, 1 male) of TTM, of whom 3 patients took treatment on an outpatient basis (obsessive-compulsive and related disorders clinic) and 2 patients at indoor (orange unit) at the Department of Psychiatry, Bangabandhu Sheikh Mujib Medical University, from January 2022 to July 2023. Out of 7 cases, 2 patients did not come after the 1st follow-up. Pharmacological management was chosen according to established guidelines. All patients were given basic psychoeducation and relevant psychological intervention. A total of 5 cases were described. The median time to receive effective psychiatric treatment is 8.6 years (4–15 years). The median time to respond after starting therapy is 6 weeks. All patients responded well to selective serotonin reuptake inhibitors. Augmentation with low-dose antipsychotics and the addition of specific pharmacologic agents have been shown to improve outcomes. Psychological management helped patients most in achieving long-term remission. Despite the prolonged treatment gap, patients of TTM showed marked improvement with combined pharmacological and psychological intervention in a short time. Further study involving a more significant number of cases is needed to support the findings.

Efficacy of Topical Azithromycin versus Systemic Doxycycline in Treatment of Meibomian Gland Dysfunction.

Ocular surface disease (OSD) is a multifactorial and highly frequent problem. Inadequate or unstable tear film is the main cause, which leads to visual impairments. One of the primary causes of OSD is meibomian gland dysfunction (MGD), with a prevalence of 3.5 to 70%. The aim of this work was to compare the efficacy of azithromycin topical eye drops versus oral doxycycline in MGD individuals. This prospective comparative cohort research was carried out on 56 patients of both sexes of any age with symptomatic MGD. Randomly, patients were classified into two equal groups: Group 1 was treated twice daily for 4 weeks with topical azithromycin 1% eye drops, while group 2 received oral doxycycline 100 mg capsules twice daily for 4 weeks. In the 1st follow-up, there was a significant difference between the studied groups in pain and discomfort degree (P value = 0.024) as group 1 showed a higher number of patients with a mild pain degree (P value = 0.013) while group 2 showed a higher number of patients with a severe pain degree (P value = 0.022). There was an insignificant difference between the studied groups in moderate pain degree and lid margin telangiectasia. Conjunctivitis, frothy discharge, and meniscus floaters were significantly higher in group 2 than in group 1 (P value = 0.013, 0.028, and 0.031, respectively). In group 1, the break-up time test was significantly higher than in group 2 (P value = 0.023). In the 2nd follow up, in group 2 only meniscus floaters were significantly higher than in group 1 (P value = 0.044), while in group 1 break-up time test was significantly higher than in group 2 (P value = 0.029). Otherwise, there is no significant difference between both the groups. Meibomian gland dysfunction (MGD) could be treated effectively with oral doxycycline and topical azithromycin by improving symptoms, clinical signs, and stabilization of tear film. Moreover, the topical azithromycin group seemed to be superior over the oral doxycycline group in improving the quality of tear film in the short term, having fewer side effects, more compliance, and better tolerability.

Assessing the outcomes of Prp and corticosteroid injections for sacroiliac joint pain

Sacroiliac joint pain is a symptom that can affect the life activities of patients in daily life. Invasive methods also occupy an important place in the treatment of this symptom. Our study evaluated the follow-up results of patients injected with Platelet-rich plasma and steroids due to sacroiliac joint pain. Patient files between the years 2018-2022 were evaluated retrospectively. Patients who underwent ultrasound-guided sacroiliac joint injection of platelet-rich plasma and steroids were divided into 2 groups. VAS and The Modified Oswestry Disability Questionnaire scores were evaluated at 1, 3, and 6 months. Eighty-seven patients were included in the study. It was understood that patients in both groups benefited after injection (p&lt;0.001). In the 1st month follow-up, it was concluded that the VAS and the Modified Oswestry Disability Questionnaire scores of the patient group who received steroids were significantly better (p&lt;0.001). In the 3rd month, the VAS (p=0.695) and the Modified Oswestry Disability Questionnaire (p=0.215) scores of both groups were similar in both groups. In the 6th month, the platelet-rich plasma group's results were significantly better (p&lt;0.001). Platelet-rich plasma and steroid injections are safe treatment methods for sacroiliac joint pain. Steroid injections in the short term and platelet-rich plasma injections in the long term are more effective.

