The role of rectal ultrasound in children with functional constipation.

AIM: The study aimed primarily to compare the transverse rectal diameter in children with functional constipation (FC) and children without constipation in different age groups, and between cases of constipation at baseline and after treatment. Secondary aim was to determine factors that could affect the transverse rectal diameter. METHODS: A controlled prospective study, including a total of 100 children between the ages of 2 and 11 years, who were divided into 50 patients suffering from constipation according to Rome IV criteria and 50 age- and sex-matched controls. Transverse rectal diameter was measured at presentation, and after 3 months of laxative therapy and behavioural modification. RESULTS: Initial rectal diameter was significantly different between cases (3.55 cm (interquartile range, IQR), 3.2-4) and controls (2.3 cm (IQR, 1.8-2.5)), P value < 0.001, and it was also significantly different between those above and below 4 years, so a separate cut-off point for diagnosis of constipation was suggested being >3 cm for the former and >2.5 cm for the latter. After 3 months of follow-up, rectal diameter significantly reduced to become 2.6 (IQR, 2-2.8), P value < 0.001. Duration of symptoms positively correlated with rectal diameter. CONCLUSIONS: Ultrasound measurement of rectal diameter is an important tool to diagnose and follow-up functional constipation in children. Different values of rectal diameter are found between those above and below 4 years of age.

First-in-Human Dose-Escalation Study of Cyclin-Dependent Kinase 9 Inhibitor VIP152 in Patients with Advanced Malignancies Shows Early Signs of Clinical Efficacy.

PURPOSE: To report on the first-in-human phase I study of VIP152 (NCT02635672), a potent and highly selective cyclin-dependent kinase 9 (CDK9) inhibitor. PATIENTS AND METHODS: Adults with solid tumors or aggressive non-Hodgkin lymphoma who were refractory to or had exhausted all available therapies received VIP152 monotherapy as a 30-minute intravenous, once-weekly infusion, as escalating doses (5, 10, 15, 22.5, or 30 mg in 21-day cycles) until the MTD was determined. RESULTS: Thirty-seven patients received ≥ 1 VIP152 dose, with 30 mg identified as the MTD based on dose-limiting toxicity of grade 3/4 neutropenia. The most common adverse events were nausea and vomiting (75.7% and 56.8%, respectively), all of grade 1/2 severity. Of the most common events, grade 3/4 events occurring in > 1 patient were neutropenia (22%), anemia (11%), abdominal pain (8%), increased alkaline phosphatase (8%), and hyponatremia (8%). Day 1 exposure for the MTD exceeded the predicted minimum therapeutic exposure and reproducibly achieved maximal pathway modulation; no accumulation occurred after multiple doses. Seven of 30 patients with solid tumors had stable disease (including 9.5 and 16.8 months in individual patients with pancreatic cancer and salivary gland cancer, respectively), and 2 of 7 patients with high-grade B-cell lymphoma with MYC and BCL2/BCL6 translocations (HGL) achieved durable complete metabolic remission (ongoing at study discontinuation, after 3.7 and 2.3 years of treatment). CONCLUSIONS: VIP152 monotherapy, administered intravenously once weekly, demonstrated a favorable safety profile and evidence of clinical benefit in patients with advanced HGL and solid tumors.

Pooled analysis of safety data from clinical trials evaluating acalabrutinib monotherapy in mature B-cell malignancies.

