Citations

Background Open and arthroscopic procedures are treatment options for patients with femoroacetabular impingement (FAI). Age has been found to be a predictive factor in the outcome of patients undergoing periacetabular osteotomy (PAO) for hip dysplasia. It is unclear if older age contraindicates joint preservation through a surgical hip dislocation (SHD). Questions/Purpose The purpose of this retrospective case series was to evaluate the short-term outcomes of patients over 40 years of age without radiographic evidence of end-stage arthritis who underwent SHD for the treatment of FAI and to determine whether older age should be a contraindication for joint-preserving procedures in these patients. Our specific aims included (1) documenting the intraoperative findings and procedures, (2) assessing pain relief provided, and (3) assessing treatment failures and postoperative complications, noting the number of patients that ultimately required total hip arthroplasty (THA). Patients and Methods All patients at age 40 and older who had SHD for the treatment of FAI were identified from a series of patients treated with SHD. Clinical notes, radiographs, and operative reports were reviewed to determine clinical results, complications, and the need for additional procedures. The minimum follow-up was 1 year (mean 3.9 years; range 1–8 years). Results At final follow-up, 11/22 (50%) of hips had pain relief, while 11/22 (50%) either continued having significant symptoms or required THA. Five (23%) reported nontrochanteric pain symptoms that were the same or worse than before surgery, and six hips (27%) underwent subsequent THA). The average time between SHD and THA was 1.9 years (0.9–6.2). The average age of patients who went on to require THA was 45 (42–50) years. Conclusions Surgical hip dislocation can be used for the treatment of FAI in patients over age 40, but strict selection criteria should be adhered to, as only half of the patients experienced significant improvement in their hip pain. THA was required in one-third of hips for continued pain and radiographic progression of arthritis. SHD for treatment of pathology that is not amenable to hip arthroscopy should remain a surgical option in older patients with FAI only if joint degeneration is not present.

AbstractSynthetic κ-opioid receptor (KOR) agonists induce dysphoric and pro-depressive effects and variations in the KOR (OPRK1) and prodynorphin (PDYN) genes have been shown to be associated with alcohol dependence. We genotyped 23 single nucleotide polymorphisms (SNPs) in the PDYN and OPRK1 genes in 816 alcohol-dependent subjects and investigated their association with: (1) negative craving measured by a subscale of the Inventory of Drug Taking Situations; (2) a self-reported history of depression; (3) the intensity of depressive symptoms measured by the Beck Depression Inventory-II. In addition, 13 of the 23 PDYN and OPRK1 SNPs, which were previously genotyped in a set of 1248 controls, were used to evaluate association with alcohol dependence. SNP and haplotype tests of association were performed. Analysis of a haplotype spanning the PDYN gene (rs6045784, rs910080, rs2235751, rs2281285) revealed significant association with alcohol dependence (p = 0.00079) and with negative craving (p = 0.0499). A candidate haplotype containing the PDYN rs2281285-rs1997794 SNPs that was previously associated with alcohol dependence was also associated with negative craving (p = 0.024) and alcohol dependence (p = 0.0008) in this study. A trend for association between depression severity and PDYN variation was detected. No associations of OPRK1 gene variation with alcohol dependence or other studied phenotypes were found. These findings support the hypothesis that sequence variation in the PDYN gene contributes to both alcohol dependence and the induction of negative craving in alcohol-dependent subjects.

