A phase II trial of UGT1A1 genotype-guided FOLFIRI plus bevacizumab as first-line therapy for advanced, unresectable colorectal cancer.

BACKGROUND: FOLFIRI is a standard regimen for metastatic colorectal cancer (mCRC). We hypothesized that a pharmacogenomic-directed strategy where more efficient irinotecan metabolizers (UGT1A1 *1/*1 homozygotes and *1/*28 heterozygotes) receive higher-than-standard irinotecan doses would improve progression-free survival (PFS) compared to non-genotype selected historical controls with acceptable toxicity. METHODS: In this phase II multicenter study irinotecan dosing in first-line FOLFIRI and bevacizumab for mCRC was based on UGT1A1 genotype with *1/*1, *1/*28, and *28/*28 patients receiving 310 mg/m2, 260 mg/m2, and 180 mg/m2, respectively. Primary endpoint was PFS. Secondary endpoints were investigator and patient-reported adverse events, and estimation of overall survival (OS). RESULTS: One-hundred patients were enrolled with 91 evaluable for PFS and 83 evaluable for best response. Median PFS was 12.5 months (90% CI 10.9, 15.4), shorter than the anticipated alternative hypothesis of 14 months. PFS by genotype was 12.5 months (90% CI 10.9, 17.4) for *1/*1, 14.6 months (90% CI 11.8, 17.5) for *1/*28, and 6 months (90% CI 2.3, 7.7) for *28/28, respectively. OS was 24.5 months (90% CI 19.1, 30.7) and by genotype was 26.5 (90% CI 19.1, 32.9), 25.9 (90% CI 17.6, 37.7), and 13.4 (90% CI 2.3, 20.5) months for *1/*1, *1/*28, and *28/*28, respectively. G3/4 toxicity was similar between all subgroups, including diarrhea and neutropenia. CONCLUSIONS: A pharmacogenomic-directed irinotecan strategy improved PFS in the *1/*1 and *1/*28 genotypes with higher rates of neutropenia and similar rates of diarrhea compared to expected with standard FOLFIRI dosing. However, improvements in response rate and PFS were modest. This strategy should not change standard practice for mCRC patients in the first-line setting.

Mid- to Long-Term Outcomes in Patients After Hip Arthroscopy With Labral Reconstruction: A Systematic Review.

Background: There is a paucity of aggregate data documenting mid- to long-term outcomes of patients after hip arthroscopy with labral reconstruction. Purpose: To report mid- to long-term outcomes in patients after undergoing either primary or revision hip arthroscopy with labral reconstruction for the treatment of irreparable labral tears. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review of the PubMed, Cochrane, and Scopus databases in May 2022 was conducted with the following keywords: "hip arthroscopy,""labral reconstruction,""irreparable,""labrum,""reconstruction,""five-year,""midterm,""5 year,""long-term,""10 year," ten-year," and "femoroacetabular impingement" using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Midterm was defined as mean 5-year follow-up, and long-term was defined as mean 10-year or longer follow-up. For each included article, the demographic, radiographic, intraoperative, and surgical variables, as well as patient-reported outcomes (PROs), psychometric thresholds, and secondary surgeries were recorded. Forest plots were created for PROs that were reported in ≥3 studies; heterogeneity was assessed using I2 values. Results: Out of 463 initial articles, 5 studies including 178 hips with primary and 41 hips with revision surgeries were included. One study had an average 5-year follow-up, three studies had a minimum 5-year follow-up and one study had a minimum 10-year follow-up. The most common indications for hip arthroscopy with labral reconstruction were irreparable labral tears. The most common PRO was the modified Harris Hip Score (mHHS), which was reported in all 5 studies. The mean preoperative mHHS ranged from 58.9 to 66, and the mean postoperative mHHS at minimum 5-year follow-up ranged from 80.2 to 89. The preoperative and postoperative mHHSs for the single long-term follow-up study were 60 and 82, respectively. All 5 studies demonstrated significant improvements in reported PROs. All 5 studies reported secondary surgery rates, with 1 study reporting rates at both 5- and 10-year follow-up. Conversion to total hip arthroplasty ranged from 0% to 27%, while overall secondary surgery rates ranged from 0% to 36%. Conclusion: Findings demonstrated that patients undergoing primary and revision hip arthroscopy with labral reconstruction experienced favorable outcomes and high rates of clinical benefit and survivorship at mid- to long-term follow-up.

