Prospective Open-label Study Research Articles

Dynamics of peritoneal transport and cardiovascular outcomes of peritoneal dialysis treatment

BACKGROUND: Solute and water transport by peritoneal membrane has significant variation between patients; the function changes significantly over time. This affects treatment outcomes and requires individual approaches. AIM: To evaluate the influence of the baseline peritoneal transport state, its dynamics during peritoneal dialysis and the possibility of long-term outcomes modification. MATERIALS AND METHODS: The dynamics of peritoneal transport of solutes (in peritoneal equilibrium test, PET) and water (in mini-PET) was evaluated in a prospective interventional open-label study with historical control among 96 unselected consecutive patients admitted in three dialysis centers with unified program of peritoneal membrane monitoring and protection. RESULTS: Compared to the matched standard arm, the increase in peritoneal solute transport was significantly slower (by 9.5%) in the observation group. Ultrafiltration in classical PET decreased more slowly (by 28%). At baseline ultrafiltration was satisfactory (the proportion of the patients with ultrafiltration less 400 ml was 7.6%); water transport by small pores did not decrease (−1.1 ± 5.9 ml/year), and the decrease in total ultrafiltration (by 32.1 ± 8.2 ml/year) was due to a decrease in free water transport (by 29.9 ± 7.6 ml/year). Negative dynamics of free water transport was associated with total glucose load and with monthly glucose load greater than 2.68 kg/month. More than one case of peritonitis was associated with a more rapid decline in free water transport. The comorbidity increased in 34 of 96 patients, with median first/last scores of 5 (4–6) and 6 (4–7) points; (Wilcoxon Z = −5.423; p 0.001). When analyzed separately by peritoneal transport category, a significant worsening of the comorbidity index was observed only for high average and high transporters (Z = −2.754, p = 0.006 and Z = −3.357, p = 0.001, respectively). CONCLUSIONS: The interaction between peritoneal transport, primarily free water transport, and cardiovascular disease is certainly two-way: deterioration of water balance due to loss of effective ultrafiltration leads to volume overload and progression of cardiovascular disease. On the other hand, cardiovascular disease contributes to peritoneal membrane damage. The most sensitive monitoring of interventions effectiveness in membrane protection and preventing cardiovascular disease progression is the separate measuring of water transport through small pores and ultrapores, which simultaneously reveals a feature of progressive peritoneal fibrosis, a potential precursor of encapsulating peritoneal sclerosis.

Cardiac transthyretin amyloidosis in patients with conduction system disease

Abstract Background/Introduction Cardiac amyloidosis (CA) is characterized by extracellular deposition of misfolded proteins in the heart. The data suggest that cardiac amyloidosis is underappreciated as a cause of common cardiac diseases or syndromes. More than 98% of currently diagnosed cardiac amyloidosis result from fibrils consisting of monoclonal immunoglobulin light chains (AL) or transthyretin (ATTR). The natural history of ATTR cardiomyopathy commonly includes both the conduction system disease and arrhythmias, which may occur years before the onset of heart failure. Conduction abnormalities are commonly encountered among patients with CA and constitute an important cause of morbidity and mortality. Most reports agree that pacemakers are most common in wild type ATTR-CA, followed by hereditary ATTR-CA and, finally, AL-CA. Purpose As unexplained LV wall thickness ≥ 12 mm is a screening sign of possible cardiac ATTR, systematicscreening for CA in patients requiring permanent pacemakers with unexplained LV wall thickness of ≥ 12 mm seems to be rational and could possibly lead to early diagnosis of cardiac ATTR. To the best of our knowledge, the usefulness of such screening has not been investigated before. This project, therefore, aims to determine the prevalence of cardiac ATTR and its subtypes in this preselected group, and to propose the most suitable battery of diagnostic procedures for this purpose. Methods Population to be tested: Consecutive patients ≥50 years referred for permanent pacemaker implantation with unexplained LV wall thickness ≥12 mm determined by echocardiography. The research protocol was that of an open-label prospective study. Biochemistry samples including serum troponin I and NT-proBNP were collected before pacemaker implantation. All patients were screened for ATTR-CA according to the recommendations of the Position statement of the ESC Working group on myocardial and pericardial diseases. Tc-DPD scintigraphy scan served as a gold standard for determining the diagnosis of cardiac ATTR. Results Out of 100 consecutive patients meeting inclusion criteria, 15 % suffered from amyloidosis (12 patients were diagnosed with ATTR and 3 with AL cardiac amyloidosis). Table 1 shows a variety of parameters, many of which differed between patient groups with and without amyloidosis, confirming the wide range of parameters significantly associated with cardiac amyloidosis; our ongoing research in this field could lead to the development of a scoring system for detection of cardiac amyloidosis. Conclusions The prevalence of cardiac amyloidosis in the investigated group was 15 %. Systematic screening for ATTR in patients with unexplained LV wall thickness ≥ 12 mm requiring permanent pacemaker implantation seems to be rational and could possibly lead to an earlier diagnosis of cardiac amyloidosis, especially ATTR.

