Prognostic scoring system for Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in children

A recent study suggests that a prognostic scoring system identified three high risk groups in children with statistically significant differences in survival curves based on the baseline characteristics that helped in risk prediction. The findings of this study were published in the journal, Pediatric Blood & Cancer.

This multicenter retrospective study included 264 children, aged 0-14 years who were diagnosed with Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH). The pediatric population was randomly divided into two groups: derivation (n=185) and verification (n=79). In order to establish a prognostic scoring system for death events, risk predictors were investigated using a Cox regression model during the follow-up period. Chronic active EBV infection (CAEBV) history, plasma EBV-DNA copy number, pulmonary infection hemorrhage of digestive tract, and hypoxemia prognostic scoring system (CEPHO-PSS) were developed which demarcated patients into low-risk (0-1 points), middle-risk (2-3 points), and high-risk (4-8 points) groups.

At the end of the study, the three risk groups showed survival curves with statistically significant differences. Receiver operating characteristic (ROC) and calibration curves in the derivation and verification cohorts, respectively, were used for internal and external verification of CEPHO-PSS, confirming good accuracy and applicability.

Thus, it can be concluded that the CEPHO-PSS may identify three risk groups in children with statistically significant differences in survival curves. This may help clinicians to check for risk prediction.

Active vitamin D treatment in mitigating the onset of sarcopenia among adults with prediabetes

A recent study showed that the use of eldecalcitol may help in preventing the onset of sarcopenia in individuals with prediabetes by enhancing skeletal muscle volume and strength.  This study’s findings were published in the Lancet Healthy Longevity.

In this randomised, placebo-controlled, double-blind, multicenter trial, a total of 1094 participants were divided into two groups, with 548 in the eldecalcitol group and 546 in the placebo group. The primary endpoint of the study was the incidence of sarcopenia over a 3-year period in the intention-to-treat population, characterised by weak handgrip strength (<18 kg for women and <28 kg for men) and low appendicular skeletal muscle index (<5·7 kg/m² for women and <7·0 kg/m² for men in bioelectrical impedance analysis). Hypercalcaemia was identified as 10·4 mg/dL (2·6 mmol/L) or higher, while a level of 11·0 mg/dL or higher was considered enough to warrant discontinuation of the study.

Eldecalcitol demonstrated a statistically significant preventive effect on the incidence of sarcopenia when compared to the placebo, with 25 participants (4.6%) out of 548 in the eldecalcitol group and 48 participants (8.8%) out of 546 in the placebo group. There was no variance in the occurrence of adverse events between the two groups.

Thus, it can be concluded that eldecalcitol could potentially prevent sarcopenia in individuals with prediabetes by increasing skeletal muscle strength and volume, ultimately reducing the risk of falls

Safety and efficacy of tirofiban before stenting for symptomatic intracranial atherosclerotic stenosis

A recent study has shown that adjuvant intravenous tirofiban before stenting may lead to a decreased likelihood of acute stent thrombosis (AST) during stent angioplasty in patients experiencing symptomatic high-grade intracranial atherosclerotic stenosis (ICAS). This study’s findings were published in the journal, Neurology.

In this prospective, multicenter, randomized clinical trial, patients with symptomatic high-grade ICAS scheduled for stent angioplasty were randomly assigned to either receive intravenous tirofiban before stenting or not, in a 1:1 ratio. The study included 100 participants in the tirofiban group and 100 participants in the control group. Primary outcomes measured were the incidence of AST within 30 minutes post-stenting, periprocedural new-onset ischemic stroke, and symptomatic intracranial hemorrhage.

At the end of the study, there was a lower incidence of AST in the tirofiban group when compared to the control group (4.0% vs 14.0%).

The above study demonstrated that the use of adjuvant intravenous tirofiban prior to stenting could potentially reduce the occurrence of AST in patients with symptomatic high-grade ICAS undergoing stent angioplasty.