Myopia Progression Among School-Aged Children in the COVID-19 Distance-Learning Era.

To investigate the effect of online learning and other environmental factors on myopia progression during the Coronavirus pandemic (COVID-19). A retrospective cohort study from 2018 to 2021. Data from children aged 6-14 were gathered during three visits: pre-pandemic, at the beginning, and during the pandemic. Demographics (hours spent on screens for educational, recreational purposes, outdoors, and type of screen), best-corrected distance visual acuity (BCDVA), uncorrected distance visual acuity (UCDVA), and cycloplegic refraction were gathered. Of 150 patients, 70 [47%] were boys. The mean age was 11 (2.4) years. Participants mainly used mobile phones (62%) and had insufficient outdoor play (88%). Of the 300 eyes, 221 (74%) showed myopia progression. A significant difference in spherical equivalent (SE) was found between pre-pandemic and post-pandemic periods (-0.29 (0.23) D vs -0.40 (0.11) D; p =0.023). Additionally, UCDVA showed a difference between the initial and 1st follow-up visits (0.57 (0.37) vs 0.64 (0.36), p =0.001), and the first and 2nd follow-up visits (0.64 (0.36) vs 0.70 (0.36), p =0.001). Significant hazard ratio for change in SE in patients with higher age (>9 years), (HR [95% confidence interval (CI)], 0.71 [0.51-0.84]), greater recreational screen usage (HR [95% CI], 1.26 [1.15-1.66]), and insufficient outdoor time (HR [95% CI], 1.45 [1.35-1.67]). Myopia progression was accelerated during the COVID-19 pandemic. Younger age, prolonged screen use, and insufficient outdoor time contributed to increased myopia progression. However, the type of device used had no significant effect.

EFFECTIVENESS OF LIRAGLUTIDE IN REDUCING BODY WEIGHT AND IMPROVING GLYCEMIC CONTROL IN PATIENTS WITH T2DM

Objective: This study aimed to determine the effects of Liraglutide on glycosylated hemoglobin (HbA1c) and body weight in patients with type 2 diabetes. Material and Methods: A prospective observational study was conducted in a private tertiary healthcare setting. A total of 58 adult patients with T2DM using oral anti-diabetic agents with or without insulin were enrolled in the study from November 2020 to April 2022. Liraglutide was administered at a dose of 0.6 mg/day which was raised to 1.2 mg/day after 1 week and later to 1.8 mg/day depending upon patient preferences and tolerability. Patients were assessed for changes in their body weight, fasting blood glucose (FBG) level, random blood glucose (RBG) level, and HbA1c at the 1st and 2nd follow-up visits of the 8th and 16th week, respectively. Results: At the 16th week, the mean weight was 100.78±17.56 vs 102.74±17.26 and 104.11±17.95 at the 8th week and baseline visit, revealing a significant difference across three-time points [F(1.4, 36.45)=8.57, p=0.003]. A post hoc pairwise analysis showed that weight significantly decreased from baseline and 16th-week follow-up visits (p=0.011). Similarly, a significant decrease was observed in mean HbA1c across three-time points [F (2, 39.40) =8.81, p=0.001]. Mean HbA1c at 16th week was 6.61±1.13% vs 8.09±1.43% at baseline (P = 0.001). No significant reduction in FBG, RBG, blood pressure, and serum lipid profile were observed. Moreover, no major side effects occurred in any patient. Conclusion: Liraglutide is an effective and well-tolerable drug in improving glycemic control, causing significant weight loss in the study population when used as a monotherapy or in combination therapy. KEYWORDS: Liraglutide, Glucagon-like peptide-1 agonist, Type 2 diabetes mellitus, Glycemic control, Weight loss

Clinicopathological profile and outcomes of treatment of head and neck cancer patients in a tertiary care center: a hospital-based prospective study

