Ectopic Calcification as Discernible Manifestation in Neonates with Pseudohypoparathyroidism Type 1a

The diagnosis of pseudohypoparathyroidism type 1a (PHP1a) is challenging, because both the osteodystrophy, such as brachydactyly and round face, and the symptomatic hypocalcemia usually develop beyond infancy. Although ectopic calcification may be an early sign of PHP1a, there are no systematic reviews regarding the time of its appearance. We here report on two PHP1a patients who presented with subcutaneous calcification in neonatal period

Patient-reported outcomes from a randomized, active-controlled, open-label, phase 3 trial of burosumab versus conventional therapy in children with X-linked hypophosphatemia

Changing to burosumab, a monoclonal antibody targeting fibroblast growth factor 23, significantly improved phosphorus homeostasis, rickets, lower-extremity deformities, mobility, and growth versus continuing oral phosphate and active vitamin D (conventional therapy) in a randomized, open-label, phase 3 trial involving children aged 1-12 years with X-linked hypophosphatemia. Patients were randomized (1:1) to subcutaneous burosumab or to continue conventional therapy. We present patient-reported outcomes (PROs) from this trial for children aged ≥ 5 years at screening (n = 35), using a Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire and SF-10 Health Survey for Children. PROMIS pain interference, physical function mobility, and fatigue scores improved from baseline with burosumab at weeks 40 and 64, but changed little with continued conventional therapy. Pain interference scores differed significantly between groups at week 40 (- 5.02, 95% CI - 9.29 to - 0.75; p = 0.0212) but not at week 64. Between-group differences were not significant at either week for physical function mobility or fatigue. Reductions in PROMIS pain interference and fatigue scores from baseline were clinically meaningful with burosumab at weeks 40 and 64 but not with conventional therapy. SF-10 physical health scores (PHS-10) improved significantly with burosumab at week 40 (least-squares mean [standard error] + 5.98 [1.79]; p = 0.0008) and week 64 (+ 5.93 [1.88]; p = 0.0016) but not with conventional therapy (between-treatment differences were nonsignificant). In conclusion, changing to burosumab improved PRO measures, with statistically significant differences in PROMIS pain interference at week 40 versus continuing with conventional therapy and in PHS-10 at weeks 40 and 64 versus baseline

Burosumab vs conventional therapy in children with X-linked hypophosphatemia:results of the open-label, phase 3 extension period

In a randomized, open-label phase 3 study of 61 children aged 1–12 years old with X-linked hypophosphatemia (XLH) previously treated with conventional therapy, changing to burosumab every 2 weeks (Q2W) for 64 weeks improved the phosphate metabolism, radiographic rickets, and growth compared with conventional therapy. In this open-label extension period (weeks 64–88), 21 children continued burosumab Q2W at the previous dose or crossed over from conventional therapy to burosumab starting at 0.8 mg/kg Q2W with continued clinical radiographic assessments through week 88. Efficacy endpoints and safety observations were summarized descriptively for both groups (burosumab continuation, n = 6; crossover, n = 15). At week 88 compared with baseline, improvements in the following outcomes were observed in the burosumab continuation and crossover groups, respectively: mean (SD) RGI-C rickets total score (primary outcome), +2.11 (0.27) and +1.89 (0.35); mean (SD) RGI-C lower limb deformity score, +1.61 (0.91) and +0.73 (0.82); and mean (SD) height Z-score + 0.41 (0.50) and +0.08 (0.34). Phosphate metabolism normalized rapidly in the crossover group and persisted in the continuation group. Mean (SD) serum alkaline phosphatase decreased from 169% (43%) of the upper limit of normal (ULN) at baseline to 126% (51%) at week 88 in the continuation group and from 157% (33%) of the ULN at baseline to 111% (23%) at week 88 in the crossover group. During the extension period, treatment-emergent adverse events (AEs) were reported in all 6 children in the burosumab continuation group and 14/15 children in the crossover group. The AE profiles in the randomized and extension periods were similar, with no new safety signals identified. Improvements from baseline in radiographic rickets continued in the extension period among children with XLH who remained on burosumab. Children who crossed over from conventional therapy to burosumab demonstrated a rapid improvement in phosphate metabolism and improved rickets healing over the ensuing 22 weeks

Impact of Gender on In-hospital Mortality in Patients with Acute Myocardial Infarction in Nagasaki

Acute myocardial infarction (AMI) is one of the leading causes of death in Japan. Immediate reperfusion therapy, includingcoronary intervention, improves patient prognosis. Despite this, females are said to be more prone to poor prognosis. A regional AMI registry in Nagasaki prefecture has been instituted recently that will evaluate whether female gender might predict short-term in-hospital death. Seventeen regional AMI centers enrolled all AMI patients from September 2014 through March 2016. A propensity score (PS) was derived using logistic regression to model the probability of females as a total function of the potential confounding covariates. Two types of PS techniques were used: PS matching and PS stratification. The consistency of in-hospital death was determined between PS matched patients of both genders. Based on PS, patients were ranked and stratified into five groups for the PS stratification. Out of 996 patients, 67 (6.7%) died during hospitalization: 31 (10.4%) out of 298 females and 36 (5.2%) out of 698 males (p < 0.0025). The proportion of cardiac and non-cardiac related death was almost same between genders (25 and 6 in female, 29 and 7 in male, respectively). Among 196 PS matched patients, there was a consistency between genders regarding in-hospital deaths (McNemar test, p = 0.6698). The 717 propensity scored patients had no significant differences between genders among propensity quintiles (Cochran-Mantel-Heanszel test, p = 0.7117). We found that gender alone is not an indicator of short-term in-hospital death in acute myocardial infarction patients