Active Treatment Research Articles

Real-World Effectiveness of Cladribine for Patients with Multiple Sclerosis: A Sicilian Multicentric Experience (Rewind Study).

Cladribine tablets are a highly effective option for the treatment of relapsingremitting multiple sclerosis (RRMS). The study aims to evaluate the effectiveness of cladribine in a real-world setting. This prospective real-world study consecutively screened all RRMS patients from seven different MS centers in Sicily (Italy) who completed the 2-year treatment course of cladribine tablets in the period between 11th March 2019 and 31st October 2021. Data about Expanded Disability Status Scale (EDSS), relapses, previous treatments, adverse events (AEs) and magnetic resonance imaging (MRI) were collected. Patients who were previously treated with other DMTs were further stratified into moderately active treatment (MAT) and highly active treatment (HAT) patients. A total of 217 patients (70% women, with a mean age of 38.4 ± 11.3 years) were enrolled. Fifty patients (23.0%) were naïve to treatment and 167 (77%) switched from other disease modifying therapies. After the second year of treatment, about 80% were EDSS progression free, 88% remained relapse-free at T24, and 48% of patients were MRI activity-free. Kaplan Meier analyses showed significant differences between MT and HAT in terms of time to first clinical relapse (HR: 2.43, IC 1.02- 5.76; p = 0.04), time to the first new T1-gadolinium enhancing lesion (HR: 3.43, IC 1.35-8.70; p = 0.009) and time to MRI worsening (HR: 2.42, IC 1.15-5.09; p = 0.02). This study confirmed that cladribine is an effective treatment for MS, particularly in naïve patients and those who have switched from MATs.

Carbon nanotube incorporated quaternized lignin-based loose nanofiltration membrane toward dye/salt separation

Lignin is a promising raw material for membrane fabrication due to its abundant oxygen-containing functional groups, branched molecular structure, and high abundance in the botanic field. In this report, polydopamine (PDA) coated carbon nanotubes (PCNTs) are synthesized. Then, a PCNT-incorporated lignin-based loose nanofiltration membrane is fabricated using quaternized lignin (QL) as a raw material, triphosgene (TP) as a crosslinker, and PCNTs as nanoadditive by interfacial polymerization. The results show that the PCNTs uniformly distribute in the QL-based separation layer providing quick diffusion paths for water molecules and salt ions. The coated PDA layer improves the chemical compatibility between the PCNTs and the separation layer. The incorporated PCNTs optimize the membrane microstructure and elevate the pure water permeance to 45.5 LMH bar-1. The membrane exhibits high rejections to various dyes (> 90%) and high salt permeation (> 90%), demonstrating an excellent dye/salt separation performance. Moreover, it has satisfactory capabilities for resisting dye adsorption and fouling, and its separation capability also has good tolerances to the acid, alkali, and active chlorine treatments. The quaternary ammonium ions and hydrophilic surface endow the membrane with favorable bactericidal property (99.3%) and bacteria-adhesion resistance. Besides, TP is a better crosslinker than trimesoyl chloride for optimizing the membrane microstructure and crosslinking degree in terms of dye/salt separation.

Hypoxia A Typical Target in Human Lung Cancer Therapy.

Lung cancer (LC) is the leading cause of cancer-related death globally. Comprehensive knowledge of the cellular and molecular etiology of LC is perilous for the development of active treatment approaches. Hypoxia in cancer is linked with malignancy, and its phenotype is implicated in the hypoxic reaction, which is being studied as a prospective cancer treatment target. The hypervascularization of the tumor is the main feature of human LC, and hypoxia is a major stimulator of neo-angiogenesis. It was seen that low oxygen levels in human LC are a critical aspect of this lethal illness. However, as there is a considerable body of literature espousing the presumed functional relevance of hypoxia in LC, the direct measurement of oxygen concentration in Human LC is yet to be determined. This narrative review aims to show the importance and as a future target for novel research studies that can lead to the perception of LC therapy in hypoxic malignancies.

Natural History of Untreated Idiopathic Sudden Sensorineural Hearing Loss.

