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Purpose To determine whether the amount of pain relief after preoperative intra‐articular (IA) anesthetic injection predicts clinical and functional outcomes after hip arthroscopy, especially when controlling for the presence of chondral degeneration. Methods We identified patients who underwent IA injection and subsequent hip arthroscopy for labral pathology between 2007 and 2013 performed by a single surgeon. Inclusion criteria were ultrasound‐ or fluoroscopic‐guided IA anesthetic injection performed at our institution, prospectively documented pre‐ and postinjection numerical rating scale pain scores, and minimum 1‐year follow‐up postoperatively. Patients were divided into 2 groups, those who received >50% pain relief from preoperative IA anesthetic injection and those who received ≤50% relief. Preoperative radiographs were reviewed, and degree of osteoarthritis was determined using the Tonnis classification system. Outcomes were assessed with Modified Harris Hip Score and Hip Outcome Score (HOS). Univariate and multivariate models were performed to assess whether percent pain relief correlated with outcome. Results Of the 319 arthroscopic hip surgeries performed between 2007 and 2013, 115 (37%) patients were lost to follow‐up, 16 (5%) patients did not receive an IA injection, 16 (5%) patients had an injection containing gadolinium, and 40 (13%) patients completed injections at an outside institution. Five (2%) patients were excluded for a history of ipsilateral hip surgery, and 3 (1%) for a history of contralateral hip surgery, leaving 96 hips in 96 patients. There were 71 females (74%) and 25 males (26%) with a mean age of 37.6 ± 14.0 years. Tonnis was grade 0, 1, and 2 for 26 (27%), 55 (56%), and 16 (17%) patients, respectively. Fifty‐one (53%) of the injections contained a corticosteroid. The mean pain relief after IA injection was 73% ± 36% (range, 0% to 100%). Twenty‐six hips (26%) had ≤50% pain relief, whereas 70 (73%) had >50% pain relief, and the median time interval from injection to surgery was 3 (range, <1 to 20) months. Outcome scores were obtained at a mean 14.8 (range, 11 to 30) months after arthroscopic surgery. Postoperative mean Modified Harris Hip Score, HOS activities of daily living, and HOS‐Sport scores were 79.2 ± 17.3, 82.6 ± 17.3, and 67.4 ± 28.2, respectively. There was no statistical correlation between percent pain relief and outcome. There was no significant difference in outcome scores between those with ≤50% and >50% pain relief. Multivariate regression analysis showed no significant predictors of outcome, including age, gender, Tonnis grade, percent relief with IA injection, or type of surgery. Conclusions In this study of patients undergoing hip arthroscopy for labral pathology, our data indicate that the amount of pain relief from IA injection may be a poor predictor of short‐term outcome, even when adjusting for chondral degeneration. Although anesthetic injections can be an important diagnostic tool in select patients, a combination of the clinical history, physical examination, and imaging findings is fundamental. Level of Evidence Level IV, therapeutic case series.

Most vertebrates, including cartilaginous fishes, maintain their plasma SO42−concentration ([SO42−]) within a narrow range of 0.2–1 mM. As seawater has a [SO42−] about 40 times higher than that of the plasma, SO42−excretion is the major role of kidneys in marine teleost fishes. It has been suggested that cartilaginous fishes also excrete excess SO42−via the kidney. However, little is known about the underlying mechanisms for SO42−transport in cartilaginous fish, largely due to the extraordinarily elaborate four-loop configuration of the nephron, which consists of at least 10 morphologically distinguishable segments. In the present study, we determined cDNA sequences from the kidney of holocephalan elephant fish ( Callorhinchus milii) that encoded solute carrier family 26 member 1 (Slc26a1) and member 6 (Slc26a6), which are SO42−transporters that are expressed in mammalian and teleost kidneys. Elephant fish Slc26a1 (cmSlc26a1) and cmSlc26a6 mRNAs were coexpressed in the proximal II (PII) segment of the nephron, which comprises the second loop in the sinus zone. Functional analyses using Xenopus oocytes and the results of immunohistochemistry revealed that cmSlc26a1 is a basolaterally located electroneutral SO42−transporter, while cmSlc26a6 is an apically located, electrogenic Cl−/SO42−exchanger. In addition, we found that both cmSlc26a1 and cmSlc26a6 were abundantly expressed in the kidney of embryos; SO42−was concentrated in a bladder-like structure of elephant fish embryos. Our results demonstrated that the PII segment of the nephron contributes to the secretion of excess SO42−by the kidney of elephant fish. Possible mechanisms for SO42−secretion in the PII segment are discussed.