Juvenile Dermatomyositis: Updates in Pathogenesis and Biomarkers, Current Treatment, and Emerging Targeted Therapies.

Juvenile dermatomyositis is a rare systemic inflammatory autoimmune disease involving muscle, skin, and vessels. Most patients do not fully respond to initial therapy, instead having a chronic refractory or polycyclic disease course. Pathogenesis is not completely understood, but immune cell dysregulation, particularly of B cells, mitochondrial dysfunction, changes in neutrophils and neutrophil extracellular traps (NETs), and increased type I and type II interferon (IFN) signaling have been described. There are limited randomized controlled trials of drugs in juvenile dermatomyositis (JDM), and treatment is largely based on lower-quality data such as case series, retrospective studies, and open-label prospective studies. These data have been compiled into expert recommendations or consensus treatment plans, which help guide therapy. While initial therapy is more standard with most including corticosteroids (high-dose oral and/or pulse intravenous methylprednisolone) and methotrexate, for refractory patients, guidelines are more varied with multiple options or combinations, including biologic therapies. There is a clear need for more efficacious and personalized therapy in JDM. Emerging treatment options worthy of further study in JDMinclude targetingIFN-signaling (JAK, IFNAR1, IFN beta),B-cells (CD20, CD19, BAFF, TACI, CD38, BCMA)including Chimeric Antigen Receptor (CAR)-T cell therapy, mitochondrial dysfunction, and NETs.

Perfusion index as an early predictor of hypotension during advanced oncothoracic operations (pilot study)

Introduction. Current standards of intraoperative monitoring significantly reduce the response time to a decrease in blood pressure, but do not include methods for predicting changes in hemodynamics to avoid the effects of systemic hypoperfusion.The objective was to evaluate the usefulness of determining the perfusion index for predicting the development of hypotension and its earlier correction during advanced oncothoracic operations.Materials and methods. A prospective open-label observational study was conducted, which included 100 patients who underwent elective oncothoracic surgery. Standard monitoring was established, as well as continuous monitoring of the perfusion index. The perfusion index value was recorded immediately before induction. The patients were divided into 2 groups: in the 1st group (n = 37), patients experienced a decrease in blood pressure, requiring vasopressor support; in the 2nd group (n = 63), no vasopressor support was required.Results. A moderate linear relationship was revealed with a correlation coefficient (r) equal to (–0.68), p < 0.001, and a strong non-linear relationship with a coefficient (ρ) equal to (–0.95), p < 0.001. To identify the relationship model, polynomial regression analysis was performed. A prognostic formula for the use of vasopressors was calculated depending on the preoperative level of perfusion index. At the next stage, a classification tree for analyzing the data array was used. The entire d data array (n = 100) is randomly divided into training (n = 70) and test samples (n = 30). It was revealed that hypotension requiring vasopressor support occurred in patients whose initial perfusion index was ≤ 2.85. ROC analysis determined an AUC of 0.952 (95% CI: 0.888–1.016).Conclusion. A low PI value before induction of anesthesia during advanced oncothoracic operations can be used to monitor the functional activity of the autonomic nervous system and predict intraoperative hypotension. Patients with a baseline PI ≤ 2.85 have a higher risk of developing hypotension during advanced oncothoracic surgery compared with those with a baseline PI ≥ 2.85. The effectiveness of the method in patients with concomitant pathologies has not been tested.

The effectiveness of the synbiotic Maxilac<sup>®</sup> for the new coronavirus infection after antibacterial therapy