Although corticosteroids and other treatments for idiopathic sudden sensorineural hearing loss (ISSNHL) have been described, understanding its prognosis without intervention provides valuable information for patient management. The objective of this study is to provide a comprehensive, quantitative statistical analysis of the natural history of untreated idiopathic sudden sensorineural hearing loss (ISSNHL). A systematic review and meta-analyses. Two independent searches of PubMed, Scopus, Web of Science, and Cochrane Library databases up to June 30, 2022, were performed. Adults with idiopathic sudden sensorineural hearing loss who received placebo or were untreated and had audiometric outcome measures in all study types were reviewed. These data indicative of the natural history of ISSNHL were analyzed, as were study characteristics related to risk of bias. Heterogeneity as assessed via I2 and random effects analyses were performed. Six studies meeting the inclusion criteria yielded 319 untreated patients whose natural history could be assessed. Heterogeneity among studies was moderate, with a variety of reported outcomes. A hearing improvement of at least 30 dB HL was observed in 36% (95% CI 0.28-0.44) of untreated patients, and of at least 10 dB HL was observed in 70% (95% CI 0.57-0.82) of untreated patients at 3 months. The mean hearing gain among untreated patients was 24.0 dB HL (95% CI 2.65-45.37) at 2-3 months. The observed natural history of ISSNHL suggests that patients can regain some hearing without active treatment. In the absence of future studies collecting prospective natural history data from untreated or placebo-treated ISSNHL patients, the data presented here provide the best available historical control data for reconsideration of results in past ISSNHL studies, as well as a roadmap for design and interpretation of future ISSNHL treatment clinical trials. Furthermore, knowing there is a statistically significant mean hearing gain of 24.0 dB HL in the untreated/placebo group provides an ethical basis for future placebo study of ISSNHL. The current status on ISSNHL management calls for a multi-institutional, randomized, double-blind placebo-controlled trial with validated outcome measures to provide science-based treatment guidance. Laryngoscope, 2024.

Vertically aligned ReS2 on MOF deorived CoS2–C hybrid as core-shell catalyst for promoting overall water splitting

The rational design of a core-shell structured electrocatalyst is important to improve the efficiency of electrocatalytic hydrogen production through water splitting. Herein, the catalyst is composed of rhenium disulfides (ReS2) vertically grown on cobalt sulfides/carbon hybrid by hydrothermal and activation treatment (CoS2–C@ReS2/CFP). The core-shell structure is constructed by sulfurizing the cobalt-based metal-organic framework, preventing the restacking of the ReS2 nanosheet, exposing more active sites, and facilitate electrolyte ion diffusion. Moreover, the CoS2–C@ReS2/CFP catalyst shows exceptional performance during the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) process in an alkaline electrolyte. At ·10 mA cm−2, the overpotentials of the CoS2–C@ReS2/CFP catalyst are 85 and 257 mV during the HER and OER processes with the small Tafel slope, low charge transfer resistance and exceptional catalytic stability. The combination of the CoS2 core and ReS2 shell is designed to adjust the adsorption energy of water molecules, promoting water dissociation, and enhancing the catalytic activity of CoS2–C@ReS2/CFP catalyst. This work provides an efficient strategy for developing the core-shell structured catalysts, potentially advancing the practical application into water splitting for hydrogen production.

Implementation of near zero fluoroscopy in supraventricular tachycardia ablation procedures: a single center experience

