Clinical Characteristics and Management of Children and Adolescents Hospitalized With Pyomyositis.

BACKGROUND: Pyomyositis, a bacterial muscle infection, is an important differential diagnosis in children and adolescents with musculoskeletal pain. In contrast to tropical regions, it is rarely recognized in temperate countries, but incidence is increasing and major studies are missing. METHODS: This retrospective multicenter study included patients <18 years of age hospitalized with pyomyositis in 11 Swiss children's hospitals between January 2010 and December 2022. Cases were identified by ICD-10 code (Myositis; M60-M60.9), and data was extracted from electronic hospital records. RESULTS: Of 331 patients identified, 102 fulfilled the case definition. Patient age at presentation ranged from 2 weeks to 17 years (median 8 years). The majority had no underlying illness and all presented with fever and localized pain. At the respective site of pyomyositis, 100 (98%) had impaired movement and 39 (38%) presented with local swelling. Pelvic (57%) and leg (28%) muscles were mostly affected. Blood or tissue cultures were obtained in 94 (92%) and 59 (57%) patients, respectively. Of those, 55 (58%) blood and 52 (88%) tissue cultures were positive, mainly for Staphylococcus aureus (35 and 19, respectively) and Streptococcus pyogene s (12 and 15, respectively). All patients received antibiotic treatment during hospitalization for a median of 10 days (interquartile range: 7-17), followed by outpatient treatment for a further median of 16 days (interquartile range: 11-22) in 95 (93%) patients. Fifty-nine (57%) patients required surgery. CONCLUSIONS: Pyomyositis is a challenging diagnosis that requires a high level of awareness. Blood and/or tissue cultures revealed S. aureus and S. pyogenes as the predominant causative agents.

Anti-mullerian hormone deficiency in girls with congenital multiple pituitary hormone deficiency.

CONTEXT: Anti-Mullerian hormone (AMH) is believed to validly reflect the ovarian reserve. We wanted to test whether congenital absence of gonadotropin stimulation of the ovaries affects AMH production. OBJECTIVE: The objective of the study was to test the validity of AMH as a marker for the ovarian reserve in females with congenital multiple pituitary hormone deficiency (MPHD; deficiency of three or more axes). DESIGN: This was a retrospective laboratory study. SETTING: The study was conducted in the Department of Pediatric Endocrinology in a tertiary center. PATIENTS: The AMH serum levels were assessed in females with congenital (n = 16; median age 12.5 y, range 0.7-31 y) or acquired (n = 20; 18.5 y, range 2-33 y) MPHD and in controls with short stature (n = 100; 9.7 y, range 2-17 y). MAIN OUTCOME MEASURE: AMH was measured by AMH Gen II ELISA from Beckmann Coulter. RESULTS: In the controls, AMH ranged between 1.8 (P3) and 67.8 pmol/L (P97). Three patients with a severe form of congenital MPHD were AMH deficient, whereas the other 33 patients with MPHD had normal AMH levels. There was significantly more AMH deficiency in congenital than in acquired MPHD (P < .05). CONCLUSIONS: Most girls with MPHD have normal serum AMH levels. However, some females with severe congenital MPHD are AMH deficient. This deficiency might be the result of the total absence of gonadotropins. In these females, AMH is unlikely to be an accurate prognostic parameter of the efficacy of fertility treatment.

Influence of dichloroacetate (DCA) on lactate production and oxygen consumption in neuroblastoma cells: is DCA a suitable drug for neuroblastoma therapy?

Many cancer cells metabolize glucose preferentially via pyruvate to lactate instead to CO(2) and H(2)O (oxidative phosphorylation) even in the presence of oxygen (Warburg effect). Dichloroacetate (DCA) is a drug which is able to shift pyruvate metabolism from lactate to acetyl-CoA (tricarboxylic acid cycle) by indirect activation of pyruvate dehydrogenase (PDH). This can subsequently lead to an increased flow of oxygen in the respiratory chain, associated with enhanced generation of reactive oxygen species (ROS) which may cause apoptosis. In order to investigate if DCA may be suitable for neuroblastoma therapy, it was investigated on three human neuroblastoma cell lines whether DCA can reduce lactate production and enhance oxygen consumption. The data show, that DCA (in the low millimolar range) is able to reduce lactate production, but there was only a slight shift to increased oxygen consumption and almost no effect on cell vitality, proliferation and apoptosis of the three cell lines investigated. Therefore, DCA at low millimolar concentrations seems to be only of minor efficacy for neuroblastoma treatment.

H(2)O(2)-mediated cytotoxicity of pharmacologic ascorbate concentrations to neuroblastoma cells: potential role of lactate and ferritin.

By intravenous (but not oral) application of ascorbate, millimolar serum concentrations can be reached, which are preferentially cytotoxic to cancer cells. Cytotoxicity is mediated by transition metal-dependent generation of H(2)O(2) in the interstitial space. In this study, the sensitivity of neuroblastoma cells (Kelly, SK-N-SH) to ascorbate and H(2)O(2) and their defense mechanisms against H(2)O(2) were investigated. Since aerobic glycolysis (the Warburg effect) is a feature of many tumour cells, their glucose consumption and lactate production were monitored. Furthermore, synthesis and release of ferritin by neuroblastoma cells were analysed in order to examine whether ferritin is possibly an iron source for H(2)O(2) generation. Ascorbate (0.6-5.0 mM) and H(2)O(2) (25-100 muM) were found to be similarly cytotoxic to Kelly and SK-N-SH cells. In each case, cytotoxicity increased if cell concentrations decreased, in accordance with low cell concentrations having lower capacities to detoxify H(2)O(2). Kelly and SK-N-SH cells produced and released remarkable amounts of lactate and ferritin. We propose the selective cytotoxicity of high dose ascorbate to tumour cells to be due to the preferential generation of H(2)O(2) in the acidic and ferritin-rich tumour microenvironment, combined with reduced defense systems against H(2)O(2) as a consequence of aerobic glycolysis.