The new coronavirus infection (COVID-19) that emerged in 2019 is a infection caused by the SARS-CoV-2 virus. Although SARS-CoV-2 predominantly affects the respiratory system, numerous studies suggest significant gastrointestinal involvement in COVID-19, particularly in children. Aim. To evaluate the effect of the synbiotic Maxilac® in children with COVID-19 after antibacterial therapy (ABT). Materials and methods. A clinical post-approval open-label observational prospective single-center study with minimal intervention was conducted. The microbiome of children with COVID-19 was studied. Twelve children with COVID-19 complicated by a bacterial infection (pneumonia, sinusitis, otitis) were included, receiving ABT and then taking the synbiotic Maxilac® for 4 weeks. Patient data were collected: symptoms, medical history, clinical status, study of intestinal microbiota (IM) by 16S sequencing, stool test for zonulin, and review of drug therapy. The material was sampled in patients with COVID-19 at 3 time points: at the time of acute COVID-19 disease, at the time of recovery from COVID-19, and 4 weeks after starting the synbiotic therapy. Results. The administration of the synbiotic Maxilac® to patients who received ABT for bacterial complications of COVID-19 relieves clinical gastroenterological symptoms, prevents the development of dysbiosis, and normalizes intestinal permeability. The results indicated significant changes in IM after ABT in complicated COVID-19 and the normalizing effect of synbiotic Maxilac® on IM during administration for 30 days. The synbiotic Maxilac® in the group of children with COVID-19 who received ABT had no side effects and was safe. Conclusion. Children with COVID-19, complicated by a bacterial infection, treated with ABT are recommended to receive the synbiotic Maxilac® for at least 30 days after recovery.

Assessment of Molecular Response to Treatment of Chronic Myeloid Leukemia at Kigali University Teaching Hospital of Kigali

Abstract Introduction/Objective Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative neoplasm that gives proliferation advantage to the granulocytes, it is one of the commonest chronic hematological malignancies and it is a burden to the world especially Rwanda. Since the introduction of Tyrosine Kinase Inhibitors (TKIs) especially the first line Imatinib in 2001, the outcomes of CML have been much improved and currently, in developed world, the life expectancy of patients with CML is almost the same as general population. However, it is not the case in developing world especially Rwanda due to limitation on access of all TKIs. The aim of this study is to assess molecular response on Imatinib of patients with CML. Methods/Case Report This was a one arm open label prospective cohort study that recruited 31 patients with CML and on Imatinib for at least three months and followed for 11 months. The clinical features at diagnosis and recruitment were captured from the hospitals filing systems and investigator’s own assessment at the time of recruitment respectively. Information was filled to a well-structured questionnaire. Lab results at the time of diagnosis was obtained from laboratories reporting systems. Samples for full blood count and BCR-ABL1/ABL1 were withdrawn from the patients at the time of diagnosis and they were run at University Teaching Hospital of Kigali (CHUK). Data analysis was performed using Statistical Package for the Social Sciences (SPSS 28) and South Texas Art Therapy Association (STATA 15.0). Results (if a Case Study enter NA) Better response according to European LeukemiaNet (ELN) defined as optimal response was found among only 38.7% and resistance to imatinib defined by ELN as Failure and warning was found in 45.2% and 16.1% respectively. The eleven months survival rate was 93.5% in which it is 85.7% among those in treatment failure group. Late presentation showed by presence of very high White Blood Cells above 100x109/L and massive splenomegaly at diagnosis, and poor adherence to Imatinib according to Morsiky Medication Adherence Scale (MMAS-8) are associated with poor molecular response to Imatinib. Conclusion CML is a serious disease especially to those who suffer from it; on time diagnosis, access to all available lines of TKIs and better follow up are crucial for patients with CML to access the same life expectancy as general population as it is in developed world.

Prevalence of iron deficiency anemia in exclusively breastfed infants after a 5-month iron supplementation

Iron deficiency anemia (IDA) is prevalent in exclusively breastfed (EBF) Thai infants. However, in Thailand, iron supplementation guidelines for EBF infants are not available. This prospective open-label study aimed to estimate the prevalence of IDA in 9-month-old EBF infants after receiving iron supplementation from 4 months of age until they consumed adequate iron-rich food. Forty-seven healthy, 4-month-old EBF infants were prescribed 1 mg/kg/day ferrous sulfate. Their complementary food records from 6 to 9 months were calculated for daily iron intake. Complete blood count and iron study were performed at 9 months of age. The results showed that the prevalence of IDA at 9 months was 6.4%. An employed caregiver and the male sex of the baby were significantly associated with iron deficiency. The food record revealed that the median daily iron intake was less than the Thai dietary reference intake recommendation. In summary, the prevalence of IDA in infants with 9 months of exclusive breastfeeding who received iron supplementation was lower than the background rate (25.7%) when iron was not prescribed. Most infants did not have adequate iron in complementary foods. Iron supplementation should be prescribed routinely during 4–9 months of age in healthy Thai EBF infants.

Efficacy of sublingual versus oral vitamin B12 supplementation for the treatment of vitamin B12 deficiency–A prospective randomised open label study

Efficacy of sublingual versus oral vitamin B12 supplementation for the treatment of vitamin B12 deficiency–A prospective randomised open label study

Ablation of Supraventricular Arrhythmias With as Low as Reasonably Achievable X-Ray exposure (AALARA): Results of Prospective, Observational, Multicenter, Multinational, Open-Label Registry Study on Real World Data Using Routine Ensite 3D Mapping During SVT Ablation.

