Local Medical Ethics Committee Research Articles

Cardiovascular calcification in hemodialysis patients: A Qatar-based prevalence and risk factors study.

Patients with end-stage kidney disease on hemodialysis (HD) have an increased risk of death due to the high prevalence of cardiovascular disease. Vascular calcification (VC) is predictive of cardiovascular disease and mortality. We conducted a study to evaluate the prevalence and risk factors for VC in dialysis patients in Qatar. This is a retrospective nationwide study including all chronic ambulatory dialysis patients in Qatar from 2020 to 2022. We used our national electronic medical record to track demographics, clinical characteristics, comorbidities, laboratory values, and diagnostic data for each patient. Calcifications were assessed by echocardiography (routinely done for all our dialysis population per national protocol), computed tomography, X-ray, and ultrasound. The study protocol was approved by the local medical research ethics committee (MRC-01-20-377). 842 HD patients were included in this study. Vascular calcifications (VC) were prevalent in 52.6% of patients. The main site of VC was Mitral valve calcifications in 55.5% of patients. Patients with VC were significantly older and had more prevalence of diabetes mellitus (p = 0.001 and p = 0.006, respectively). There was no statistically significant difference between patients with calcifications and patients without calcifications regarding serum calcium, phosphorus, and PTH level. In multivariate analysis, age and diabetes significantly increased the risk factor for calcification (95% CI 1.033-1.065, p < 0.0001, and 95% CI 1.128-2.272, p < 0001, respectively). Moreover, higher vitamin D levels and higher doses of IV Alfacalcidol were significant risk factors for calcifications (95% CI 1.005-1.030, p < 0.007, and 95% CI 1.092-1.270, p < 0.0001, respectively). Our study found that vascular calcification was widespread among our dialysis population in Qatar. Implementing the practice of echocardiography in dialysis patients was extremely helpful and the most productive in detecting vascular calcification. Diabetes mellitus almost doubles the risk for vascular calcifications in dialysis patients. These results are beneficial in identifying risk factors for vascular calcification, which can help stratify dialysis patients' risk of cardiovascular disease and optimize prevention efforts.

Clinical and Laboratory Features of Sickle Cell Disease S/D Punjab: Impact of HbF and Hydroxyurea.

Sickle cell disease (SCD) is a major public health issue worldwide with high morbidity and mortality. SCD SD Punjab is the third most common genotype of SCD in Oman and is associated with several serious complications. The aim of the study is to establish the clinical and laboratory features of SCD patients with SD double heterozygotes and study the impact of haemoglobin F, hydroxyurea, and other modulators on the disease severity. We analysed the electronic medical records of 52 consecutive SCD patients who were diagnosed as double heterozygote SD Punjab between 2006 and 2022. The study was approved by the local medical research and ethics committee. The data captured included SCD-related complications and current clinical and laboratory indices. Data from other studies on other SCD genotypes were used as historical controls. 52 patients (31 males, 21 females) who formed this cohort had a median age of 32 years with an interquartile range (IQR) of 21-39.8 years. 37(71.2%) had <3 VOC per year, whereas 15 (28.8%) patients had ≥3 vasooclusive (VOC) episodes per year. SCD-related complications included Acute Chest Syndrome (ACS) (48%), Gall stones (26.9%), Avascular necrosis (AVN) (28.8%), Stroke (13.5%) and splenic sequestration (7.7%), whereas 5 (9.6%) patients of this cohort died. Surgical and Autosplenectomy were seen in 18 (34.6%). These findings were similar to other SCD genotypes in this community. 19 (57.6%) were taking Hydroxyurea (HU) amongst the 33 patients who were prescribed HU. Haematological parameters showed a median (IQR) Hb (g/dl), MCV (fl), Retic count (%), WBC count(×109/L) and Platelet count(×109/L) of 9.7 (8.5-11.3), 74.9 (68.4-79.8), 4 (3.2-5.7), 9.9 (8.1-12.6) and 309 (239-428) respectively. The haemoglobin electrophoresis showed an elevated HbF, whereas serum bilirubin and LDH were elevated amongst the biochemical parameters. The use of hydroxyurea showed no impact on VOC, ACS, AVN, Stroke or mortality. SD Punjab is the third most common SCD genotype in Oman and was associated with recurrent VOC, ACS, AVN, and gall stones comparable to other SCD genotypes. Patients with > 3 VOC/year had significantly increased incidence of Stroke, AVN, and gallstones. However, HU was not associated with improved prognosis and better survival in this cohort of patients.