Long-term Survivorship and Outcomes of Patients Without Dysplasia Undergoing Capsular Repair During Primary Hip Arthroscopy for Femoroacetabular Impingement Syndrome.

BACKGROUND: There is a paucity of literature evaluating long-term outcomes and survivorship of patients undergoing primary hip arthroscopy with capsular repair for femoroacetabular impingement syndrome (FAIS). PURPOSE: To report 10-year survivorship and patient-reported outcomes (PROs) after primary hip arthroscopy with capsular repair for FAIS and evaluate the effect of capsular repair in patients at the highest risk for conversion to arthroplasty. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Data were prospectively collected and retrospectively reviewed on all patients undergoing primary hip arthroscopy with capsular repair between October 2008 and February 2011. Patients with a minimum 10-year follow-up on the modified Harris Hip Score (mHHS), Nonarthritic Hip Score (NAHS), and visual analog scale for pain (VAS) scores were selected. The preoperative and minimum 10-year follow-up Hip Outcome Score-Sports Specific Subscale (HOS-SSS) scores were also reported, if available. Patients with ipsilateral hip surgery, worker's compensation, Tönnis osteoarthritis grade >1, and hip dysplasia (lateral center-edge angle <25°) were excluded. Survivorship, PROS, and clinical benefit-minimal clinically important difference (MCID) and Patient Acceptable Symptom State (PASS)-were reported. An additional propensity-matched subanalysis was performed on patients at the highest risk for conversion to arthroplasty, comparing patients undergoing capsular repair to patients with unrepaired capsules. RESULTS: A total of 145 (n = 130 patients) out of 180 eligible hips (n = 165 patients) had a minimum 10-year follow-up (80.6%). Also, 126 hips (86.9%) belonged to women, and 19 hips (13.1%) belonged to men. The mean patient age was 30.3 ± 12.9 years. The survivorship rate was 91% at the 10-year follow-up. The cohort experienced significant improvements (P < .001) in the mHHS, NAHS, HOS-SSS, and VAS for pain scores. Moreover, the cohort achieved high rates of the PASS for the mHHS (89.8%), high rates of the MCID for the mHHS (82.4%), and high rates of the MCID for VAS for pain (80.6%) scores. In the propensity-matched subanalysis performed on patients with the highest risk for arthroplasty, 29 hips with capsular repair were matched to 81 hips with unrepaired capsules. While both groups experienced significant improvements in all PROs (P < .05), the group without capsule repair trended toward a higher conversion to arthroplasty rate when compared with the repair group. In addition, an odds ratio was calculated for the likelihood of converting to arthroplasty after having an unrepaired capsule compared with capsular repair (2.54 [95% CI, 0.873-7.37]; P = .087). CONCLUSION: Patients undergoing primary hip arthroscopy with capsular repair experienced a high survivorship rate of 91% at a minimum 10-year follow-up. Patients who did not convert to arthroplasty saw favorable improvements in PROs and achieved high clinical benefit rates. In addition, among those patients at the highest risk for conversion to arthroplasty, a trend toward greater survivorship was observed with capsular repair.

What does visual snow look like? Quantification by matching a simulation.

The primary symptom of visual snow syndrome (VSS) is the unremitting perception of small, flickering dots covering the visual field. VSS is a serious but poorly understood condition that can interfere with daily tasks. Several studies have provided qualitative data about the appearance of visual snow, but methods to quantify the symptom are lacking. Here, we developed a task in which participants with VSS adjusted parameters of simulated visual snow on a computer monitor until the simulation matched their internal visual snow. On each trial, participants (n = 31 with VSS) modified the size, density, update speed, and contrast of the simulation. Participants' settings were highly reliable across trials (intraclass correlation coefficients > 0.89), and they reported that the task was effective at stimulating their visual snow. On average, visual snow was very small (less than 2 arcmin in diameter), updated quickly (mean temporal frequency = 18.2 Hz), had low density (mean snow elements vs. background = 2.87%), and had low contrast (average root mean square contrast = 2.56%). Our task provided a quantitative assessment of visual snow percepts, which may help individuals with VSS communicate their experience to others, facilitate assessment of treatment efficacy, and further our understanding of the trajectory of symptoms, as well as the neural origins of VSS.

Viral Conjunctivitis Rates Unchanged Before and During the COVID-19 Pandemic in an Ophthalmology Clinic.

