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A 75-year-old Caucasian woman presented with sudden-onset multifocal scotomas in her right eye's central vision for 1 day. There were subtle white intraretinal foveal lesions that correlated with patchy inner retinal hyperreflectivity on optical coherence tomography, suggestive of paracentral acute middle maculopathy. Initial cerebrovascular work-up was negative. Review of systems was positive for lethargy and jaw claudication. The sedimentation rate and c-reactive protein were elevated, but platelet count was normal. The patient was started on 60 mg oral prednisone daily and underwent bilateral temporal artery that confirmed the diagnosis of giant cell arteritis.

To report patient-reported outcomes (PROs) and survivorship following revision hip arthroscopy in patients aged ≥40 years and to compare these results with a propensity-matched primary hip arthroscopy control group.Data were prospectively collected and retrospectively reviewed for all patients who underwent revision hip arthroscopy between June 2008 and January 2019. Patients were included if they were ≥40 years of age at the time of surgery and had minimum 2-year follow-up for the modified Harris Hip Score, Nonarthritic Hip Score, Visual Analog Scale for pain, and the Hip Outcome Score-Sports Specific Subscale. Patients who had a previous hip condition, or those who lacked minimum 2-year follow-up, were excluded. The revision group was further analyzed by conducting a 1:1 propensity-matched sub-analysis to a primary hip arthroscopy control group based on age, sex, body mass index, and acetabular labrum articular disruption grade. Statistical significance was set at P.05.Eighty-nine hips (92.7% follow-up) were included, with 66.3% being females. The mean age, body mass index, and follow-up time were 49.4 ± 8.0 years, 26.6 ± 4.1, and 62.7 ± 38.5 months, respectively. Significant improvement in all PROs (P.001) was reported, and 71.8%, 58 74.4%, and 65.2% achieved the minimal clinically important difference for the modified Harris Hip Score, Nonarthritic Hip Score, and Hip Outcome Score-Sports Specific Subscale, respectively. Eighty-seven revision hips were successfully propensity-matched to 87 primary hips. Both groups reported similar improvement for all PROs, but the relative risk of conversion to total hip arthroplasty was 2.63 times greater (95% confidence interval 1.20-5.79) for the revision group.Patients aged ≥40 years who underwent revision hip arthroscopy reported significant improvement in all PROs at a mean follow-up of 62.7 months with favorable rates of achieving the minimal clinically important difference. When compared to the propensity-matched control group, both achieved similar rates of improvement, but the revision group was 2.63 times more likely to convert to total hip arthroplasty.III. case-control study.

Background: Few studies have compared outcomes, return to sport (RTS), and continuation of sport (CTS) after primary hip arthroscopic surgery between matched groups of male and female athletes with a minimum 5-year follow-up. Purpose: (1) To report minimum 5-year patient-reported outcome (PRO) scores as well as RTS and CTS rates for elite female athletes undergoing hip arthroscopic surgery for femoroacetabular impingement syndrome (FAIS) and (2) to compare clinical results with those of a matched control group of elite male athletes. Study Design: Cohort study; Level of evidence, 3. Methods: Data were prospectively collected and retrospectively reviewed for elite (collegiate or professional) female athletes who underwent primary hip arthroscopic surgery for FAIS between March 2009 and March 2016. Inclusion criteria were preoperative and minimum 5-year scores for the modified Harris Hip Score, Nonarthritic Hip Score, Hip Outcome Score–Sport Specific Subscale, and visual analog scale for pain. Exclusion criteria were Tönnis grade >1, hip dysplasia, previous ipsilateral hip surgery/conditions, and those unwilling to participate. Rates of achieving the minimal clinically important difference (MCID), Patient Acceptable Symptom State (PASS), and maximum outcome improvement satisfaction threshold (MOIST) were recorded in addition to RTS. CTS was also recorded and defined as athletes reporting continued sport activity at a minimum 5-year follow-up after initially reporting returning to sport. Elite female athletes were propensity matched in a 1:1 ratio to elite male athletes for comparison. Results: A total of 81 hips in elite female athletes that underwent primary hip arthroscopic surgery met the inclusion criteria, and follow-up was available for 65 hips (80.2%) at a mean of 67.6 ± 6.5 months, with a mean age of 24.3 ± 6.8 years. Female athletes demonstrated significant improvements in all recorded PRO scores; achieved the MCID, PASS, and MOIST at high rates; returned to sport at a rate of 80.4%; and continued sport at a rate of 97.1%. Female athletes demonstrated lower preoperative PRO scores compared with male athletes, but postoperative PRO scores; improvements in scores; rates of achieving the MCID, PASS, MOIST; and RTS and CTS rates were similar between female and male athletes. Conclusion: Elite female athletes undergoing primary hip arthroscopic surgery for FAIS demonstrated favorable PRO scores and high RTS and CTS rates at a minimum 5-year follow-up. These results were comparable with those of a propensity-matched control group of elite male athletes.

To report minimum 2-year follow-up patient-reported outcomes and return-to-sport (RTS) rates in athletes undergoing concomitant hip arthroscopy and periacetabular osteotomy (PAO) to treat acetabular dysplasia and intra-articular pathologies such as cam deformity and labral tears.We reviewed the data of consecutive athletes undergoing concomitant primary hip arthroscopy and PAO for acetabular dysplasia and cam deformity from November 2010 to December 2018. Patients were included in the study if they had the following preoperative and minimum 2-year postoperative scores: modified Harris Hip Score (mHHS), Nonarthritic Hip Score (NAHS), and Hip Outcome Score-Sport-Specific Subscale (HOS-SSS). The percentage of patients who achieved the minimal clinically important difference was recorded, in addition to RTS status.A total of 29 athletes (29 hips) were included, with a mean follow-up time of 34.1 ± 7.9 months, mean age of 26.0 ± 8.7 years, and mean body mass index of 23.7 ± 3.4. These athletes showed significant improvements in the mHHS, NAHS, and HOS-SSS from baseline to latest follow-up (P.001). The minimal clinically important difference was achieved at high rates for the mHHS (82.8%), NAHS (86.2%), and HOS-SSS (79.3%). Athletes who attempted to RTS successfully returned at a rate of 81.8%.Athletes undergoing concomitant hip arthroscopy and PAO showed significant improvements in patient-reported outcomes at minimum 2-year follow-up and had an RTS rate of 81.8%.Level IV, retrospective case series.

Background: The minimal clinically important difference (MCID), Patient Acceptable Symptom State (PASS), substantial clinical benefit (SCB), and maximum outcome improvement (MOI) satisfaction threshold for the Hip Outcome Score Sport-Specific Subscale (HOS-SSS) have not been established in athletes undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS). Purpose: To determine threshold MCID, PASS, SCB, and MOI satisfaction threshold values for the HOS-SSS in athletes undergoing hip arthroscopy for FAIS at minimum 2–year follow–up. Study Design: Cohort study (Diagnosis); Level of evidence, 3. Methods: Anchor questions were administered to recreational, organized amateur, high school, college, and professional athletes who underwent primary hip arthroscopy for FAIS between May 2015 and March 2019. Patients were included if they were younger than 50 years, answered the anchor questions, and had preoperative and minimum 2–year follow–up for the HOS-SSS, modified Harris Hip Score (mHHS), Non-Arthritic Hip Score (NAHS), and visual analog scale (VAS) for pain. Exclusion criteria were Tönnis grade >1, hip dysplasia (lateral center–edge angle Results: A total of 225 athletes who underwent primary hip arthroscopy met the inclusion criteria. Of those athletes, 200 (88.9%) who had minimum 2–year follow–up and information regarding return to sport (RTS) were included. The cohort included 124 (62.0%) women and 76 (38.0%) men with a mean ± standard deviation age of 29.4 ± 10.4 years, body mass index of 25.6 ± 5.4, and follow–up of 29.5 ± 5.1 months. Athletes experienced significant improvements in HOS-SSS, mHHS, NAHS, and VAS from preoperative to latest postoperative follow–up ( P < .001), and mean satisfaction was 8.2. The RTS rate was 83.7%. ROC analysis determined that the PASS, MOI satisfaction threshold, SCB absolute score, SCB change score, and MCID (baseline/change score methods) for the HOS-SSS were 77.0, 44.6%, 92.7, 30.6, and 10.6, respectively, with athletes achieving thresholds at high rates (80.0%, 80.5%, 45.0%, 54.0%, and 79.5%, respectively). Conclusion: This study identified values for the HOS-SSS that can be used to define clinically meaningful outcomes in athletes after primary hip arthroscopy for FAIS. The PASS, MOI satisfaction threshold, SCB absolute score, SCB change score, and MCID for the HOS-SSS at minimum 2–year follow–up in athletes after primary hip arthroscopy were 77.0, 44.6%, 92.7, 30.6, and 10.6, respectively.

