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.

KIAA2022 is an X-linked intellectual disability (XLID) syndrome affecting males more severely than females. Few males with KIAA2022 variants and XLID have been reported. We present a clinical report of two unrelated males, with two nonsense KIAA2022 pathogenic variants, with profound intellectual disabilities, limited language development, strikingly similar autistic behavior, delay in motor milestones, and postnatal growth restriction. Patient 1, 19-years-old, has long ears, deeply set eyes with keratoconus, strabismus, a narrow forehead, anteverted nares, café-au-lait spots, macroglossia, thick vermilion of the upper and lower lips, and prognathism. He has gastroesophageal reflux, constipation with delayed rectosigmoid colonic transit time, difficulty regulating temperature, several musculoskeletal issues, and a history of one grand mal seizure. Patient 2, 10-years-old, has mild dysmorphic features, therapy resistant vomiting with diminished motility of the stomach, mild constipation, cortical visual impairment with intermittent strabismus, axial hypotonia, difficulty regulating temperature, and cutaneous mastocytosis. Genetic testing identified KIAA2022 variant c.652C > T(p.Arg218*) in Patient 1, and a novel nonsense de novo variant c.2707G > T(p.Glu903*) in Patient 2. We also summarized features of all reported males with KIAA2022 variants to date. This report not only adds knowledge of a novel pathogenic variant to the KIAA2022 variant database, but also likely extends the spectrum by describing novel dysmorphic features and medical conditions including macroglossia, café-au-lait spots, keratoconus, severe cutaneous mastocytosis, and motility problems of the GI tract, which may help physicians involved in the care of patients with this syndrome. Lastly, we describe the power of social media in bringing families with rare medical conditions together.

Objective To elucidate the role of integrin α1β1 in chondrocyte responses to inflammatory interleukin-1α (IL-1) and anabolic transforming growth factor-β1 (TGF-β1) in the knee. Methods Intracellular calcium transient responses to IL-1 and TGF-β1 were measured in wild type and integrin α1-null chondrocytes using real time ex vivo confocal microscopy and immunohistochemistry was performed to analyze TGF-β1-mediated activation of Smad2/3 in tibial and femoral chondrocytes. Results Loss of integrin α1β1 reduces intracellular calcium transient response to IL-1, while it enhances chondrocyte responses to TGF-β1 as measured by intracellular calcium transients and activation of downstream Smad2/3. Conclusions Integrin α1β1 plays a vital role in mediating chondrocyte responses to two contrasting factors that are critical players in the onset and progression of osteoarthritis - inflammatory IL-1 and anabolic TGF-β. Further investigation into the molecular mechanisms by which integrin α1β1 mediates these responses will be an important next step in understanding the influence of increased expression of integrin α1β1 during the early stages of osteoarthritis on disease progression.

<b><i>Introduction:</i></b> Late preterm infants (LPIs) are infants born between 34^0/7 and 36^6/7 weeks gestation. Morbidities in these infants are commonly considered a result of prematurity; however, some research has suggested immaturity may not be the sole cause of morbidities. We hypothesize that antecedents leading to late preterm birth are associated with different patterns of morbidities and that morbidities are the result of gestational age superimposed by the underlying etiologies of preterm delivery. <b><i>Methods:</i></b> This is a retrospective cohort study of late preterm neonates born at a single tertiary care center. We examined neonatal morbidities including apnea of prematurity, hyperbilirubinemia, hypoglycemia, and the requirement for continuous positive airway pressure (CPAP). Multivariable logistic regression analysis was performed to estimate the risk of each morbidity associated with 3 categorized antecedents of delivery, that is, spontaneous preterm labor, preterm premature rupture of membranes (PPROM), and medically indicated birth. We calculated the predictive probability of each antecedent resulting in individual morbidity across gestational ages. <b><i>Results:</i></b> 279 LPIs were included in the study. Decreasing gestational age was associated with significantly increased risk of apnea of prematurity, hyperbilirubinemia, and requirement of CPAP. In our cohort, the risk of hypoglycemia increased with gestational age, with the greatest incidence at 36⁰⁻⁶ weeks. There was no significant association of risk of selected morbidities and the antecedents of late preterm delivery, with or without adjustment for gestational age, multiple gestation, small for gestational age (SGA), antenatal steroids, and delivery method. <b><i>Discussion and Conclusion:</i></b> This study found no difference in morbidity risk related to 3 common antecedents of preterm birth in LPIs. Our research suggests that immaturity is the primary factor in determining adverse outcomes, intensified by factors resulting in prematurity.