Background: Millions of acute conjunctivitis cases occur in the United States annually. The impact of COVID-19 mitigation practices on viral conjunctivitis incidence within ophthalmology clinics has not been reported. We hypothesized that viral conjunctivitis rates would decrease with implementation of such practices. Methods: A retrospective chart review was conducted at a single academic center's ophthalmology clinics. Electronic health record data was queried using ICD-10 diagnostic codes to include 649 patients aged 2-97 with viral, bacterial, or allergic conjunctivitis diagnosed either before (6/1/2018-5/1/2019) or during (6/1/2020-5/1/2021) COVID-19 precautions. Conjunctivitis rates per ophthalmology clinic visit were compared using rate-ratio analysis. Logistic regression evaluated the effects of age, sex, and race among those with conjunctivitis. Results: A total of 66,027 ophthalmology clinic visits occurred during the study period. Viral conjunctivitis rates per visit did not significantly change after enacting COVID-19 mitigation strategies, but allergic conjunctivitis rates significantly increased (viral: RR 0.82, 95% CI 0.51 to 1.31, p=0.408; allergic: RR 1.70, 95% CI 1.43 to 2.03, p<0.001). When controlling for time, younger age (≤ median age 55) (p=0.005) and Caucasian race (p=0.009) were associated with higher viral conjunctivitis frequency. Conclusion: Contrary to trends reported in emergency departments, viral conjunctivitis rates within an ophthalmology clinic did not significantly change after COVID-19 mitigation strategies, though allergic conjunctivitis rates increased. Patients' avoidance of emergency departments during the pandemic may have contributed. Further investigation is required to explore variation in ophthalmology patient populations and needs based on care setting.

A retrospective review included 649 patients with viral, bacterial, or allergic conjunctivitis diagnosed at a single center's ophthalmology clinics before (6/1/2018­5/1/2019) or during (6/1/2020­5/1/2021) COVID-19 precautions. Contrary to emergency department experiences, viral conjunctivitis rates did not significantly change after COVID-19 precautions. However, allergic conjunctivitis rates significantly increased. Conjunctivitis presentation in ophthalmology clinics differed from that reported in emergency departments, warranting further evaluation of variation in patient needs by setting.

Association of Patient-Reported Social Needs with Emergency Department Visits and Hospitalizations Among Federally Qualified Health Center Patients.

BACKGROUND: Health care systems are increasingly screening for unmet social needs. The association between patient-reported social needs and health care utilization is not well understood. OBJECTIVE: To investigate the association between patient-reported social needs, measured by the Protocol for Responding to and Assessing Patients' Assets, Risks, and Experiences (PRAPARE), and inpatient and emergency department (ED) utilization. DESIGN: This cohort study analyzed merged 2017-2019 electronic health record (EHR) data across multiple health systems. PARTICIPANTS: Adult patients from a federally qualified health center (FQHC) in central North Carolina who completed PRAPARE as part of a primary care visit with behavioral health services. MAIN MEASURES: The count of up to 12 unmet social needs, aggregated as 0, 1, 2, or 3 + . Outcomes include the probability of an ED visit and hospitalization 12 months after PRAPARE assessment, modeled by logistic regressions controlling for age, sex, race, ethnicity, comorbidity burden, being uninsured, and prior utilization in the past 12 months. KEY RESULTS: The study population consisted of 1924 adults (38.7% male, 50.1% Black, 36.3% Hispanic, 55.9% unemployed, 68.2% of patients reported 1 + needs). Those with more needs were younger, more likely to be unemployed, and experienced greater comorbidity burden. 35.3% of patients had ED visit(s) and 36.3% had hospitalization(s) 1 year after PRAPARE assessment. In adjusted analysis, having 3 + needs was associated with a percentage point increase in the predicted probability of hospitalization (average marginal effect 0.06, SE 0.03, p < 0.05) compared with having 0 needs. Similarly, having 2 needs (0.07, SE 0.03, p < 0.05) or 3 + needs (0.06, SE 0.03, p < 0.05) was associated with increased probability of ED visits compared to 0 needs. CONCLUSIONS: Patient-reported social needs were common and associated with health care utilization patterns. Future research should identify interventions to address unmet social needs to improve health and avoid potentially preventable escalating medical intervention.

In-Clinic Detection of Optic Disc Drusen Using Hand-Held Ultrasound Technology.

Neuro-ophthalmologists commonly receive referrals for possible papilloedema. One common cause of oedematous-appearing optic nerves is optic disc drusen (ODD). We describe a novel, handheld, portable ultrasound device that can be used to identify ODD in cases of suspected papilloedema. We demonstrate here that this portable ultrasound system can detect ODD in the outpatient ophthalmology and neurology settings. The portable version demonstrates several advantages. The device can be carried into the office, readily reducing visit times and office space. It is much more affordable than a traditional ultrasound machine. Images can be uploaded to a secure server and imported into the patient's chart. These cases represent one potential ophthalmological application of this novel technology that could augment the ophthalmological examination and improve patient care in the future.

