The calcium-sensing receptor (CaSR) regulates PTH secretion to control the extracellular calcium concentration in adults, but its role in fetal life is unknown. We used CaSR gene knockout mice to investigate the role of the CaSR in regulating fetal calcium metabolism. The normal calcium concentration in fetal blood is raised above the maternal level, an increase that depends upon PTH-related peptide (PTHrP). Heterozygous (+/-) and homozygous (-/-) disruption of the CaSR caused a further increase in the fetal calcium level. This increase was modestly blunted by concomitant disruption of the PTHrP gene and completely reversed by disruption of the PTH/ PTHrP receptor gene. Serum levels of PTH and 1, 25-dihydroxyvitamin D were substantially increased above the normal low fetal levels by disruption of the CaSR. The free deoxypyridinoline level was increased in the amniotic fluid (urine) of CaSR-/- fetuses; this result suggests that fetal bone resorption is increased. Placental calcium transfer was reduced, and renal calcium excretion was increased, by disruption of the CaSR. These studies indicate that the CaSR normally suppresses PTH secretion in the presence of the normal raised (and PTHrP-dependent) fetal calcium level. Disruption of the CaSR causes fetal hyperparathyroidism and hypercalcemia, with additional effects on placental calcium transfer.

The Third International Conference on Controversies in Vitamin D was held in Gubbio, Italy, September 10–13, 2019. The conference was held as a follow‐up to previous meetings held in 2017 and 2018 to address topics of controversy in vitamin D research. The specific topics were selected by the steering committee of the conference and based upon areas that remain controversial from the preceding conferences. Other topics were selected anew that reflect specific topics that have surfaced since the last international conference. Consensus was achieved after formal presentations and open discussions among experts. As will be detailed in this article, consensus was achieved with regard to the following: the importance and prevalence of nutritional rickets, amounts of vitamin D that are typically generated by sun exposure, worldwide prevalence of vitamin D deficiency, the importance of circulating concentrations of 25OHD as the best index of vitamin D stores, definitions and thresholds of vitamin D deficiency, and efficacy of vitamin D analogues in the treatment of psoriasis. Areas of uncertainly and controversy include the following: daily doses of vitamin D needed to maintain a normal level of 25OHD in the general population, recommendations for supplementation in patients with metabolic bone diseases, cutaneous production of vitamin D by UVB exposure, hepatic regulation of 25OHD metabolites, definition of vitamin D excess, vitamin D deficiency in acute illness, vitamin D requirements during reproduction, potential for a broad spectrum of cellular and organ activities under the influence of the vitamin D receptor, and potential links between vitamin D and major human diseases. With specific regard to the latter area, the proceedings of the conference led to recommendations for areas in need of further investigation through appropriately designed intervention trials. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

A lthough guidelines are available for managing hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) 1,2 and our understanding of these diseases is growing, their incidence does not seem to be decreasing. 3 And the toll is high. About 10% of patients put on mechanical ventilation develop VAP, 3 and the mortality rate in VAP has been estimated at 13%. 4 Together, HAP and VAP accounted for 22% of hospital-acquired infections in a 2014 survey of 183 US hospitals. 5 Patients with VAP face a longer hospital course and incur higher healthcare costs than similarly ill patients without VAP. 1 This review discusses the diagnosis, management, and prevention of HAP and VAP using the 2016 guidelines from the Infectious Diseases Society of America (IDSA) and American Thoracic Society (ATS), 1 as well as recent literature regarding controversial topics such as the role for procalcitonin testing and adjunctive inhaled aminoglycosides. ■ TERMSHAP is a new pneumonia (a lower respiratory tract infection verifi ed by the presence of a new pulmonary infi ltrate on imaging) that develops more than 48 hours after admission in nonintubated patients.VAP, the most common and fatal nosocomial infection of critical care, is a new pneumonia that develops after 48 hours of endotracheal intubation. Importantly, by the time of VAP onset, patients may have already been extubated.

Granulomatous mastitis is an uncommon inflammatory disease that typically presents with painful breast lesions. Recent publications have brought to light a specific subset of granulomatous mastitis patients with a distinct histological pattern of disease termed, “cystic neutrophilic granulomatous mastitis” (CNGM). Although many cases of granulomatous lobular mastitis have been thought to be idiopathic, this rare subset of an uncommon disease has been linked to infections with Corynebacterium species. Herein, a cohort of CNGM patients from a large, tertiary care, North‐American, academic medical center is presented. Correlative demographic, clinical, radiographic, pathologic, microbiologic, management, and outcomes data are provided. Collaborative communication between specialists to accurately diagnose and manage these patients is essential to decreasing potential morbidity.