The Fractional exhaled Nitric Oxide (FeNO)- test as add-on test in the diagnostic work-up of asthma: a study protocol.

Asthma is a common disease characterized by chronic inflammation of the lower airways, bronchial hyperactivity, and (reversible) airway obstruction. The Global Initiative of Asthma Guideline recommends a flowchart to diagnose asthma with first-step spirometry with reversibility and a bronchial challenge test (BPT) with histamine or methacholine as a second step [1]. The BPT is considered burdensome, time-consuming for patients and staff, can cause side effects, and is expensive. In addition, this test strongly encumbers lung function capacity. Elevated Nitric Oxide (NO) is associated with airway eosinophilic inflammation in asthma patients and can be measured in exhaled air with the Fractional exhaled (Fe) NO-test. This low-burden FeNO-test could be used as an 'add-on' test in asthma diagnostics [2, 3]. This multi-center prospective study (Trial number: NCT06230458) compares the 'standard asthma diagnostic work-up' (spirometry with reversibility and BPT) to the 'new asthma diagnostics work-up' (FeNO-test as an intermediate step between the spirometry with reversibility and the BPT), intending to determine the impact of the FeNO-based strategy, in terms of the number of avoided BPTs, cost-effectiveness and reduced burden to the patient and health care. The cost reduction of incorporating the FeNO-test in the new diagnostic algorithm will be established by the number of theoretically avoided BPT. The decrease in burden will be studied by calculating differences in the Visual Analogue Scale (VAS) -score and Asthma Quality of Life Questionnaire (AQLQ) -score after the BPT and FeNO-test with an independent T-test. The accuracy of the FeNO-test will be calculated by comparing the FeNO-test outcomes to the (gold standard) BPTs outcomes in terms of sensitivity and specificity. The intention is to include 171 patients. The local medical ethics committee approved the proposed study and is considered a low-burden and risk-low study. The local medical ethics committee registration number: R23.005. Strengths: This is the first study that investigates the value of the FeNO-test (cut off ≥ 50 ppb) as an add-on test, to determine the impact of the FeNO-based strategy, in terms of the number of avoided BPTs, cost-effectiveness, and reduced burden on the patient and health care. High FeNO levels may also be observed in other diseases such as eosinophilic chronic bronchitis and allergic rhinitis. The FeNO-test can be used to rule in a diagnosis of asthma with confidence, however, due to the poor sensitivity it is not suitable to rule out asthma.

Shared decision-making for non-operative management versus operative management of hip fractures in selected frail older adults with a limited life expectancy: a protocol for a nationwide implementation study

Background and purposeRecent research has highlighted non-operative management (NOM) as a viable alternative for frail older adults with hip fractures in the final phase of life. This study aims to...

Effects of 6 weeks of cryotherapy plus compression therapy after total or unicompartmental knee arthroplasty: protocol for a single-centre, single-blind randomised controlled trial

IntroductionEffective rehabilitation after total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA) is often impeded by pain and swelling. Beneficial short-term effects in terms of pain and opioid use after...

Is there a reactive IgG antibody for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in maternal breast milk?

Restricted data on the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reactive IgG antibodies by breast milk to infants, born to mothers who did not know if they had coronavirus disease 2019 (COVID-19), are presented. The objective of the present work was to demonstrate the existence of specific IgG antibodies against the SARS‐CoV‐2 virus in the milk of breastfeeding mothers in the suburban area of Şanlıurfa, Türkiye. This retrospective analysis examined the medical records of maternal and neonatal data for all 51 newborns to 50 mothers from September to October 2020. The present work was approved by the local medical ethics committee. Written informed consent was obtained from the mothers. Testing SARS-CoV-2 reactive IgG was performed using ELISA assay. SARS-CoV-2 reactive IgG were detected in 58% of breast milk. Over the past year, SARS-CoV-2 reactive IgG identified in breast milk of mothers without symptoms of viral respiratory infection (self-reported diagnosis) was 12.5 times lower than mothers with symptoms. The IgG responses were different between symptomatic and asymptomatic mothers’ and infants’ samples. These results propose that along with the COVID-19 pandemic, breastfeeding could be safe, and the existence of SARS-CoV-2-reactive IgG antibodies in breast milk could provide passive immunity to breastfed infants, and keep them safe against COVID-19 infection.