KRAS and NRAS mutations occur in 45% of colorectal cancers, with combined MAPK pathway and CDK4/6 inhibition identified as a potential therapeutic strategy. In the current study, this combinatorial treatment approach was evaluated in a co-clinical trial in patient-derived xenografts (PDX), and safety was established in a clinical trial of binimetinib and palbociclib in patients with metastatic colorectal cancer with RAS mutations. Across 18 PDX models undergoing dual inhibition of MEK and CDK4/6, 60% of tumors regressed, meeting the co-clinical trial primary endpoint. Prolonged duration of response occurred predominantly in TP53 wild-type models. Clinical evaluation of binimetinib and palbociclib in a safety lead-in confirmed safety and provided preliminary evidence of activity. Prolonged treatment in PDX models resulted in feedback activation of receptor tyrosine kinases and acquired resistance, which was reversed with a SHP2 inhibitor. These results highlight the clinical potential of this combination in colorectal cancer, along with the utility of PDX-based co-clinical trial platforms for drug development. Significance: This co-clinical trial of combined MEK-CDK4/6 inhibition in RAS mutant colorectal cancer demonstrates therapeutic efficacy in patient-derived xenografts and safety in patients, identifies biomarkers of response, and uncovers targetable mechanisms of resistance.

To report and compare, according to sex and age, minimum 2-and minimum 5-year patient-reported outcome scores (PROs) and survivorship in a large cohort of patients who underwent primary hip arthroscopy for femoroacetabular impingement syndrome (FAIS).Data from February 2008 to September 2018 were reviewed. Patients aged 60 and younger who underwent primary hip arthroscopy with minimum 2-year follow-up were included. Exclusion criteria were Tönnis grade1, hip dysplasia, previous hip conditions, or any labral treatment different than repair. Minimum 5-year PROs were also collected. All patients included were divided into groups by sex. For further analysis, males and females were stratified according to age:21 years old, 21-30 years old, 31-40 years old, 41-50 years old, and 51-60 years old.In total, 1,326 hips had minimum 2-year follow-up, including 860 (64.9%) females and 466 males (35.1%), with a mean age of 31.6 years (range, 12.8-60.9 years) and a mean follow-up of 58.7 ± 28.9 months. Of those, 772 had minimum 5-year follow-up, 515 females (66.7%), and 257 males (33.3%) with a mean age of 31.7 years (range, 13.1-60.7 years) and a mean follow-up of 78.5 ± 23.0 months. All patients showed significant improvements in PROs at minimum 2-and 5-year follow-up (P.001). Between sex analysis revealed comparable PROs at latest follow-up between females and males across any age group. Within sexes, and when sexes were combined, patients21 years old had significantly better outcomes compared to other age groups. There were more females21 years old that required revision arthroscopy than males21 years old (P = .015). Conversion to total hip arthroplasty (THA) showed no significant difference between sexes (P.05). Rates of THA were21 years (.8%), 21-30 years (2.1%), 31-40 years (4%), 41-50 years (8.9%), and 51-60 years (14.3%).Following primary hip arthroscopy for FAIS, all patients reported significant improvements in all PROs at minimum 2-and minimum 5-year follow-up, with females and males achieving similar success. Age affected outcomes, with patients under 21 years old reporting better scores regardless of sex. Although the conversion rate to THA was similar between the sexes, it was lower in the younger ages groups in both sexes.III, retrospective comparative observation trial.

To report minimum 2-year patient-reported outcome measures (PROMs) following primary hip arthroscopy for femoroacetabular impingement syndrome (FAIS) and painful external snapping hip (ESH) treatment and ESH resolution, and to compare these PROMs to a benchmark FAIS propensity-matched control group without ESH.Data were prospectively collected and retrospectively reviewed between November 2009 and April 2018. Patients were eligible if they were preoperatively diagnosed with FAIS and painful ESH and received primary hip arthroscopy to address these pathologies. ESH was treated with gluteus maximus and iliotibial band releases. Inclusion criteria were baseline and minimum two-year follow-up scores for the modified Harris Hip Score, Nonarthritic Hip Score, Hip Outcome Score-Sport Specific Subscale, and visual analog scale for pain. Exclusion criteria were Tönnis grade1 and previous hip conditions. A secondary subanalysis was performed to benchmark these outcomes to a FAIS propensity-matched control group without ESH, according to age, sex, body mass index (BMI), Tönnis grade, and preoperative lateral center-edge and α-angles using a 1:3 ratio. The minimal clinically important difference (MCID) and the maximum outcome improvement (MOI) rates were reported.Twenty-two hips (21 patients) were included. The mean age, BMI, and follow-up were 31.3 years ± 14.0, 26 kg/mFollowing primary hip arthroscopy for FAIS and painful ESH, patients demonstrated significant improvement in all PROMs, and the rate of resolution of ESH was 100% at minimum two-year follow-up: with gluteus maximus and iliotibial band releases. Functional outcomes and rates of MCID and MOI achievement were comparable to a FAIS propensity-matched benchmark control group without ESH.Level III, retrospective comparative study.

1) To report minimum 2- and 5-year outcomes of high-level athletes who did not return to sport (RTS) after hip arthroscopy for reasons unrelated to their hip (T athletes) and 2) to benchmark these findings against a propensity-matched control group of high-level athletes who returned to sport (RTS athletes).Data were prospectively collected and retrospectively reviewed for professional, collegiate, and high school athletes between April 2008 and October 2015, who underwent primary hip arthroscopy. Athletes were considered eligible if they did not return to sport for reasons unrelated to their hip such as loss of interest, graduation, or a lifestyle transition (T athletes). Inclusion criteria were preoperative and minimum 5-year postoperative patient-reported outcomes (PROs) for the modified Harris Hip Score (mHHS), Non-Arthritic Hip Score (NAHS), Hip Outcome Score-Sports Specific Subscale (HOS-SSS), and the visual analog scale (VAS) for pain. Clinical outcomes were assessed using the minimal clinically important difference (MCID) and maximum outcome improvement satisfaction threshold (MOIST). T athletes were then propensity-matched to a control group of high-level athletes who returned to sport after hip arthroscopy (RTS athletes) for comparison.Twenty-seven T hips (25 patients) were included in the analysis with a mean follow-up time of 38.9 ± 16.8 and 72.1 ± 16.8 months for minimum 2- and 5-year outcomes, respectively. They demonstrated significant improvement in all measured PROs. When compared to a propensity-matched control group of RTS athletes, T athletes demonstrated similar improvement in PROs (mHHS, NAHS, and HOS-SSS) and achieved MCID at similar rates for NAHS (T: 77.8% vs RTS: 68.8%; P = .570) and HOS-SSS (T: 70.3% vs RTS: 76.6%, P = .824) compared to RTS athletes; however T athletes demonstrated higher rates of achieving MCID for mHHS (T: 88.9% vs RTS: 72.9% P = .033).Athletes who did not return to sport for reasons unrelated to their hip demonstrated favorable outcomes at minimum 2- and 5-year follow-up. They had similar PROs and rates of achieving MCID for HOS-SSS compared to a propensity-matched control group of high-level athletes who returned to sport. Return to sport status may not necessarily be correlated to the patient's perception of their own outcome.III, retrospective cohort study.

Background: Favorable short-term outcomes in competitive basketball players have been reported. Midterm outcomes in these athletes and how they compare with athletes in sports with similar demands have not been well established. Purpose: (1) To report minimum 5-year patient-reported outcomes (PROs) and return to sports data in competitive basketball players undergoing primary hip arthroscopy for femoroacetabular impingement syndrome (FAIS) and (2) to compare outcomes with a propensity-matched control group of other cutting sports athletes. Study Design: Cohort study, Level of evidence, 3. Methods: Data were prospectively collected and retrospectively reviewed for basketball players who competed at the professional, collegiate, high school, or competitive amateur levels and underwent primary hip arthroscopy for FAIS between May 2009 and March 2016. Patients with preoperative and minimum 5-year postoperative outcomes for the modified Harris Hip Score (mHHS), Nonarthritic Hip Score (NAHS), Hip Outcome Score–Sports Specific Subscale (HOS-SSS), and visual analog scale (VAS) for pain were included. Patients were propensity matched to athletes in other cutting sports (soccer, lacrosse, field hockey, and tennis) according to age, sex, body mass index (BMI), and preoperative competition level for comparison. Results: A total of 28 competitive basketball players were included, with a mean follow-up time of 67.1 ± 5.1 months and a mean BMI of 23.7 ± 4; there were 12 (42.9%) female athletes. The cohort was composed of 1 professional, 10 collegiate, 13 high school, and 4 organized amateur athletes. They demonstrated significant improvements in all recorded PROs from baseline to the minimum 5-year follow-up ( P < .001) and had high rates of achieving the minimal clinically important difference (MCID) for the mHHS (75%), NAHS (75%), HOS-SSS (67.9%), and VAS for pain (71.4%). Furthermore, 76.5% of basketball players who returned to sports were still competing at a minimum of 5 years postoperatively. When compared with a propensity-matched cohort of other cutting athletes, basketball athletes demonstrated a significantly higher acetabular labrum articular disruption (ALAD) grade ( P < .001) and trended toward a higher Outerbridge grade of the acetabular cartilage ( P = .067). Despite this, basketball players demonstrated similar preoperative, postoperative, and improvement scores in all recorded PROs. Moreover, both groups exhibited similar rates of achieving psychometric thresholds and rates of continued sports participation at minimum 5-year follow-up. Conclusion: Competitive basketball players undergoing primary hip arthroscopy for FAIS demonstrated significant improvements in all recorded PROs and high rates of continued play at a minimum 5-year follow-up. When compared with a control group of other cutting sports athletes, basketball players exhibited more severe ALAD grades intraoperatively but similar midterm outcomes.