Abstract Background Supraventricular tachycardia (SVT) are common cardiac arrhythmias, and catheter ablation has proven to be a very effective treatment, but exposes patients and healthcare providers to radiation. "Near Zero Fluoroscopy" (NZF) techniques, utilizing advanced imaging, aim to reduce radiation exposure while maintaining efficacy. Purpose To present an analysis of near-zero fluoroscopy in SVT ablation procedures, in a tertiary center, since its implementation. Methods We prospectively enrolled 446 SVT-diagnosed patients for this study. All of them underwent NZF procedures using the same specific 3D mapping system, between January/19 and December/22. Patients with atrial fibrillation or macroreentrant atrial tachycardias or when a different mapping system was used, were excluded. All patients provided informed consent. Results Our population had 266 (60%) females and a median age of 39 (IQR 24-51) years. AVNRT was the most frequent arrhythmia documented (229 cases, 51%), followed by Accessory Pathways (AP) (201 cases, 45%) and focal atrial tachycardia (AT) (16 cases, 4%). The ablation success rate was high (405/418, 97%). There was no ablation attempt in 12 patients (9 APs and 3 ATs) and the unsuccessful ablations (7/418 cases, 1,67%) were APs. Overall, fluoroscopy time was 1.1 minutes (IQR 0-2.6). There was no statistically significant difference in the distribution of fluoroscopy time among the types of SVT based on the Kruskal-Wallis test (p 0.14). Observing trends of fluoroscopy use through time, we acknowledge the presence of a learning curve, leading towards shorter times of X-ray during procedures along the first 3 years of implementation of a near-zero strategy. Median times (IQR) of fluoroscopy were as follows: 2019 – 2.25 (0.45-3.4) min; 2020 – 1 (0-2.5) min; 2021 – 0 (0-1.9) min; 2022 – 0.55 (03.05) min. (see BoxPlot) Pairwise comparisons using the Wilcoxon rank-sum test with continuity correction revealed statistically significant differences in medians between all pairs of years, with p-values adjusted for multiple comparisons using the Bonferroni method (p<0.01). In 2022, fluoroscopy time increased, when compared to 2021. We believe this finding can be explained by the fact that in 2022, our department received a new fellow and a young EP consultant (coming from a center where NZF was not the standard for SVT ablation), both being in the lab on a daily basis, explaining this upward trend in fluoroscopy time. There were no acute complications requiring hospital admission or active treatment. Conclusion Our results emphasize the potential of near-zero fluoroscopy techniques to enhance safety and reduce radiation exposure while maintaining a high level of procedural efficacy in the treatment of SVT cases. Absence of acute complications highlighted the safety of these approaches.

Predicting Unplanned Readmissions to the Intensive Care Unit in the Trauma Population.

Background: Unplanned readmission to intensive care units (UR-ICU) in trauma is associated with increased hospital length of stay and significant morbidity and mortality. We identify independent predictors of UR-ICU and construct a nomogram to estimate readmission probability. Materials and Methods: We performed an IRB-approved retrospective case-control study at a Level I trauma center between January 2019 and December 2021. Patients with UR-ICU (n = 175) were matched with patients who were not readmitted (NR-ICU) (n = 175). Univariate and multivariable binary linear regressionanalyses were performed (SPSS Version 28, IBM Corp), and a nomogram was created (Stata 18.0, StataCorp LLC). Results: Demographics, comorbidities, and injury- and hospital course-related factors were examined as potential prognostic indicators of UR-ICU. The mortality rate of UR-ICU was 22.29% vs 6.29% for NR-ICU (P < .001). Binary linear regression identified seven independent predictors that contributed to UR-ICU: shock (P < .001) or intracranial surgery (P = .015) during ICU admission, low hematocrit (P = .001) or sedation administration in the 24hours before ICU discharge (P < .001), active infection treatment (P = .192) or leukocytosis on ICU discharge (P = .01), and chronic obstructive pulmonary disease (COPD) (P = .002). A nomogram was generated to estimate the probability of UR-ICU and guide decisions on ICU discharge appropriateness. Discussion: In trauma, UR-ICU is often accompanied by poor outcomes and death. Shock, intracranial surgery, anemia, sedative administration, ongoing infection treatment, leukocytosis, and COPD are significant risk factors for UR-ICU. A predictive nomogram may help better assess readiness for ICU discharge.

Foveal atrophy in patients with active central serous chorioretinopathy at first presentation: characteristics and treatment outcomes

Background/aimsThis study aimed to investigate the clinical characteristics and treatment outcomes of patients with active central serous chorioretinopathy (CSC) and foveal atrophy.MethodsPatients diagnosed with active idiopathic CSC using multimodal imaging...