Photobiomodulation and glass ionomer sealant as complementary treatment for hypersensitivity in molar incisor hypomineralisation in children: protocol for a blinded randomised clinical trial

IntroductionPhotobiomodulation has been widely used as a complementary treatment for dentin hypersensitivity, with reports of clinical success. However, the literature offers only one study, in which photobiomodulation was used for...

Find: Immunomodulation after a fasting mimicking diet analyzed by Nanostring and multispectral flowcytometry in healthy volunteers: A pilot study.

e14560 Background: An increasing number of clinical trials, including our randomized phase III trial (NCT05503108), are investigating the potential benefit of short-term fasting using a fasting mimicking diet (FMD) on the anti-tumor effect of chemotherapy. Preclinical research suggests that FMD promotes infiltration of CD8+ T-cells, while decreasing regulatory T-cells (Treg). Extensive immunoprofiling is needed to investigate the immunomodulatory effects of FMD alone and guide ongoing translational trials on FMD as an adjunct to chemotherapy in patients with cancer. Methods: FIND is a prospective pilot study, which included 9 healthy volunteers who followed a 4-day FMD every 3 weeks, 2 times (NCT04833439). Peripheral blood samples were collected in a fed state (baseline), after overnight fasting (overnight) and directly after the second cycle of FMD (final). Metabolic markers (IGF1, glucose, ketone bodies) to ensure ketosis were measured in the plasma. The RNA from white blood cells was isolated and transcriptomics was performed with the Nanostring IO360 human Pancancer panel, and analyzed by nSolver Advanced analysis, Graphpad Prism and String analysis. Statistical testing was done using Wilcoxon signed-rank tests in R-studio. In addition, 40-plex spectral AURORA flow cytometry for immune cell composition with FlowJo analysis was performed. This study was approved by the local Medical ethical committee (NL76033.058.21). Results: Paired analysis of the Nanostring data identified 56 differentially expressed genes (DEG) comparing baseline and final samples initially, of which 19 genes showed at least 1.2 log2 fold-change in at least half of the participants. String analysis indicated that the DEGs were associated with fatty-acid metabolism, T-cell and myeloid cell function and immune regulatory pathways. Cell typing showed an increase in cytotoxic NK CD56dim cells (p=0.031) and a decrease in Tregs decreased (p=0.063) after FMD. In-depth analysis of gene specific pathway enrichment and immune cell profiling by flow cytometry will be presented. Conclusions: The expression profile of 56 genes in circulating immune cells changed after 2 FMD cycles, next to fatty-acid metabolism affecting the composition and function of both T-cells and myeloid cells and their regulation. Altogether, FMD induced immunological changes that could support cancer treatment and guide immunomonitoring in future trials evaluating the effects of FMD in cancer treatment. Clinical trial information: NCT04833439 .

Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) in adults with chronic stroke: protocol of a randomised controlled trial

IntroductionStroke causes multiple deficits including motor, sensitive and cognitive impairments, affecting also individual’s social participation and independence in activities of daily living (ADL) impacting their quality of life. It has...

Cerebrospinal Fluid and Plasma Amine Profiles in Interictal Migraine.