Semirigid ureteroscopy and tamsulosin therapy for dilation prior to flexible ureteroscopy

According to a recent study, the utilization of tamsulosin therapy and semirigid ureteroscopy for dilation prior to flexible ureteroscopy enhanced the success of primary flexible ureteroscopy advancement to the renal collecting system. This study's findings were published in the World journal of urology.

This prospective study included 170 patients who were randomly divided into two groups who had renal stones < 2 cm and underwent retrograde flexible ureteroscopy and laser lithotripsy. Group A (n=85), was administered a placebo for a duration of one week before the flexible ureteroscopy. On the other hand, group B (n=85), received a daily dosage of 0.4 mg tamsulosin for one week prior to the surgery. Additionally, they underwent active dilatation using semirigid ureteroscopy before the flexible ureteroscopy procedure. The ability of the flexible ureteroscope to reach the collecting system in both groups was evaluated during the same operative session. The operative outcomes and complications for both groups were also collected and analyzed.

The flexible ureteroscope demonstrated successful access to the kidney in 61 patients within group B, while in group A, it was only successful in 28 cases (71.4% vs 32.9%). Within group A, 33 patients (38.8%) reported lower urinary tract symptoms, while only 17 patients (20.2%) in group B experienced the same.

It can be concluded that using tamsulosin therapy and semirigid ureteroscopy as dilatation methods prior to flexible ureteroscopy may improve the success of primary flexible ureteroscopy in advancing to the renal collecting system.

Tebentafusp provides overall survival benefit compared to nivolumab plus ipilimumab in first-line metastatic uveal melanoma

According to a recent study, a propensity score analysis indicated an overall survival benefit for tebentafusp compared to nivolumab plus ipilimumab (N+I) in patients with untreated metastatic uveal melanoma (mUM). This study’s findings were published in the journal, Annals of oncology.

In this study, the overall survival (OS) of patients with untreated mUM were compared between those treated with tebentafusp or pembrolizumab (IMCgp100-202) and those treated with N+I (GEM1402) using propensity scoring methods. The analyses were adjusted using propensity score-based inverse probability of treatment weighting (IPTW), balancing age, baseline lactate dehydrogenase (LDH), sex, baseline alkaline phosphatase, Eastern Cooperative Oncology Group status, disease location, and time from primary diagnosis to metastasis. The OS was evaluated using Cox proportional hazard models and IPT-weighted Kaplan-Meier.

In the primary IPTW analysis, a total of 240 patients out of 252 who were assigned to receive tebentafusp from IMCgp100-202 were included, and 45 out of the 52 patients who underwent N+I treatment from GEM-1402 were also considered. After adjusting for IPTW, tebentafusp showed a favorable OS, with a hazard ratio (HR) of 0.52. The one-year OS for tebentafusp was 73%, while it was 50% for the N+I group. Sensitivity analyses consistently demonstrated a superior OS for tebentafusp, with all IPTW HRs ≤0.61.

Based on the above results, a propensity score analysis determined that tebentafusp provided  a similar  OS benefit compared to N+I in patients with untreated mUM. 

Maralixibat improves health-related quality of life in pediatric patients with Alagille Syndrome

A recent study demonstrated that the ileal bile acid transporter inhibitor maralixibat improves health-related quality of life (HRQoL) in children with Alagille syndrome. This study was published in The Journal of Pediatrics.

The ICONIC trial was a phase 2 study, having a 4-week double-blind, placebo-controlled, randomized drug withdrawal period. The study included 27 children having Alagille syndrome with moderate-to-severe pruritus. From baseline to week 48, the treatment response to maralixibat was noted using Itch-Reported Outcome (Observer) score. The HRQoL was assessed based on the certain scale scores that included Pediatric Quality of Life Inventory Generic Core, Family Impact, and Multidimensional Fatigue scale scores.

At week 48, twenty patients attained an Itch-Reported Outcome (Observer) treatment score response. The mean (SD) change in Multidimensional Fatigue score was higher was higher for responders over non-responders. The Pediatric Quality of Life Inventory Generic Core and Multidimensional Fatigue scores showed smaller and non-statistically significant point estimates.