#1371 Cutaneous manifestations in hemodialysis patients and assessment of the changes in quality of life after 12 weeks of treatment by dermatologist

Abstract Background and Aims Cutaneous manifestations are frequently found in end-stage kidney disease (ESKD) and disturbing quality of life of patients under maintenance hemodialysis. Even dialysis patients frequently visit the hospital, they do not receive active dermatologic care. The aim of this study is to assess the cutaneous manifestations of hemodialysis patients and to investigate changes in quality of life before and after active treatment by dermatologists. Method A 12-weeks, prospective study was conducted with two centers of hemodialysis. Patients in one center received dermatologic intervention and patients in another center received supportive management by nephrologist. Patients scored their quality of life using questionnaires, Dermatology Life Quality index (DLQI) and Skindex-29, on start of study and 12 weeks later. Patients were matched between two groups according to propensity score. Simple and multiple linear regression were used to identify associations of dermatologic treatment and improvement of quality of life. Results A total of 120 patients from two dialysis centers were included in this study, of whom 65 as intervention group and 55 of control group. About 93.8% of patients had dermatologic manifestations, and pallor and xerosis accounted for the most proportion. Improvement in quality of life as assessed by the DLQI were confirmed after 12 weeks in overall population. However, the active intervention by a dermatologist did not affect the improvement of quality of life significantly. Conclusion Patients treated with dermatologic intervention by dermatologist had not improved in quality of life compared with control group. It is important for a nephrologist to carefully assess skin issues of patients with ESKD and provide the best possible treatment.

A Randomized, Double-Blind, Placebo-Controlled Clinical Trial on the Effect of a Dietary Supplement Containing Dry Artichoke and Bergamot Extracts on Metabolic and Vascular Risk Factors in Individuals with Suboptimal Cholesterol Levels

The aim of this study was to assess whether dietary supplementation with a nutraceutical blend comprising extracts of bergamot and artichoke—both standardized in their characteristic polyphenolic fractions—could positively affect serum lipid concentration and insulin sensitivity, high-sensitivity C-reactive protein (hs-CRP), and indexes of non-alcoholic fatty liver disease (NAFLD) in 90 healthy individuals with suboptimal cholesterol levels. Participants were randomly allocated to treatment with a pill of either active treatment or placebo. After 6 weeks, the active-treated group experienced significant improvements in levels of triglycerides (TG), apolipoprotein B-100 (Apo B-100), and apolipoprotein AI (Apo AI) versus baseline. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high density lipoprotein cholesterol (Non-HDL-C), and hs-CRP also significantly decreased in the active-treated group compared to both baseline and placebo. At the 12-week follow-up, individuals allocated to the combined nutraceutical experienced a significant improvement in TC, LDL-C, Non-HDL-C, TG, Apo B-100, Apo AI, glucose, alanine transaminase (ALT), gamma-glutamyl transferase (gGT), hs-CRP, several indexes of NAFLD, and brachial pulse volume (PV) in comparison with baseline. Improvements in TC, LDL-C, Non-HDL-C, TG, fatty liver index (FLI), hs-CRP, and endothelial reactivity were also detected compared to placebo (p &lt; 0.05 for all). Overall, these findings support the use of the tested dietary supplement containing dry extracts of bergamot and artichoke as a safe and effective approach for the prevention and management of a broad spectrum of cardiometabolic disorders.

Interventions for insomnia in cancer patients and survivors-a comprehensive systematic review and meta-analysis.

Considering the persistent nature and higher prevalence of insomnia in cancer patients and survivors compared to the general population, there is a need for effective management strategies. This systematic review and meta-analysis aimed to comprehensively evaluate the available evidence for the efficacy of pharmacological and non-pharmacological interventions for insomnia in adult cancer patients and survivors. Following the PRISMA guidelines, we analyzed data from 61 randomized controlled trials involving 6528 participants. Interventions included pharmacological, physical, and psychological treatments, with a focus on insomnia severity and secondary sleep and non-sleep outcomes. Frequentist and Bayesian analytical strategies were employed for data synthesis and interpretation. Cognitive-Behavioral Therapy for Insomnia (CBT-I) emerged as the most efficacious intervention for reducing insomnia severity in cancer survivors, and further demonstrated significant improvements in fatigue, depressive symptoms, and anxiety. CBT-I showed a large post-intervention effect (g = 0.86; 95%CI : 0.57-1.15) and a medium effect at follow-up (g = 0.55; 0.18-0.92). Other interventions like BWL therapy, sleep medication, melatonin, exercise, mind-body therapies, and mindfulness-based therapies showed benefits, but the evidence for their efficacy was less convincing compared to CBT-I. Brief Behavioral Therapy for Insomnia showed promise as a less burdensome alternative for patients in active cancer treatment. CBT-I is supported as first-line treatment for insomnia in cancer survivors, with significant benefits observed across sleep and non-sleep outcomes. The findings also highlight the potential of less intensive alternatives. The research contributes valuable insights for clinical practice and underscores the need for further exploration into the complexities of sleep disturbances in cancer patients and survivors.