The reduction of fluoroscopic exposure during catheter ablation of supraventricular arrhythmias is widely adopted by experienced electrophysiology physicians with a relatively short learning curve and is becoming the standard of care in many parts of the world. While observational studies in the United States and some parts of Western Europe have evaluated the minimal fluoroscopic approach, there are scarce real-world data for this technique and the generalizability of outcomes in other economic regions. The AALARA study is a prospective, observational, multicenter, and multinational open-label study. Patients were recruited from 13 countries across Central Eastern Europe, North and South Africa, the Middle East, and the CIS (Commonwealth of Independent States), with different levels of operator expertise using minimal fluoroscopic exposure techniques. Data on radiation exposure, procedural success, complications, recurrence, and quality of life changes were collected and analyzed. A total of 680 patients were enrolled and followed for 6 months. The majority were ablation naïve with the commonest arrhythmia ablated being typical AVNRT (58%) followed by Atrial Flutter (23%). Zero fluoroscopy exposure was observed in almost 90% of the cases. Fluoroscopy was most commonly used during the ablation phase of the procedure. We observed a high acute success rate (99%), a low complication rate (0.4%), and a 6-month recurrence rate of 3.8%. There was a significant improvement in the patient's symptoms and quality of life as measured by patient global assessment. The routine use of a 3D mapping system during right-sided ablation was associated with low radiation exposure and associated with high acute success rate, low complications, and recurrence rate along with significant improvement in quality of life. The data confirm the reproducibility of this approach in real-world settings across different healthcare systems, and operator experience supporting this approach to minimize radiation exposure without compromising efficacy and safety. NCT04716270.

The effectiveness and acceptability of systemic enzyme therapy in the complex treatment of vulvovaginitis caused by opportunistic microorganisms: Open-label single-center prospective comparative randomized study

Background. Vulvovaginal infections are the most common, studied, and still causing many questions. It has been established that the disturbance of the ratio of the vaginal microbiota components does not always lead to a disorder since the development and outcome of the disorder largely depend on the state of the macroorganism, including the state of its immune system. To date, the only method for assessing the state of local immunity is smear microscopy with counting leukocytes. An alternative to leukocyte counting is the assessment of immunological parameters (e.g., the transcriptional profile of cytokine genes). An integrated approach to assessing the state of microbiocenosis (the ratio of lactobacilli and opportunistic pathogens) and local mucosal immunity, considering the individual genetic characteristics of patients and microorganisms, makes it possible to optimize treatment methods for vaginitis. One of the ways to increase the effectiveness of treatment and prevention of the recurrence of infectious and inflammatory diseases in gynecology is systemic enzyme therapy based on the complex effect of a specially selected combination of plant and animal origin enzymes on key physiological and pathophysiological processes in the body. Aim. To study the clinical effect and the effect of combined therapy with an antibiotic and a medicinal product, including a complex of enzymes of plant and animal origin (Wobenzym) on the state of the vaginal microbiota, the expression of cytokine genes, and the recurrence rate in patients with bacterial vulvovaginitis. Materials and methods. An open-label, single-center, prospective, comparative, randomized study enrolled 88 patients according to inclusion criteria. After randomization of patients into 2 groups, the main group received combination therapy (clindamycin vaginal cream 2% and Wobenzym), and patients of the comparison group received standard therapy only (clindamycin vaginal cream 2%). Short-term and long-term endpoints were defined. The primary endpoints included the assessment of symptoms, the change over time of the number of leukocytes in Gram-stained smears, and the recurrence rate; the secondary endpoints were the study of the change over time of the inflammation index, the results of the assessment of the state of the vaginal microbiota by real-time quantitative polymerase chain reaction using the Femoflor 16 reagent kit and a microbiological study. Results. When used in combination, Wobenzym potentiates the antibacterial properties of clindamycin, reduces the inflammation index, promotes the growth of the normal microbiota of the vagina (Lactobacillus spp.), prevents the growth of opportunistic microorganisms and, as a result, prevents the recurrence of vulvovaginitis. Conclusion. The results support the use of combination therapy (antibiotic + Wobenzym) to improve the effectiveness of therapy and maintain normocenosis.

An Oral Botanical Supplement Improves Small Intestinal Bacterial Overgrowth (SIBO) and Facial Redness: Results of an Open-Label Clinical Study.