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Globally head and neck cancers constitute among the 10 most common cancers. The study's main purpose was to study the epidemiological and demographic factors and outcomes of treatment of head and neck cancer patients in a tertiary centre. A Chi-square test was used to analyse the association of various factors. Statistical package for the social sciences (SPSS) version 20 was used for statistical analysis.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; In this prospective observational study, 52 patients with head and neck cancers were evaluated and data regarding age, gender, risk factors, clinical features, grading, staging, and treatment modality received were taken. Presenting symptoms of patients at the 1st follow-up (at 1 month), 2nd follow-up (at 2 months), and 3rd follow-up (at 6 months) were statistically analysed. &lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Results showed that the mean age group was between 61 to 70 years. Gender distribution showed that 75% were males and 25% were females. The most common site of malignancy was the oropharynx (23.08%). The majority of the tumors were squamous cell carcinoma (88.46%) and are of moderately differentiated type (53.85%). Majority of the tumors (42.31%) presented with stage III lesions. Most of the patients 35 (67.31%) received concurrent chemoradiation (CT-RT). The most common complaint in the first and second follow-up was mucositis.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; The majority of the tumors are squamous cell carcinoma and are moderately differentiated. Most of the tumors were in stage III, and most received chemoradiation (CT-RT) for treatment.&lt;/p&gt;

A clinical pharmacological evidence-based analytical research study on the clinical pharmacokinetic dose-dependent correlation of oral haematinics with the obstetric and gynaecological global anaemic patients’ recovery rate

Background: The goal of iron therapy is to repair the haemoglobin deficit and replenish storage iron. Oral haematinics are the treatment of choice, due to their higher effectiveness, higher safety, higher ease of administration, higher patient compliance, better accessibility, no occurrence of nosocomial infections and lower cost. This analytical evidence-based clinical research was conducted for the molecular pharmacokinetic study of the pharmacological response and adherence of the patients to oral haematinics, in global tertiary medical care centres.Methods: 100 anaemic patients, who were treated for moderate iron-deficiency anaemia, were prescribed oral haematinics, such as, ferrous ascorbate, ferrous sulphate, ferrous fumarate and ferric ammonium citrate, containing 60 mg of elemental iron, once to thrice daily, with or after meals, according to the progress of the disease, treatment regimen scheduling, occurrence or non-occurrence of adverse drug reactions and prognosis of the patient. The pharmacokinetic dose-dependent percentage recovery rate of the patients on 1st (30th day), 2nd (60th day) and 3rd (90th day) months and follow-up (105th day) visits, was finally deduced from the patients’ recovery features of symptoms and signs, and the confirmatory laboratory investigations recordings, with the efficacy and safety evaluation findings.Results: During the oral haematinics treatment, the pharmacokinetic dose-dependent percentage recovery rate of the patients was 29% on 30th day, 62% on 60th day, 93% on 90th day and 100% on 105th day of treatment.Conclusions: All the oral haematinics treated global anaemic patients had shown 100% recovery rate in tertiary medical care centres.

49 GLOBAL LONGITUDINAL STRAIN TO EVALUATE THE SUCCESSFUL OF MEDICAL TREATMENT IN SECONDARY CARDIAC LYMPHOMA: A CASE REPORT

Abstract Background Cardiac lymphoma is often lately diagnosed and associated with a poor outcome because of delayed treatment. We report the case of a patient with diffuse large B-cell lymphoma (DLBCL) massively infiltrating the heart, who showed significant improvement in echocardiographic features after high-dose chemotherapy. Case summary A 39-year-old female was admitted to our hospital after a vasovagal syncope secondary to excisional biopsy of an inguinal lymph node. Symptoms and signs were consistent with heart failure. Brain natriuretic peptide was markedly elevated (472 pg/ml). Transthoracic echocardiography (TTE) revealed moderate hypertrophy of both ventricles, with preserved left ventricular ejection fraction, reduced function of the right ventricle and a monophasic diastolic pattern. Left Ventricular Global longitudinal strain (LV GLS) was significantly reduced (up to -5%). These findings led us to the strong suspicion of biventricular infiltrative heart disease. Positron emission tomography-computed tomography (PET-CT) scan showed metastases to the kidneys, mesenteric and skeletal systems. The results of histological analysis and immunohistochemical staining confirmed the diagnosis of stage IV-B DLBCL. Prompt and aggressive treatment was initiated, performing a multiparametric cardiac monitoring based on biomarkers and TTE prior to and after each cycle of chemotherapy. We early observed a significant reduction of myocardial infiltration with an impressive recovery of LV GLS up to -10% after the 1st cycle of chemotherapy. The echocardiographic abnormalities of the right chambers resulted totally restored. Complete regression of the cardiac lymphoma was obtained, with a recovery of LV GLS up to -11.2% at the end of protocol and -16.8% at the 1st month follow-up. The PET-CT scan confirmed the recovery of the heart. Discussion In this case, functional heart improvement due to total regression of cardiac lymphoma has been early detected by strain imaging. GLS could be an early indicator of therapy responsiveness and may be implemented in routinely evaluation of these patients with infiltrative cardiac diseases.

