The Clinicopathological Correlation and Outcome of Glomerulonephritis With Crescent: A Single-Center Study.

BACKGROUND: There is a lack of standardized treatments for patients with less than 50% crescents observed in their renal biopsies. This study aimed to analyze the crescent percentage, clinicopathological characteristics, and renal prognosis of glomerulonephritis (GN) cases with at least one crescentic lesion. MATERIALS AND METHODS: This retrospective cohort study was conducted at the Indira Gandhi Institute of Medical Sciences, Patna, from January 2016 to December 2020. Consecutive patients (aged between 18 and 65 years) with renal biopsy findings suggestive of GN and at least one crescent were included in the study. Demographic details and clinical presentation were collected from the medical records. RESULTS: A total of 145 patients were included. The mean (standard deviation (SD)) age was 33.06 (11.739) years. Hemoptysis was significantly higher in the ≥50% crescent group (P=0.011). Rapidly progressive glomerulonephritis (RPGN) was significantly higher in the ≥50% crescent group (P<0.001). There was a significant difference observed in mean creatinine (P=0.001), mean crescents (P<0.001), and mean urine polymerase chain reaction (PCR) (P=0.031). Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis was significantly higher in the ≥50% crescent group (P<0.001). Complete remission decreased as crescents increased. In GN with crescent, the presence of fibrous crescents (≥50%) is associated with a higher rate of treatment resistance (100%) compared to fibrocellular (58.33%) and cellular crescents (6.25%). In the ≥50% crescent group, death was significantly higher in patients with fibrous crescent age (57.14%). CONCLUSION: Crescent percentage and crescent age were found to be significantly related to greater risk of renal failure and resistance to treatment.

A synbiotic intervention modulates meta-omics signatures of gut redox potential and acidity in elective caesarean born infants.

BACKGROUND: The compromised gut microbiome that results from C-section birth has been hypothesized as a risk factor for the development of non-communicable diseases (NCD). In a double-blind randomized controlled study, 153 infants born by elective C-section received an infant formula supplemented with either synbiotic, prebiotics, or unsupplemented from birth until 4 months old. Vaginally born infants were included as a reference group. Stool samples were collected from day 3 till week 22. Multi-omics were deployed to investigate the impact of mode of delivery and nutrition on the development of the infant gut microbiome, and uncover putative biological mechanisms underlying the role of a compromised microbiome as a risk factor for NCD. RESULTS: As early as day 3, infants born vaginally presented a hypoxic and acidic gut environment characterized by an enrichment of strict anaerobes (Bifidobacteriaceae). Infants born by C-section presented the hallmark of a compromised microbiome driven by an enrichment of Enterobacteriaceae. This was associated with meta-omics signatures characteristic of a microbiome adapted to a more oxygen-rich gut environment, enriched with genes associated with reactive oxygen species metabolism and lipopolysaccharide biosynthesis, and depleted in genes involved in the metabolism of milk carbohydrates. The synbiotic formula modulated expression of microbial genes involved in (oligo)saccharide metabolism, which emulates the eco-physiological gut environment observed in vaginally born infants. The resulting hypoxic and acidic milieu prevented the establishment of a compromised microbiome. CONCLUSIONS: This study deciphers the putative functional hallmarks of a compromised microbiome acquired during C-section birth, and the impact of nutrition that may counteract disturbed microbiome development. TRIAL REGISTRATION: The study was registered in the Dutch Trial Register (Number: 2838 ) on 4th April 2011.

Growth of children with food allergies in Singapore.

