Summary Background Reoperation rates are high after surgery for hip fractures. We investigated the effect of a sliding hip screw versus cancellous screws on the risk of reoperation and other key outcomes. Methods For this international, multicentre, allocation concealed randomised controlled trial, we enrolled patients aged 50 years or older with a low-energy hip fracture requiring fracture fixation from 81 clinical centres in eight countries. Patients were assigned by minimisation with a centralised computer system to receive a single large-diameter screw with a side-plate (sliding hip screw) or the present standard of care, multiple small-diameter cancellous screws. Surgeons and patients were not blinded but the data analyst, while doing the analyses, remained blinded to treatment groups. The primary outcome was hip reoperation within 24 months after initial surgery to promote fracture healing, relieve pain, treat infection, or improve function. Analyses followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT00761813. Findings Between March 3, 2008, and March 31, 2014, we randomly assigned 1108 patients to receive a sliding hip screw (n=557) or cancellous screws (n=551). Reoperations within 24 months did not differ by type of surgical fixation in those included in the primary analysis: 107 (20%) of 542 patients in the sliding hip screw group versus 117 (22%) of 537 patients in the cancellous screws group (hazard ratio [HR] 0.83, 95% CI 0.63–1.09; p=0.18). Avascular necrosis was more common in the sliding hip screw group than in the cancellous screws group (50 patients [9%] vs 28 patients [5%]; HR 1.91, 1.06–3.44; p=0.0319). However, no significant difference was found between the number of medically related adverse events between groups (p=0.82; appendix); these events included pulmonary embolism (two patients [<1%] vs four [1%] patients; p=0.41) and sepsis (seven [1%] vs six [1%]; p=0.79). Interpretation In terms of reoperation rates the sliding hip screw shows no advantage, but some groups of patients (smokers and those with displaced or base of neck fractures) might do better with a sliding hip screw than with cancellous screws. Funding National Institutes of Health, Canadian Institutes of Health Research, Stichting NutsOhra, Netherlands Organisation for Health Research and Development, Physicians’ Services Incorporated.

The pulmonary macrophage plays a primary role in the immunological defense of the lung. Although many studies have been devoted to elucidation of its phagocytic and secretory functions, little is known of its membrane transport properties or of how it regulates intracellular pH (pHi). The purpose of this study, therefore, was to determine base-line pHi and the mechanism(s) by which the cell recovers pHi when challenged with an intracellular acid load. Through the use of the pH-sensitive fluorescent dye, 2,7-biscarboxyethyl-5(6)-carboxy-fluorescein (BCECF), base-line pHi was estimated to be 7.24 +/- 0.03. Cells were acidified by two methods, nigericin and weak acids, while recovery (dpHi/dt) was monitored. The rate of recovery was found to be independent of external Na+ and K+ and was insensitive to amiloride. Pretreatment with 4,4'-diiso-thiocyanatostilbene-2,2'-disulfonic acid, an inhibitor of Cl- -HCO3- exchange, was also without effect on recovery from an intracellular acid load in these cells, under nominally HCO3- -free conditions. In contrast, N-ethylmaleimide (NEM) and N,N'-dicyclohexylcarbodiimide, nonspecific inhibitors of proton adenosinetriphosphatases (ATPases), virtually abolished pHi recovery. Efflux of H+ equivalents by pulmonary macrophages was measured by techniques involving both pH stat titration and the effect on fluorescence of extracellular BCECF. Basal H+ extrusion was approximately 2.75 +/- 0.64 nmol H+.min-1.10(6) cells-1 and was enhanced to approximately 26.0 +/- 6.95 nmol H+.min-1.10(6) cells-1 in acid-loaded cell suspensions. The basal rate of H+ extrusion was reduced to approximately 0.84 +/- 0.31 nmol H+.min-1.10(6) cells-1 in the presence of 1 mM NEM. These results suggest that recovery of cytoplasmic pH from an intracellular acid load, as well as regulation of pHi, under the conditions examined, is not mediated by a Na+-H+ exchanger in these cells. Rather, the data are consistent with the presence of an H+-ATPase in the plasma membrane of pulmonary macrophages.

Skeletal metastases exert a profound effect on patients and society, and will be encountered by most orthopedic surgeons. Once a primary malignancy is diagnosed, multidisciplinary management should focus on maximizing the quality of life while minimizing disease-and treatment-related morbidity. This may be best achieved with discerning attention to the unique characteristics of primary cancer types, including pathologic fracture healing rates, longevity, and efficacy of adjuvant therapies. Some lesions may respond well to nonsurgical measures, whereas others may require surgery. A single surgical intervention should allow immediate unrestricted activity and outlive the patient. In certain scenarios, a therapeutic benefit may be provided by excision with a curative intent. In these scenarios, or when endoprosthetic reconstruction is necessary, patients may be best referred to an orthopedic oncologist.

Endocytotic vesicles (i.e., endosomes) were prepared from rabbit renal cortex following the intravenous injection of horseradish peroxidase. The endosomal population was derived from a 100,000-g pellet and was found at equilibrium in the lightest area of a sucrose density gradient. This population was separate from other organelles as determined by enzyme markers and had a 2.5-fold enrichment of horseradish peroxidase specific activity compared with the homogenate specific activity corrected for soluble horseradish peroxidase activity. The endosomes contain an oligomycin-insensitive, electrogenic H+-translocating ATPase. They also contain an electroneutral Na+-H+ exchanger. This exchanger is not inhibited by amiloride, and lithium is not a substrate for the exchanger. Lithium does inhibit the Na+-H+ exchanger when added prior to the addition of sodium. The Michaelis constant for sodium of the endosomal Na+-H+ exchanger was found to be 10.0 mM. These data indicate that a population of endosomes from rabbit renal cortex contain an electrogenic H+-ATPase and an electroneutral Na+-H+ exchanger and that the exchanger is distinct from the brush-border membrane Na+-H+ antiporter.