Autologous Matrix-Induced Chondrogenesis for the Treatment of Hip Acetabular Chondral Lesions Demonstrates Improved Outcomes: A Systematic Review.

PURPOSE: To systematically investigate the outcomes of patients who underwent autologous matrix-induced chondrogenesis (AMIC) during hip arthroscopy for the treatment of acetabular chondral lesions due to femoroacetabular impingement syndrome (FAIS). METHODS: PubMed and Cochrane were queried in June 2022 to conduct this systematic review using the following keywords: "femoracetabular impingement," "arthroscopy," "microfracture," and "autologous matrix-induced chondrogenesis." Articles were included if they reported on patient-reported outcomes of AMIC during hip arthroscopy to treat chondral lesions of the hip. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria. Each study was queried for demographics, lesion classification, surgical treatment, patient-reported outcome scores, revision arthroscopy, and conversion to THA. A qualitative sub-analysis was performed to compare patients undergoing AMIC to patients undergoing microfracture alone if included studies also assessed results of microfracture alone. RESULTS: Four studies met inclusion criteria and assessed 209 hips undergoing AMIC. The included studies consisted of 99 male and 110 female patients. Mean postoperative follow-up ranged from 1 to 8 years, and mean patient age ranged from 34.3 to 45 years. Three of the four included studies reported the modified Harris Hip Scores (mHHS) and all three of these studies reported statistically significant improvement in the mHHS at final follow-up (p<0.001) with mean preoperative values ranging from 44.5-62.8 and mean postoperative values ranging from 78.8-95.8. Two of the four studies compared patients treated with AMIC to microfracture alone. In these two studies, the AMIC groups reported 0 patients converting to THA while the microfracture alone groups reported a highly variable rate of conversion to THA (2% - 32.6%). CONCLUSION: Patients who underwent hip arthroscopy and AMIC for the treatment of FAIS and acetabular chondral lesions demonstrated improved patient reported outcomes and low rates of secondary surgeries at short-term follow-up.

Clinical genetics in breast cancer.

As genetic testing becomes increasingly more accessible and more applicable with a broader range of clinical implications, it may also become more challenging for breast cancer providers to remain up-to-date. This review outlines some of the current clinical guidelines and recent literature surrounding germline genetic testing, as well as genomic testing, in the screening, prevention, diagnosis, and treatment of breast cancer, while identifying potential areas of further research.

Female Patients Undergoing Latarjet Surgery Show Similar 2-Year Secondary Surgery Rates but Greater Risk of Emergency Department Visits Compared With a Matched Cohort of Male Patients.

PURPOSE: To evaluate sex-based differences in 30-day postoperative emergency department (ED) visits, 90-day complication rates, and 2-year secondary surgery rates after the Latarjet procedure for the treatment of recurrent shoulder instability. METHODS: A national administrative claims database was used to identify patients with International Classification of Diseases, Tenth Revision (ICD-10) diagnosis codes for shoulder subluxation or dislocation on the day of first-time stabilization with the Latarjet technique between 2015 and 2021. Male patients were matched 4:1 to female patients based on age, Elixhauser Comorbidity Index (ECI) score, and body mass index class. Rates of 30-day ED visits and 90-day complications were compared between cohorts, and risk factors for ED visits were identified by multivariate regression. The incidence of secondary surgery within 2 years was compared by Kaplan-Meier analysis. RESULTS: Prior to matching, 1,059 male and 360 female patients met the inclusion and exclusion criteria. Subsequent 4:1 (male-to-female) matching controlling for age, ECI score, and body mass index yielded 694 male and 185 female patients who underwent the Latarjet procedure. The overall incidence of 30-day ED visits was 9.3%, with an incidence of 8.2% for male patients and 13.5% for female patients. On the basis of multivariate logistic regression, these 30-day ED visits were associated with female sex (odds ratio, 1.79; P = .029) and incrementally higher ECI scores; relative to an ECI score of 0, ECI scores of 1 to 2, 3 to 4, and 5 or greater were associated with odds ratios of 5.31 (P = .006), 8.12 (P < .001), and 12.84 (P < .001), respectively. Ninety-day complications occurred in 1.5% of the total cohort, and the incidence was not statistically different between sexes. Overall, 2-year secondary surgery rates were similar between male and female patients (5.1% and 6.7%, respectively; P = .4). CONCLUSIONS: Female patients undergoing the Latarjet procedure for recurrent shoulder instability showed similar 90-day complication and 2-year secondary surgery rates to a matched cohort of male patients. Female sex, along with ECI score, however, was associated with a greater rate of 30-day ED visits. LEVEL OF EVIDENCE: Level III, retrospective comparative case series.

