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Introduction: Long-term proton pump inhibitor (PPI) use has been associated with hypomagnesemia. It is unknown how frequently PPI use is implicated in patients with severe hypomagnesemia, and its clinical course or risk factors. Methods: All patients with severe hypomagnesemia from 2013 to 2016 in a tertiary center were assessed for likelihood of PPI-related hypomagnesemia using Naranjo algorithm, and we described the clinical course. The clinical characteristics of each case of PPI-related severe hypomagnesemia was compared with three controls on long-term PPI without hypomagnesemia, to assess for risk factors of developing severe hypomagnesemia. Results: Amongst 53,149 patients with serum magnesium measurements, 360 patients had severe hypomagnesemia (<0.4 mmol/L). 189 of 360 (52.5%) patients had at least possible PPI-related hypomagnesemia (128 possible, 59 probable, two definite). 49 of 189 (24.7%) patients had no other etiology for hypomagnesemia. PPI was stopped in 43 (22.8%) patients. Seventy (37.0%) patients had no indication for long-term PPI use. Hypomagnesemia resolved in most patients after supplementation, but recurrence was higher in patients who continued PPI, 69.7% versus 35.7%, p = 0.009. On multivariate analysis, risk factors for hypomagnesemia were female gender (OR 1.73; 95% CI: 1.17-2.57), diabetes mellitus (OR, 4.62; 95% CI: 3.05-7.00), low BMI (OR, 0.90; 95% CI: 0.86-0.94), high-dose PPI (OR, 1.96; 95% CI: 1.29-2.98), renal impairment (OR, 3.85; 95% CI: 2.58-5.75), and diuretic use (OR, 1.68; 95% CI: 1.09-2.61). Conclusion: In patients with severe hypomagnesemia, clinicians should consider the possibility of PPI-related hypomagnesemia and re-examine the indication for continued PPI use, or consider a lower dose., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Seah, Tan, Teh, Loh, Tan, Goh, Malakar, Aw, Lau, Dhalliwal, Kui, Kam, Khoo, Tay, Tan, Au, Soh, Zhang, King, Gani and Puar.)

Bisphosphonates (BP) are the most commonly prescribed effective form of osteoporosis treatment with adverse effects associated with prolonged use such as atypical femoral fractures (AFF). Asians have an elevated risk of AFF at 5 to 6 times those of whites and Hispanics. In this study, we characterize factors associated with AFF and its mortality in a single center in Singapore. We conducted a cohort study of subjects older than 50 years admitted to Changi General Hospital (CGH), Singapore, with fragility subtrochanteric femoral fractures from 2009 to 2015. Using the ASBMR 2014 criteria, fractures are classified into atypical and typical subtrochanteric femoral fractures. CGH uses a nationalized electronic health record that allows review of information on patients' demographics, clinical history and previous investigations. Mortality was assessed as of December 31, 2019. Between 2009 and 2015, there were 3097 hip fractures, of which 393 were subtrochanteric femoral fractures and 69 were classified as AFF by ASBMR 2014 criteria. A total of 52.2% of AFF occurred with BP exposure of median duration 56.5 (28 to 66) months. Multivariate regression showed that BP exposure was associated with the highest risk of AFF (odds ratio [OR] = 6.65 [2.35-18.9]). AFF patients had higher 5-year survival (0.85 versus 0.62, p  = 0.001) compared with typical subtrochanteric fracture patients. However, after adjusting for variables, the type of subtrochanteric femoral fractures were no longer significantly associated with progression to death, whereas older age, higher mean Charlson comorbidity score, and Malay ethnicity were the strongest predictors of death. AFF constitutes a small proportion of hip and femoral fractures with prolonged BP use being the highest risk factor for its development. There is no evidence of increased mortality or morbidity in patients with AFF compared with the typical subtrochanteric fracture. The fear of AFF should not impede treatment of typical osteoporotic fractures in this population. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., (© 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

Introduction: This is the first report of which the authors are aware to describe this c.2166delinsGG mutation in X-linked hypophosphataemia and to describe normalisation of renal threshold for phosphate excretion after parathyroidectomy for tertiary hyperparathyroidism in X-linked hypophosphataemia., Case Presentation: We present the case of a 34-year-old Caucasian woman with X-linked hypophosphataemia. She developed tertiary hyperparathyroidism with markedly high bone turnover requiring total parathyroidectomy and had prolonged requirement for intravenous calcium infusion after surgery. She had a novel mutation in her phosphate-regulating gene with homologies to endopeptidases on the X-chromosome and had an unusual degree of dependence on phosphate supplementation. Prior to operative intervention she had a trial of cinacalcet that improved bone turnover markers when used in isolation but which led to a paradoxical rise in parathyroid hormone levels when given with phosphate supplementation. After correction of hungry bone syndrome, the renal phosphorus threshold normalised as a manifestation of hypoparathyroid state despite marked elevation in level of fibroblast growth factor 23., Conclusions: This case illustrates the risk of tertiary hyperparathyroidism as a complication of treatment for hypophosphataemia; it highlights the morbidity associated with hungry bone syndrome and provides novel insight into renal handling of phosphorus.