AbstractRecently, we showed that increased miR-181a expression was associated with improved outcomes in cytogenetically normal acute myeloid leukemia (CN-AML). Interestingly, miR-181a expression was increased in CN-AML patients harboring CEBPA mutations, which are usually biallelic and associate with better prognosis. CEBPA encodes the C/EBPα transcription factor. We demonstrate here that the presence of N-terminal CEBPA mutations and miR-181a expression are linked. Indeed, the truncated C/EBPα-p30 isoform, which is produced from the N-terminal mutant CEBPA gene or from the differential translation of wild-type CEBPA mRNA and is commonly believed to have no transactivation activity, binds to the miR-181a-1 promoter and up-regulates the microRNA expression. Furthermore, we show that lenalidomide, a drug approved for myelodysplastic syndromes and multiple myeloma, enhances translation of the C/EBPα-p30 isoform, resulting in higher miR-181a levels. In xenograft mouse models, ectopic miR-181a expression inhibits tumor growth. Similarly, lenalidomide exhibits antitumorigenic activity paralleled by increased miR-181a expression. This regulatory pathway may explain an increased sensitivity to apoptosis-inducing chemotherapy in subsets of AML patients. Altogether, our data provide a potential explanation for the improved clinical outcomes observed in CEBPA-mutated CN-AML patients, and suggest that lenalidomide treatment enhancing the C/EBPα-p30 protein levels and in turn miR-181a may sensitize AML blasts to chemotherapy.

BackgroundRight heart failure is an important cause of morbidity and mortality in primary pulmonary hypertension. In a recent prospective, randomized study of severely symptomatic patients, treatment with prostacyclin (epoprostenol) produced improvements in hemodynamics, quality of life, and survival. This article describes the echocardiographic characteristics of participants in this trial; the relationships of echocardiographic variables to hemodynamic parameters, exercise capacity, and quality of life; and the echocardiographic changes associated with prostacyclin therapy.Methods and ResultsThe 81 patients enrolled in this multicenter trial were randomized to treatment with a long-term infusion of prostacyclin in addition to conventional therapy (n=41) or conventional therapy alone (n=40) for 12 weeks. Echocardiograms and assessments of hemodynamics, exercise capacity, and quality of life were performed before and after the treatment phase. On baseline evaluation, patients had marked right ventricular dilatation and dysfunction, abnormal septal curvature, and significant tricuspid regurgitation with a high regurgitant velocity. Pericardial effusions were common. More pronounced abnormalities in right heart structure and function were associated with higher pulmonary arterial and mean right atrial pressures, lower cardiac index, and impaired exercise capacity but had no predictable relationship to quality-of-life indicators. The 12-week infusion of prostacyclin had beneficial effects on right ventricular size, curvature of the interventricular septum, and maximal tricuspid regurgitant jet velocity.ConclusionsThe echocardiographic manifestations of severe primary pulmonary hypertension reflect abnormalities in hemodynamics and exercise capacity. Prostacyclin has beneficial effects on right heart structure and function that may contribute to the clinical improvement and prolonged survival observed with this drug.

Abstract Transmission of pathogens from donor to recipient is a potential complication of organ transplantation. Herein, we describe the clinical course and outcomes of 4 transplant recipients who received tissues from a donor with multi‐organ infection with Klebsiella pneumoniae carbapenemase ( KPC )‐producing K. pneumoniae . Recipient 1 underwent simultaneous liver and kidney transplantation for alpha‐1 antitrypsin deficiency and alcohol‐related cirrhosis, and acute tubular necrosis, respectively. Soon after transplantation, he developed an infected hematoma and peritonitis due to KPC ‐producing K. pneumoniae despite receiving tigecycline prophylaxis. He was treated with a prolonged course of tigecycline, amikacin, and meropenem, in conjunction with surgical evacuation and percutaneous drainage of the infected fluid collections. Recipient 2 underwent living‐donor liver transplantation for cholangiocarcinoma and primary sclerosing cholangitis using vein graft from the donor infected with KPC ‐producing K. pneumoniae . Culture of the preservation fluid containing the vein graft was positive for KPC ‐producing K. pneumoniae . The patient received preemptive amikacin and tigecycline, and he did not develop any infection (as evidenced by negative surveillance blood cultures). The isolates from the donor and Recipients 1 and 2 were indistinguishable by pulsed‐field gel electrophoresis. Recipients 3 and 4 underwent kidney and heart transplantation, respectively; both patients received perioperative tigecycline prophylaxis and did not develop infections due to KPC ‐producing K. pneumoniae . All transplant recipients had good short‐term outcomes. These cases highlight the importance of inter‐institutional communication and collaboration to ensure the successful management of recipients of organs from donors infected with multidrug‐resistant organisms.