Coronary intravascular lithotripsy for severe coronary artery calcification: The disrupt CAD I-IV trials.

Coronary artery calcification (CAC) severity is associated with increased vessel inflammation, atherosclerosis, stent failure, and risk of percutaneous coronary intervention-related complications. Current modalities for CAC modification include atherectomy techniques (rotational, orbital, and laser) and balloon modification (cutting and scoring). However, these methods are limited by their risk of slow flow/no reflow, coronary dissection, perforation, and myocardial infarction. Intravascular lithotripsy (IVL) emits high-energy sonic waves that induce calcium fractures within a target lesion to improve vessel compliance for stent placement. Low rates of major cardiac adverse events (MACE) and high rates of procedural and angiographic success were observed with IVL in the Disrupt CAD I-IV trials. Optical coherence tomography sub-studies identified calcium fracture as the likely etiology of improved vessel compliance and increased luminal diameter post-IVL. Rates of MACE, procedural, and angiographic success were consistent across the Disrupt CAD trials, suggesting IVL is less operator-dependent compared to other calcium-modifying techniques. Coronary IVL offers interventional cardiologists a safe and effective method of severe CAC modification, while providing reproducible outcomes.

Corticosteroid Injections Administered Within 4 Weeks Prior to Hip Arthroscopy Are Associated With Higher Rates of Postoperative Infection.

PURPOSE: To evaluate the association between the timing of intra-articular hip corticosteroid injections and the risk of postoperative infection in patients undergoing hip arthroscopy. METHODS: The 2010-2021 PearlDiver M157 administrative claims database was queried for patients who underwent hip arthroscopy. Patients who received intra-articular corticosteroid injections within 12 weeks prior to arthroscopy were matched 1:1 to patients who did not receive such injections based on age, sex, and Elixhauser Comorbidity Index, as well as the presence of diabetes mellitus, hypertension, obesity, and tobacco use. Those with injections prior to arthroscopy were subdivided based on having received injections within 12 weeks prior to surgery. To verify that the corticosteroid injections and surgical procedures were conducted in the hip joint, Current Procedural Terminology codes were used. By use of Current Procedural Terminology and International Classification of Diseases (ninth revision and tenth revision) coding, postoperative surgical-site infection after corticosteroid injection was evaluated. The impact of the timing of preoperative corticosteroid injections on the incidence of postoperative infection was evaluated using multivariable logistic regression analysis. RESULTS: A total of 12,390 hip arthroscopy cases were identified, including 3,579 patients who received corticosteroid injections 0 to 4 weeks prior to surgery; 4,759, within 4 to 8 weeks prior to surgery; and 4,052, within 8 to 12 weeks prior to surgery. Compared with controls, patients who received corticosteroid injections within 0 to 4 weeks preoperatively had a significantly higher rate of surgical-site infection (odds ratio, 2.43; P = .0001). No significant differences in infection rates were observed at the later time intervals (4-8 weeks or 8-12 weeks). Furthermore, in comparison to controls, patients who received corticosteroid injections had a significantly higher rate of wound dehiscence (odds ratio, 1.84; P = .0007). CONCLUSIONS: Intra-articular corticosteroid injections within 4 weeks prior to hip arthroscopy were significantly associated with increased surgical-site infection rates after hip arthroscopy surgery. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Osteochondral Allograft or Autograft Transplantation of the Femoral Head Leads to Improvement in Outcomes but Variable Survivorship: A Systematic Review.