Low Sustainability of Weight Loss Among Patients with Non-alcoholic Fatty Liver Disease

Background: Weight loss, though difficult to attain and sustain over time, remains the cornerstone of non-alcoholic fatty liver disease (NAFLD) treatment. We aimed to describe weight changes among NAFLD patients. Methods: This was a retrospective, cohort study of consecutively-identified NAFLD patients with &gt;2 clinic visits from March2007–April2018. Weight changes from baseline were categorized into weight gain, weight loss, and no change. Baseline liver and metabolic biochemistries and non-invasive liver fibrosis tests were correlated with the final weight changes. Succeeding weight changes after the initial follow-up visits were used to determine sustainability of weight loss. Results: Of the 240 patients included, 123 (51.2%), 93 (38.8%), and 24 (10%) had weight gain, weight loss, and no change, respectively. Only 12.5% had &gt;5% weight loss. Duration of follow-up was significantly longer for patients with weight loss (p&lt;0.001). None of the baseline demographic and laboratory data were associated with weight loss. Patients with weight loss also did not have significant changes to their biochemistries and non-invasive liver fibrosis tests compared to patients with weight gain/no change. Compared to patients with weight gain after the initial follow-up, where only 11.8% were able to lose weight on the final visit, 73.1% of patients who lost weight after the initial follow-up were able to sustain their weight loss on the final visit. Conclusions: Weight loss is achieved in only a third of NAFLD patients. Although 73% of patients who lost weight initially were able to sustain it, patients who gained weight after the 1st follow-up were unlikely to lose weight on further follow-up. Key words: Non-alcoholic fatty liver disease, weight loss, sustainability

In Vivo Generation of Memory-like NK Cells for the Treatment of AML and Myelodysplastic Syndrome; Early Clinical Applications of INKmuneTM