#968 Impact of the presence of acute kidney injury at the time of renal biopsy on long-term prognosis of IgA nephropathy

Abstract Background and Aims IgA nephropathy is the most common primary glomerular disease and an important cause of end-stage renal disease. Factors such as decreased renal function, persistent proteinuria, hypertension, and older age predict a poor prognosis in IgA nephropathy. Current international prediction tools for IgA nephropathy determine prognosis based on renal function using estimated glomerular filtration rate (eGFR) at the time of kidney biopsy. However, we observed differences in prognosis between patients with and without concurrent acute kidney injury (AKI) at the time of kidney biopsy. Therefore, we aimed to investigate whether renal function at the time of renal biopsy is a suitable indicator for assessing the long-term prognosis of patients with IgA nephropathy with AKI. Method We retrospectively analyzed a total of 185 patients who were diagnosed with IgA nephropathy between 2009 and 2016 at the Gyeongsang National University Hospital. Clinical data, including pathological, demographic, and laboratory findings of patients, were used. We divided the patients into two groups based on the progression rate of kidney function per year, ‘Progression’ or ‘Non-progression group’. AKI was defined according to the KDIGO Clinical Practice Guidelines. Results Among a total of 185 patients, 113 showed a sustained decline in eGFR of more than 1 ml/min/1.73 m2 per year. The mean eGFR level of the non-progression group was significantly lower than that of the progression group (p = 0.027). The percentage of patients with AKI in the non-progression group was 25%, which was higher than that in the progression group (p &amp;lt; 0.001). The two groups had no significant differences in comorbid disease, medications at kidney biopsy, and treatment. In sub-analysis, the mean eGFR at kidney biopsy was significantly lower than that in the non-AKI group (p &amp;lt; 0.001). The mean estimated risk, calculated by the international prediction tool, was significantly lower in the AKI group. On the other hand, the mean rate of actual GFR decline per year was higher in the non-AKI group (p &amp;lt; 0.001). Conclusion We confirmed a discrepancy between the predicted prognosis and the actual decline in GFR, particularly in the AKI group. We found that AKI at the time of renal biopsy was a good long-term prognostic factor. There is a need to conduct further research to confirm whether this is due to early detection of AKI and early active treatment.

#157 UNI-494 Phase I tolerability and pharmacokinetics: trial in progress

Abstract Background and Aims Acute kidney injury (AKI) is a clinical syndrome defined by the sudden loss of kidney function, resulting in an inability to maintain electrolyte, acid-base and water balance. Currently, there are no effective treatments for AKI approved by the US Food and Drug Administration or the European Medicines Agency (EMA); management of the condition is primarily supportive. The most common cause of AKI was thought to be ischemia. However, more recently the focus has shifted from clinical causes to the underlying cellular processes inherent in these situations, in particular the dysfunction of mitochondria in AKI. UNI-494 is a novel nicotinamide ester derivative and selective mitochondrial ATP-sensitive potassium channel activator that improves mitochondrial function and may be beneficial for several disease states, including AKI. This study aims to evaluate the safety, tolerability, and pharmacokinetics of UNI-494. Method This is a single-center, double-blind, placebo-controlled, randomized single ascending dose (SAD) (Part 1) and multiple ascending dose (MAD) (Part 2) study in healthy male subjects and female subjects of non-childbearing potential. Part 1 will enroll up to approximately 40 subjects in 5 cohorts of 8 subjects each (randomized to a ratio of 6 active and 2 placebo per cohort). There will be an interim decision meeting after each cohort/period, to review the safety, tolerability, and PK data up to 48 h post-dose in order to decide the dose level for the subsequent cohort. Part 2 will enroll approximately 20 subjects in 2 cohorts of 10 subjects each, randomized to a ratio of 8 active treatment to 2 placebo who will be dosed for 5 days. The dose level for the Part 2 Cohort 1 will be selected based on the safety, tolerability and PK data from Part 1. Results We intend to present results elucidating safety, tolerability, and pharmacokinetics of UNI-494 in healthy subjects. Conclusion The safety, tolerability, and pharmacokinetics of UNI-494 in healthy subjects will be evaluated in this study.

