Response to Alpelisib in Clinically Distinct Pediatric Patients With PIK3CA -related Disorders.

PIK3CA -related disorders include vascular malformations, potential overgrowth of various tissues, limb abnormalities, disordered soft tissue, and/or fatty hyperplasia that often leads to significant morbidity. Alpelisib, a targeted inhibitor of p110α, an enzyme encoded by the PIK3CA gene, has demonstrated success in a cohort of patients with PIK3CA -driven overgrowth syndromes. We describe the clinical course of 2 pediatric patients treated with alpelisib under the Novartis Managed Access Program. Both patients, though clinically distinct, demonstrate improvements in overgrowth volumes/extent, function of their affected limb, and quality of life, without significant adverse effects after prolonged treatment.

Pediatric Non-Myofibroblastic Primitive Spindle Cell Tumors with ALK Gene Rearrangements and Response to Crizotinib.

We describe two poorly differentiated, non-myofibroblastic (SMA-, S100+, CD34±), spindle cell neoplasms with immunohistochemical positivity for ALK and with ALK gene rearrangements leading to PLEKHH2::ALK and CLTC::ALK fusions, respectively. ALK protein overexpression and/or gene fusions should be evaluated in poorly differentiated spindle cell neoplasms, even when there is an absence of a myofibroblastic phenotype. A positive ALK evaluation has therapeutic implications as both tumors responded to single-agent treatment with the tyrosine kinase inhibitor crizotinib.

Unsuspected, disseminated coccidioidomycosis without maternofetal morbidity diagnosed by placental examination: case report and review of the literature.

Historically, untreated disseminated coccidioidomycosis during pregnancy was thought to be associated with 100% maternal fatality and 50% fetal mortality and was the leading cause of maternal deaths in areas of endemicity. As recently as 1995, therapeutic abortions and early deliveries were advocated in certain contexts. This report describes an unrecognized case of disseminated coccidioidomycosis diagnosed at the time of placental examination in a woman who completed her pregnancy without significant maternofetal complications. This case suggests that abortion and early delivery may not be necessary, because the possibility of an uncomplicated pregnancy exists. It is likely that other similar cases exist but remain underreported or underdiagnosed because of the mild, nondescript nature of the illness and low clinical suspicion. Although this mother and infant had good clinical outcomes, thorough travel histories and consideration of the associated travel-related diseases are important because of the possibility of serious, potentially avoidable clinical consequences.

Improved Magnetic Resonance Imaging Utilization for Children with Musculoskeletal Infection.

BACKGROUND: Magnetic resonance imaging (MRI) with sedation is an important resource used to evaluate children with musculoskeletal infection. This study assesses the impact of multidisciplinary guidelines and continuous process improvement on MRI utilization at a tertiary pediatric medical center. METHODS: A multidisciplinary team developed a guideline for MRI with sedation, and it was implemented at our institution. Scan duration, anatomic regions imaged, sequences performed, timing of surgical intervention, length of hospital stay, and readmissions for these children were compared with these measures among a cohort of similar children who had been treated prior to guideline implementation. Comparative data were gathered for the subsequent cohort to determine any impact of the continued process improvement program on MRI utilization. Statistical comparison was performed to determine significant differences between groups. RESULTS: Children evaluated prior to the guideline implementation had 9.0 MRI sequences per scan, an MRI scan duration of 111.6 minutes, and a hospital stay of 7.5 days. In comparison, children in the initial MRI guideline cohort had 7.5 sequences per scan, a scan duration of 76.1 minutes, and a hospital stay of 5.4 days. Children in the subsequent guideline cohort had 6.5 sequences per scan, a scan duration of 56.3 minutes, and a hospital stay of 5.0 days. The rate of immediate surgical procedure under continued anesthesia was 16.7% prior to the guideline, 50.5% among children in the initial guideline cohort, and 64% among children in the subsequent guideline cohort. Differences between cohorts were significant (p < 0.0001). In aggregate, 264 hours of MRI scan time and 809 hospital bed-days were conserved for more than thirty months. CONCLUSIONS: This initiative promoted improvement in diagnostic efficiency, therapeutic consistency, and patient safety for children with musculoskeletal infection. CLINICAL RELEVANCE: The findings of this study illustrate the beneficial impact of interdisciplinary coordination of care on clinical outcomes for children with musculoskeletal infection. Tangible improvements occurred for both length of stay and resource utilization.

Radioiodine studies, low serum thyrotropin, and the influence of statin drugs.

BACKGROUND: A low serum thyrotropin (TSH) concentration is an excellent predictor of hyperthyroidism, either overt or subclinical. Whether statin use influences the ability of a low serum TSH measurement to detect hyperthyroidism has not been evaluated. METHODS: In a cohort of 307 patients with low or undetectable serum TSH concentrations suggestive of hyperthyroidism, we determined whether concurrent statin use influenced the results of radioiodine uptakes and scans. Participants included 29 patients taking a statin medication and 278 who were not taking a statin. Radioiodine uptakes and scans were interpreted by board-certified nuclear medicine physicians. RESULTS: Sixteen of the 29 patients who were taking a statin (55%) had normal radioiodine uptakes and scans despite their low serum TSH. The remaining 13 low-TSH patients who were taking a statin (45%) had abnormal uptakes and scans, most commonly showing diffuse thyroid hyperplasia with increased radioiodine uptake. In contrast, the vast majority of the 278 patients not taking a statin had abnormal uptakes and scans (84%), while only 16% of them had normal uptakes and scans (p < 0.001 vs. those on statins). The age- and sex-adjusted odds ratio of a statin user with a low serum TSH having normal radioiodine studies (as opposed to abnormal studies) was 3.6 (95% CI, 1.6-8.4). CONCLUSION: In patients with a low serum TSH concentration, normal thyroid function and morphology, as assessed by radioiodine studies, were much more common if the patient was taking a statin. Statins may falsely lower the serum TSH without altering thyroid function ("pseudohyperthyroidism") or, alternatively, statins may improve thyroid function in patients with hyperthyroidism.