Background: Patient-reported outcomes (PROs) and return to sports (RTS) have not been established in athletes undergoing primary hip arthroscopy and subspine decompression for femoroacetabular impingement syndrome (FAIS) and subspine impingement (SSI). Purpose: (1) To report minimum 2-year PROs and RTS in competitive athletes undergoing primary hip arthroscopy for treatment of FAIS with subspine decompression for treatment of SSI and (2) to compare clinical results with a matched control group of athletes without SSI. Study Design: Cohort study, Level of evidence, 3. Methods: Data were reviewed for professional, collegiate, and high school athletes undergoing primary hip arthroscopy for FAIS with arthroscopic subspine decompression for SSI between February 2011 and October 2018. Inclusion criteria included preoperative and minimum 2-year follow-up scores for the modified Harris Hip Score, Nonarthritic Hip Score, Hip Outcome Score–Sport Specific Subscale, and visual analog scale for pain. Rates of achieving the minimal clinically important difference (MCID) were also calculated. For comparison, athletes in the SSI group were propensity matched according to age at the time of surgery, sex, body mass index, lateral center-edge angle, alpha angle, sport level, acetabular labrum articular disruption grade, and sport type to a control group of athletes without SSI. Results: A total of 30 SSI athletes were included in the study, with a mean plus or minus standard deviation follow-up of 32.1 ± 7.1 months and age of 20.9 ± 5.7 years. The SSI cohort demonstrated significant improvement in all recorded PROs ( P < .001), returned to sports at high rates (88.5%), and achieved the MCID for the Hip Outcome Score–Sport Specific Subscale at a high rate (80.0%). Furthermore, these patients had a low rate of undergoing revision surgery (6.7%). When compared with a propensity-matched control group of 59 athletes, the SSI group demonstrated similar rates of RTS, revision, and achieving the MCID for all PROs. Conclusion: Competitive athletes with FAIS and SSI who underwent primary hip arthroscopy and subspine decompression had favorable outcomes and high RTS rates at minimum 2-year follow-up. These results were comparable with those of a control group of athletes without SSI undergoing primary hip arthroscopy.

Background: The incidence of revision hip arthroscopy with labral reconstruction in athletes is increasing. However, the outcomes of revision hip arthroscopy with labral reconstruction in athletes have not been well established. Purposes: (1) To report minimum 2–year patient–reported outcome (PRO) scores and return to sports (RTS) characteristics for high–level athletes undergoing revision hip arthroscopy with labral reconstruction and (2) to compare clinical results with those of a propensity–matched control group of high–level athletes undergoing revision hip arthroscopy with labral repair. Study Design: Cohort study; Level of evidence, 3. Methods: Data were prospectively collected and retrospectively reviewed for athletes at any level who underwent a revision hip arthroscopy and a labral reconstruction between April 2010 and March 2019. Minimum 2–year PROs were reported for the modified Harris Hip Score (mHHS), the Nonarthritic Hip Score (NAHS), the Hip Outcome Score–Sport Specific Subscale (HOS-SSS), the visual analog scale (VAS) for pain, and RTS. The percentages of athletes achieving the minimal clinically important difference (MCID) and the maximum outcome improvement satisfaction threshold (MOIST) were also recorded. These patients were propensity matched in a 1: 1 ratio to athletes undergoing revision hip arthroscopy with labral repair for comparison. Results: A total of 46 athletes (N = 47 hips) were reported from 50 (n = 51 hips) athletes who underwent revision with labral reconstruction. A subanalysis of 30 propensity–matched athletes undergoing revision labral reconstruction was performed, with a mean follow–up time of 26.3 ± 2.4 months and an age of 28.5 ± 10.1 years, and compared with a revision labral repair group. Significant improvements were obtained for the mHHS, the NAHS, the HOS-SSS, and the VAS from preoperative to the latest follow–up ( P < .001), with an achievement MCID rate of 61.5%, 72%, 62.5%, and 76.9% for the mHHS, the NAHS, the HOS-SSS, and the VAS, respectively. The rate for re–revision surgery (2 tertiary arthroscopy and 1 conversion to total hip arthroplasty) was 10%, and 14 patients (63.6%) were able to RTS. Improvements in PROs, rates of achieving MCID/MOIST, rate of re–revision surgery (re-revision hip arthroscopy, P = .671; conversion to total hip arthroplasty, P > .999), and RTS rate ( P = .337) were similar when compared with those of the propensity–matched control labral repair group ( P > .05). Conclusion: Revision hip arthroscopy with labral reconstruction, in the context of an irreparable labral tear, seems to be a valid treatment option in the athletic population, demonstrating significant improvements in all PROs and low rates of undergoing revision surgery. Athletes experienced a similar magnitude of improvement in PROs, RTS rate, and revision surgery rate to that of a propensity–matched control group of athletes undergoing revision hip arthroscopy with labral repair.

Background The ideal cardiac risk stratification strategy for orthotopic liver transplantation (OLT) is unknown. Our institution performed coronary angiography for asymptomatic OLT candidates at high risk for CAD : ≥65 years of age, diabetic and ≥55 years of age or diagnosed ≥5 years, abnormal stress test, or at the discretion of the OLT committee. Methods The analysis included 301 consecutive, asymptomatic OLT candidates who underwent coronary angiography. The primary outcome was the prevalence of obstructive CAD. Results At 2-year follow-up, OLT was performed in 44.9%, and 42.2% died. The prevalence of obstructive CAD, involvement of the proximal or mid LAD, and 3-vessel CAD were 10.3%, 6.6%, and 0.7%, respectively. Percutaneous and surgical revascularization were performed in 7.0% and 1.3%, respectively. Stress test was performed in 54.8%. The sensitivity and specificity of stress testing were 0% and 87.1%, respectively. The negative and positive predictive values of stress testing were 91.4% and 0%, respectively. Chest computed tomography (CT) was performed in 83.1%. Moderate or severe coronary artery calcification (CAC) was present in 47.8%. The sensitivity and specificity of moderate or severe CAC were 88.9% and 57.3%, respectively. The negative and positive predictive values of moderate or severe CAC were 97.7% and 20.2%, respectively. Multivariate analysis demonstrated that CAC was an independent predictor of obstructive CAD (HR 10.7; 95% CI 3.2–37.9; p Conclusions The prevalence of obstructive CAD in asymptomatic OLT candidates at high risk was uncommon. Alternative diagnostic strategies may be preferred to coronary angiography.

Predictors of outcomes in adolescent athletes undergoing hip arthroscopy have not been established. The purpose of this study was to identify factors correlated with achieving the Patient Acceptable Symptomatic State (PASS) for the Hip Outcome Score-Sports Specific Subscale (HOS-SSS) at a minimum 5-year follow-up in adolescent athletes undergoing primary hip arthroscopy.Data were reviewed on adolescent (below 18 y old) athletes who underwent primary hip arthroscopy for femoroacetabular impingement syndrome between March 2008 and October 2015. Patients were included if they participated in sport within 1 year before surgery and had preoperative, 2-year, and minimum 5-year postoperative patient-reported outcome (PRO) scores for the modified Harris Hip Score, HOS-SSS, Visual Analog Scale for pain (VAS), and Non-Arthritic Hip Score (NAHS). Patients were divided into 2 groups based on whether they achieved PASS for HOS-SSS. Demographics, intraoperative findings, radiographic variables, surgical treatments, and PRO were compared. Multivariate logistic regression with corresponding odds ratios (ORs) quantified the correlation between variables and achievement of the PASS.A total of 123 athletes with a mean age of 16.2±1.1 years were included. These athletes demonstrated significant imrpovement from preoperative to minimum 5-year follow-up for all recorded PROs (P0.001). The multivariate logistic regression model identified preoperative NAHS (P=0.019, OR: 1.033), 2-year postoperative HOS-SSS (P=0.014, OR: 1.037), and 2-year postoperative VAS (P=0.003, OR: 0.590) as statistically significantly correlated with achieving the PASS. Athletes with a 2-year postoperative VAS pain score ≤2 achieved PASS at a rate of 81.9%, while those with a score2 achieved PASS at a rate of 24.1% (P0.001, OR: 14.2, 95% confidence interval: 5.23-38.7).Favorable outcome were achieved at mid-term follow-up in adolescent athletes undergoing primary hip arthroscopy. Preoperative NAHS, 2-year postoperative HOS-SSS, and 2-year postoperative VAS pain scores were correlated with achieving the PASS for HOS-SSS at a minimum 5-year follow-up. Patients with 2-year postoperative VAS ≤2 were significantly more likely to achieve the PASS at 5-year follow-up than those with scores2.Level III-case-control study.

