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Tubulointerstitial nephritis (TIN) or acute interstitial nephritis (AIN) is a renal lesion characterized by inflammatory infiltrate limited to the renal interstitium and tubules. Three-fourths of the cases are drug induced, other causes being systemic and autoimmune diseases, and infections. Various drugs have been implicated, the most common being antibiotics such as β-lactams. Cephalosporins causing AIN have been reported uncommonly, particularly in children. Although renal biopsy confirms the diagnosis, urinalysis provides pertinent diagnostic clues against the backdrop of the clinico-laboratory profile. The presence of white blood cells, white cell casts, and red blood cells in urine sediment have been described in literature. However, a relatively normal urinalysis may be present in some cases and may pose a diagnostic challenge. We present a case of ceftriaxone-induced AIN in a child with bland urine sediment at initial presentation. To the best of our knowledge, this is the first report of ceftriaxone-induced AIN in the pediatric age group.

Summary: Background: The phenotypical profile of cardiovascular malformations in patients with congenital rubella syndrome (CRS) is varied. We aimed to describe the profile of cardiac defects among CRS patients detected in the sentinel CRS surveillance in India during 2016–22. Methods: Sentinel sites enrolled infants with suspected CRS based on presence of cardiac defects, hearing impairment, eye signs, or maternal history of febrile rash illness. Suspected CRS cases underwent detailed systemic examination, including echocardiography and serological investigation for rubella. Cardiac defects were categorized as ‘Simple’ or ‘Complex’ as per the National Heart, Lung, and Blood Institute classification. We compared the distribution of cardiac defects among laboratory confirmed CRS cases and seronegative discarded cases. Findings: Of the 4578 suspected CRS cases enrolled by 14 sites, 558 (12.2%) were laboratory confirmed. 419 (75.1%) laboratory confirmed cases had structural heart defects (simple defects: n = 273, 65.2%, complex defects: n = 144, 34.4%), with ventricular septal defect (42.7%), atrial septal defect (39.4%), patent ductus arteriosus (36.5%), and tetralogy of Fallot as the commonest defects (4.5%). Laboratory confirmed CRS cases had higher odds of left to right shunt lesions (OR = 1.58, 95% CI: 1.15–2.17). This was mainly on account of a significant association of PDA with CRS (OR = 1.77, 95% CI: 1.42–2.21). Mortality was higher among CRS patients with complex heart defects (HR = 2.04, 95% CI: 1.26–3.30). Interpretation: Three-fourths of the laboratory confirmed CRS cases had structural heart defects. CRS patients with complex cardiac defects had higher mortality. Detecting CRS infection early and providing timely intervention for cardiovascular defects is critical for the management of CRS patients. Funding: Ministry of Health and Family Welfare, Govt of India, through Gavi, the Vaccine Alliance.

Background: Tuberculosis (TB) is a common disease, especially in low-income countries, with a varied clinical spectrum involving multiple organs. Although liver abscess can be seen in 70% of patients with miliary tuberculosis, isolated tuberculous liver abscess (ILTA) is rare in immunocompetent children. Liver involvement, though seen in up to 70% of patients as a part of miliary TB, isolated tuberculous liver abscess (ITLA) is rare in 13 children. Objective: The present systematic review focuses on demographic parameters, clinical presentations, duration of antitubercular treatment, and the need for surgical intervention and recurrence in children with tuberculous liver abscess. Methods: A comprehensive search was done in major databases PubMed and Google Scholar using defined search terms encompassing case reports or case series on isolated tubercular liver abscess in children. The identified reports underwent screening by three different authors for inclusion and exclusion criteria. Results: The median (interquartile range [IQR]) age of presentation was 9.5 (6.5) years, with a slightly higher prevalence in females (59%). The most common presenting symptom was fever (95%), followed by abdominal pain (68%). Hepatomegaly was seen in 90% of cases and jaundice in 16%. The median (IQR) duration of antitubercular treatment was 6 (4) months and surgical intervention was required for 14 (63%) children. The resolution time of the ITLA varied across the children, with a median (IQR) time being 2 (7) months. Conclusion: Pediatric tubercular liver abscess requires a high index of suspicion, particularly in endemic countries like India. Children with liver abscess should be evaluated for TB, if response to initial management is poor. Early diagnosis and prompt treatment with systemic antitubercular treatment are associated with a favorable outcome.