Natural killer (NK) cells can have potent anti-tumour responses and recently highlighted potential for memory-like functions, but the best approach to generate memory-like NK (mlNK) cells remains unclear. Priming of NK cells with the pharmaceutical-grade, replication incompetent tumour cell product, INKmuneTM generates tumour-induced mlNK (TIML-NK) cells with enhanced cytokine production and cytotoxicity against multiple NK-resistant tumour target cell lines in vitro, analogous to previously reported cytokine-primed memory-like NK cells. In addition, proteomic profiling of TIML-NK cells revealed differential abundance of proteins involved in promoting mitochondrial survival and function as well as critical nutrient receptors, which may provide a unique benefit of NK cell activation whilst sparing mitochondrial damage typically associated with cytokine-mediated activation. INKmune priming increased NK glycolysis and oxidative phosphorylation whilst enhancing mitochondrial respiratory capacity and maintaining glycolytic reserve. Four patients have been treated with a cycle of three, weekly infusions of 1x108 INKmuneTM cells. All patients received all three doses without incident and without side effects. Patient 1 was a 78yr old man with A 3yr history of refractory MLD MDS who was transfusion and platelet dependent and required G-CSF. Within 7 days of first infusion, over 50% of his peripheral blood NK cells activated and this increased with each dose. By day +29, 72% of his NK cells were activated and this remained above 68% at day +119 when monitoring ended. His ECOG status fell from 2 pre-treatment to 0 at D+119 and his RAD-1 ctDNA from 45 to 38. Analysis of systemic cytokines showed increases in MIP-1a/b, TNF-a and sIL2R which paralleled the changes in percentages of CD69+ NK cells. IL6 levels peaked after the second infusion but levels remained low and there was no evidence of CRS. At one year follow-up he remained well, platelet and G-CSF independent, with reduced transfusion requirements and had resumed playing sport with friends. Subjects 2, 3 and 4, were all multiply relapsed and refractory AML patients; two of whom had relapsed after HLA-mismatched HSCT. All showed rapid activation of peripheral NK cells post infusion with sustained activity throughout follow-up. In all cases these activated NK cells killed NK-resistant tumour cells in vitro without additional activation. Subject 2 was a neutropenic 21yr old female with 70% a mixed chimera and refractory AML (M2) post VUD HSCT at time of treatment. Within 1 month of initiation of INKmune treatment she was discharged with PMN >500 and her mixed chimera resolved to full donor chimera. At Day 140 post INKmune her bone marrow NK cells remained highly activated (>60% CD69+, K562 and Raji lysis of >70%). Her AML recurred 4 months post INKmune infusion and she died from relapsed disease 8 months after INKmune treatment. Subject 3 was a 21yr old male with refractory AML (M6) after two failed HSCT (haplo m/m and VUD). He showed the same rapid generation of activated NK cells in vivo but to a lesser degree (maximum 35% CD69+, sustained increased lysis of K562 but no lysis of Raji cells) and no evidence of clinical improvement. Subject 4, a multiply relapsed AML patient has just been treated and has shown peripheral NK proliferation and maturation at D+8. The subject experienced no adverse effects post 1st and 2nd doses and further follow-up will be presented. INKmuneTM infusions proved safe and led to rapid and sustained activation of peripheral NK cells with concomitant increases in relevant systemic cytokines. The TIML-NK have a distinct phenotypic, proteomic and metabolomic signature which mirrors the activity in vitro and in vivo. This is the first time memory-like NK cells have been generated in vivo without the need for cytokine induction or support and our findings inform the development of more optimal NK cell-based immunotherapeutic strategies for cancer. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Quality of Life Assessment in Patients of Stage V Chronic Kidney Disease

Introduction: Despite ongoing advances in the treatment of chronic kidney disease (CKD), the mortality rate, and level of health-related quality of life (HRQOL) for the CKD population remain significantly higher than for the general population. The importance of measuring end-stage renal failure (ESRF) patients' quality of life in relation to healthcare lies in not only providing absolute survival but also the quality of that survival. Due to cost constraints, the profile of chronic kidney disease patients and their treatment in Bangladesh is almost identical to that of India, with patients frequently requesting a reduction in the frequency of dialysis sessions, the use of less expensive dialyzers, dialyzer reuse, and the absence of erythropoietin therapy. Hence, augmenting the QOL may perhaps be a challenge and an observable fact of specific interest for renal healthcare teams. This study is intended to assess KDQOL among patients receiving hemodialysis for 8 hours, and 12 hours per week, patients receiving CAPD, and patients of CKD stage V who decline any form of renal replacement therapy, and remained on conservative treatment. The aim of the study was to assess the quality of life among patients of CKD Stage V. Methods: This cross-sectional study was carried out at the Department of Nephrology, Dhaka Medical College Hospital and BIRDEM general hospital. The patients who received consultation at the Outdoor Department of selected hospital from November 2010 to October 2011. The study assess the of Quality of Life, and Cost Effectiveness on different modalities of treatment among the patients of chronic kidney disease stage V, and also to find out the best modality of dialysis. A total number of 134 consecutive patients were enrolled in this study, out of which 42 patients who were advised to commence renal replacement therapy, and after counseling opted to remain in conservative treatment were considered as GROUP I, 39 patients who received hemodialysis 8 hours per week were considered as GROUP II, 30 patients who received hemodialysis 12 hours per week in one or more centers were considered as GROUP III, and 23 patients who received Continuous Peritoneal Dialysis at least 3 exchanges per day were considered as GROUP IV. Result: Mean age was almost similar in all four groups, and most of the patients were 5th decade, and above. Male was predominant in all four groups, and the male-female ratio was almost 2:1 in the whole study patients. Diabetic nephropathy and glomerulonephritis were more common etiology of CKD in all four groups. Monthly expenditure was significantly (p&lt;0.05) higher in group IV, followed by group III, group II, and group I in all three follow-ups, however, monthly expenditure was almost similar between group III, and group IV (p&gt;0.05) but the mean monthly expenditure was higher in group IV patients. Mean serum Creatinine was lowest in group IV followed by group III, group II, and group I in descending order. Serum albumin was low in all the groups but almost parallel in all follow-ups in group II, groups I, and group IV, whereas the lowest was in group II followed by group I and group IV, but declined in group III during the 2nd, and 3rd follow-up from 1st follow-up. Hemoglobin level consistently remained within the target range in group IV in all follow-ups but below the target range in group I followed by group II, and group III in ascending order. The physical component score increased significantly in Group III, and Group IV at consecutive follow-ups, however, it was higher in Group IV. Similarly, the mental component score was recorded highest in Group IV, followed by group III, group II, and group I. Regarding mortality, it was observed that more than half of the patients were expired in group I, one-third in group II, and 16.7% in group III, and only 8.7% in group IV during final follow-up. Conclusion: Patients receiving continuous ambulatory peritoneal dialysis achieved the best clinical parameters in terms of control of blood pressure, and volume overload. On the other hand, parameters were a lot away from the desired target in patients receiving hemodialysis for 8 hours per week, and they did not have significantly better parameters in comparison to those who were only on conservative treatment. The scenario of serum albumin, and serum creatinine, though complicated by the existence of malnutrition, were in best approximation to the desired level in these patients. According to the age-sex-matched risk categorization of the patients, it was found that the majority of patients on conservative treatment were in more than the average risk category.