Background The ideal drug-eluting stent (DES) for the treatment of unprotected left main coronary artery (ULMCA) is unknown. We compared percutaneous coronary intervention (PCI) using durable polymers versus early-generation, thicker strutted and coated bioabsorbable polymers for ULMCA disease. Methods Patients who underwent ULMCA PCI (893 patients) from April 2008 to November 2014 were identified from the Grand-DES registry. The primary end point was 3-year target lesion failure (TLF) after propensity score matching. Results The final analysis included 754 patients (84.4%) and 139 patients (15.6%) in the durable and bioabsorbable polymer group, respectively. The groups differed significantly in lesion and procedural characteristics. Propensity score-matched analysis revealed a trend toward a lower 3-year TLF in the durable polymer group (log rank p=0.071). Independent predictors of 3-year TLF were chronic kidney disease, presentation with acute myocardial infarction, and a two-stenting technique for ULMCA lesions. Definite/probable stent thrombosis rates at 3-years were low in both groups (0.8% vs. 0.7%, p=0.925). Conclusions The safety of ULCMA PCI was excellent, and durable and bioabsorbable polymer DES provided similar clinical outcomes at 3-year follow-up. Landmark analysis revealed that the durable polymer group had a lower TLF rate from 9 months. Further studies are needed to confirm these results.

Background: There is a paucity of literature evaluating the outcomes of adolescent patients undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS) with a discrete traumatic event related to an injury. Purpose: (1) To evaluate 5-year outcomes of adolescents undergoing hip arthroscopy for FAIS with traumatic injuries (TIs) and (2) to compare the traumatic group with a propensity-matched control group of patients with atraumatic injuries. Study Design: Cohort study; Level of evidence, 3. Methods: Data were reviewed for all adolescent patients (Results: A total of 31 patients (32 hips) with TI, out of 39 total patients (40 hips) (80%), were included with a mean follow-up time of 72.2 ± 24.1 months and age of 15.8 ± 1.3 years. The TI group demonstrated significant improvement in all patient-reported outcomes (PROs) ( P < .001) and demonstrated high rates of MCID (78.3%) and PASS (91.3%) for the mHHS. When compared with a propensity-matched control group of 64 AHS hips (57 patients), the TI group demonstrated similar rates of improvement in all PROs, as well as rates of achieving the MCID, PASS, and MOIT for all PROs; however, the TI group demonstrated significantly higher revision rates compared with controls (28.1% vs 6.3%; P = .008). Conclusion: Adolescent patients with TIs undergoing hip arthroscopy demonstrated favorable outcomes for all PROs ( P < .001) and achieved high rates of MCID (78.3%) and PASS (91.3%) for the mHHS. When compared with a propensity-matched control group of adolescents with atraumatic injuries undergoing hip arthroscopy, they achieved similar levels of improvement, postoperative scores, and clinical benefit thresholds; however, reoperation rates were higher in the TI group compared with controls.

A healthy 7-year-old girl underwent a routine eye examination and was referred for unilateral, left optic nerve swelling. Best-corrected visual acuity in the affected eye was 20/20 with full Ishihara color plates and no relative afferent pupillary defect. Initial extensive workup was normal for any cause of unilateral disk swelling. When the patient returned a few years later with decreased vision, a thickened, gray-white preretinal tissue with surrounding retinal contraction and a surrounding charcoal gray lesion had developed in her optic nerve. Spectral-domain optical coherence tomography over the optic nerve demonstrated distortion of the inner retinal architecture, a dense epiretinal membrane, and high internal reflectivity. Clinical examination and imaging revealed a diagnosis of combined hamartoma of the retina and retinal pigment epithelium.

Objectives The safety and efficacy of an initial intravenous bolus of low-dose heparin (40 IU/kg) was evaluated in biomarker negative patients undergoing percutaneous coronary intervention (PCI). Background A bolus of 70–100 IU/kg of heparin is currently recommended for patients undergoing PCI. However, the ideal dose of heparin has not been evaluated in a randomized trial. The higher dose of 100 IU/kg may increase the risk of bleeding. An initial bolus of low-dose heparin may be advantageous to avoid supratherapeutic activating clotting times (ACT) while still allowing for the administration of additional heparin if the ACT is subtherapeutic. Methods From January 2008 to February 2020, 904 patients undergoing elective transfemoral PCI received an initial bolus of 40 IU/kg of heparin. Patients who underwent transradial PCI were not included. Patients were routinely pretreated with dual antiplatelet therapy. The primary end point was the composite of cardiac death, myocardial infarction (MI), urgent target vessel revascularization (TVR) for ischemia, or major bleeding within 30 days after PCI. Results The initial mean activating clotting time was 235.4 ± 26.6 s. The clinical event rates were low: the primary end point occurred in 5.3%, cardiac death in 1.0%, MI in 3.1%, urgent TVR in 0.7% and major bleeding in 1.9%. Stent thrombosis was uncommon (0.2%). No patients developed profound thrombocytopenia. Three patients (0.3%) had acute limb ischemia that required revascularization. Conclusion An initial strategy of low-dose heparin is associated with low ischemic and bleeding complications in biomarker negative patients who undergo transfemoral PCI.

The innate immune regulator STING is a critical sensor of self- and pathogen-derived DNA. DNA sensing by STING leads to the induction of type-I interferons (IFN-I) and other cytokines, which promote immune-cell-mediated eradication of pathogens and neoplastic cells1,2. STING is also a robust driver of antitumour immunity, which has led to the development of STING activators and small-molecule agonists as adjuvants for cancer immunotherapy3. Pain, transmitted by peripheral nociceptive sensory neurons (nociceptors), also aids in host defence by alerting organisms to the presence of potentially damaging stimuli, including pathogens and cancer cells4,5. Here we demonstrate that STING is a critical regulator of nociception through IFN-I signalling in peripheral nociceptors. We show that mice lacking STING or IFN-I signalling exhibit hypersensitivity to nociceptive stimuli and heightened nociceptor excitability. Conversely, intrathecal activation of STING produces robust antinociception in mice and non-human primates. STING-mediated antinociception is governed by IFN-Is, which rapidly suppress excitability of mouse, monkey and human nociceptors. Our findings establish the STING-IFN-I signalling axis as a critical regulator of physiological nociception and a promising new target for treating chronic pain.

Background: The maximal outcome improvement threshold for willingness to undergo revision hip arthroscopy (MOWT) has not been defined yet. Purpose: To determine the percentage MOWT in patients who underwent revision hip arthroscopy and to identify predictors of achieving the MOWT. Study Design: Case-control study; Level of evidence, 3. Methods: An anchor question was provided to patients who underwent revision hip arthroscopy between April 2008 and June 2020 who returned for follow-up between August 2019 and June 2021 at one institution. Patients were included if they underwent revision hip arthroscopy, had answered the anchor question, and had baseline and postoperative minimum 1-year follow-up scores for the modified Harris Hip Score (mHHS), Nonarthritic Hip Score (NAHS), and the visual analog scale (VAS) for pain. Exclusion criteria were Tönnis grade >1, hip dysplasia, previous hip conditions, or unwillingness to participate. Receiver operating characteristic analysis was used to determine the MOWT. Multivariate logistic regression was used to determine intraoperative predictors of achieving the MOWT. Results: In total, 153 patients (163 hips) were included, with 117 female hips (71.8%), a mean patient age of 34.3 ± 12.4 years, and an average follow-up time of 61.6 ± 42.7 months. It was determined that 77.3% of the patients reported that they would choose to undergo the revision hip arthroscopy again. The MOWT for the mHHS, NAHS, and VAS was 43.1%, 53%, and 33.4%, respectively. The probability of choosing to undergo revision surgery if the MOWT was achieved was 77.5%, 77.6%, and 79.2%, for the mHHS, NAHS, and VAS, respectively. Patients with residual cam-type morphology, which was addressed during the revision, were 2.3 times more likely to achieve the MOWT for the VAS ( P = .014). Conclusion: Patients who improved 43.1%, 53%, and 33.4% of their MOWT for the mHHS, NAHS, and VAS, respectively, were likely to be willing to undergo revision hip arthroscopy again. Moreover, the presence of residual cam-type femoroacetabular impingement morphology before their revision surgery was identified as a predictor to achieve the MOWT for the VAS.

To determine the normal variance of the mean macular ganglion cell layer (GCL) volume among subjects without significant ocular pathology using SPECTRALIS optical coherence tomography (OCT).Fifty subjects underwent a baseline scan using SPECTRALIS OCT followed by 2 more studies with (reg-ON) and without (reg-OFF) eye registration all taken at the same session. The mean GCL volume was measured using built-in SPECTRALIS software. Eyes with macular pathology were excluded. The reproducibility of the measurements of the GCL volume was evaluated with Bland-Altman plots and limits of agreement, intraclass correlation coefficient (ICC), and the coefficient of repeatability (CR).A total of 98 eyes met criteria for the analysis. The mean GCL volume difference was 0.0002 ± 0.029 and -0.0005 ± 0.035 mm 3 for scans 1 versus 2 (baseline vs reg-ON) and 3 (baseline vs reg-OFF), respectively. The ICCs were 0.985 and 0.977 for the baseline vs reg-ON and reg-OFF groups. The CR for baseline vs reg-ON was 0.056 while CR for baseline vs reg-OFF was 0.069. Ninety percent of eyes fell within 0.04 mm 3 of test-retest reliability.Our model found a predictable threshold of 0.07 mm 3 or less for SPECTRALIS OCT mean GCL volume variance, which did not significantly change with eye registration in eyes without macular pathology. Clinicians may also consider a threshold of 0.04 mm 3 when determining stable vs progressive changes in mean GCL volume using this device.