BACKGROUND: Although it is known that children with food allergies are at risk of impaired growth, this has not been well studied in South-East Asia. OBJECTIVE: The aim of this cross-sectional study is to survey the growth of children with food allergies in Singapore and the factors impacting it. METHODS: Anthropometric data, demographic data, type of food allergy, foods eliminated, and atopic comorbidities were recorded. Malnutrition was defined using World Health Organization standards (≤-2 z-score for weight-for-height [WH], weight-for-age [WA], and height-for-age [HA]). RESULTS: Seventy-four patients (51% male) were recruited over 1 month, with median age at diagnosis of 8 months (interquartile range [IQR], 4-13 months) and at data collection of 25 months (IQR, 14-48 months). Sixty-two (84%) had IgE-mediated allergy, 8 (11%) mixed IgE and non-IgE, and 4 (5%) non-IgE-mediated allergy. Food exclusions: 55% one food, 27% two foods, 8% three to four foods, and 10% ≥5 foods. Only 1% were underweight (WA ≤ -2 z-score) and 3% had WA ≥ +2 z-score. Having a mixed type food allergy significantly reduced WA (p = 0.023). WA was significantly lower for those referred to the dietitian (p = 0.027). 5.4% were stunted (HA ≤ -2 z-score). Factors significantly associated with stunting were underlying eczema (p = 0.03) and having an IgE-mediated (p = 0.03) or mixed type food allergy (p = 0.002). One point four percent (1.4%) were undernourished (WH ≤ -2 z-score) and 1.4% were overweight (WH ≥ +2 z-score). Multivariate regression analysis found that children with mixed type food allergies were significantly shorter (z-score -1 lower). Children had a lower WA if they had skin involvement as part of their symptom presentation. CONCLUSION: This is the first survey documenting growth in children with food allergy in Singapore. Eczema, IgE-mediated and mixed type allergies are associated with poorer growth rates in these children. Early, individualised nutritional intervention is recommended for all children with food allergy.

Malaria vaccine candidate based on Duffy-binding protein elicits strain transcending functional antibodies in a Phase I trial.

Reticulocyte invasion by Plasmodium vivax requires interaction of the Duffy-binding protein (PvDBP) with host Duffy antigen receptor for chemokines (DARCs). The binding domain of PvDBP maps to a cysteine-rich region referred to as region II (PvDBPII). Blocking this interaction offers a potential path to prevent P. vivax blood-stage growth and P. vivax malaria. This forms the rationale for development of a vaccine based on PvDBPII. Here we report results of a Phase I randomized trial to evaluate the safety and immunogenicity of recombinant PvDBPII formulated with glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE). Thirty-six malaria-naive, healthy Indian male subjects aged 18-45 years were assigned into three cohorts corresponding to doses of 10, 25 and 50 µg of PvDBPII formulated with 5 µg of GLA-SE. Each cohort included nine PvDBPII/GLA-SE vaccinees and three hepatitis B control vaccine recipients. Each subject received the assigned vaccine intramuscularly on days 0, 28 and 56, and was followed up till day 180. No serious AE was reported and PvDBPII/GLA-SE was well-tolerated and safe. Analysis by ELISA showed that all three doses of PvDBPII elicited antigen-specific binding-inhibitory antibodies. The 50 µg dose elicited antibodies against PvDBPII that had the highest binding-inhibitory titres and were most persistent. Importantly, the antibody responses were strain transcending and blocked receptor binding of diverse PvDBP alleles. These results support further clinical development of PvDBPII/GLA-SE to evaluate efficacy against sporozoite or blood-stage challenge in controlled human malaria infection (CHMI) models and against natural P. vivax challenge in malaria endemic areas.

Cashew nut allergy in Singaporean children.

BACKGROUND: There has been an increasing trend of nut allergies in Singapore. OBJECTIVE: The aim of this study was to review the clinical characteristics of children with cashew nut allergy. METHODS: A retrospective analysis was conducted in a tertiary paediatric referral centre in Singapore from 2008 to 2015. A total of 99 subjects with positive specific IgE (≥0.35 IU/L) to cashew nut were identified. Clinical features including demographics, clinical reaction to cashew nut, associations with other nuts and test specific measurements were recorded. RESULTS: The results showed that cutaneous symptoms (71.2%) were the most common allergic manifestations. Anaphylaxis occurred in 3.8% of children. In addition, all cashew nut allergic subjects were cross-reactive (either sensitized or allergic) to pistachio. Cross-reactivity rate with peanuts was 53.8%. There was a strong prevalence of atopy among cashew nut allergic subjects. CONCLUSION: In conclusion, cashew nut allergy is a significant tree nut allergy in Singapore.

Effect of Synbiotic on the Gut Microbiota of Cesarean Delivered Infants: A Randomized, Double-blind, Multicenter Study.