PURPOSE: To review patient-reported outcomes (PROs) and survivorship in patients undergoing osteochondral autograft or allograft transplantation (OAT) of the femoral head. METHODS: PubMed, Cochrane Center for Register of Controlled Trials, and Scopus databases were searched in November 2022 with an updated search extending to December 2023 using criteria from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the following keywords: (hip OR femoral head) AND (mosaicplasty OR osteochondral allograft OR osteochondral autograft OR osteochondral lesion). Articles were included if they evaluated postoperative PROs in patients who underwent OAT of the femoral head and had a study size of 5 or more hips (n ≥ 5). Survivorship was defined as freedom from conversion to total hip arthroplasty. For PROs evaluated in 3 studies or more, forest plots were created and I2 was calculated. RESULTS: Twelve studies were included in this review, with a total of 156 hips and a mean follow-up time ranging between 16.8 and 222 months. In total, 104 (66.7%) hips were male while 52 (33.3%) were female. Age of patients ranged from 17.0 to 35.4 years, while body mass index ranged from 23.3 to 28.1. Eight studies reported on osteochondral autograft transplantation and 4 studies on osteochondral allograft transplantation. Three studies reported significant improvement in at least 1 PRO. Survivorship ranged from 61.5% to 96% at minimum 2-year follow-up and from 57.1% to 91% at minimum 5-year follow-up. At a follow-up of less than 5 years, osteochondral allograft transplantation studies showed 70% to 87.5% survivorship, while autograft varied from 61.54% to 96%. CONCLUSIONS: Patients with osteochondral lesions of the femoral head who underwent osteochondral autograft or allograft transplantation demonstrated improved PROs but variable survivorship rates. LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies.

Comprehensive Landscape of BRAF Variant Classes, Clonalities, and Co-Mutations in Metastatic Colorectal Cancer Using ctDNA Profiling.

Although V600E accounts for the majority of the BRAF mutations in metastatic colorectal cancer (mCRC), non-V600 BRAF variants have been shown in recent years to represent a distinct molecular subtype. This study provides a comprehensive profile of BRAF variants in mCRC using a large genomic database of circulating tumor DNA (ctDNA) and analyzing clinical outcomes in a cohort of patients with atypical (non-V600) BRAF variants (aBRAF; class II, class III, unclassified). Overall, 1733 out of 14,742 mCRC patients in the ctDNA cohort had at least one BRAF variant. Patients with atypical BRAF variants tended to be younger and male. In contrast to BRAFV600E, BRAF class II and III variants and their co-occurrence with KRAS/NRAS mutations were increased at baseline and especially with those patients predicted to have prior anti-EGFR exposure. Our clinical cohort included 38 patients with atypical BRAF mCRC treated at a large academic referral center. While there were no survival differences between atypical BRAF classes, concurrent RAS mutations or liver involvement was associated with poorer prognosis. Notably, patients younger than 50 years of age had extremely poor survival. In these patients, the high-frequency KRAS/NRAS co-mutation and its correlation with poorer prognosis underlines the urgent need for novel therapeutic strategies. This study represents one of the most comprehensive characterizations to date of atypical BRAF variants, utilizing both ctDNA and clinical cohorts.

Impact of KRAS mutations and co-mutations on clinical outcomes in pancreatic ductal adenocarcinoma.

The relevance of KRAS mutation alleles to clinical outcome remains inconclusive in pancreatic adenocarcinoma (PDAC). We conducted a retrospective study of 803 patients with PDAC (42% with metastatic disease) at MD Anderson Cancer Center. Overall survival (OS) analysis demonstrated that KRAS mutation status and subtypes were prognostic (p < 0.001). Relative to patients with KRAS wildtype tumors (median OS 38 months), patients with KRASG12R had a similar OS (median 34 months), while patients with KRASQ61 and KRASG12D mutated tumors had shorter OS (median 20 months [HR: 1.9, 95% CI 1.2-3.0, p = 0.006] and 22 months [HR: 1.7, 95% CI 1.3-2.3, p < 0.001], respectively). There was enrichment of KRASG12D mutation in metastatic tumors (34% vs 24%, OR: 1.7, 95% CI 1.2-2.4, p = 0.001) and enrichment of KRASG12R in well and moderately differentiated tumors (14% vs 9%, OR: 1.7, 95% CI 1.05-2.99, p = 0.04). Similar findings were observed in the external validation cohort (PanCAN's Know Your Tumor® dataset, n = 408).

Establishing Optic Nerve Diameter Threshold Sensitive and Specific for Optic Atrophy Diagnosis.