To report the histological findings and clinical course of 2 patients with microcyst-like epithelial keratopathy (MEK) associated with antibody-drug conjugate, depatuxizumab mafodotin.Case series.Two patients with glioblastoma multiforme participating in a phase 3 clinical trial of the antibody-drug conjugate, depatuxizumab mafodotin, presented with bilateral MEK. Confocal imaging showed multiple large, round, hyperreflective lesions in the epithelium. Epithelial debridement was performed for symptomatic relief in both patients. Along with aggressive lubrication, bandage contact lenses, and reduction in the chemotherapeutic dose to maintenance levels, both patients experienced symptomatic improvement. However, MEK lesions recurred after re-epithelialization. Immunohistochemistry of the diseased epithelium showed immunoglobulin (Ig)G-positive granular cytoplasmic inclusions and increased cell apoptosis.Depatuxizumab mafodotin accumulates in the basal corneal epithelium resulting in MEK because of increased apoptosis. Frequent lubrication and bandage contact lenses can provide symptom relief.

Regorafenib is a tyrosine kinase inhibitor approved by the FDA for the treatment of patients with chemotherapy refractory metastatic colorectal cancer (mCRC). Regorafenib inhibits signaling through multiple receptors associated with angiogenesis, metastasis, and tumor immunity. Here, we report biomarker results from LCCC1029, a randomized, placebo-controlled, phase II trial of chemotherapy ± regorafenib in patients with second-line mCRC. A panel of 20 soluble protein biomarkers (termed the Angiome) was assessed in the plasma of 149 patients from the LCCC1029 trial both at baseline and along the treatment continuum. Baseline protein levels were analyzed for prognostic and predictive value for progression-free survival (PFS) and overall survival (OS). Changes in protein levels during treatment were analyzed for potential pharmacodynamic effects. Six markers (HGF, IL6, PlGF, VEGF-R1, OPN, and IL6R) were found to be prognostic for PFS. Nine markers (IL6, TIMP-1, PlGF, VCAM-1, ICAM-1, OPN, TSP-2, HGF, and VEGF-R1) were prognostic for OS. Higher baseline levels of OPN (Pintx = 0.0167), VCAM-1 (Pintx = 0.0216), and PDGF-AA (Pintx = 0.0435) appeared to predict for PFS benefit from regorafenib compared with placebo. VCAM-1 was also potentially predictive of OS benefit from regorafenib compared with placebo (Pintx = 0.0124). On-treatment changes of six markers reflected potential on-target effect of regorafenib. Consistent results were observed in an Italian cohort where 105 patients with late-stage mCRC received regorafenib monotherapy. The key findings of this study suggest that VCAM-1 may be a predictive biomarker for regorafenib benefit, while multiple protein markers may be prognostic of outcome in patients with mCRC.

Purpose of review Eye pain is one of the most common presenting symptoms in ophthalmology. It can range from bothersome to debilitating for patients, and it can be vexing for clinicians, especially in the white and quiet eye. The purpose of this review is to provide updates of recent literature regarding eye pain and to communicate our current understanding regarding the evaluation and management of conditions that cause eye pain with a relatively normal examination. Recent findings This review concerns recent literature regarding eye pain in the white and quiet eye. It is arranged by cause of pain and discusses dry eye syndrome, recurrent corneal erosion, postrefractive surgical pain, eye strain, intermittent angle closure, benign essential blepharospasm, trochleodynia, trochleitis and trochlear headache, and posterior scleritis. Summary Eye pain in the white and quiet eye remains a difficult-to-navigate topic for practitioners. However, a careful history and focused physical examination can elucidate the diagnosis in many cases. Recent updates to the literature have advanced our knowledge of how to identify and treat the underlying causes of eye pain.

Older patients who undergo coronary interventions are at greater risk of ischemic events and less likely to tolerate prolonged dual antiplatelet therapy (DAPT) due to bleeding risk. The COMBO biodegradable polymer sirolimus-eluting stent promotes rapid endothelialization through endothelial progenitor cell capture technology which may be advantageous in elderly patients. We compared 1-year clinical outcomes and DAPT cessation events in patients >75 versus ≤75 years from the MASCOT registry. MASCOT was a prospective, multicenter cohort study of all-comers undergoing attempted COMBO stenting. The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, myocardial infarction (MI) not clearly attributed to a nontarget vessel or clinically driven target lesion revascularization. Bleeding was adjudicated using the Bleeding Academic Research Consortium criteria. Adjusted outcomes were analyzed using Cox regression methods. The study included 18% (n = 479) patients >75 years and 72% (n = 2,135) patients ≤75 years. One-year TLF occurred in 4.6% patients >75 years versus 3.1% patients ≤75years of age, p = 0.10; adj hazard ratio 1.36, 95% confidence intervals 0.77 to 2.38, p = 0.29. There were no significant differences in cardiac death (1.7% vs 1.3%, p = 0.55), MI (2.1% vs 1.2%, p = 0.14), target lesion revascularization (1.7% vs 1.4%, p = 0.60) and definite stent thrombosis (0.8% vs 0.4%, p = 0.19). Major Bleeding Academic Research Consortium 3,5 bleeding (3.1% vs 1.5%, p = 0.01) and DAPT cessation rates (32.4% vs 23.0%, p 75 years treated with COMBO stents had similar TLF but significantly greater incidence of bleeding than younger patients and DAPT cessation in one-third of patients over 1 year.

Background The COMBO drug-eluting stent combines sirolimus-elution from a biodegradable polymer with an anti-CD34+ antibody coating for early endothelialization. Objective We investigated for geographical differences in outcomes after percutaneous coronary intervention (PCI) with the COMBO stent among Asians and Europeans. Methods The COMBO Collaboration is a pooled patient-level analysis of the MASCOT and REMEDEE registries of all-comers undergoing attempted COMBO stent PCI. The primary outcome was 1-year target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (TV-MI) and target lesion revascularization (TLR). Results This study included 604 Asians (17.9%) and 2775 Europeans (82.1%). Asians were younger and included fewer females, with a higher prevalence of diabetes mellitus but lower prevalence of other comorbidities than Europeans. Asians had a higher prevalence of ACC/AHA C type lesions and received longer stent lengths. More Asians than Europeans were discharged on clopidogrel (86.5% vs 62.8%) rather than potent P2Y12 inhibitors. One-year TLF occurred in 4.0% Asians and 4.1% of Europeans, p = 0.93. The incidence of cardiac death was higher in Asians (2.8% vs. 1.3%, p = 0.007) with similar rates of TV-MI (1.5% vs. 1.2%, p = 0.54) and definite stent thrombosis (0.3% vs. 0.5%, p = 0.84) and lower incidence of TLR than Europeans (1.0% vs. 2.5%, p = 0.025). After adjustment, differences for cardiac death and TLR were no longer significant. Conclusions In the COMBO collaboration, although 1-year TLF was similar regardless of geography, Asians experienced higher rates of cardiac death and lower TLR than Europeans, while incidence of TV-MI and ST was similar in both regions. Adjusted differences did not reach statistical significance. Clinicaltrial.gov identifier-numbers NCT01874002 (REMEDEE Registry), NCT02183454 (MASCOT registry).

Schizophrenia is a complex disorder that is diagnosed mainly with clinical observation and evaluation. Recent studies suggest that many people with schizophrenia have abnormalities in the function of the N-methyl- d -aspartate receptor (NMDAR). The retina is part of the central nervous system and expresses the NMDAR, raising the possibility of the early detection of NMDAR-related schizophrenia by detecting differences in retinal function. As a first-step, we used two non-invasive outpatient tests of retinal function, the photopic negative response (PhNR) of the light-adapted flash-electroretinogram (PhNR-fERG) and the pattern ERG (PERG), to test individuals with schizophrenia and controls to determine if there were measurable differences between the two populations. The PhNR-fERG showed that males with schizophrenia had a significant increase in the variability of the overall response, which was not seen in the females with schizophrenia. Additionally at the brightest flash strength, there were significant increases in the PhNR amplitude in people with schizophrenia that were maximal in controls. Our results show measurable dysfunction of retinal ganglion cells (RGCs) in schizophrenia using the PhNR-fERG, with a good deal of variability in the retinal responses of people with schizophrenia. The PhNR-fERG holds promise as a method to identify individuals more at risk for developing schizophrenia, and may help understand heterogeneity in etiology and response to treatment.