We determined the effect of short-chain galacto-oligosaccharides (scGOS), long-chain fructo-oligosaccharides (lcFOS) and Bifidobacterium breve M-16V on the gut microbiota of cesarean-born infants. Infants were randomized to receive a standard formula (control), the same with scGOS/lcFOS and B. breve M-16V (synbiotic), or with scGOS/lcFOS (prebiotic) from birth until week 16, 30 subjects born vaginally were included as a reference group. Synbiotic supplementation resulted in a higher bifidobacteria proportion from day 3/5 (P < 0.0001) until week 8 (P = 0.041), a reduction of Enterobacteriaceae from day 3/5 (P = 0.002) till week 12 (P = 0.016) compared to controls. This was accompanied with a lower fecal pH and higher acetate. In the synbiotic group, B. breve M-16V was detected 6 weeks postintervention in 38.7% of the infants. This synbiotic concept supported the early modulation of Bifidobacterium in C-section born infants that was associated with the emulation of the gut physiological environment observed in vaginally delivered infants.

A stepwise approach in the management of chronic spontaneous urticaria in children.

BACKGROUND: There is limited literature in the management of chronic urticaria in children. Treatment algorithms are generally extrapolated from adult studies. OBJECTIVE: Utility of a weight and age-based algorithm for antihistamines in management of chronic spontaneous urticaria (CSU) in childhood. To document associated factors that predict for step of control of CSU and time taken to attain control of symptoms in children. METHODS: A workgroup comprising of allergists, nurses, and pharmacists convened to develop a stepwise treatment algorithm in management of children with CSU. Sequential patients presenting to the paediatric allergy service with CSU were included in this observational, prospective study. RESULTS: Ninety-eight patients were recruited from September 2012 to September 2013. Majority were male, Chinese with median age 4 years 7 months. A third of patients with CSU had a family history of acute urticaria. Ten point two percent had previously resolved CSU, 25.5% had associated angioedema, and 53.1% had a history of atopy. A total of 96.9% of patients achieved control of symptoms, of which 91.8% achieved control with cetirizine. Fifty percent of all the patients were controlled on step 2 or higher. Forty-seven point eight percent of those on step 2 or higher were between 2 to 6 years of age compared to 32.6% and 19.6% who were 6 years and older and lesser than 2 years of age respectively. Eighty percent of those with previously resolved CSU required an increase to step 2 and above to achieve chronic urticaria control. CONCLUSION: We propose a weight- and age-based titration algorithm for different antihistamines for CSU in children using a stepwise approach to achieve control. This algorithm may improve the management and safety profile for paediatric CSU patients and allow for review in a more systematic manner for physicians dealing with CSU in children.

Tolerance to etoricoxib in children with nonsteroidal anti-inflammatory drug hypersensitivity.

BACKGROUND: Cyclooxygenase-2 (COX-2) inhibitors have been found to be safe alternatives in adults with cross-intolerant hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs). However they are usually not prescribed in children and there is little information about their tolerance in the pediatric age group. OBJECTIVE: This study aims to evaluate the tolerance to etoricoxib in children with hypersensitivity to multiple antipyretics. METHODS: A retrospective case series of children diagnosed with hypersensitivity reactions to NSAIDs and/or paracetamol who underwent a drug provocation test (DPT) with etoricoxib. Information on atopy, family history of allergic diseases, and medication usage was collected. Outcomes of the DPTs and tolerance to etoricoxib were also evaluated. RESULTS: A total of 24 children, mean age 13.5 years, had a diagnosis of cross-intolerant hypersensitivity to NSAIDs and/or paracetamol. All except one patient successfully tolerated an oral challenge with etoricoxib. Of those who passed the DPT, the majority continued to use etoricoxib with no problems. It was found to be moderately effective in reducing fever and pain. CONCLUSION: Etoricoxib can be used as a safe alternative in older children with hypersensitivity to multiple antipyretics.

Gum pigmentation: an unusual adverse effect of sublingual immunotherapy.

Sublingual immunotherapy has gained acceptance amongst the paediatric community as it is very well tolerated and is safe. The adverse effects of this therapy is minimal consisting mainly of local side effects within the oral cavity such as itching of the mouth, swelling of the lips and less frequently abdominal pain, wheezing and urticaria has been described. This report is to highlight another local side effect of sublingual immunotherapy which has been observed in 3 of our patients. This is pigmentation of the gums which can occur anytime during the course of the immunotherapy. It resolves on stopping the immunotherapy and is likely due to a local inflammatory process occurring in the gums of these children. There is no associated pain or itching with the pigmentation. It can persist as long as the child is on the immunotherapy.