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BackgroundFor large scale epidemiological studies clinical assessments and radiographs can be impractical and expensive to apply to more than just a sample of the population examined. The study objectives were to develop and validate two novel instruments for self-reported knee malalignment and foot rotation suitable for use in questionnaire studies of knee pain and osteoarthritis.MethodsTwo sets of line drawings were developed using similar methodology. Each instrument consisted of an explanatory question followed by a set of drawings showing straight alignment, then two each at 7.5° angulation and 15° angulation in the varus/valgus (knee) and inward/outward (foot) directions. Forty one participants undertaking a community study completed the instruments on two occasions. Participants were assessed once by a blinded expert clinical observer with demonstrated excellent reproducibility. Validity was assessed by sensitivity, specificity and likelihood ratio (LR) using the observer as the reference standard. Reliability was assessed using weighted kappa (κ). Knee malalignment was measured on 400 knee radiographs. General linear model was used to assess for the presence of a linear increase in knee alignment angle (measured medially) from self-reported severe varus to mild varus, straight, mild valgus and severe valgus deformity.ResultsObserver reproducibility (κ) was 0.89 and 0.81 for the knee malalignment and foot rotation instruments respectively. Self-reported participant reproducibility was also good for the knee (κ 0.73) and foot (κ 0.87) instruments. Validity was excellent for the knee malalignment instrument, with a sensitivity of 0.74 (95%CI 0.54, 0.93) and specificity of 0.97 (95%CI 0.94, 1.00). Similarly the foot rotation instrument was also found to have high sensitivity (0.92, 95%CI 0.83, 1.01) and specificity (0.96, 95%CI 0.93, 1.00). The knee alignment angle increased progressively from self reported severe varus to mild varus, straight, mild valgus and severe valgus knee malalignment (ptrend <0.001).ConclusionsThe two novel instruments appear to provide a valid and reliable assessment of self-reported knee malalignment and foot rotation, and may have a practical use in epidemiological studies.

Heterozygous pathogenic variants in <i>SPTB</i> cause autosomal dominant hereditary spherocytosis, an important cause of neonatal nonimmune hemolytic anemia. Biallelic mutations are rarely reported, all with severe neonatal presentation. We describe rapid (68 h) genomic diagnosis of homozygous β-spectrin deficiency in a newborn with severe transfusion-dependent hemolytic anemia, conjugated hyperbilirubinemia, and progressive liver failure. Trio whole-exome sequencing identified a novel biallelic <i>SPTB</i> variant (c.6119C>T; p.Thr2040Ile) located in the critical spectrin repeat region. Pretransfusion blood film showed marked spherocytosis including microspherocytes and nucleated erythrocytes, and eosin-5-maleimide (E5M) staining was markedly reduced, supporting pathogenicity. Both asymptomatic heterozygous parents demonstrated mildly reduced E5M staining, with occasional spherocytes and elliptocytes. Early molecular diagnosis facilitated hypertransfusion to suppress ineffective erythropoiesis and reverse hepatic dysfunction. This report broadens the genotypic and phenotypic spectrum of spectrin deficiency and highlights the utility of rapid genomic testing in facilitating early diagnosis and informing targeted therapy in critically ill patients.

Oesophageal perforation is severe complication secondary to instrumentation of the upper gastrointestinal tract in neonates. Prompt and accurate diagnosis is crucial. Non-operative management is effective for the majority, though morbidity is common.