Summary Background Patients with Crohn's disease ( CD ) have serologic responses to various microbial antigens. Serologic markers are associated with aggressive forms of disease and can be detected before onset of symptoms. Their utility in pre‐clinical disease or prediction of complicated disease course before diagnosis is unclear. Aim To evaluate the pattern of serologic anti‐microbial antibodies long prior to diagnosis and the subsequent risk of complicated Crohn's disease at diagnosis. Methods Sera from 100 US military personnel with Crohn's disease were obtained from the Department of Defense Serum Repository. For each patient, four samples were obtained at different time points before and around diagnosis, and were tested for 6 microbiota‐directed antibodies ( ASCA ‐IgA, ASCA ‐IgG, anti‐OmpC, anti‐ CB ir1, anti‐A4‐Fla2 and anti‐FlaX). Associations between the presence and accumulation of Crohn's disease anti‐microbial antibodies before diagnosis and with the later development of complications were evaluated. Results Overall, 65 patients were positive for at least one Crohn's disease associated anti‐microbial antibody in the earliest available sample, at a median of 6 years before Crohn's disease diagnosis (interquartile range, 5.6–8.2). The number of positive anti‐microbial antibodies increased up to the time of Crohn's disease diagnosis. Complicated disease developed around the time of diagnosis in 24 patients. The proportion of positive antimicrobial antibodies before diagnosis was higher in patients with complicated vs. noncomplicated Crohn's disease. There was an inverse relationship between the time to first complication and the magnitude of serologic response before diagnosis. Conclusion The presence and accumulation of circulating anti‐microbial antibodies years before Crohn's disease diagnosis was associated with complicated Crohn's disease at or shortly after diagnosis.

Background BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. Methods We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. Results The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). Conclusions These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.

Previous genome‐wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. A fine‐mapping study across 2.06 Mb (chr8:127,561,724–129,624,067, hg19) in 55,540 breast cancer cases and 51,168 controls within the Breast Cancer Association Consortium was conducted. Three additional independent association signals in women of European ancestry, represented by rs35961416 (OR = 0.95, 95% CI = 0.93–0.97, conditional p = 5.8 × 10−6), rs7815245 (OR = 0.94, 95% CI = 0.91–0.96, conditional p = 1.1 × 10−6) and rs2033101 (OR = 1.05, 95% CI = 1.02–1.07, conditional p = 1.1 × 10−4) were found. Integrative analysis using functional genomic data from the Roadmap Epigenomics, the Encyclopedia of DNA Elements project, the Cancer Genome Atlas and other public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r2 = 0.77), were putatively functional variants for two of the five independent association signals. The results highlighted multiple 8q24 variants associated with breast cancer susceptibility in women of European ancestry.

Purpose To compare clinical and functional outcomes of surgically treated medial and lateral knee dislocations. Methods A retrospective review of the medical records of patients who presented with knee dislocations was conducted. We identified patients who underwent surgical treatment of KDIII‐M (anterior cruciate ligament/posterior cruciate ligament/medial collateral ligament) or KDIII‐L (anterior cruciate ligament/posterior cruciate ligament/lateral collateral ligament) knee dislocation as documented by the Schenck classification. Minimum 2‐year follow‐up with Lysholm and International Knee Documentation Committee (IKDC) outcome scores was required for inclusion. Postoperative range of motion, ligamentous examination, and conversion to total knee arthroplasty were also collected. Data were analyzed using univariate and multivariate statistical models with P < .05 considered significant. Results A total of 56 patients met the inclusion criteria, 24 with the KDIII‐M injury pattern (43%) and 32 with the KDIII‐L injury pattern (57%), with a mean age of 34 years (range, 16 to 62 years) and a mean follow‐up of 6.5 years (range, 2 to 20 years). Patients undergoing medial repairs had worse outcomes for both the Lysholm score ( P = .008) and IKDC score ( P = .003). In addition, female sex was linked to worse outcomes (Lysholm score, 58.8 ± 21.5 v 77.8 ± 21.1, P < .01; IKDC score, 54.9 ± 23.7 v 75.2 ± 20.2, P < .01). No differences in outcome were found between patients with and patients without peroneal nerve injury (Lysholm score, P = .81; IKDC score, P = .77). No difference in laxity testing was found between the 2 groups. Conclusions In patients undergoing multiligament knee reconstruction, our data suggest that those who undergo medial repair for knee dislocations are not as likely to achieve positive results as those who undergo reconstruction or lateral reconstruction/repair, regardless of the status of the peroneal nerve. In addition, medial reconstruction had comparable outcomes to those in patients treated with lateral reconstruction/repair. Lastly, female patients showed less favorable clinical outcomes than male patients. Level of Evidence Level III, retrospective comparative study.