Small intestinal bacterial overgrowth (SIBO) is a common, yet underdiagnosed, gut condition caused by gut dysbiosis. A previous study has shown the potential of herbal therapy, providing equivalent results to rifaximin. The objective of this study was to assess how the use of an oral botanical regimen may modulate the gut microbiome, facial erythema, and intestinal permeability in those with SIBO. This was an open-label prospective study of adults that had lactulose breath test-confirmed SIBO. Participants received a 10-week oral supplementation of a Biocidin liquid tincture and GI Detox+. If participants were found to be non-responsive to treatment after 10 weeks with a persistently positive lactulose breath test, a third oral supplement, Olivirex, was administered for an additional 4 weeks. Lactulose breath tests were administered at baseline, weeks 6, 10, and 14 to assess for SIBO status. A high-resolution photographic analysis system was utilized to analyze changes in facial erythema. Stool sample collections and venipuncture were performed to analyze the gut microbiome and intestinal permeability. A total of 33 subjects were screened with breath testing, and 19 subjects were found to have SIBO. Three of the subjects withdrew during the screening period prior to baseline, and sixteen subjects enrolled. Four subjects dropped out after baseline. Hydrogen-dominant SIBO was the most common subtype of SIBO, followed by methane and hydrogen sulfide. The botanical regimen was most effective for hydrogen- and hydrogen sulfide-dominant SIBO, leading to negative breath test results at week 10 in 42.8% and 66.7% of participants, respectively. Compared to baseline, supplementation with the botanical regimen led to positive shifts in short-chain fatty acid-producing bacteria such as A. muciniphila, F. prausnitzii, C. eutectus, and R. faecis by 31.4%, 35.4%, 24.8%, and 48.7% percent at week 10, respectively. The mean abundance of Firmicutes decreased by 20.2%, Bacteroides increased by 30%, and the F/B ratio decreased by 25.4% at week 10 compared to baseline. At week 10, there was a trending 116% increase in plasma LPS/IgG (p = 0.08). There were no significant changes in plasma zonulin, DAO, histamine, DAO/histamine, LPS/IgG, LPS/IgA, or LPS/IgM. Facial erythema was not statistically different at week 6, but at week 10, there was a 20% decrease (p = 0.001) in redness intensity. Among the patients that extended to week 14, there was no statistical change in erythema. Supplementation with an antimicrobial botanical supplemental regimen may have therapeutic potential in hydrogen and hydrogen-sulfide subtypes of SIBO. Furthermore, the botanical supplemental regimen may reduce facial erythema, increase SCFA-producing bacteria, decrease the F/B ratio, and modulate markers of intestinal permeability.

Off-label letrozole for tubal pregnancy monotherapy is not an alternative to methotrexate: a prospective cohort study.

Inhibition of estradiol production by letrozole may interfere with physiological effects of progesterone necessary to maintain the pregnancy. Treatment of tubal pregnancy (TP) with letrozole would allow to avoid the disadvantages of methotrexate (MTX). The aim was to compare the effectiveness of letrozole with MTX in the management of TP. A prospective open-label cohort study was conducted among women with TP and increasing B-human chorionic gonadotropin (B-hCG) concentrations. MTX was administered in a single dose of 100 mg intravenously, while letrozole in a dose of 5 mg orally for 10 days. Blood parameters (B-hCG, hemoglobin, creatinine, urea, transaminases, bilirubin) were tested on days 0, 4 and 7. Out of 22 eligible women, 14 received MTX and received 8 letrozole. Mean age, lesion diameter, gestation age in the MTX vs letrozole arm were: 31 vs 32 years (p = 0.3), 13.2 vs 16.3 mm (p = 0.1), 7 + 1 vs 7 + 0 weeks (p = 0.6), respectively. In case of 4 women treated with letrozole and in 2 treated with MTX (4/8, 50% vs 2/14, 14.3%, p = 0.07) the treatment was unsuccessful. There were no significant differences in blood parameters on days 0, 4 and 7 between both arms, except for the increasing urea concentration in the letrozole arm (p = 0.01). Even though the results did not reach statistical significance, it is likely that a larger study sample would confirm the trend of letrozole being less effective. The results did not support the use of letrozole in the studied regimen as an alternative to MTX.

Treatment of Neuropsychiatric Symptoms in Alzheimer’s Disease with a Cannabis-Based Magistral Formulation: An Open-Label Prospective Cohort Study

Plain Language SummaryThere is a need for an alternative treatment to significantly improve NPS in AD and decrease the caregiver’s stress as well as the financial burden resulting from polypharmacy and institutionalization. Any promising treatment should be safe and reduce the risk of adverse effects. This study evaluated the efficacy of a CBD-rich oil in treating NPS in a cohort of 59 patients with AD over a follow-up of more than 1 year, with a specific focus on its impact on caregiver burden. The study showed a significant reduction in the NPI-Q severity and caregiver’s distress scores after 3 months of intervention, and sustained for up to 24 months of follow-up. Notably, the effectiveness was independent of age, sex, years with AD, type of acetylcholinesterase inhibitors, and NPI-Q severity score before CBD treatment. A low CBD dose and a slow dose titration improve tolerance. These results may indicate that alleviating NPS in people with AD facilitates daily caregiving and improves caregivers’ emotional and physical distress.