Impaired amine metabolism has been associated with the etiology of migraine, that is, why patients continue to get migraine attacks. However, evidence from cerebrospinal fluid (CSF) is lacking. Here, we evaluated individual amine levels, global amine profiles, and amine pathways in CSF and plasma of interictal migraine patients and healthy controls. CSF and plasma were sampled between 8:30 am and 1:00 pm, randomly and interchangeably over the time span to avoid any diurnal and seasonal influences, from healthy volunteers and interictal migraine patients, matched for age, sex, and sampling time. The study was approved by the local medical ethics committee. Individual amines (n=31), global amine profiles, and specific amine pathways were analyzed using a validated ultraperformance liquid chromatography mass spectrometry platform. We analyzed n=99 participants with migraine with aura, n=98 with migraine without aura, and n=96 healthy volunteers. Univariate analysis with Bonferroni correction indicated that CSF L-arginine was reduced in migraine with aura (10.4%, p< 0.001) and without aura (5.0%, p= 0.03). False discovery rate-corrected CSF L-phenylalanine was also lower in migraine with aura (6.9%, p= 0.011) and without aura (8.1%, p= 0.001), p= 0.088 after Bonferroni correction. Multivariate analysis revealed that CSF global amine profiles were similar for both types of migraine (p= 0.64), but distinct from controls (p= 0.009). Global profile analyses were similar in plasma. The strongest associated pathways with migraine were related to L-arginine metabolism. L-Arginine was decreased in the CSF (but not in plasma) of interictal patients with migraine with or without aura, and associated pathways were altered. This suggests that dysfunction of nitric oxide signaling is involved in susceptibility to getting migraine attacks. ANN NEUROL 2023;93:715-728.

Longitudinal Effects of 1-Year Smoking Cessation on Human Bronchial Epithelial Transcriptome

Longitudinal Effects of 1-Year Smoking Cessation on Human Bronchial Epithelial Transcriptome

Expression of Concern: Polymorphisms of the Serotonin Transporter Gene and Their Relation to Premature Ejaculation in Individuals from Iran.

No AccessJournal of UrologyExpression of Concern10 Jan 2023Expression of Concern: Polymorphisms of the Serotonin Transporter Gene and Their Relation to Premature Ejaculation in Individuals from Iranis a expression-of-concern ofPolymorphisms of the Serotonin Transporter Gene and Their Relation to Premature Ejaculation in Individuals from Iran Mohammad Reza Safarinejad Mohammad Reza SafarinejadMohammad Reza Safarinejad *Correspondence: P.O. Box 19395-1849, Tehran, Iran telephone: 0098 21 22454499; FAX: 0098 21 22456845; E-mail Address: [email protected] More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003111AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookLinked InTwitterEmail "Expression of Concern: Polymorphisms of the Serotonin Transporter Gene and Their Relation to Premature Ejaculation in Individuals from Iran." The Journal of Urology, Publish Ahead of Print, pp. – Study received local medical ethical committee approval. From the Urology and Nephrology Research Center, Shahid Beheshti University (MC), Tehran, Iran© 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of Urology16 Apr 2009Polymorphisms of the Serotonin Transporter Gene and Their Relation to Premature Ejaculation in Individuals from Iran Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mohammad Reza Safarinejad *Correspondence: P.O. Box 19395-1849, Tehran, Iran telephone: 0098 21 22454499; FAX: 0098 21 22456845; E-mail Address: [email protected] More articles by this author Expand All Study received local medical ethical committee approval. Advertisement PDF downloadLoading ...

Expression of Concern: Evaluation of Semen Quality, Endocrine Profile and Hypothalamus-Pituitary-Testis Axis in Male Patients With Homozygous β-Thalassemia Major.

No AccessJournal of UrologyExpression of Concern10 Jan 2023Expression of Concern: Evaluation of Semen Quality, Endocrine Profile and Hypothalamus-Pituitary-Testis Axis in Male Patients With Homozygous β-Thalassemia Majoris a expression-of-concern ofEvaluation of Semen Quality, Endocrine Profile and Hypothalamus-Pituitary-Testis Axis in Male Patients With Homozygous β-Thalassemia Major Mohammad Reza Safarinejad Mohammad Reza SafarinejadMohammad Reza Safarinejad *Correspondence: P.O. Box 19395-1849, Tehran, Iran telephone: 0098 21 22454499; FAX: 0098 21 22456845; E-mail Address: [email protected] More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003116AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookLinked InTwitterEmail "Expression of Concern: Evaluation of Semen Quality, Endocrine Profile and Hypothalamus-Pituitary-Testis Axis in Male Patients With Homozygous β-Thalassemia Major." The Journal of Urology, Publish Ahead of Print, pp. – Study received local medical ethical committee approval. From the Urology and Nephrology Research Center, Shahid Beheshti University (M.C), Tehran, Iran© 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of Urology18 Apr 2008Evaluation of Semen Quality, Endocrine Profile and Hypothalamus-Pituitary-Testis Axis in Male Patients With Homozygous β-Thalassemia Major Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mohammad Reza Safarinejad *Correspondence: P.O. Box 19395-1849, Tehran, Iran telephone: 0098 21 22454499; FAX: 0098 21 22456845; E-mail Address: [email protected] More articles by this author Expand All Study received local medical ethical committee approval. Advertisement PDF downloadLoading ...