Purpose of review Ocular myasthenia gravis (OMG) is a complex condition with heterogenous phenotypes and ill-defined diagnostic criteria. Understanding concomitant risk factors and autoimmune serology can help inform prognosis for generalization and guide treatment. Recent findings Although antibodies to acetylcholine receptors or muscle-specific kinase likely increase risk of generalization, they are less frequent in OMG. Patients without either antibody tend to have a milder disease process and often have variable antibodies to other end-plate proteins such as LRP4, agrin, or cortactin. The treatment of OMG begins with pyridostigmine and is supplemented by oral prednisone if treatment-resistant or high risk for generalization. Variable oral prednisone regimens have been used with success and further immunosuppression may be best achieved with mycophenolate mofetil and azathioprine. Checkpoint inhibitor-induced myasthenia gravis is increasingly recognized and likely has high rates of mortality associated with myocarditis. Summary Our understanding of OMG and its variable phenotypes continues to evolve. Autoantibody testing increasingly provides valuable diagnostic and prognostic information. Despite these improvements, a lack of quality treatment trials creates significant challenges for evidence-based management guidelines.

Background: The effect of high body mass index (BMI) on outcomes in athletes has not been established. Purpose: (1) To report minimum 2-year patient-reported outcome (PRO) scores and return to sports (RTS) for high-level athletes with high BMI undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS) and (2) to compare results with a propensity-matched control group of high-level athletes with a normal BMI. Study Design: Cohort study; Level of evidence, 3. Methods: Data were collected on all professional, collegiate, and high school athletes who had a high BMI (>30) and who had undergone primary hip arthroscopy for FAIS between January 2010 and December 2018. RTS status and minimum 2-year PROs were collected for the modified Harris Hip Score (mHHS), Non-Arthritic Hip Score (NAHS), Hip Outcome Score–Sports Specific Subscale (HOS-SSS), and visual analog scale (VAS) for pain. The percentage of patients achieving the minimal clinically important difference (MCID) and Patient Acceptable Symptom State (PASS) were also recorded. These patients were propensity matched in a 1:3 ratio to high-level athletes with a normal BMI for comparison. Results: A total of 30 high-level athletes with a high BMI were included with a mean follow-up of 49.4 ± 29.5 months. They demonstrated significant improvement from preoperatively to latest follow-up for mHHS, NAHS, HOS-SSS, and VAS ( P < .001). When outcomes were compared with a propensity-matched control group of 90 athletes with a normal BMI, athletes with a high BMI had worse acetabular cartilage injury and were more likely to undergo acetabular microfracture ( P < .001). Athletes with a high BMI demonstrated lower postoperative scores for NAHS when compared with athletes with a normal BMI (88.06 ± 9.37 [range, 60-100] and 90.25 ± 10.79 [range, 48.75-100], respectively; P = .049). Athletes with a high BMI also demonstrated worse postoperative scores for HOS-SSS when compared with athletes with a normal BMI (77.22 ± 18.31 [range, 22.22-100] and 82.38 ± 22.79 [range, 2.78-100], respectively; P = .038). Rates of achieving MCID for the high-BMI and normal-BMI groups were comparable in mHHS (90.0% and 77.8%, respectively; P = .185) and HOS-SSS (90.0% and 82.2%, respectively; P = .397). PASS rates were also comparable between the high- and normal-BMI groups for mHHS (90.0% and 87.8%, respectively; P > .999) and HOS-SSS (70.0% and 71.1%, respectively; P = .908). Athletes with a high BMI also returned to sports at a lower rate compared with athletes with a normal BMI, but this did not reach statistical significance ( P = .479). Conclusion: Athletes with a high BMI undergoing primary hip arthroscopy for FAIS demonstrated significant improvement in PROs and favorable rates achieving clinically meaningful improvement. When compared with a control group of high-level athletes with a normal BMI, they exhibited similar rates of achieving psychometric thresholds and RTS rates. At short-term follow-up, high BMI did not adversely affect outcomes of high-level athletes undergoing primary hip arthroscopy.

To compare minimum 2-year postoperative patient-reported outcome (PRO) scores and return to sport between competitive athletes undergoing primary hip arthroscopy for femoroacetabular impingement syndrome with interportal capsulotomy repair and competitive athletes with an unrepaired interportal capsulotomy.Data on all consecutive competitive athletes who underwent primary hip arthroscopy for femoroacetabular impingement syndrome between February 2012 and December 2018 were collected. Athletes were divided into 2 groups: those who underwent repair and those without repair. Athletes were considered eligible if they participated in sports within 1 year prior to surgery. Patients were eligible if the return-to-sport status and the following preoperative and minimum 2-year postoperative PROs were available: modified Harris Hip Score, Nonarthritic Hip Score (NAHS), Hip Outcome Score-Sport-Specific Subscale (HOS-SSS), and visual analog scale (VAS) score for pain. Patients were excluded if they underwent prior hip surgery, had Workers' Compensation, were unwilling to consent, had a Tönnis grade greater than 1, or had a previous hip condition. The percentages of patients achieving the minimal clinically important difference (MCID) and maximum outcome improvement satisfaction threshold were recorded. Athletes who underwent interportal capsulotomy repair were propensity score matched in a ratio of 2:1 to athletes without interportal capsulotomy repair according to age, sex, body mass index, sport level, and acetabular labrum articular disruption grade.Forty-nine athletes (53 hips) without repair with an average follow-up time of 36.5 ± 10.2 months and age of 32.1 ± 13.3 years were matched to 79 athletes (84 hips) with repair with an average follow-up time of 41.3 ± 9.4 months and age of 30.1 ± 12.1 years. Athletes in the repaired group showed significantly greater improvements in the NAHS, HOS-SSS, and VAS score and significantly higher rates of achievement of the MCID for the HOS-SSS compared with athletes in the unrepaired group.Competitive athletes who underwent primary hip arthroscopy with interportal capsulotomy repair showed a significantly greater magnitude of improvement in PRO scores (NAHS, HOS-SSS, and VAS score) and rates of achieving the MCID (HOS-SSS) compared with a propensity score-matched control group of competitive athletes with an unrepaired interportal capsulotomy.Level III, retrospective comparative therapeutic trial.

ECT2 is an activator of RHO GTPases that is essential for cytokinesis. In addition, ECT2 was identified as an oncoprotein when expressed ectopically in NIH/3T3 fibroblasts. However, oncogenic activation of ECT2 resulted from N-terminal truncation, and such truncated ECT2 proteins have not been found in patients with cancer. In this study, we observed elevated expression of full-length ECT2 protein in preneoplastic colon adenomas, driven by increased ECT2 mRNA abundance and associated with APC tumor-suppressor loss. Elevated ECT2 levels were detected in the cytoplasm and nucleus of colorectal cancer tissue, suggesting cytoplasmic mislocalization as one mechanism of early oncogenic ECT2 activation. Importantly, elevated nuclear ECT2 correlated with poorly differentiated tumors, and a low cytoplasmic:nuclear ratio of ECT2 protein correlated with poor patient survival, suggesting that nuclear and cytoplasmic ECT2 play distinct roles in colorectal cancer. Depletion of ECT2 reduced anchorage-independent cancer cell growth and invasion independent of its function in cytokinesis, and loss of Ect2 extended survival in a KrasG12D Apc-null colon cancer mouse model. Expression of ECT2 variants with impaired nuclear localization or guanine nucleotide exchange catalytic activity failed to restore cancer cell growth or invasion, indicating that active, nuclear ECT2 is required to support tumor progression. Nuclear ECT2 promoted ribosomal DNA transcription and ribosome biogenesis in colorectal cancer. These results support a driver role for both cytoplasmic and nuclear ECT2 overexpression in colorectal cancer and emphasize the critical role of precise subcellular localization in dictating ECT2 function in neoplastic cells. Significance: ECT2 overexpression and mislocalization support its role as a driver in colon cancer that is independent from its function in normal cell cytokinesis.

We report novel case of a 57-year-old woman who developed bilateral ocular ischemic syndrome in the setting of chronic angle closure glaucoma without associated angle neovascularization. Detailed is a course in which markedly prolonged, elevated intraocular pressure led to significantly reduced arterial perfusion at the level of the central retinal artery, leading to the clinical picture of ocular ischemic syndrome.

Purpose of review This review will extensively cover the clinical manifestations, causes, diagnostic evaluation, and management strategies of downbeat nystagmus (DBN). Recent findings Historically, MRI to assess for structural lesions at the cervicomedullary junction has been the primary diagnostic test in the evaluation of DBN since the 1980s. In recent years, there is increasing awareness of nonstructural causes of DBN including gluten ataxia, nutritional deficiencies, and paraneoplastic syndromes, among others. Medical management with aminopyridines has become first-line therapy in addition to disease-specific therapies. Summary DBN is a common form of acquired nystagmus and the differential diagnosis remains broad, including both benign and potentially fatal causes. For practical purposes, the causes can be categorized as structural vs. nonstructural with MRI as the ideal, initial diagnostic study to differentiate the two. General therapeutic options include pharmacotherapy to enhance Purkinje cell function, strabismus surgery or prisms to shift null points, and behavioural changes. Disease-specific treatment is necessarily broad, though a significant proportion of patients will be idiopathic.

