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.

Sugemalimab plus chemotherapy improved progression-free survival and overall survival in advanced ESCC patients

A recent study demonstrated that the utilization of sugemalimab alongside chemotherapy significantly improved progression-free survival and overall survival in treatment-naïve individuals with advanced esophageal squamous cell carcinoma (ESCC). This study’s findings were published in the journal, Nature medicine.

A total of 540 adults, ranging in age from 18 to 75 years, who were diagnosed with locally advanced, unresectable, recurrent or metastatic ESCC and had not undergone any previous systemic treatment, were enrolled in this multicenter, double-blinded, randomized, phase 3 trial. The patients were randomly assigned in a 2:1 ratio to receive either sugemalimab, an anti-PD-L1 antibody at a dose of 1,200 mg or placebo every 3 weeks for a maximum period of 24 months. Additionally, all the randomized patients underwent chemotherapy consisting of cisplatin (80 mg m^-2  on day 1) and 5-fluorouracil (800 mg m^-2 day^-1 on days 1-4) every 3 weeks for a maximum of six cycles. The study assessed both progression-free survival and overall survival outcomes.

With a median follow-up of 15.2 months, the extension of progression-free survival showed statistical significance when comparing sugemalimab plus chemotherapy to placebo plus chemotherapy (median 6.2 months vs 5.4 months). Additionally, overall survival was better with sugemalimab plus chemotherapy when compared to placebo plus chemotherapy (median 15.3 months vs 11.5 months). There was a notably higher objective response rate (60.1% vs 45.2%) observed with sugemalimab plus chemotherapy compared to placebo plus chemotherapy.

Thus, it can be concluded that the combination of sugemalimab and chemotherapy led to a notable extension in both progression-free survival and overall survival among treatment-naïve individuals with advanced ESCC.

Impact of intensified androgen blockade in patients with high-risk biochemically relapsed castration-sensitive prostate cancer

A recent study showed that intensified AR blockade for a finite period extends prostate-specific antigen progression-free survival (PSA-PFS) while maintaining a manageable safety profile, without negatively impacting the time needed for testosterone recovery. This study’s findings were published in the Journal of clinical oncology.

The PRESTO trial was a randomized, open-label, phase III study that involved 503 patients diagnosed with biochemically recurrent prostate cancer (BRPC) and PSA doubling time of 9 months or less. Patients were randomly divided into one of three groups in a 1:1:1 ratio. These groups consisted of a 52-week treatment course with ADT (androgen-deprivation therapy) control, ADT combined with apalutamide, or ADT combined with apalutamide and AAP (abiraterone acetate plus prednisone). The primary endpoint of the trial was to evaluate PSA-PFS, which was defined as having a serum PSA level exceeding 0.2 ng/mL after the completion of the assigned treatment.

The median PSA level was determined to be 1.8 ng/mL (IQR, 1.0-3.6). During the initial planned interim analysis, it was observed that both experimental groups exhibited a significant prolongation in PSA-PFS when compared to the control group (median, ADT + apalutamide was 24.9 months vs 20.3 months for ADT alone; median, ADT + apalutamide + AAP was 26.0 months vs 20.0 months for ADT alone). There was no notable difference in the median time for testosterone recovery across the different treatment arms.

The above results demonstrated that the use of intensified AR blockade for a finite period has been found to PSA-PFS while maintaining a manageable safety profile and not interfering with testosterone recovery time. Consideration should be given to adding apalutamide to androgen deprivation therapy in high-risk BRPC patients.

Evaluation of the diagnostic accuracy of point-of-care ultrasound for pediatric distal forearm fractures

According to a recent study, clinician-performed point-of-care ultrasound proved to be more precise in diagnosing clinically nondeformed distal forearm injuries in children and adolescents compared to clinician-interpreted radiographic imaging. The findings of this study were published in the journal, Annals of emergency medicine.