Effect of anatomical differences and intraocular lens design on negative dysphotopsia.

To assess the effect of ocular anatomy and intraocular lens (IOL) design on negative dysphotopsia (ND). Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands. Ray-tracing study based on clinical data. Ray-tracing simulations were performed to assess the effect of anatomical differences and differences in IOL design on the peripheral retinal illumination. To that end, eye models that incorporate clinically measured anatomical differences between eyes of patients with ND and eyes of pseudophakic controls were created. The anatomical differences included pupil size, pupil centration, and iris tilt. The simulations were performed with different IOL designs, including a simple biconvex IOL design and a more complex clinical IOL design with a convex-concave anterior surface. Both IOL designs were analyzed using a clear edge and a frosted edge. As ND is generally considered to be caused by a discontinuity in peripheral retinal illumination, this illumination profile was determined for each eye model and the severity of the discontinuity was compared between eye models. The peripheral retinal illumination consistently showed a more severe discontinuity in illumination with ND-specific anatomy. This difference was the least pronounced, 8%, with the frosted edge clinical IOL and the most pronounced, 18%, with the clear edge biconvex IOL. These results show that small differences in the ocular anatomy or IOL design affect the peripheral retinal illumination. Therewith, they can increase the severity of ND by up to 18%.

CHANGES OF THE ZONA GLOMERULOSA IN HUMAN ADRENALS FROM BIRTH TO 40 YEARS OF AGE

Objective: Antibodies to CYP11B2 (aldosterone synthase) allow imaging of the zona glomerulosa (zG) by immunohistochemistry. Studies demonstrate that the area and continuity of the zG decreases with aging and accumulations of aldosterone-producing cell clusters occur. Research on age-related changes in the zG in younger patients and comparison of both adrenals is limited. Therefore, the objective of this study was to elucidate age-related changes of the zG by quantifying CYP11B2 expression in adrenals of patients below the age of 40 years. Design and method: We collected human adrenals from autopsy cases, that were anonymized except for age, sex and medical history. We excluded adrenal glands of patients with premature birth, hypertension, cardiovascular disease, adrenal tumors, use of steroids. In case of two available adrenals in one patient, one was randomly selected of the two. We validated software for automated quantification by comparing manually outlined CYP11B2 expressing area with automated outlined area. We then used this automated method to quantify CYP11B2 expressing area, CYP11B2 continuity and mean and maximum CYP11B2 depth. If the zG was discontinuous, mean length of ‘gaps’ between ZG tissue was calculated. We also determined the structural similarity between both adrenals of the same case. The study was approved by the local Medical Ethics Committee. Results: There was a negative correlation between age and CYP11B2 expressing area (rs = -.63); negative correlation between age and CYP11B2 continuity (rs = -.80); positive correlation with age and mean gap length (rs = 0.71); positive correlation between age and maximum CYP11B2 depth (rs = .30, P = &lt;0.001) and no correlation between age and mean CYP11B2 depth (rs = .01, p = &lt;0.001). The intraclass correlation coefficient between both adrenals of one subject for CYP11B2 expressing area was 0.78 (95%CI = 0.56–0.89), for CYP11B2 continuity 0.94 (95%CI = 0.88–0.97) and for mean gap length 0.76 (95%CI = 0.32–0.81). Conclusions: We demonstrate a decrease in CYP11B2 area and continuity, whilst the mean gap length and maximum CYP11B2 depth increases, which we consider as involution and clustering of the zG. This is seen in both adrenals and therefore suggests a common process. The relation with the development of aldosterone-producing adenoma remains to be determined.