Pregnancy Outcomes of Nifedipine Compared With Labetalol for Oral Treatment of Mild Chronic Hypertension

OBJECTIVE: To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial. METHODS: We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140–159/90–104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine. Although active compared with standard care groups were randomized, medication assignment within the active treatment group was not random but based on clinician or patient preference. The primary outcome was the occurrence of superimposed preeclampsia with severe features, preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The key secondary outcome was small for gestational age (SGA) neonates. We also compared medication adverse effects between groups. Relative risks (RRs) and 95% CIs were estimated with log binomial regression to adjust for confounding. RESULTS: Of 2,292 participants analyzed, 720 (31.4%) received labetalol, 417 (18.2%) received nifedipine, and 1,155 (50.4%) received no treatment. The mean gestational age at enrollment was 10.5±3.7 weeks; nearly half of participants (47.5%) identified as non-Hispanic Black; and 44.5% used aspirin. The primary outcome occurred in 217 (30.1%), 130 (31.2%), and 427 (37.0%) in the labetalol, nifedipine, and standard care groups, respectively. Risk of the primary outcome was lower among those receiving treatment (labetalol use vs standard adjusted RR 0.82, 95% CI, 0.72–0.94; nifedipine use vs standard adjusted RR 0.84, 95% CI, 0.71–0.99), but there was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR 0.98, 95% CI, 0.82–1.18). There were no significant differences in SGA or serious adverse events between participants receiving labetalol and those receiving nifedipine. CONCLUSION: No significant differences in predetermined maternal or neonatal outcomes were detected on the basis of the use of labetalol or nifedipine for treatment of chronic hypertension in pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02299414.

Patterns of care at the end of life: a retrospective study of Italian patients with advanced breast cancer.

To better understand the type of care offered to Italian patients with advanced breast cancer at the End-of-Life (EoL), we conducted a retrospective observational study. EoL was defined as the period of six months before death. One hundred and twenty-one patients with advanced breast cancer (ABC) treated at IRCCS San Martino Policlinic Hospital who died between 2017 and 2021 were included. Data about patient, disease, and treatment characteristics from breast cancer diagnosis to death, along with information about comorbidities, medications, imaging, specialist evaluations, hospitalization, palliative care and home care, hospice admissions, and site of death were collected. 98.3% of the patients received at least one line of active treatment at EoL; 52.8% were hospitalized during the selected period. Palliative (13.9%), psychological (7.4%), and nutritional evaluations (8.2%) were underutilized. Palliative home care was provided to 52% of the patients. Most of the patients died at home (66.1%) and fewer than one out of five (18.2%) died at the hospital. Among the patients who died at home, 27.3% had no palliative support. Our findings indicate that palliative care in EoL breast cancer patients is still inadequate. Only a minority of patients had psychological and nutritional support While low nutritional support may be explained by the fact that typical symptoms of ABC do not involve the gastrointestinal tract, the lack of psychological support suggests that significant barriers still exist. Data on the site of death are encouraging, indicating that EoL management is increasingly home centered in Italy.

Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in hematologic malignancies: a living systematic review (protocol)

Objective To determine the efficacy and safety of CAR-T therapy in the treatment of patients with hematologic malignancies, in comparison with other current therapies. Design A living systematic review Methods We will include randomized trials evaluating the effect of CAR-T therapy versus other active treatments, hematopoietic stem cell transplantation, best supportive care or any other intervention in patients with hematologic malignancies. Non-randomized primary studies will be searched in case we found no direct evidence from randomized controlled trials. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. Efficacy measures will include overall survival rate, overall response rate, complete response/remission (CR) rate, partial response/remission (PR) rate, relapse from CR, progression-free survival, and time from CAR-T infusion to transplantation. Safety measures will include serious adverse events, the incidence of cytokine release syndrome, graft-versus-host disease, neurotoxicity, and total adverse events. Quality of life will also be assessed. Meta-analyses will be carried out to summarize the results. We will apply the GRADE approach to assess the certainty of the evidence for each outcome. A living, web-based version of this review will be openly available until there is solid evidence to respond to the review objective. We will resubmit it for publication every time the conclusions change or whenever there are substantial updates.