BACKGROUND: Tumors with homologous recombination deficiency (HRD) show high sensitivity to platinum salts and poly(ADP-ribose) polymerase–inhibitors in several malignancies. In colorectal cancer (CRC), the role of HRD alterations is mostly unknown. METHODS: Next-generation sequencing, whole transcriptome sequencing, and whole exome sequencing were conducted using CRC samples submitted to a commercial Clinical Laboratory Improvement Amendments certified laboratory. Tumors with pathogenic and/or presumed pathogenic mutations in 33 genes involved in the homologous recombination pathway were considered HRD, the others were homologous recombination proficient (HRP). Furthermore, tumor samples from patients enrolled in the phase III TRIBE2 study comparing upfront FOLFOXIRI+bevacizumab vs FOLFOX+bevacizumab were analyzed with next-generation sequencing. The analyses were separately conducted in microsatellite stable or proficient mismatch repair (MSS/pMMR) and microsatellite instable-high or deficient mismatch repair (MSI-H/dMMR) groups. All statistical tests were 2-sided. RESULTS: Of 9321 CRC tumors, 1270 (13.6%) and 8051 (86.4%) were HRD and HRP, respectively. HRD tumors were more frequent among MSI-H/dMMR than MSS/pMMR tumors (73.4% vs 9.5%; P

To compare a minimum of two-year follow-up patient-reported outcome scores (PROs) in patients who underwent revision hip arthroscopy for acetabular circumferential labral reconstruction (CLR) and segmental labral reconstruction (SLR) using propensity-matched groups, in the setting of irreparable labral tear.Prospectively collected data were retrospectively reviewed for patients who underwent revision hip arthroscopy from April 2010 to September 2018. Patients were included if they underwent labral reconstruction and had preoperative and minimum 2-year PROs. Patients unwilling to participate, with Tönnis grade1, or hip dysplasia were excluded. Patients in the CLR group were propensity-matched on the basis of age, sex, body mass index, and Tönnis grade to patients in the SLR group in a 1:1 ratio. The minimal clinically important difference (MCID) and the patient-acceptable symptomatic state (PASS) rates were calculated.Twenty-six hips (25 patients) with CLR were propensity-matched to 26 hips (26 patients) with SRL. The mean follow-up time 25.92 and 27.78 months for the CLR and SLR, respectively (P = .845). Groups reported comparable findings for sex (P = .773), age (P = .197), body mass index (P = .124), preoperative Tönnis grade (P = .124), lateral-center edge angle (P = .144), and alpha angle (P = .264), and comparable improvement for all PROs at minimum 2-year follow-up. Patient satisfaction was similar (P = .612). Rates of achievement for the MCID and PASS were comparable.Following revision hip arthroscopy, patients who underwent CLR or SLR for complete and segmental irreparable labral tears, respectively, reported significant and comparable postoperative improvement for all PROs and rate of achievement for the MCID and PASS at a minimum 2-year follow-up.III, retrospective comparative therapeutic trial.

Endovascular therapy is a viable treatment option for symptomatic peripheral artery disease (PAD). Diabetes mellitus is a major risk factor for PAD. We evaluated the long-term impact of diabetes mellitus in patients with PAD who underwent endovascular therapy. In this prospective registry of 765 patients who underwent endovascular therapy for symptomatic PAD, 560 had diabetes and 205 did not have diabetes. Propensity score matching (PSM) analysis was performed to adjust for any potential confounders. The primary endpoints were 5-year major adverse cardiac and cerebrovascular events (MACE) and major adverse limb events (MALE). After PSM analysis, baseline clinical and limb characteristics were similar in patients with diabetes and in patients without diabetes. Patients with diabetes had a higher rate of major hematoma (> 4 cm) (9.9% vs 3.3%, p = 0.038). At 5-year clinical follow-up, patients with diabetes and patients without diabetes had similar rates of MACE (20.7% vs 20.7%, log rank p = 0.989) and MALE (19.8% vs 24.5%, log rank p = 0.312), as well as the individual endpoints. In subgroup analysis adjusted by PSM, female patients with diabetes had a higher risk of MALE (hazard ratio 0.31, 95% CI 0.13–0.69, p = 0.004). Although there was a higher rate of major hematoma, patients with diabetes who underwent endovascular therapy had similar 5-year cardiac and vascular outcomes compared with patients without diabetes. Bleeding avoidance strategies, including optimal antiplatelet and antithrombotic therapy, and meticulous vascular access techniques, are needed in patients with diabetes to reduce the risk of bleeding and its deleterious impact on morbidity and mortality.

Typical optic neuritis is an idiopathic demyelinating condition that is often associated with multiple sclerosis. This has been well characterized and has an excellent prognosis. Atypical optic neuritis can result from an inflammatory, infectious, or autoimmune disorder. Differentiating the two types of optic neuritis is paramount and may be challenging early on in the clinical course. This review describes the recent literature describing the pathophysiology, clinical presentation, neuroimaging, and management of these disorders.

Background The International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration aimed to evaluate whether 3 months of adjuvant chemotherapy are noninferior to 6 months. Our study objectives were to characterize medical oncologists’ perspectives toward the results of the IDEA collaboration and to evaluate how IDEA impacted prescribing patterns of adjuvant FOLFOX and CAPOX in colon cancer. Materials and Methods A list of questions developed by four medical oncologists regarding IDEA results were formulated and distributed online to gastrointestinal medical oncologists globally. Descriptive statistics and chi-square tests were used to summarize information. Results Of 174 responses, 145 were complete and analyzed. Responses were obtained globally from South America (53%); the U.S. and Canada (28%); Europe, Australia, and New Zealand (12%); and Asia (7%). Most clinicians (98%) were aware of the IDEA study. Prior to IDEA, clinicians preferred FOLFOX over CAPOX (81% vs. 19%). Subsequent to IDEA, 55% of clinicians preferred CAPOX over FOLFOX (odds ratio, 5.0; 95% confidence interval, 3.0–8.5; p < .01 compared with pre-IDEA). Two thirds (68%) of responders tailored duration of adjuvant therapy based on risk stratification. Most oncologists (76%) were more willing to discontinue oxaliplatin early if toxicities develop after the results of IDEA. Half of responders (50%) found that IDEA increased their confidence in decision making for adjuvant treatment; 36% were unchanged, and 15% indicated decreased confidence. Less than half (48%) were comfortable communicating the study results and the concept of a noninferiority trial with patients. Conclusion IDEA appears to have shifted clinician preference from FOLFOX to CAPOX for adjuvant therapy, and most clinicians now use a risk-stratified approach in determining duration of adjuvant therapy. Patient education resources may facilitate better communication of IDEA results to patients.

Cycline antibiotics (CAs) are commonly used to treat acne, blepharitis, and dry eye syndrome. Prescribers or patients may hesitate to use Cas because they may increase the risk of pseudotumor cerebri syndrome (PTCS).We sought to assess whether CA use is associated with an increased risk of PTCS or papilledema and whether the risk depends upon dosage or duration of CA intake.We studied patients 12 to 65 years of age who were diagnosed with acne, blepharitis, or dry eye syndrome, who were enrolled in a nationwide managed care network between January 1, 2001 and December 31, 2015, and who had no preexisting diagnosis of papilledema or PTCS. Multivariable Cox regression modeling was used to assess the risk of developing papilledema or PTCS from exposure to CAs.Among the 728,811 eligible enrollees (mean age, 34.7 years; 72% female), 42.0% filled ≥1 CA prescription. Of the 305,823 CA users, 170 (0.06%) were diagnosed with papilledema or PTCS. By comparison, of the 57.0% with no record of CA use, 121 (0.03%) were diagnosed with papilledema or PTCS (P .0001). In the unadjusted model, every additional year of CA use was associated with a 70% (doxycycline: hazard ratio, 1.70 [95% confidence interval 0.98-2.97]; P = .06) or 91% (minocycline: hazard ratio, 1.91 [95% confidence interval 1.11-3.29]; P = .02) increased hazard of papilledema/PTCS relative to nonusers of CAs. After adjustment for confounders, the increased hazard of PTCS/papilledema with CA use was no longer statistically significant (P = .06, doxycycline; P = .08, minocycline).This study relies on claims data, which lack clinical data.This study offers some evidence that CAs may increase the risk of PTCS/papilledema. However, after accounting for confounding factors in our multivariable models, we found no statistically significant association between CA use and the development of PTCS. Moreover, there was no dose-response effect whereby greater CA use was associated with a higher PTCS risk.