Objective: To compare long-term results of percutaneous iliac artery stenting (PCIS) with aortobifemoral (ABF) grafting for patients with symptomatic iliac artery occlusions., Methods: A retrospective review of 229 patients (January 2000 to December 2011) with symptomatic iliac artery occlusions was performed. In 100 patients, 103 PCIS procedures were performed, and 101 patients underwent ABF grafting. Outcome data including periprocedural complications, improvement in ankle-brachial index, morbidity, and mortality were collected in a vascular registry. Kaplan-Meier estimates for patency and survival were analyzed. Univariate (Fisher exact test) and multivariate analyses of variables associated with the loss of primary patency were performed., Results: Patients in the ABF grafting group were younger (60 ± 0.9 years old vs 65 ± 1.2 years old; P = .002) and more commonly had a history of nicotine abuse (97% vs 86%; P = .002), chronic obstructive pulmonary disease (85% vs 70%; P = .02), and a greater incidence of superficial femoral artery disease (45% vs 24%; P = .001). The most common presenting symptoms in both groups consisted of intermittent claudication (66% ABF vs 71% PCIS), rest pain (20% ABF vs 17% PCIS), and ulceration or gangrene of toes (14% ABF vs 15% PCIS). At 72 months, the primary patency for ABF bypass was greater than for PCIS (91% vs 73%; P = .010). Secondary patency rates were equivalent in both groups (98% ABF vs 85% PCIS). Survival in the ABF bypass group was significantly greater than in the PCIS group (76% vs 68%; P = .013). Hyperlipidemia (hazard ratio, 2.55; P = .049) and concurrent superficial femoral artery lesion (hazard ratio, 2.61; P = .026) were factors associated with the loss of primary patency for the entire cohort. The average hospital stay was 7 ± 2 days in the ABF group and 1 ± 0.3 days in the PCIS group (P = .0001). There were no periprocedural deaths in the PCIS group; there were four deaths in the ABF group (P = .058). In the PCIS group, ankle-brachial index increased from 0.66 to 0.89, and in the ABF group, ankle-brachial index increased from 0.54 to 0.98 (both groups, P < .001)., Conclusions: This study demonstrates that PCIS remains a suitable, less invasive first-line therapy for iliac artery occlusions. PCIS has lower morbidity, shorter hospital length of stay, and equivalent secondary patency but inferior primary patency compared with ABF., (Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Context: Offspring birthweight is inversely associated with future maternal cardiovascular mortality, a relationship that has yet to be fully elucidated. Endothelial progenitor cells (EPCs) are thought to play a key role in vasculogenesis, and EPC numbers reflect cardiovascular risk., Objective: Our objective was to ascertain whether EPC number or function was reduced in mothers of low-birthweight infants., Design and Setting: This was a prospective cohort study in a general antenatal department of a university maternity hospital., Participants: Twenty-three mothers of small for gestational age (SGA) infants (birthweight < 10th centile) and 23 mothers of appropriate for gestational age (AGA) infants (birthweight ≥ 10th centile) were recruited., Main Outcome Measures: Maternal EPC number and function, conventional cardiovascular risk markers, and cord blood adiponectin were measured., Results: Median EPC count was lower (294 vs. 367, P = 0.005) and EPC migration was reduced (0.91 vs. 1.59, P < 0.001) in SGA compared with AGA infants, with no difference in EPC adhesion (0.221 vs. 0.284 fluorescence units, P = 0.257). Maternal triglyceride levels were higher in SGA than AGA infants (0.98 vs. 0.78 mmol/liter, P = 0.006), but there was no difference in cholesterol, glucose, insulin, glycosylated hemoglobin, adiponectin, or blood pressure. There was a moderate monotone (increasing) relationship between birthweight and umbilical cord blood adiponectin (r = 0.475, P = 0.005)., Conclusion: Giving birth to an SGA infant was associated with lower maternal EPC number and reduced migratory function. Cord blood adiponectin was significantly correlated with birthweight.

We have generated a YAC contig of at least 3.3 Mb from the proximal region of In(17)4 of mouse chromosome 17. This region corresponds to DNA lost in the gastrulation mutant tw18, which belongs to the tcl-4 complementation group. Our most proximal and distal probes lie within the deletion-3.3 Mb apart-indicating that we have not cloned the entire region. The deleted region is contained in a genetic interval of less than 1 cM, suggesting that some suppression of recombination must occur.