PURPOSE: To determine a potential threshold optic nerve diameter (OND) that could reliably differentiate healthy nerves from those affected by optic atrophy (OA) and to determine correlations of OND in OA with retinal nerve fiber layer (RNFL) thickness, visual acuity (VA), and visual field mean deviation (VFMD). METHODS: This was a retrospective case control study. Magnetic resonance (MR) images were reviewed from individuals with OA aged 18 years or older with vision loss for more than 6 months and an OA diagnosis established by a neuro-ophthalmologist. Individuals without OA who underwent MR imaging of the orbit for other purposes were also collected. OND was measured on coronal T2-weighted images in the midorbital section, 1cm posterior to the optic disc. Measurements of mean RNFL thickness, VA and VFMD were also collected. RESULTS: In this study 47 OA subjects (63% women, 78 eyes) and 75 normal subjects (42.7% women, 127 eyes) were assessed. Healthy ONDs (mean 2.73 ± 0.24 mm) were significantly greater than OA nerve diameters (mean 1.94 ± 0.32 mm; P < 0.001). A threshold OND of ≤2.3 mm had a sensitivity of 0.92 and a specificity of 0.93 in predicting OA. Mean RNFL (r = 0.05, p = 0.68), VA (r = 0.17, p = 0.14), and VFMD (r = 0.18, p = 0.16) were not significantly associated with OND. CONCLUSION: ONDs are significantly reduced in patients with OA compared with healthy nerves. A threshold OND of ≤2.3 mm is highly sensitive and specific for a diagnosis of OA. OND was not significantly correlated with RNFL thickness, VA, or VFMD.

Dancers Show Significant Improvement in Outcomes and Favorable Return-to-Dance Rates After Primary Hip Arthroscopy With Femoral Head Cartilage Status Being a Predictor of Secondary Surgical Procedures at Mid-Term Follow-Up.

PURPOSE: To report minimum 5-year follow-up patient-reported outcome measurement (PROM) scores and return-to-dance rates in dancers who underwent primary hip arthroscopy and to identify predictors of secondary surgical procedures. METHODS: Prospectively collected data from patients who underwent hip arthroscopy between May 2010 and June 2016 were retrospectively reviewed. Patients were included if they participated in dance at any level 1 year prior to surgery and had preoperative and minimum 5-year follow-up scores consisting of the modified Harris Hip Score, Nonarthritic Hip Score, Hip Outcome Score-Sports Specific Subscale, and visual analog scale pain score. The exclusion criteria were previous hip conditions, previous ipsilateral hip surgery, Tönnis grade greater than 1, or lateral center-edge angle less than 18°. The minimal clinically important difference (MCID) was reported. Dancers who discontinued dance for reasons other than pain in the operative hip were excluded from the return-to-dance analysis. A logistic regression model was used to identify predictors of secondary surgical procedures. RESULTS: Fifty-one hips (48 female dancers) were included. The average age and average follow-up period were 29.8 ± 17.2 years and 79.1 ± 23.2 months, respectively. Improvement in all PROM scores (P < .001) was reported. Achievement rates of the MCID for the modified Harris Hip Score, Nonarthritic Hip Score, and visual analog scale pain score were 83.3%, 85.7%, and 85.7%, respectively. Revision hip arthroscopy was performed in 5 dancers (9.8%). Conversion to total hip arthroplasty was performed in 4 dancers (7.8%). The return-to-dance rate was 78.6%, with 57.6% returning to the preinjury performance level or a higher level. Higher femoral head Outerbridge grade was identified as a predictor of secondary surgical procedures (P = .045; odds ratio, 6.752 [95% confidence interval, 1.043-43.688]). CONCLUSIONS: After primary hip arthroscopy, dancers experienced significant improvement in all PROM scores collected and achieved the MCID at a high rate at minimum 5-year follow-up. The return-to-dance rate in dancers who did not discontinue dance because of lifestyle transitions was 78.6%, with 57.6% returning to the preinjury performance level or a higher level. Higher femoral head Outerbridge grade was found to be a predictor of secondary surgical procedures. LEVEL OF EVIDENCE: Level IV, case series.

A multi-centre case series of patients with coexistent intracranial hypertension and malignant arterial hypertension.