Introduction Symptomatic Metastatic Epidural Spinal Cord Compression (MESCC) afflicts up to 10% of all cancer patients and is associated with shortened survival and worsened quality of life. This study aims to identify the key survival prognostic factors in MESCC patients who were surgically treated for a single symptomatic lesion. Material and Methods 142 MESCC patients were enrolled in a prospective North American multi-center study and followed postoperatively for 12 months. Using univariate analyses, Kaplan-Meier methods, and log-rank tests the prognostic value of various clinical predictors were assessed. Non-collinear predictors with p < 0.05 in univariate analyses were included in the final Cox proportional hazards model. Results The overall median survival was 7.7 months (range: 3 days – 35.6 months); breast cancer had the longest median survival (12.1 months). Ten patients (7%), whose primary cancer were lung (3), kidney (3), sarcoma (2), prostate (1), and breast (1), died within 30-days postoperatively and 88 had died at 12 months (62%). Univariate analyses yielded eight significant predictors for survival: the growth of primary tumor (Tomita Grade 1 vs Grade 2 and 3), BMI, gender, preoperative SF-36 physical component, EQ-5D, and ODI scores as well as the presence of either visceral or extraspinal bony metastasis. The multiple regression analysis revealed that the Tomita grade (Grade 1 vs Grade 2 and 3; HR: 2.81, p = 0.007), the absence of visceral metastasis (HR: 2.01; p = 0.0044), and higher score on SF-36 physical component (HR: 0.95, p < 0.0001) were independent predictors for longer survival regardless of the selection method used (backward, forward, or stepwise). Conclusion Slow growing tumor (Tomita Grade 1), absence of visceral metastasis, and lower degree of preoperative physical disability, as reflected by a higher score on the SF-36 physical component questionnaire, are good prognostic factors for survival in selected patients who underwent surgical treatment for a focal symptomatic MESCC lesion.

Introduction Although surgery is being increasingly used in patients with Metastatic Epidural Spinal Cord Compression (MESCC) as a complementary strategy to radiation and chemotherapy, the impact of surgery on quality of life (QoL) is not well established. This study aimed to prospectively evaluate survival, neurological, functional, and QoL outcomes in MESCC patients undergoing operative management. Material and Methods A total of 142 surgically treated patients with a single symptomatic MESCC lesion enrolled in a prospective North American multi-center study were followed for 12 months. Clinical data, such as Brief Pain Inventory (BPI), ASIA, SF-36, Oswestry Disability Index (ODI), and EQ-5D scores, were obtained both pre- and post-operatively. Results The median survival was 7.7 months. The 30-day and 12-month mortality rates were 9% and 62%, respectively. Six weeks post-operatively, ambulatory status ( p = 0.02) and bladder control ( p = 0.03) were significantly improved. Overall, 67.5% of ASIA B, C, or D patients gained at least 1 grade after surgery, 25% remained stable, and 7.5% deteriorated. ODI, EQ-5D, BPI scores were significantly improved at each follow-up (p ≤ 0.01). SF-36 scores were generally higher after surgery for mental and physical components, and for all domains except energy/fatigue. The incidence of wound complications was 10% and 2 patients required a second surgery (screw malposition and epidural hematoma). Conclusion Surgical intervention, as a complementary adjunct to radiation and chemotherapy, provides immediate and sustained improvement in pain, neurological, functional, and QoL outcomes with acceptable risks in patients with a focal symptomatic MESCC lesion.

Monocyte‐derived cells, constituents of the cancer microenvironment, support chronic lymphocytic leukemia (CLL) cell survival in vitro via direct cell‐cell interaction and secreted factors. We hypothesized that circulating absolute monocyte count (AMC) reflects the monocyte‐derived cells in the microenvironment, and that higher AMC is associated with increased CLL cell survival in vivo and thus inferior CLL patient outcomes. We assessed the extent to which AMC at diagnosis of CLL is correlated with clinical outcomes, and whether this information adds to currently used prognostic markers. We evaluated AMC, clinically used prognostic markers, and time to event data from 1,168 CLL patients followed at the Mayo Clinic, the Duke University Medical Center, and the Durham VA Medical Center. Elevated AMC was significantly associated with inferior clinical outcomes, including time to first therapy (TTT) and overall survival (OS). AMC combined with established clinical and molecular prognostic markers significantly improved risk‐stratification of CLL patients for TTT. As an elevated AMC at diagnosis is associated with accelerated disease progression, and monocyte‐derived cells in the CLL microenvironment promote CLL cell survival and proliferation, these findings suggest that monocytes and monocyte‐derived cells are rational therapeutic targets in CLL. Am. J. Hematol. 91:687–691, 2016. © 2016 Wiley Periodicals, Inc.