Background Direct stenting offers many potential advantages in appropriately selected lesions. Coronary artery calcification increases the complexity and risk of adverse events associated with percutaneous coronary intervention. This study aimed to examine the feasibility of direct stenting after treatment with orbital atherectomy (OA). Methods ORBIT II was a single-arm trial enrolling 443 subjects with de novo severely calcified coronary lesions treated with OA; direct stenting was utilized in 59.0% of cases. Procedural outcomes and 3-year major adverse cardiac event (MACE) rates were compared in subjects treated with pre-stent balloon dilatation versus direct stenting after OA. Results Procedural success (84.2% vs. 93.3%; p = 0.004) was significantly higher in the direct stenting cohort. 3-year MACE occurred less frequently in the direct stenting cohort (29.9% vs. 19.1%; p = 0.006), driven by lower rates of myocardial infarction and target lesion revascularization . In a propensity matched analysis, procedural success and 3-year MACE rates were similar in the pre-stent balloon dilatation and direct stenting groups (85.0% vs. 91.8%; p = 0.122 and 28.2% vs. 19.6%; p = 0.078, respectively). Conclusions Orbital atherectomy facilitates direct stenting and is associated with high procedural success and favorable 3-year outcomes in carefully selected patients. Randomized studies are needed to assess the optimal strategy after lesion preparation with OA.

Background A balance between autonomy and supervision can be difficult to obtain in medical education. In this study, we sought to determine whether the presence and level of supervision of ophthalmology resident outpatient clinic correlates with metrics of resident success, professionalism and stress. Methods A survey was emailed to all US ophthalmology program directors requesting it be forwarded to PGY4 residents. Questions included whether their program provided a resident-hosted outpatient clinic, and if so, whether residents were mandated to discuss every patient with faculty. Residents were assigned to three categories based on this question (0: no clinic, 1: mandated faculty input, 2: discretionary faculty input). Success metrics included numbers of manuscripts submitted, OKAP scores and success in obtaining fellowships. Professionalism metrics included rating comfort obtaining informed consent, breaking bad news, managing time in clinic, and confidence in providing care in various settings. Residents affirming participation in a continuity clinic also provided perceptions of the level of supervision and how the clinic affected stress. Results Category 1 residents perceived somewhat too much supervision, while category 2 residents felt that they had somewhat insufficient supervision. The majority of residents in either category did not feel that the continuity clinic affected their overall stress, although those who reported a change in stress usually indicated that the presence of the clinic increased stress. There were no other statistically significant differences between the responses from any category. Conclusions The presence of a resident-hosted continuity clinic neither adds nor detracts from the success or sense of professionalism of ophthalmology residents. However, when such a clinic is present, the degree of supervision appears to correlate inversely with resident perception of autonomy. These results suggest that the decision of a training program to offer a clinic hosted by residents offering comprehensive continuity care can be informed primarily by faculty and trainee philosophy and personal preferences without comprising education quality, clinical efficiency, residents’ perception of stress or their success in fellowship matching. Electronic supplementary material The online version of this article (10.1186/s12909-019-1620-0) contains supplementary material, which is available to authorized users.

CRLX101 is a nanoparticle-drug conjugate with a camptothecin payload. We assessed the toxicity and pathologic complete response (pCR) rate of CRLX101 with standard neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer. A single-arm study was conducted with a 3 + 3 dose escalation phase Ib followed by phase II at the maximum tolerated dose (MTD). Thirty-two patients were enrolled with 29 (91%) patients having T3/4 and 26 (81%) N1/2 disease. In phase Ib, no patient experienced a dose limiting toxicity (DLT) with every other week dosing, while 1/9 patients experienced a DLT with weekly dosing. The weekly MTD was identified as 15 mg/m2. The most common grade 3-4 toxicity was lymphopenia, with only 1 grade 4 event. pCR was achieved in 6/32 (19%) patients overall and 2/6 (33%) patients at the weekly MTD. CRLX101 at 15 mg/m2 weekly with neoadjuvant CRT is a feasible combination strategy with an excellent toxicity profile. Clinicaltrials.gov registration NCT02010567.

Purpose: To describe the demographic and clinical characteristics of patients with thyroid eye disease (TED) who present with predominate superior rectus/levator complex involvement.Methods...

The authors report the case of a 75-year-old man with preexisting glaucoma and recurrent retinal detachment who underwent intraocular silicone oil placement OD resulting in subsequent retrolaminar silicone oil migration to the optic chiasm and vision loss OS. MRI showed silicone oil tracking posteriorly along the right optic nerve to the chiasm. He was placed on high-dose corticosteroids and underwent a successful optic nerve sheath fenestration with improvement of vision in the contralateral eye. Clinicians should be cognizant of the potential for translaminar posterior migration of intraocular silicone oil, as well as the utility of optic nerve sheath fenestration to decompress the anterior visual pathways and restore vision.

Purpose To identify clinical and radiographic factors that predict return to sport in athletes undergoing hip arthroscopy and to determine thresholds for significant predictors. Methods Data were reviewed on all patients who underwent primary hip arthroscopy between November 2008 and August 2018. Patients were included if they played professional, college, or high school sports within 1 year before surgery and had preoperative, 3-month, 1-year, and 2-year postoperative patient-reported outcome scores for modified Harris Hip Score, Hip Outcome Score-Sport Specific-Subscale, and Nonarthritic Hip Score. Rates of achieving the minimal clinically important difference also were evaluated. Patients were divided into groups based on whether they returned to sport at the same or greater level. Multivariate logistic regression and receiver operator characteristic analysis were used to evaluate the correlation between significant variables and return to sport. Results A total of 136 patients with a mean age of 20.8 ± 7.07 years were included. Among athletes who attempted to return, professional and collegiate athletes returned to sport at any level at a rate of 85.0% (51/60), and high-school athletes returned at a rate of 88.1% (52/59). Competition level, postoperative alpha angle, change in alpha angle, and postoperative patient-reported outcomes were significantly different between groups. Athletes who returned to sport achieved the minimal clinically important difference for Hip Outcome Score–Sport Specific-Subscale at significantly higher rates than athletes who did not return to sport (91.6% vs 71.7%, P = .002, S = 8.97). The multivariate logistic regression model identified postoperative alpha angle as a statistically significant predictor of return to sport (P 9.97 [odds ratio 0.85, 95% confidence interval 0.79-0.91]). The receiver operator characteristic curve for postoperative alpha angle demonstrated acceptable discrimination between patients returning to sport and patients not returning to sport with an area under the curve of 0.71 and a threshold value of 46°. Athletes with a postoperative alpha angle ≤46° returned to sport at significantly higher rates than those with a postoperative alpha angle >46° [(P 9.97 [odds ratio 6.3, 95% confidence interval 2.6-15.2]). Conclusions Postoperative alpha angle was identified as a predictor of return to sport in athletes. The odds of returning to sport were 6.3 times greater in athletes with postoperative alpha angles ≤46° compared with athletes with angles >46°. Level of Evidence III, retrospective cohort study.

Performing germline and somatic sequencing in locally advanced and metastatic pancreatic cancer can identify potentially targetable genomic aberrations that impact current standard treatment options or eligibility for biomarker-targeted clinical trials. Testing for deleterious germline mutations in BRCA1/2 impacts patient selection for platinum-based chemotherapy regimens and selection of patients who are candidates to receive maintenance therapy with olaparib. Additional germline mutations also similarly introduce potential vulnerabilities to the cancers that arise and may be targeted by clinical trials. Somatic mutation testing also provides opportunities for optimal selection of patients for biomarker-driven clinical trials. Although KRAS mutations are found in 90% to 93% of pancreatic cancers, there are increasing opportunities for therapies against particular mutant KRAS isoforms, especially with the advent of KRAS G12C–specific small molecule inhibitors, and KRAS targeting trials will increasingly require identification of the specific KRAS mutation present. There are also a range of tumor site–agnostic molecular features, such as microsatellite instability and NTRK fusions that, although rarely found in pancreatic cancers, impact selection of patients who have the potential for dramatic benefit with immune checkpoint inhibitors such as pembrolizumab or TRK inhibitors such as larotrectinib or entrectinib, respectively, and thus motivate broader somatic mutation and fusion testing for patients with locally advanced and metastatic pancreatic cancers. Multiple other rare actionable aberrations, particularly gene fusions in the 8% to 10% of KRAS wild-type pancreatic cancers, are also known, and enrollment in basket trials for these rare patient cohorts is highly encouraged.

A 65-year-old man with end-stage renal disease on peritoneal dialysis was admitted for new onset binocular double vision, failure to thrive, and debilitating right-sided headaches. Medical history was significant for tympanomastoidectomy for polymicrobial mastoiditis and treatment with IV antibiotics. MRI brain without contrast was read by radiology initially as showing expected postsurgical changes; however, given patient's history of mastoiditis infection, there was a high clinical suspicion for Gradenigo syndrome. MRI brain was repeated with gadoxetate contrast to minimize the risk of nephrogenic systemic fibrosis (NSF) in a patient with severe renal disease and this revealed an intracranial empyema involving both the trigeminal and abducens nerves confirming the diagnosis of Gradenigo syndrome. This case presented a diagnostic challenge because of suboptimal visualization on initial nonenhanced MRI. Gadoxetate was chosen because of its unique properties including high hepatobiliary excretion making it a safer form of gadolinium-based contrast agent that may not have the potential to precipitate NSF.