OBJECTIVE: To describe the clinical characteristics, outcomes, and management of a large cohort of patients with concomitant malignant arterial hypertension and intracranial hypertension. METHODS: Design: Retrospective case series. SUBJECTS: Patients aged ≥ 18 years with bilateral optic disc oedema (ODE), malignant arterial hypertension and intracranial hypertension at five academic institutions. Patient demographics, clinical characteristics, diagnostic studies, and management were collected. RESULTS: Nineteen patients (58% female, 63% Black) were included. Median age was 35 years; body mass index (BMI) was 30 kg/m2. Fourteen (74%) patients had pre-existing hypertension. The most common presenting symptom was blurred vision (89%). Median blood pressure (BP) was 220 mmHg systolic (IQR 199-231.5 mmHg) and 130 mmHg diastolic (IQR 116-136 mmHg) mmHg), and median lumbar puncture opening pressure was 36.5 cmH2O. All patients received treatment for arterial hypertension. Seventeen (89%) patients received medical treatment for raised intracranial pressure, while six (30%) patients underwent a surgical intervention. There was significant improvement in ODE, peripapillary retinal nerve fibre layer thickness, and visual field in the worst eye (p < 0.05). Considering the worst eye, 9 (47%) presented with acuity ≥ 20/25, while 5 (26%) presented with ≤ 20/200. Overall, 7 patients maintained ≥ 20/25 acuity or better, 6 demonstrated improvement, and 5 demonstrated worsening. CONCLUSIONS: Papilloedema and malignant arterial hypertension can occur simultaneously with potentially greater risk for severe visual loss. Clinicians should consider a workup for papilloedema among patients with significantly elevated blood pressure and bilateral optic disc oedema.

Medicaid Insurance Is Associated With More Complications and Emergency Department Visits but Equivalent 5-Year Secondary Surgery Rate After Primary Hip Arthroscopy.

PURPOSE: To compare 90-day complications, 30-day emergency department (ED) visits, and 5-year rate of secondary surgeries for patients with Medicaid vs commercial insurance undergoing primary hip arthroscopy for femoroacetabular impingement syndrome (FAIS) and/or labral tears using a large national database. METHODS: The PearlDiver Mariner151 database was used to identify patients with International Classification of Diseases, Tenth Revision diagnosis codes for FAIS and/or labral tear who underwent primary hip arthroscopy with femoroplasty, acetabuloplasty, and/or labral repair between 2015 and 2021. Patients with Medicaid were matched 1:4 to a control group of commercially insured patients based on age, sex, body mass index, and Elixhauser Comorbidity Index. Rates of 90-day complications and 30-day ED visits were compared using multivariate regression models. Five-year rates of secondary surgeries-revision arthroscopy or total hip arthroplasty-were compared between cohorts by Kaplan-Meier analysis. RESULTS: A total of 2,033 Medicaid patients were matched with 8,056 commercially insured patients. Rates of adverse events were low; however, Medicaid patients were significantly more likely than commercially insured patients to experience any 90-day complication (2.12% vs 1.43%; odds ratio [OR], 1.2; P = .02). Medicaid patients also experienced more 30-day ED visits than commercially insured patients (8.61% vs 4.28%), and on multivariate logistic regression, insurance status was the strongest determinant of 30-day ED visits (relative to commercial, Medicaid OR, 2.02; P < .001). Despite these differences, 5-year rates of secondary surgeries were comparable between groups (6.1% vs 6.0%; P = .6). CONCLUSIONS: In this large national database study, Medicaid patients undergoing primary hip arthroscopy showed significantly greater odds of experiencing 90-day postoperative complications and 30-day ED visits compared to commercially insured patients. Nevertheless, both groups had similar survivorship rates at 5-year follow-up, similar to prior estimates irrespective of insurance. These results document encouraging secondary surgery rates in Medicaid patients.

Heparin Dosing During Percutaneous Coronary Intervention and Obesity.

ABSTRACT: Unfractionated heparin is the most common anticoagulant used during percutaneous coronary intervention. Practice guidelines recommend an initial weight-based heparin bolus dose between 70 and 100 U/kg to achieve target activated clotting time (ACT) of 250-300 seconds. The impact of severe obesity on weight-based heparin dosing is not well studied. We performed a retrospective analysis of 424 patients undergoing percutaneous coronary intervention who received heparin for anticoagulation. We collected detailed data on cumulative heparin administration and measured ACT values in this cohort. We performed separate analyses to identify clinical predictors that may affect dose-response curves. There was significant variability in dosing with mean dose of 103.9 ± 32-U/kg heparin administered to achieve target ACT ≥ 250 seconds. Women received higher initial heparin doses when adjusted for weight than men (97.6 ± 31 vs. 89 ± 28 U/kg, P = 0.004), and only 49% of patients achieved ACT ≥ 250 s with the initial recommended heparin bolus dose (70-100 U/kg). Lower heparin dose (U/kg) was required in obese patients to achieve target ACT. In multivariate linear regression analysis with ACT as dependent variable, after inclusion of weight-based dosing for heparin, body mass index was the only significant covariate. In conclusion, there is significant variability in the therapeutic effect of heparin, with a lower weight-adjusted heparin dose required in obese patients.