Background: Echinococcosis is a zoonotic tapeworm infection caused by Echinococcus granulosus, occasionally affecting humans. The larval infection most commonly affects the liver and lungs and very rarely the kidneys. Objective: The present systematic review compiles data regarding clinical presentations, diagnostic modalities, management strategies and recurrences in children with isolated renal hydatid cysts. Methods: A comprehensive search was done in major databases PubMed and Google Scholar using defined search terms encompassing case reports or case series on isolated renal hydatid cysts in children. The identified reports underwent screening by three different authors for inclusion and exclusion criteria. Results: The median (range) age at presentation of isolated renal hydatid disease was 10 (6) years with female preponderance (52.7%). Most common presenting symptom and sign were abdominal pain (64.8%) and palpable abdominal mass (56.7%), respectively. Ultrasonography (94.5%) was most common diagnostic method. Patients were primarily managed with surgical interventions (95.5%) and only 2/37 were managed solely by medical management for a median duration of 3.5 weeks. Laparoscopic cystectomy was the most commonly used surgical procedure (45.9%). Recurrence was observed to be rare, seen in only 3 cases. Conclusion: Hydatid cysts need to be considered in the differential diagnosis of renal cysts. Radiological evaluation with pathological confirmation enables diagnosis. Surgery combined with adjuvant anti-parasitic chemotherapy is used to treat the condition.

BackgroundIn India, under-five children with Severe Acute Malnutrition (SAM) are referred to Nutritional Rehabilitation Centers (NRCs). NRCs screen the causes of SAM including tuberculosis (TB). The national TB programme recommends upfront testing with a rapid molecular test if TB is suspected in children.ObjectiveWe estimated the yield of and adherence to the TB diagnostic guidelines (clinical assessment and assessment for microbiological confirmation) among under-five children with SAM admitted at NRCs (six in district Sagar and four in district Sheopur) of Madhya Pradesh, India in 2017. We also explored the challenges in screening from the health care providers' perspective.MethodsIt was an explanatory mixed method study. The NRC records were reviewed This was followed by three key informant interviews and three focus group discussions among staff of NRC and TB programme. Manual descriptive thematic analysis was performed.ResultsOf 3230, a total of 2665(83%) children underwent Mantoux test, 2438(75%) underwent physical examination, 2277(70%) were asked about the symptoms suggestive of TB, 1220(38%) underwent chest radiograph and 485(15%) were asked for recent contact with TB. A total of 547(17%) underwent assessment for microbiological confirmation. Of 547, a total of 229 gastric aspirate specimens underwent rapid molecular test (24% positive) and 318 underwent sputum microscopy (44% positive). A total of 223 were diagnosed as TB (195 microbiologically and 28 clinically confirmed) and 209 were initiated on anti-TB treatment. The treatment outcome was favourable (cure or treatment completed) for 70(31%) and not recorded for 121(54%). The main perceived challenges in screening for TB were poor team skills, lack of diagnostic facilities and poor understanding of the guidelines due to inadequate training.ConclusionThough NRCs provided a unique window of opportunity for the screening and management of TB among under-five children with SAM, the utilization of this opportunity remained suboptimal.

Prostate cancer (PCa) is the second most common cancer diagnosed in men. While radical prostatectomy and radiotherapy are often successful in treating localised disease, post-treatment recurrence is common. As the androgen receptor (AR) and androgen hormones play an essential role in prostate carcinogenesis and progression, androgen deprivation therapy (ADT) is often used to deprive PCa cells of the pro-proliferative effect of androgens. ADTs act by either blocking androgen biosynthesis (e.g. abiraterone) or blocking AR function (e.g. bicalutamide, enzalutamide, apalutamide, darolutamide). ADT is often effective in initially suppressing PCa growth and progression, yet emergence of castrate-resistant PCa and progression to neuroendocrine-like PCa following ADT are major clinical challenges. For this reason, there is an urgent need to identify novel approaches to modulate androgen signalling to impede PCa progression whilst also preventing or delaying therapy resistance.The mechanistic convergence of androgen and epitranscriptomic signalling offers a potential novel approach to treat PCa. The epitranscriptome involves covalent modifications of mRNA, notably, in the context of this review, the N(6)-methyladenosine (m6A) modification. m6A is involved in the regulation of mRNA splicing, stability, and translation, and has recently been shown to play a role in PCa and androgen signalling. The m6A modification is dynamically regulated by the METTL3-containing methyltransferase complex, and the FTO and ALKBH5 RNA demethylases.Given the need for novel approaches to treat PCa, there is significant interest in new therapies that target m6A that modulate AR expression and androgen signalling. This review critically summarises the potential benefit of such epitranscriptomic therapies for PCa patients.