Based on the results of the study, it can be concluded that maralixibat shows significant improvement in pruritis, thereby enhancing the quality of life in the affected children.

Clinical efficacy of a multitarget urine DNA test for urothelial carcinoma detection

According to a recent study, the multitarget urine tumor DNA test (UI-Seek) has displayed a robust performance and has substantial potential in detecting urothelial carcinoma (UC) at an early stage. This study’s findings were published in the journal, Molecular Cancer.

In order to generate a UC-score, the prediction model was created in a retrospective cohort (n = 382) by integrating assays for FGFR3 and TERT mutations, as well as aberrant ONECUT2 and VIM methylation. The test performance was later validated in a double-blinded, multicenter, prospective trial (n = 947).

The test performance demonstrated a sensitivity of 91.37% and a specificity of 95.09%. Sensitivity was 75.81% for low-grade Ta tumors and over 93% for high-grade Ta and higher stages (T1 to T4). UI-Seek simultaneously identified both bladder and upper urinary tract tumors with sensitivities above 90%. No significant confounding effects were noted with non-UC malignancies or benign urological diseases. The test exhibited higher sensitivities compared to urine cytology, the NMP22 test, and UroVysion FISH, while maintaining comparable specificities. Additionally, the single-target accuracy exceeded 98% as confirmed by Sanger sequencing. The post-surgery UC-score decreased in 97.7% of the subjects.

From the above study, it can be concluded that UI-Seek displays strong performance and has considerable potential for the timely detection of UC.

Sustained and moderating effects of a behavioural sleep intervention for autistic children

A recent study suggests that the Sleeping Sound intervention showed sustained improvements in child sleep among autistic children. The study’s findings were published in the Journal of Autism and Developmental Disorders.

This was a randomized controlled trial which included 150 autistic children aged 5-13 years, who had sleep problems. They were randomized either to the Sleeping Sound intervention or Treatment as Usual (TAU).

At the 12-month follow-up, the caregivers of the children reported a greater reduction in sleep problems in the Sleeping Sound group when compared to the TAU group. Those children who were taking sleep medication, children with greater autism severity, and children of parents who were not experiencing psychological distress showed greater long-term benefits with the intervention. Based on the above results, it can be concluded that Sleeping Sound intervention may show sustained improvements in child sleep.

Effect of vitamin D3 supplementation in pregnancy on risk of autism and Attention Deficit Hyperactive Disorder

According to a recent study, maternal preintervention 25(OH)D (maternal 25-hydroxy-vitamin D) when given at a higher dose, decreased the risk of autism, decreased the risk of ADHD diagnosis, and lowered autistic symptom load. The conclusions of this study were published in the American Journal of Clinical Nutrition.

This randomized study was part of the COpenhagen Prospective Study on Neuro-PSYCHiatric Development (COPYCH) project and consisted of 700 healthy mother-child pairs who enrolled at the 24^th week of pregnancy. 25(OH)D was measured at inclusion and 623 mothers underwent randomization to receive either the high-dose of 2800 IU/d (n=315) or standard dose of 400 IU/d (n=308) Vitamin D3 until one week after childbirth. At 10 years of age, diagnoses and symptom load of autism and ADHD, respectively was made utilizing the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version.

At the end of the study, it was seen from the psychopathologic evaluation that 591 (10-year old) children completed it. Out of this, 16 and 65 children were identified with autism and ADHD, respectively. A total of 496 children participated in the vitamin D3 trial (high-dose: 246; standard-dose: 250), out of which 12 and 58 children were identified with autism and ADHD, respectively.

Based on the above results, it can be concluded that higher levels of maternal preintervention 25(OH)D may be associated with a decreased risk of autism, lower autistic symptom load, and decreased risk of ADHD diagnosis. However, supplementation with high-dose vitamin D3 may not be associated with the risk of autism and ADHD.