Bruton tyrosine kinase (BTK) inhibition is an effective therapy for many B-cell malignancies. Acalabrutinib is a next-generation, potent, highly selective, covalent BTK inhibitor. To characterize acalabrutinib tolerability, we pooled safety data from 1040 patients with mature B-cell malignancies treated with acalabrutinib monotherapy in nine clinical studies (treatment-naïve: n = 366 [35%], relapsed/refractory: n = 674 [65%]; median [range] age: 67 [32-90] years; median [range] prior treatments: 1 [0-13]; median [range] duration of exposure: 24.6 [0.0-58.5] months). The most common adverse events (AEs) were headache (38%), diarrhea (37%), upper respiratory tract infection (22%), contusion (22%), nausea (22%), fatigue (21%), and cough (21%). Serious AEs (SAEs) occurred in 39% of patients; pneumonia (6%) was the only SAE that occurred in ≥2%. Deaths due to AEs occurred in 52 patients (5%); pneumonia (n = 8) was the only fatal AE to occur in ≥3 patients. AEs led to treatment discontinuation in 9%. Rates for the AEs of interest (all grades) included infections (67%), hemorrhages (46%), neutropenia (16%), anemia (14%), second primary malignancies (12%), thrombocytopenia (9%), hypertension (8%), and atrial fibrillation (4%). This pooled analysis confirmed acalabrutinib's tolerability and identified no newly emerging late toxicities, supporting acalabrutinib as a long-term treatment for patients with mature B-cell malignancies.

Enhancement of low-fat Feta cheese characteristics using probiotic bacteria.

The objective of this study was to manufacture low-fat Feta cheese (LFC) using different types of starter cultures, such as yogurt (Y) cultures (Streptococcus thermophilus and Lactobacillus bulgaricus), bifidobacterium (B) cultures (Bifidobacterium bifidum and Bifidobacterium longum), and mixed of them (Y + B) at different rates (0.4, 0.5, and 0.6%). The Y + B cultures improved the flavor and body and texture of LFC, especially at a ratio of 0.4 + 0.6% and 0.5 + 0.5%, which is similar to the typical full-fat Feta cheese. Also, the LFC maintained a higher number of probiotics and lactic acid bacteria after 30 d of storage at a range of 5 to 7 log cfu/g.

Vitamin D Increases Percentages of Interleukin-10 Secreting Regulatory T Cells in Children with Cow's Milk Allergy.

Cow's milk allergy (CMA) is known to be either IgE- or non-IgE mediated. Regulatory T (Treg) cell defect is involved in the pathogenesis of both types. Vitamin D has been suggested to improve the generation of allergen-specific Treg cell populations with the potential to provide safe and long-term alleviation of disease symptoms. This study aimed to assess Vitamin D status in children with physician-diagnosed CMA and to investigate the effect of in vitro cultivation with Vitamin D on the percentage of antigen-driven CD4+CD25highFoxp3+IL10+ Treg cells following in vitro stimulation of cells with cow's milk allergen in culture. This cross-sectional study included 20 children with CMA and 20 healthy age and sex-matched children as a control group. All patients were subjected to clinical evaluation, cow's milk skin prick test (SPT), cow's milk elimination and oral re-challenge test in patients with negative cow's milk SPT and in those with gastrointestinal presentation, measurement of serum Vitamin D level and assessment of the percentage of antigen-driven CD4+CD25highFoxp3+IL10+ Treg cells in response to stimulation with cow's milk allergen extract with and without Vitamin D in culture. Vitamin D deficiency was detected in 80% of children with CMA. Percentage of Foxp3+ and IL10+ co-expression on Treg cells was significantly increased after stimulation with cow's milk allergen extract in the presence of Vitamin D. A significant positive correlation was observed between serum Vitamin D level and percentage of antigen-driven CD4+CD25highFoxp3+IL10+ Treg cells as well as level of Foxp3+ and IL10+ co-expression on Treg cells at baseline (control cultures without stimulation) and after PBMCs stimulation with cow's milk allergen extract in the presence of Vitamin D. Re-stimulation with cow's milk allergen extract was performed in vitro in order to evaluate milk-induced immune stimulation and regulation. In conclusion, patients with CMA whether IgE- or non-IgE mediated had Vitamin D deficiency with a decreased number of CD4+CD25highFoxp3+IL10+ Treg cells which increased after in vitro addition of Vitamin D with increased Foxp3 and IL10 co-expression.

Effect of passive smoking on blood lymphocyte apoptosis in children.