Endometrial factors in the implantation failure spectrum: protocol of a MUltidisciplinary observational cohort study in women with Repeated Implantation failure and recurrent Miscarriage (MURIM Study)

IntroductionWomen with repeated implantation failure (RIF) and unexplained recurrent miscarriage (RM) are proposed to be at opposite ends of the implantation spectrum, with RM representing an overly receptive endometrium (implantation...

Distribution of Patients with Resistant Plantar Fasciitis And Their Response to Percutaneous Partial Plantar Fascia Release under Tibial Nerve Block

Backgrounds and objectives:&nbsp; Plantar fasciitis is considered to be the most popular cause of heel pain. The corticosteroid injection is the second line treatment for these patients whose fail in conservative management of the plantar fasciitis. Surgery is the last line in treatment, that varies into many approaches. This is a clinical trial to assess the benefit of one of these approaches (partial percutaneous plantar fascia release)that would be done under tibial nerve block in various patients with plantar fasciitis that resistant to the previous treatments. Methods: After local medical ethics committee approve a total of 126 patients diagnosed with resistant plantar fasciitis were collected, classified according to different items and treated on by partial percutaneous plantar fascia release under tibial nerve block by ultrasound guidance. The participants were continuously checked up for possible complications during one year. Results:&nbsp; The average age of the patients were participated in this study was 44.97 ± 7.3 years. The majority of the patients were females (almost 78%). The majority of the patients had functional problem at work or home (approximately 80%). This study detected that around 54.0% of the patients had right side plantar fasciitis, about 30% had left side and almost 16% had bilateral. 122 of 126 patients received three times steroid injections for treatment. The patients satisfaction for the percutaneous fasciotomy outcomes were approximately (94%) of the patients. Conclusion: This study showed that partial percutaneous plantar fascia release for plantar fasciitis patients under tibial nerve block is a safe medical surgery with considerable healing ability for them

Clinical analysis of alcoholic pellagra: A single‐center retrospective study

Pellagra caused by niacin deficiency in alcoholics can be easily misdiagnosed because of similar symptoms to other alcohol-related diseases and the lack of the classical triad of signs. This study aimed to define the clinical presentation of alcoholic pellagra for early diagnosis and timely treatment. The clinical data of 16 alcohol-dependent patients who had pellagra and treated in our hospital from January 2002 to December 2019 were retrospectively analyzed. The local medical ethics committee approval (Medical Ethics Committee of Affiliated Hospital of XuZhou Medical University, XYFY2020-KL247-02) for this study has been obtained. The main complaints of the 16 patients were skin lesions (six cases), diarrhea (six cases), and mental disorders (four cases). Then, 13 cases had typical skin lesions, and 3 patients had a full spectrum of diarrhea, dementia, and dermatitis (3D). In terms of the main diagnosis, 2 patients had pellagra and Wernicke's encephalopathy, 3 patients had pellagra and alcohol-withdrawal syndrome, and the other patients had pellagra. After sufficient amounts of niacin and multivitamin B were given, clinical symptoms improved rapidly, and no sequelae were observed during follow-up. Pellagra is rarely manifested as a full 3D spectrum, with only one or two characteristics, which lack diagnostic specificity, especially in individuals with alcoholism. Physicians should maintain a high degree of suspicion of niacin deficiency in alcoholics. Alcohol-dependent patients with pellagra may be accompanied by complications of Wernicke's encephalopathy and alcohol-withdrawal syndrome. Prompt identification and timely treatment with a sufficient amount of niacin in combination with other vitamins and a certain amount of Zn can achieve a good prognosis of pellagra.

Comparison of MynxGrip vascular closure device and manual compression for closure after femoral access angiography: a randomized controlled trial: the closure devices used in every day practice study, CLOSE-UP III trial