Saturday, June 18, 20222:00 PM - 3:00 PM PL01 Presentation Time: 2:00 PM: Kinetic Antigen-Specific T-cell Receptor Profiling in Cervical Cancer Patients Treated with Standard-of-Care Chemoradiation and Brachytherapy

<h3>Purpose</h3> Chemoradiation (CRT) may modulate the intratumoral and peripheral immune milieu by serving as an <i>in situ</i> vaccine. The impact of the rapid dose delivery of brachytherapy (BT) on the T-cell repertoire has not been examined. HPV-related cancers express viral oncoproteins E6/E7, which could function as tumor antigens (Ag) and are thus ideal for investigating the impact of CRT in generating tumor-specific immunity. <h3>Methods</h3> 11 pts with cervical cancer were enrolled on a multi-institutional prospective tissue banking protocol from 1/2020—2022. Pts underwent standard external beam RT (EBRT) spanning 5-7 wks with concurrent weekly 40mg/m² cisplatin, then BT boost with either high dose rate (HDR) in 5 fx or pulse dose rate (PDR) in 2 fx. Cervical tumor swabs were taken at 5 timepoints: <b>baseline</b> (<b>T1</b>), <b>wk 1</b> (<b>T2</b>, after 5 fx), <b>wk 3</b> (<b>T3</b>, after 10-15 fx), <b>wk 5</b> (<b>T4</b>, at conclusion of EBRT and prior to 1st BT), prior to 2nd BT (<b>T4B</b>), and at <b>1st follow-up</b> (<b>T5</b>, 12 wks post-treatment). Samples underwent functional expansion of HPV Ag-specific T cells before DNA extraction and multiplex deep sequencing of the CDR3 region of TCR-β using immunoSEQ PCR (Adaptive Biotech). TCR productive frequency (freq), templates, clonality, and rearrangements were compared across timepoints. Separately, HPV-responsive T-cell clones underwent <i>ex vivo</i> expansion by incubation with HPV long peptide sequences of E6/E7 overnight (ON). TCR sequences were compared between HPV-stimulated T cells and evaluated against incubations with CEF (positive control peptides) or media (negative control). Statistical analysis was via Mann-Whitney U. <h3>Results</h3> Median age was 47 yrs (range 27-57). 6 pts (54.5%) had SCC; 5 (45.5%) had adenocarcinoma. 4 pts (36.4%) had FIGO 2018 ≤Stage IIB disease, 45.5% were Stage III, and 18.2% were Stage IVA/B. 7 pts (63.6%) received PDR BT and 4 pts (36.4%) underwent HDR BT. At median follow-up of 7.5 mo, all pts are alive and with NED. In serially sampled peritumoral microenvironment (TME) isolates, TCR productive clonality increased after first BT, culminating in a significant increase at T5 during the first post-treatment follow-up (<b>Fig 1A</b>). There was a trend (ns) toward increased productive templates throughout CRT and BT (<b>Fig 1B</b>), but this decreased by T5. Productive freq was significantly higher at T5 compared to prior to BT (T1—T4), <b>Fig 1C</b>. Productive rearrangements trended toward abundance throughout CRT and BT (ns), but decreased at T5 (<b>Fig 1D</b>). Functional HPV Ag stimulation assays of peritumoral T-cells in the full cohort did not show significant changes in the TCR repertoire after ON incubation with HPV E6/7 peptides. However, 4 pts had notable E6/E7-responsive increases in these metrics at either T4 or T4B—namely, abundance of productive templates (ranges: 1.9—30.3 fold-increase from baseline), freq (1.25—5.5), rearrangements (1.5—13.8), and clonality (1.31—3.8). <h3>Conclusions</h3> We characterized TCR remodeling during BT in this first translational analysis, demonstrating (i) increased peritumoral TCR productive freq and clonality post-BT at T5, and (ii) transient rise in productive templates and rearrangements through CRT and BT, with a numeric return to baseline post-BT at T5. Some pts had functional Ag-specific activation upon HPV stimulation during and after BT. These findings suggest that despite the cytotoxic effects of radiation, BT alters the TME to facilitate expansion of specific T-cell populations, which may contribute to treatment efficacy.