BACKGROUND: Passive smoking is a well-known risk factor for both recurrent respiratory infections and disturbed lipid profile. Whether passive smoking problems are related to altered lymphocyte survival and its relation to altered lipid profile are the points of concern in this work. MATERIALS AND METHODS: Urinary cotinine and creatinine levels as well as lipid profile and flow cytometric assessment of apoptosis of peripheral blood lymphocytes (PBL) were assessed in 26 children with history of indoor exposure to cigarette smokers in comparison with 14 matched children with no such history. RESULTS: Lipid profile showed significantly higher mean levels of triglycerides, cholesterol and low-density lipoprotein (LDL) and significantly lower mean levels of high-density lipoprotein (HDL) in passive smoking children compared to nonpassive-smoking ones. Furthermore, cotinine parameters were positively correlated with triglycerides and LDL and negatively correlated with HDL. Early apoptosis of PBL was significantly higher in exposed vs nonexposed ones. CONCLUSIONS: Passive smoking in children could be a risk factor for enhanced lymphocytic apoptosis. It is possible that altered lipid profile may play a role in the increased risk. The impact of this lymphocytic derangement on increased frequency of infections is noticeable.

Renal effects of ularitide in patients with decompensated heart failure.

BACKGROUND: Renal function frequently deteriorates in decompensated heart failure (DHF) patients, and one determinant is reduced renal blood flow. This may, in part, result from low cardiac output (CO), reduced mean arterial pressure (MAP), and venous congestion. The combined impact of both venous congestion (elevated right atrial pressure [RAP]) and low MAP are reflected by a reduced pressure gradient MAP-RAP. This study investigated the renal effects of ularitide, a synthetic version of the renal natriuretic peptide urodilatin in DHF patients. METHODS: In SIRIUS II, a double-blind phase II trial, 221 patients hospitalized for DHF (with dyspnea at rest or minimal activity, cardiac index or=18 mm Hg) were randomized to a single 24-hour infusion of ularitide (7.5, 15, or 30 ng/kg per minute) or placebo added to standard therapy. RESULTS: Estimated glomerular filtration rate, serum creatinine, creatinine clearance, and blood urea nitrogen (BUN) were not impaired by ularitide throughout infusion and during a 2-day follow-up period. At 24 hours, 15 ng/kg per minute ularitide reduced BUN levels (-4.07 +/- 12.30 vs -0.20 +/- 7.50 for placebo, P < .05). Ularitide at 15 and 30 ng/kg per minute rapidly elevated CO with sustained effects. Although 15 ng/kg per minute ularitide preserved the pressure gradient MAP-RAP, 30 ng/kg per minute ularitide reduced MAP-RAP by -7.8 +/- 10.6 mm Hg vs -2.4 +/- 9.8 mm Hg for placebo (P < .01, at 6 hours). A strong inverse correlation between MAP-RAP and BUN levels (Corr = -0.50579, P = .00015) was observed with 15 ng/kg per minute ularitide. CONCLUSIONS: Single 24-hour infusions of ularitide at 15 ng/kg per minute preserved short-term renal function in DHF patients possibly by both elevating CO and maintaining the MAP-RAP pressure gradient.

Rectal bleeding in Egyptian children.

AIM: In a prospective study to outline the aetiology of bleeding per rectum (BPR) in Egyptian infants and children, a subsidiary aim was to define some of the clinical characteristics of the different aetiologies. SUBJECTS AND METHODS: 194 children with BPR are described. The diagnostic work-up included laboratory investigations, radiological and endoscopic assessment, radio-isotope scanning, angiography and histopathological examination of mucosal biopsies, as appropriate. RESULTS: Ages ranged from 3 to 192 months with a mean (SD) of 49.8 (43.5). Infectious enterocolitis was the most common cause (37.1%). Others included colorectal polyps (21.1%), chronic colitis (16%) including inflammatory bowel diseases (5.2%), allergic colitis (2.6%), solitary rectal ulcer syndrome (1.5%) and non-specific colitis (6.7%). Intussusception and Meckel's diverticulae were the cause in 7.3% and 2.6%, respectively, while other aetiologies included vascular (6.2%), systemic (3.6%), local anal (3.1%) and upper gastro-intestinal causes (1.5%). In 1.5% of cases, the cause remained 'obscure'. CONCLUSION: In Egyptian children, infectious enterocolitis followed by colorectal polyps and chronic colitis are major causes of BPR.