Autosomal dominant hypocalcemia (ADH) type 1 and 2 are disorders of calcium homeostasis caused by gain of function variants. The calcium-sensing receptor (CaSR) is a class C GPCR that responds to elevated extracellular calcium (Ca²⁺ _o) by inhibiting parathyroid hormone (PTH) secretion and promoting renal excretion of Ca²⁺ and other salts to restore physiologically normal Ca²⁺ _o concentrations. CaSR negative allosteric modulators (NAMs) transiently raise PTH levels in individuals with ADH1, restoring Ca²⁺ _o concentration to a physiological normal range. Herein we disclose the discovery of a chemoreactive NAM (ATF936-NCS, 4) for the CaSR that (i) is wash-resistant indicative of irreversible receptor binding and (ii) stimulates prolonged PTH release in vivo. This 'first-in-class' chemical probe will provide invaluable insight towards the development of longer acting NAMs for the treatment of ADH.

Purpose: Infection following total hip arthroplasty is a challenging and devastating complication. In two-stage revision arthroplasty, antibiotic spacers, although efficacious, can be associated with an unacceptable rate of mechanical complications (e.g., fracture, dislocation). This series describes 15 patients with infected total hip prostheses treated with hybrid cement-screw fixation constrained liner antibiotic spacers to enhance stability and minimize mechanical complications. Materials and Methods: All patients with an infected hip prosthesis undergoing two-stage revision arthroplasty at a single academic medical center were identified and screened for inclusion. Clinical and radiographic data including patient demographics and outcome measures were collected and retrospectively analyzed. Results: Two patients died of unrelated causes at an average of 6-week postoperatively. Infections in the remaining thirteen patients (100%) were successfully eradicated; all underwent uncomplicated revision arthroplasty at a mean duration of 99.5 days after the placement of the antibiotic spacer. No dislocations, fractures, or other mechanical failures of any spacer were observed in this series. Conclusion The hybrid cement-screw fixation technique for constrained liner antibiotic spacers is a reliable and effective treatment method for eradicating prosthetic joint infections without mechanical complications.

Displaced pelvic ring injuries can be challenging to even the experienced orthopedic traumatologist. A temporary external fixation to table construct provides a quick, simple, and accessible means of external skeletal fixation to reliably obtain and maintain stable hemipelvis reduction on the operating room table. The contralateral hemipelvis can be stabilized to the table by use of Steinman pins safely inserted into the subtrochanteric and anterior column regions and later connected to external fixator bars attached to the table. With rigid stabilization, the displaced contralateral pelvic fragment(s) can be reduced in a more vector intentional manner with greater force than the traditional means of pelvic reduction can allow. The skeletal-table fixation technique is presented along with two cases, a combined pelvic-acetabular injury and an isolated pelvic ring injury.