Postoperative Sedation in Free Microvascular Tissue Transfer in Head and Neck Cancer: A Comparison of Fentanyl and Morphine

Background and Aims: Head-and-neck cancer surgeries with microvascular free flap reconstruction require endotracheal tube retention for 24–48 h postoperatively. Many regimes have been used for analgesia and sedation. The efficacy of fentanyl and morphine for post-operative analgosedation was compared by evaluating the need for additional sedatives to achieve optimum sedation scores. The secondary objective included analgesia, haemodynamic stability and a re-exploration rate. Methods: This was an open-label prospective study. A sample size of 36 was calculated in each group with α = 0.05 and a power of 80% to detect a 50% difference between the groups. Ninety adult patients were allocated to receive either fentanyl (Group F) or morphine (Group M). The Richmond agitation sedation score, Behavioural pain scale score, requirement of rescue hypnotic drug, pulse rate, systolic and diastolic blood pressures and re-explorations were recorded postoperatively. Haemodynamic parameters and sedation were analysed by two-way repeated measures of analysis variances. Pain scores were analysed using the Chi-square test. Results: When titrating to optimal sedation, in Group M, more patients needed intravenous midazolam boluses (n = 42, 93.3%) as compared to Group F (n = 33, 73.3%) (P = 0.011). More subjects in Group M required propofol infusion (n = 15, 33.3%) than in Group F (n = 4, 8.9%) (P = 0.009). Mean behavioural pain scores were significantly higher in Group M (score 1: P = 0.005 and score 2: P =0.001). The difference in the mean systolic, diastolic blood pressure, pulse rate, respiratory rate and re-exploration rate between the two groups was statistically insignificant. Conclusion: For analgesia-based sedation of spontaneously breathing intubated patients after head-and-neck cancer reconstructive surgeries, fentanyl is more effective than morphine in terms of ease of titration, sedation quality and analgesia. Both are safe for post-operative sedation regarding haemodynamic stability, tube retention and maintenance of spontaneous respiration.

432. POSTOPERATIVE SAFETY AND TOLERABILITY OF INTRAMUSCULAR OCTREOTIDE IN PATIENTS WITH GASTROESOPHAGEAL CANCER: AN OPEN-LABEL PHASE 2 PILOT STUDY

Abstract Background Dietary peptides are believed to contribute to persistent weight loss following gastrectomy or esophagectomy due to cancer. Previous studies have suggested that this effect might be partially mitigated by octreotide. This study aims to investigate the safety and tolerability of intramuscular Sandostatin® LAR depot 10mg, including the frequency and nature of adverse events. It serves as a pilot study for future research aiming to comprehensively assess its effects. Methods A prospective open-label phase-2 study was conducted from November 2021 to June 2023. Twenty patients (10 undergoing gastrectomy, 10 undergoing esophagectomy) were enrolled. Patients received three doses of intramuscular Sandostatin® LAR depot 10mg at 7 days, 1 month, and 2 months post-surgery. All patients were evaluated at 7 days, 1, 2, 3, and 6 months post-surgery. The primary endpoint was safety, determined by the incidence and nature of adverse events, with no occurrence of serious or severe events defined as successful. Tolerability was defined as at the completion of the treatment protocol by at least 90% of patients. Secondary endpoints included weight loss (percent from baseline), Health-Related Quality of Life (assessed via EORTC-QLQ-C30 and OG25 at baseline, 1, 2, 3, and 6 months post-surgery), and the proportion of subjects requiring enteral nutrition via jejunostomy. Results The study protocol was completed by 95% of participants. No serious or severe adverse events were reported. Median weight loss at 6 months was 11% (3 months: 7%, 2 months: 4%, 1 month: 5%). Mean and median Global Quality of Life (part of EORTC-QLQ-C30) remained unchanged at 6 months compared to baseline (mean: 67.6 vs. 67.2; median 66.7 [25-100] vs 70.8 [16.7-100]). The percentage of subjects requiring enteral nutrition was 40%, 30%, and 15% at 1, 2, and 3 months respectively. Conclusion This pilot study suggests that Sandostatin® LAR depot was well tolerated and safe, with no serious or severe adverse events observed. Weight loss, Health Related Quality of Life, and the proportion of subjects requiring enteral nutrition were consistent with expectations. Future studies should consider a double-blinded randomized controlled design preferably with dose-response assessment for more robust investigation.

