Nephropathy in a Child with Severe Recessive Dystrophic Epidermolysis Bullosa Treated with Cyclophosphamide: A Case Report.

Long-term inflammation and recurrent skin infection in recessive dystrophic epidermolysis bullosa (RDEB) are associated with the presence of immunoglobulin A (IgA)-containing immune complexes in the glomerulus. Only eight pediatric RDEB cases with IgA nephropathy (IgAN) have been documented in English-language literature. Most RDEB patients with IgAN progress to kidney failure within 5 years of diagnosis, indicating that these patients may require more intensive early treatment compared to those with primary IgAN. However, diagnosing IgAN in RDEB cases with severe cutaneous manifestations can be challenging. Herein, we report a rare case of nephropathy in an 11-year-old boy with severe RDEB and a frameshift mutation on the COL7A1 gene, which may manifest as kidney disorders. He presented with persistent hematuria and progressing proteinuria. A presumptive IgAN diagnosis was based on clinical features and increased IgA serum levels, as kidney biopsy was refused by his parents. Nephrotic-range proteinuria persisted despite initial steroid and lisinopril treatment. Monthly intravenous cyclophosphamide (IV CPA; 500 mg/m2) led to proteinuria remission and preservation of kidney function for 2 years posttreatment. We conclude that COL7A1 mutations may result in extracutaneous manifestations, including kidney disorders. The association between IgA-containing immune complex deposits in the glomerulus and recurrent skin infection in RDEB may indicate IgAN, particularly when kidney biopsy is infeasible due to severe skin manifestations. In our case, positive results with IV CPA suggest further investigation is needed to explore its potential role in non-rapidly progressing IgAN in children with RDEB.

Diagnostic accuracy of gastroesophageal reflux disease questionnaire for gastroesophageal reflux disease: A systematic review and meta-analysis.

BACKGROUND: The use of a symptom-based gastroesophageal reflux disease (GERD) questionnaire (GerdQ) for GERD diagnosis has gained interest due to its greater efficacy and ease of use than other available questionnaires. However, different guidelines have given inconsistent recommendations regarding using GerdQ as a diagnostic test. This meta-analysis summarized the diagnostic accuracy of GerdQ for diagnosing GERD. METHODS: Studies published up to April 12, 2023, and indexed in MEDLINE, EMBASE, SCOPUS, Web of Science, and the Cochrane Library were searched. Diagnostic test accuracy studies comparing GerdQ with upper endoscopy and/or pH-metry for GERD diagnosis in adult patients with symptoms suggestive of GERD were included. The study quality was assessed using the QUADAS-2 tool. Meta-analysis using bivariate (Reitsma) analysis was done to summarize the overall sensitivity, specificity, likelihood ratios (LRs), and diagnostic odds ratio (DOR). The summary receiver operating characteristics (SROC) curve was visualized, and the area under the ROC (AUC) was calculated. KEY RESULTS: A total of 13 studies with 11,166 participants were included in the meta-analysis. The pooled sensitivity, specificity, positive LR, negative LR, and DOR for GerdQ (cut-off value of ≥8) were 66.9% (95% CI 56.4%-73.1%), 65.2% (95% CI 56.4%-73.1%), 1.93 (95% CI 1.55-2.42), 0.51 (95% CI 0.38-0.66), and 3.89 (95% CI 2.44-5.89), respectively. The overall AUC from the SROC was 0.705. The subgroup analysis showed similar pooled sensitivity, specificity, and DOR between Asian and non-Asian studies. CONCLUSIONS & INFERENCES: GerdQ had moderate sensitivity and specificity for GERD diagnosis. GerdQ can still be recommended as a diagnostic tool for GERD, especially when the PPI test is unavailable or contraindicated.

Distal renal tubular acidosis presenting with an acute hypokalemic paralysis in an older child with severe vesicoureteral reflux and syringomyelia: a case report.

BACKGROUND: Distal renal tubular acidosis (dRTA) is the most common type of renal tubular acidosis (RTA) in children. Pediatric dRTA is usually genetic and rarely occurs due to acquired issues such as obstructive uropathies, recurrent urinary tract infections (UTIs), and chronic kidney disease (CKD). Although persistent hypokalemia frequently occurs with dRTA, acute hypokalemic paralysis is not frequently reported, especially in older children. CASE PRESENTATION: An eight-year-old girl presented with an acute first episode of paralysis. A physical examination revealed normal vital signs, short stature consistent with her genetic potential, and decreased muscle strength of her upper and lower extremities. Preexisting conditions included stage 4 CKD due to recurrent UTIs, severe vesicoureteral reflux and bilateral hydronephrosis, neurogenic bladder, and multisegment thoracic syringomyelia. Her laboratory work-up revealed hypokalemic, hyperchloremic metabolic acidosis with a normal anion gap. She also had a urine osmolal gap of 1.9 mOsmol/kg with a high urine pH. Intravenous potassium replacement resulted in a complete resolution of her paralysis. She was diagnosed with dRTA and discharged with oral bicarbonate and slow-release potassium supplementation. CONCLUSIONS: This case report highlights the importance of considering dRTA in the differential diagnosis of hypokalemic acute paralysis in children. Additionally, in children with neurogenic lower urinary tract dysfunction and recurrent UTIs, early diagnosis of spinal cord etiology is crucial to treat promptly, slow the progression of CKD, and prevent long-term complications such as RTA.

Prognostic Value of COX-2, NF-κB, and Sp1 Tissue Expressions in Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is deadly cancer with a poor prognosis. Molecular prognostic markers are needed to predict the patient's survival. The cyclooxygenase-2 enzyme (COX-2) and its 2 major transcription factors--nuclear factorkappa B (NF-κB) and specificity protein 1 (Sp1)--are activated during inflammation caused by neoplasia. Several studies have investigated the association between the COX-2, NF-κB, and Sp1 tissue expressions with the patient's overall survival. Therefore, we conducted this systematic review and meta-analysis to evaluate those studies. METHODS: We searched for relevant articles from the MEDLINE database through June 2020. Studies were eligible if they included dichotomized tissue protein expression status and the overall survival as the outcome. We used RevMan and ProMeta programs to perform the meta-analysis. RESULTS: We identified 11 eligible studies. The meta-analysis showed that COX-2 tissue expression was associated with decreased overall survival (crude HR = 1.35; 95% CI, 1.05-1.74), although the result was not significant when controlling for other covariates. The NF-κB tissue expression was associated with decreased overall survival (crude HR = 2.18; 95% CI, 1.49-3.18), although it was not significant when controlling for other covariates. The Sp1 tissue expression showed significantly decreased overall survival even when adjusted with other covariates (aHR = 3.47; 95% CI, 1.52-7.94). The limitations included searching only for English publications and the substantial heterogeneity among the studies. CONCLUSION: COX-2, NF-κB, and Sp1 tissue expressions have the potential to be used as prognostic markers in PDAC. Further studies are still needed to clarify the associations.