BackgroundComplications related to femoral artery access for coronary angiography (CAG) is a safety concern. Vascular closure devices (VCDs) have been developed to reduce the rate of complications after femoral artery access. We compared the safety and efficacy of the MynxGrip VCD versus manual compression (MC) after femoral access CAG in a randomized controlled trial.MethodsThe study was a randomized, single center, non-blinded, two-arm non-inferiority trial. The study was stopped prematurely because of low inclusion rate.ResultsWe randomized 869 patients to closure with the MynxGrip VCD or MC and 865 entered analyses. The incidence of the primary endpoint of major adverse vascular events (MAVE) after 30 days was 1.2% in the MynxGrip group and 0% in the MC group (p = 0.06). The median time to hemostasis was 4 [3:5] minutes and 10 [7:11] minutes in the MynxGrip group and MC group, respectively (p < 0.0001). The corresponding median times to mobilization was 73 [65:87] minutes and 76 [70:88] minutes (p = 0.01).ConclusionsMAVE was rare after closure of femoral arterial access by both the MynxGrip VCD and MC. We found a numerical difference in favour of MC but this did not reach statistical significance. Time to hemostasis was shorter in the MynxGrip group when compared to the MC group.Trial registrationThe study was approved by the local medical ethics committee and registered at clinicaltrials.org (ClinicalTrials identifier: NCT02237430 11/09/2014).

Viability of Chimeric Antigen Receptor T Cell Therapy in Latin America

Introduction: Treatment of diffuse large B cell lymphoma (DLBCL) may be a challenge for Latin American countries. Thus, novel strategies to reduce the economic burden of oncological care are necessary. In Brazil, the DLBCL annual incidence is approximately 6.000 cases, among which 30% will relapse or become refractory (R/R). In this scenario, the limited access to the new therapies reinforce the need to develop new local technologies and improve research initiatives. Here we report the development and clinical application of a Brazilian platform to manufacture genetically modified T-cells to treat patients with R/R leukemia and lymphomas, which may also help reverse the poor prognosis of these patients in low and middle-income countries. Patients and Methods: All patients were referred to our center to consider compassionate use of anti-CD19 CAR-T cell therapy. The treatment was authorized by the local medical ethical committee. Once patients were deemed to be eligible for CAR-T, they were scheduled for lymphopheresis and the cells were processed and cryopreserved. During the manufacturing process and after completion of lymphophersis, all three patients received bridging therapy. Prior to infusion of CAR-T, patients were given lymphodepletion chemotherapy with cyclophosphamide and fludarabine for 3 days. Patients were monitored daily for the occurrence of cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS), which were graduated according to the criteria of the American Society for Transplantation and Cellular Therapy. These treatments were only available because we developed a Brazilian platform to manufacture genetically modified T-cells. Firstly, we developed and validated in vitro and in vivo anti-CD19 CAR T cell expression, expansion, and cytotoxicity. Secondly, in-house lentiviral good-manufacturing practice (GMP) protocols were established for clinical purposes. Thirdly, we upscaled the manufacturing process into the GMP facility originally developed for MSCs and adapted it to genetically modified T-cells. Finally, in-house procedures to deliver anti-CD19 CAR T cells for clinical use were established according to the Brazilian Health Regulatory Agency (ANVISA) policies. Once these steps were implemented, we were able to treat the first three patients of a patient with CAR-T cells produced in Latin America. Results: Two patients presented CAR-T cell expansion after the procedure (Figure 1). Within thirty days after the infusion one patient achieved complete response, one had partial response and one was not evaluated (Table 1). All patients had CRS and only one had ICANS. Two patients died, one from infection and other from intracranial hemorrhage due to domestic accident, — and — days after CAR-T cell infusion, respectively. Discussion: At least two of the reported patients presented improvement of their disease. The other one died before the expected response could have been evaluated. None of the patients died from complications related to manufacturing or infusion procedures, highlighting an acceptable safety profile of the platform. Although these are preliminary results, the CAR-T cell expansion profile, presence of systemic inflammatory response and lack of early disease progression suggest the treatment effectiveness. Conclusion: Apart from all the scientific challenges, this experience highlights the feasibility to implement a viable and efficient CAR-T platform in middle-income countries. Besides, implementation of advanced cellular therapy can also contribute to enhancing the quality of other cellular therapies. [Display omitted] DisclosuresGuerino-Cunha: Novartis: Other: Speaker; BMS: Other: Speaker; Janssen: Other: Speaker. Calado: Instituto Butantan: Consultancy; Alexion Brasil: Consultancy; Team Telomere, Inc.: Membership on an entity's Board of Directors or advisory committees; Novartis Brasil: Honoraria; Agios: Membership on an entity's Board of Directors or advisory committees; AA&MDS International Foundation: Research Funding.