Left atrial appendage emptying velocity and left ventricular function as predictors of inotropic support in patients undergoing elective off-pump coronary artery bypass grafting

Abstract Background: Patients undergoing elective off-pump coronary artery bypass grafting (CABG) are at risk of hemodynamic instability, ischemia, arrhythmia, and dysfunction. These events need to be managed by pharmacological supports or relieving of mechanical obstruction (octopus) of the heart to maintain the hemodynamic stability. There is a paucity of data on the effect of left ventricular (LV) dysfunction on left atrial appendage (LAA) emptying velocity. We evaluated the relationship between LV function and LAA emptying velocity and requirement of inotropic support perioperatively. Materials and Methods: In this prospective open-label all-comer study, fifty patients undergoing elective off-pump CABG under general anesthesia, we measured LAA emptying velocity by pulsed wave Doppler and evaluated if it could predict the need for inotropes perioperatively. It is a case series of 50 patients without a comparator arm. We measured pulsed wave Doppler across the mitral valve leaflet and early mitral inflow velocity (Evel) and late mitral inflow velocity, tissue Doppler at the lateral annulus of the mitral valve (e’) and also calculated the ratio of Evel and e’. Need for inotrope in the intraoperative and postoperative period was captured perioperatively. Vasoactive-inotropic score (VIS) was calculated for all the patients. Results: The VIS was significant (P < 0.0001, with odds ratio of 131.6 and confidence interval of 95% (0.9–1). However, there was no significant correlation between ejection fraction (EF) and VIS (P = 0.87). In patients with the need of inotropes, LAA emptying velocity was significantly increased in the postgrafting period as compared to the pregrafting period (75.64 cm/s vs. 57.9 cm/s, P < 0.001). Conclusion: The assessment of LAA emptying velocity value was a useful predictor of the need of inotropic support during off-pump surgery, especially during Obtuse marginal and Ramus grafting. This study paves the need of larger case–control studies to validate the findings.

Immunogenicity and Safety of SARS-CoV-2 Protein Subunit Recombinant Vaccine (IndoVac®) as a Heterologous Booster Dose against COVID-19 in Indonesian Adolescents.

Adolescents are vulnerable to Coronavirus disease 2019 (COVID-19) infections; thus, their antibodies should be maintained above the protective value. This study aimed to evaluate the immune response and safety to the SARS-CoV-2 protein subunit recombinant vaccine (IndoVac®) as a heterologous booster dose against COVID-19 in Indonesian adolescents. This open-label prospective intervention study enrolled 150 clinically healthy adolescents aged 12-17 years who had received complete primary doses of the CoronaVac® vaccine from Garuda Primary Care Centres in Bandung City. The result of immunogenicity was presented with a 95% confidence interval (CI) and analyzed with t-tests from 14 days and 3, 6, and 12 months. The neutralizing antibody geometric mean titers (GMTs) (IU/mL) at baseline and 14 days after booster dose were 303.26 and 2661.2, respectively. The geometric mean fold rises (GMFR) at 3, 6, and 12 months after booster dose were 6.67 (5.217-8.536), 3.87 (3.068-4.886), and 2.87 (2.232-3.685), respectively. Both the neutralizing antibody and IgG antibody were markedly higher in the adolescents than in the adults at every timepoint. The incidence rate of adverse effects (AEs) until 28 days after booster dose was 82.7%, with a higher number of local events reported. Most reported solicited AEs were local pain followed by myalgia with mild intensity. Unsolicited AEs varied with each of the incidence rates < 10%, mostly with mild intensity. Adverse events of special interest (AESI) were not observed. At the 12-month follow-up after the booster dose, four serious adverse events (SAEs) not related to investigational products and research procedures were noted. This study showed that IndoVac® has a favorable immunogenicity and safety profile as a booster in adolescents and that the antibody titer decreases over time.

Comparing Skin and Serum Testing to Direct Challenge Outcomes in Children With β-Lactam Allergies