A prospective cohort study on the association between grip strength and cognitive function in adults aged 50 years and above

Objective: To evaluate the association between grip strength (GS) and cognitive function in a population-based longitudinal cohort of Chinese adults aged ≥50 years. Methods: The study population of 3 600 adults was from the baseline survey and two rounds of follow up of World Health Organization (WHO) study of global ageing and adult health (SAGE) in five districts of Shanghai (Hongkou, Huangpu, Minhang, Qingpu and Pudong) after excluding individuals with self-report stroke and depression. The effects of baseline GS on cognitive function and its changes were evaluated. Factor analysis was applied to generate an overall cognition score based on verbal recall trials, verbal fluency test, forward digit span test and backward digit span test. Linear mixed effects model was used to examine the predictive capability of baseline GS for changes in cognitive function. Results: A total of 3 600 participants aged (61.2±8.1) years at baseline survey were included in this study, including 1 668 (46.3%) men and 1 932 (53.7%) women. The average of baseline GS and total cognitive function score were (28.19±12.18) kg and (58.93±14.56) respectively. Cognitive function score declined significantly during the follow-up, however, the changes were different among different age groups, education level groups and household income groups. After adjusted for age, education level, marital status, household income, co-morbidity of chronic conditions, drinking status, smoking status, physical activity level, vegetable/fruit intakes and BMI, no relationships between the baseline GS and cognitive score at baseline survey and at 1st follow-up were observed, however, compared with lower GS quartile group, there was a significant relationship between higher baseline GS level and better cognitive function at 2nd follow-up. The participants with highest GS quartile had better cognitive performance over time (male: β=1.938,95%CI:0.644-3.231,P=0.003, female: β=2.192,95%CI:0.975-3.409,P<0.001 and those aged 50-64 years: β=1.652,95%CI:0.646-2.659,P=0.001) than those with the lowest quartile. Conclusions: Higher baseline GS was significantly related to better cognitive function with slow decline. Thus, it is an indicator of cognitive function in middle-aged and elderly Chinese.

Early evaluation of subclinical cardiotoxicity in patients with lung cancer receiving immune checkpoint inhibitors by cardiovascular magnetic resonance: a prospective observational study.