This was an open-label, multicenter, diagnostic randomized controlled trial where 270 participants were enrolled. Eligible patients were randomly assigned to undergo initial imaging either through point-of-care ultrasound conducted by an emergency department (ED) clinician or through radiography (135 randomized to each imaging group). The primary outcome was the treating clinician's diagnostic accuracy in comparison to the reference standard diagnosis. The reference standard diagnosis was determined retrospectively by a panel of experts, which included an emergency physician, pediatric orthopedic surgeon, and pediatric radiologist. This panel thoroughly reviewed all imaging and follow-up data.

At the end of the study, it was observed that in the point-of-care ultrasound group, 132 (97.8%) participants were accurately diagnosed by ED clinicians, while in the radiograph group, 112 (83.0%) participants received correct diagnoses. Point-of-care ultrasound demonstrated superior accuracy in detecting "buckle" fractures (AD=18.5%) and "other" fractures (AD=17.1%).

Thus, it can be concluded that clinician-performed point-of-care ultrasound demonstrated superior accuracy in diagnosing clinically nondeformed distal forearm injuries in children and adolescents compared to clinician-interpreted radiographic imaging in the ED.

Effect of early vitamin D supplementation on the occurrence of preeclampsia in primigravid women

A recent study found that administration of a monthly dose (60,000 IU) of vitamin D supplementation during the early stages of pregnancy demonstrated a notable decrease in the occurrence of preeclampsia. The study results were published in the journal, BMC pregnancy and childbirth.

This randomised clinical trial included 1300 primigravid women (median maternal age: 21 years; the median gestational age: 15 weeks) who were randomly assigned in a 1:1 ratio to either the supplemented (A) or control (B) group. Pregnant women in group A received a monthly dose of cholecalciferol (60,000 IU) orally for 6 months during antenatal care, while the control group (B) did not receive any vitamin D supplementation or placebo. Serum 25(OH)D levels were checked at the beginning and at 34 weeks of gestation, with outcomes assessed monthly until delivery.

In the intervention group, there was a significant decrease in the risk of preeclampsia (RR = 0.36) and preterm delivery (RR = 0.5). Moreover, an RR of 0.43 was identified for low birth weight and the RR for caesarean section was 0.63. The supplemented group demonstrated significantly higher APGAR scores at the 5th minute and a larger size of newborns.

The above results demonstrate that a single monthly dosage of vitamin D supplementation in early pregnancy had a substantial impact on lowering the occurrence of preeclampsia, as well as mitigating the associated complications experienced by both the mother and the fetus.

Sacituzumab govitecan safe and significantly beneficial over chemotherapy in treating metastatic breast cancer

According to a recent study, sacituzumab govitecan was safe and significantly beneficial over chemotherapy in treating metastatic breast cancer. This study's result were published in the journal, Lancet.

The TROPiCS-02 was a randomized, phase 3, multi-centre, open-label trial that included 543 patients with confirmed hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ and HER2-). They were randomly assigned in a 1:1 ratio to receive either sacituzumab govitecan (n=272) or chemotherapy (n=271; eribulin, vinorelbine, capecitabine, or gemcitabine). The patients had received at least one previous endocrine therapy, a taxane, as well as a CDK4/6 inhibitor in any setting and 2-4 previous chemotherapy regimens for metastatic disease. The study's primary endpoint was progression-free survival while the secondary endpoints included objective response rate (ORR), overall survival, and patient-reported outcomes.

At the end of the study, it was observed that sacituzumab govitecan significantly improved overall survival. Also, ORR was significantly improved with sacituzumab govitecan as was time to deterioration of global health status and quality of life. The safety profile of sacituzumab govitecan was in accordance with those of the ASCENT trial and primary analysis of TROPiCS-02.

Based on the results of this study, it can be concluded that sacituzumab govitecan may be used as a new treatment option for patients with  pretreated metastatic breast cancer as it may demonstrate statistically significant and clinically meaningful benefits with a manageable safety profile.