BackgroundThere is a scarcity of prospective studies investigating the relative roles of skin prick and intradermal testing, serum-specific Immunoglobulin E, and extended oral challenges in diagnosing children with reported beta-lactam allergies. ObjectiveTo determine the sensitivity and specificity of skin testing and serum-specific Immunoglobulin E in children with beta-lactam allergies, with immediate and non-immediate historic reactions. MethodsFour hundred children with parent-reported beta-lactam allergies were recruited into an open-label prospective study. Detailed allergy histories were collected. Those with medically observed and documented histories of anaphylaxis, requiring epinephrine, or SCARs were excluded. In total, 380 children underwent all testing modalities and a direct provocation test. Each child was followed up for a minimum of three years. ResultsTrue allergy in children was uncommon, 8·3% reacted to the direct provocation challenge or the 5-day extended oral provocation challenge. Children reporting cephalosporin allergy or a reaction within one year were more likely to react to direct provocation testing. The sensitivity, specificity, and positive predictive value of skin testing was 12·5%, 98·8% and 20·0% for direct challenge outcomes, 4·76%, 99·0% and 25·0% for extended challenge outcomes, and 6·9%, 99·0% and 40·0% for both challenges combined. Follow-up investigations revealed that 5·7% of children had a mild repeat reaction and 2·7% continued to avoid the culprit despite successful delabeling. The relabeling rate for children readmitted to hospital was 15% with the relabeing being unfounded. ConclusionGenuine beta-lactam allergies were rare, with over 90% of children effectively delabeled. Skin and serum-specific Immunoglobulin E testing did not aid the diagnosis of beta-lactam antibiotic allergy in children, regardless of medical history. Extended oral challenges proved valuable in confirming allergies and boosted parental confidence.

A randomized controlled trial analyzing nonthermal atmospheric plasma for the treatment of verruca vulgaris in pediatric patients

BackgroundVerruca vulgaris (VV) is a common viral disease in children. Treatment options are often not well-tolerated in children due to pain or adverse effect risk. Nonthermal atmospheric plasma (NTAP), which generates reactive oxygen/nitrogen species, is well-tolerated and without adverse effects. ObjectiveDetermine efficacy of NTAP as compared to standard of care (SOC) therapy for VV in children. MethodsThis prospective open-label study randomized lesions 1:1 to receive NTAP or SOC (cryotherapy). Patients were treated at 4-week intervals for a maximum of 3 treatments. They were evaluated four weeks post-final treatment for sustained response. Primary outcome was lesion response. Results112 VV lesions in 14 patients were enrolled. Patients were mostly white (92.9%) males (71.4%) with mean age of 9.5 [±2.5] years. Responses of SOC- and NTAP-treated lesions respectively included: no response (5.4%, 7.1%); partial response (33.9%, 41.1%); and complete resolution (60.7%, 51.8%; p-value=0.679). Patients were more likely to report pain in SOC lesions post-treatment (p-value<0.001). No significant adverse events (AEs) occurred. LimitationsLimitations include single-site, maximum of three treatments, and short post-treatment follow-up. ConclusionNTAP is an efficacious, safe intervention for treatment of VV in children.

Phase I Study of Intravitreal Injection of Autologous CD34+ Stem Cells from Bone Marrow in Eyes with Vision Loss from Retinitis Pigmentosa

PurposeTo evaluate the feasibility and safety of intravitreal injection of autologous CD34+ stem cells from bone marrow (BMSCs) in eyes with vision loss from retinitis pigmentosa (RP). DesignPhase I prospective open-labeled single center study. ParticipantsSeven eyes (7 patients) with RP with best corrected visual acuity (BCVA) of 20/100 to 20/400 or visual field constriction to within 10 degrees. MethodsA comprehensive exam with ETDRS BCVA, macular optical coherence tomography, perimetry, fluorescein angiography was performed at baseline, 1 to 3 months, and 6 months after study treatment. Bone marrow aspiration, isolation of CD34+ BMSCs under Good Manufacturing Practice (GMP) conditions, and intravitreal cell injection were performed on the same day. The CD34+ cells were isolated from bone marrow using a Ficoll gradient and the Miltenyi CliniMACs system. Isolated CD34+ cells were released for clinical use if viability, sterility and purity met the release criteria accepted by the Food and Drug Administration for this clinical study. Main Outcome MeasuresNumber of CD34+ cells isolated for injection and adverse events associated with study treatment during follow-up. Secondary outcome measures are changes in BCVA and perimetry. ResultsAll isolated CD34+ cells passed the release criteria. A mean of 3.26 + 0.66 million viable CD34+ cells (range 1.6 to 7.05 million) were injected intravitreally per eye. No adverse event was noted during the study follow-up except for one participant who was noted with transient cells in the anterior chamber with mild elevation in intraocular pressure at 18 hours after study injection which normalized by 24 hours. BCVA remained within 2 lines of baseline or improved in all participants at 6 months follow-up. Perimetry was stable or improved in all eyes during study follow-up except one eye with transient improvement at 1 month and worsening of both eyes at 6 months. ConclusionIntravitreal injection of autologous CD34+ BMSCs is feasible and appears to be well tolerated in eyes with vision loss from RP. A larger randomized prospective study would be needed to evaluate further the safety and potential efficacy of this cell therapy for vision loss associated with RP.