BackgroundFew studies have focused on the subclinical cardiotoxicity of immune checkpoint inhibitors (ICIs) in cancer patients. This study aimed to evaluate the manifestations of subclinical cardiotoxicity of ICI therapy using cardiovascular magnetic resonance (CMR) and to explore whether CMR parameters can help predict cardiotoxicity at the early stage of ICI therapy.MethodsA prospective, longitudinal study was conducted among patients with lung cancer. The patients were planned to undergo serial CMRs before (baseline), 3 weeks after (1st follow-up), and 3 months after (2nd follow-up) the initiation of ICI therapy, respectively. Patients with 3 CMRs were included in the analysis. Serial quantitative measurements based on CMR were compared using one-way repeated measures analysis of variance (RM-ANOVA). On the basis of cancer therapy-related cardiac dysfunction (CTRCD) observed at the second follow-up, patients were categorized into a CTRCD group and a non-CTRCD group. Baseline clinical and CMR parameters and the relative reduction of left ventricular global strain at the second follow-up was compared between the CTRCD group and the non-CTRCD group. Receiver operating characteristic (ROC) analysis was used to identify CTRCD that developed 3 months after ICI therapy.ResultsA total of 36 patients with 3 CMRs (60.7±9.2 years old, 77.8% male) were included in the analysis. Left ventricular-global radial strain (LV-GRS) decreased significantly at the second follow-up (37.9%±8.5% vs. 33.1%±1.0%; P=0.014), but left ventricular ejection fraction (LVEF) did not change significantly (51.5%±6.0% vs. 49.2%±6.5%; P>0.05). A total of 7 patients (19.4%) had developed CTRCD by the second follow-up. Baseline clinical and CMR parameters did not differ between the CTRCD group and the non-CTRCD group (P>0.05 for all). In the CTRCD group, the left ventricular-global circumferential strains (LV-GCSs) showed significant reductions at both the first and second follow-up (P=0.008 and 0.035, respectively), but the LVEF only showed a significant reduction at the second follow-up (P<0.001). The relative reduction of LV-GRS at the second follow-up was significantly higher in the CTRCD group than in the non-CTRCD group (29.8%±25.8% vs. 6.8%±20.4%; P=0.036) and was used to predict CTRCD developed at the 3-month timepoint after ICI therapy [area under the curve (AUC) =0.759; P=0.036].ConclusionsIn the early stage of ICI therapy, assessment of myocardial strain can be used to detect subclinical left ventricular systolic dysfunction in patients with lung cancer earlier than LVEF. The relative reduction of LV-GRS can be used to predict CTRCD 3 months after ICI therapy.

PULMONARY TUBERCULOSIS MORTALITY AND ITS RISK FACTORS AMONG PATIENTS WITH TYPE 2 DIABETES AND PULMONARY TUBERCULOSIS IN FOUR COMMUNITY HOSPITALS, CENTRAL THAILAND

Background: Tuberculosis (TB), a communicable disease, is currently a significant health problem in Thailand. Type 2 diabetes (T2D) is an indicator of poor TB outcomes; however, data according to specific antihyperglycemic use and tuberculosis outcomes in community hospital settings in Thailand remain limited. We aimed to determine TB mortality as well as explore the demographic and clinical risk factors among patients with pulmonary TB and underlying T2D.&#x0D; Methods: A retrospective cohort study was conducted between January 1, 2013, and December 31, 2020, to determine tuberculosis mortality and its risk factors among patients with T2D and pulmonary TB visiting three community hospitals, in central Thailand. T2D and pulmonary TB were determined according to the International Classification of Diseases, Tenth Revision codes presented in medical records. TB mortality data were reviewed and retrieved from the tuberculosis treatment cards. Patients were classified as “dead” when they died before completing treatment regardless of the causes. Multivariable cox proportional regression analysis was performed to obtain the adjusted hazard ratios (AHR) and 95% confidence interval (CI) of factors related to TB mortality.&#x0D; Results: A total of 133 patients with T2D and pulmonary TB were enrolled in the present study; 74 (55.6%) participants were males. At baseline, the average age of participants was 57.29+12.51 years. During the study period, the TB mortality rate was 15.74 (95% CI 8.13-27.50) deaths per 100 person-years. The independent risk factors for TB mortality included age ≥70 years (AHR 5.45, 95% CI; 1.36-21.84), use of insulin (AHR 4.62, 95% CI; 1.11-19.21), and positive sputum test result at 1st follow-up (AHR 16.10, 95% CI; 2.10-123.40).&#x0D; Conclusion: TB mortality among patients with T2D should be emphasized. Insulin use may be a proxy indicator for poor glycemic control associated with mortality. Additionally, elderly patients should be closely observed for successful treatment as well as monitoring for any adverse events.