Efficacy and safety of transcutaneous auricular vagus nerve stimulation (ta-VNS) in the treatment of tinnitus: protocol for an updated systematic review and meta-analysis

IntroductionWith an increasing incidence and significant effects on patients, tinnitus has become a major disease burden. There is a dearth of therapies with established efficacy for tinnitus. Transcutaneous auricular vagus...

A Pilot Study of Ketotifen in Patients Aged 8-17 Years with Functional Dyspepsia Associated with Mucosal Eosinophilia.

Mast cells have been implicated in abdominal pain-associated disorders of gut-brain interaction, such as functional dyspepsia. As such, ketotifen, a second-generation antihistamine and mast cell stabilizer, could represent a viable treatment option in these conditions. The primary aim of the current pilot study was to assess clinical response to ketotifen and assess pharmacokinetics in youth with functional dyspepsia. We conducted a pilot randomized, double-blind, placebo-controlled, cross-over trial of ketotifen in 11 youth with functional dyspepsia and duodenal mucosal eosinophilia with 4 weeks of active treatment at a dose of 1 mg twice daily. Global clinical response was graded on a 5-point Likert Scale. A single plasma sample was obtained at steady state for pharmacokinetic analysis. Ketotifen was not superior to placebo with regard to global clinical response. Only 18% of patients demonstrated a complete or near-complete clinical response. The estimated half-life was 3.3 h. While ketotifen was not superior to placebo, this study highlights several important challenges for developing drug trials for youth with chronic abdominal pain. Recommendations are made for designing a larger treatment trial for ketotifen in this patient group. This study was registered at ClinicalTrials.gov: NCT02484248.

Complications of Injection Laryngoplasty

Injection laryngoplasty (IL), commonly used to treat unilateral vocal cord paralysis, aims to improve glottic insufficiency, while preventing aspiration and enhancing voice quality by injecting material into the vocal cords. Moreover, recent advancements in endoscopic technology and biomaterials facilitated this procedure in the office setting under local anesthesia. IL is generally considered a safe procedure due to its minimally invasive nature. However, as clinical cases increase, reports of various complications associated with IL are also on the rise. These complications are typically not serious and they improve spontaneously with follow-up. However, they can often lead to serious issues affecting the patient’s safety and function, requiring active treatment or management. In this article, we will review possible complications that may arise during and after IL.

An assessment of the direct and indirect costs of breast cancer treatment in leading cancer hospitals in Ghana.

In Ghana, breast cancer remains the most common cancer and the leading cause of cancer deaths among women. The cost of treating cancer is huge and poses a great challenge for patients, their families, and health care systems. While comprehensive studies have been conducted on the economic burden of cancers in developed economies such as the EU and the US, there are limited studies in Africa, and Ghana, in particular. This study quantitatively assessed Ghana's direct and indirect costs of breast cancer treatment. Primary data were collected using a questionnaire administered to 217 breast cancer patients at the Korle-Bu and Komfo Anokye Teaching Hospitals, Ghana's two leading hospitals, and Sweden Ghana Medical Centre. Direct and indirect costs were computed using the Cost-of-Illness Approach. Quantitative analysis was done using multivariate linear regression. The findings showed that the breast cancer patients studied paid a median amount of Ghana cedis (GHC) 31,021.0 (IQR; 25,262.5-42,147.0), approximating USD 5,500.2 (IQR: 4,477.0-7,469.2 USD) for their treatment within one year of active treatment in 2019. About 61.9% (95% CI: 61.8-62.0%) of this cost was direct cost, while the remaining 38.1% (95% CI: 38.0-38.1%) was indirect cost. Patients who sought care from public facilities for breast cancer paid a median amount of GHC 29,606.3 (USD 5,249.3), while those who sought care from private facilities paid GHC 55,071.2 (USD 9,744.4). Findings from the multivariate linear regression indicate that being married/cohabiting, divorced/separated and having tertiary level education predicted higher cost of breast cancer treatment while patients on retirement and patients in the middle stage (Stage II) of breast cancer diagnoses were associated with lower cost of breast cancer treatment. The cost of breast cancer treatment poses a significant burden on patients and their families. There is a need for increased public funding for breast cancer treatment to reduce the huge economic burden its treatment poses for patients and their families.