STING controls nociception via type I interferon signalling in sensory neurons.

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.

Elpistostege and the origin of the vertebrate hand.

The evolution of fishes to tetrapods (four-limbed vertebrates) was one of the most important transformations in vertebrate evolution. Hypotheses of tetrapod origins rely heavily on the anatomy of a few tetrapod-like fish fossils from the Middle and Late Devonian period (393-359 million years ago)1. These taxa-known as elpistostegalians-include Panderichthys2, Elpistostege3,4 and Tiktaalik1,5, none of which has yet revealed the complete skeletal anatomy of the pectoral fin. Here we report a 1.57-metre-long articulated specimen of Elpistostege watsoni from the Upper Devonian period of Canada, which represents-to our knowledge-the most complete elpistostegalian yet found. High-energy computed tomography reveals that the skeleton of the pectoral fin has four proximodistal rows of radials (two of which include branched carpals) as well as two distal rows that are organized as digits and putative digits. Despite this skeletal pattern (which represents the most tetrapod-like arrangement of bones found in a pectoral fin to date), the fin retains lepidotrichia (fin rays) distal to the radials. We suggest that the vertebrate hand arose primarily from a skeletal pattern buried within the fairly typical aquatic pectoral fin of elpistostegalians. Elpistostege is potentially the sister taxon of all other tetrapods, and its appendages further blur the line between fish and land vertebrates.

Author Correction: Elpistostege and the origin of the vertebrate hand.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genetic subgroups inform on pathobiology in adult and pediatric Burkitt lymphoma.

Burkitt lymphoma (BL) accounts for most pediatric non-Hodgkin lymphomas, being less common but significantly more lethal when diagnosed in adults. Much of the knowledge of the genetics of BL thus far has originated from the study of pediatric BL (pBL), leaving its relationship to adult BL (aBL) and other adult lymphomas not fully explored. We sought to more thoroughly identify the somatic changes that underlie lymphomagenesis in aBL and any molecular features that associate with clinical disparities within and between pBL and aBL. Through comprehensive whole-genome sequencing of 230 BL and 295 diffuse large B-cell lymphoma (DLBCL) tumors, we identified additional significantly mutated genes, including more genetic features that associate with tumor Epstein-Barr virus status, and unraveled new distinct subgroupings within BL and DLBCL with 3 predominantly comprising BLs: DGG-BL (DDX3X, GNA13, and GNAI2), IC-BL (ID3 and CCND3), and Q53-BL (quiet TP53). Each BL subgroup is characterized by combinations of common driver and noncoding mutations caused by aberrant somatic hypermutation. The largest subgroups of BL cases, IC-BL and DGG-BL, are further characterized by distinct biological and gene expression differences. IC-BL and DGG-BL and their prototypical genetic features (ID3 and TP53) had significant associations with patient outcomes that were different among aBL and pBL cohorts. These findings highlight shared pathogenesis between aBL and pBL, and establish genetic subtypes within BL that serve to delineate tumors with distinct molecular features, providing a new framework for epidemiologic, diagnostic, and therapeutic strategies.

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.

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.

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.

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.

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.

Glenohumeral Superior Translation and Subacromial Contract Pressure Are Both Improved With Superior Capsular Reconstruction: A Systematic Review and Meta-analysis of Biomechanical Investigations.

PURPOSE: To review cadaveric studies evaluating the biomechanical outcomes of superior capsular reconstruction (SCR) with different graft types for the treatment of irreparable rotator cuff (RTC) tears. METHODS: PubMed, Cochrane, and Embase were queried in January 2022 to conduct this meta-analysis using the following key words: "superior capsule reconstruction," "superior capsular reconstruction," and "biomechanics." Articles were included if they reported glenohumeral superior translation or subacromial contact pressure following SCR in cadaveric RTC tears. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. Number of shoulders, graft types, and biomechanical outcomes were recorded and analyzed with forest plots. RESULTS: Twelve studies (95 shoulders) were included in the statistical analysis. There was a significant reduction in glenohumeral superior translation following SCR compared with RTC tear across 10 studies (79 shoulders) with standardized mean difference (SMD) -2.48 mm; confidence interval (CI) -3.28 mm, -1.69 mm. The SMD between fascia lata graft and RTC tear was -3.84 mm (CI -4.82 mm, -2.86 mm) and between dermal allograft and RTC tear was -2.05 mm (CI -3.10 mm, -1.00 mm). There was a significant reduction in subacromial contact pressure following SCR compared with RTC tear across 5 studies (55 shoulders) with SMD -3.49 MPa (CI -4.54 MPa, -2.44 MPa). The SMD between fascia lata graft and RTC tear was -3.21 MPa (CI -5.08 MPa, -1.34 MPa) and between dermal allograft and RTC tear was -3.89 MPa (CI -5.91 MPa, -1.87 MPa). CONCLUSIONS: Independent of graft type, biomechanical studies suggest that SCR improves glenohumeral superior translation and subacromial contact pressure in comparison with RTC tear at time zero. There was no definitive evidence identified in this study to suggest a biomechanically superior SCR graft option. CLINICAL RELEVANCE: Investigating the biomechanical outcomes of several graft types for superior capsular reconstruction will help surgeons better understand the efficacies of different graft types for use in superior capsule reconstruction surgery.

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. METHODS: PubMed and Cochrane were queried in June 2022 to conduct this systematic review using the following keywords: "femoroacetabular 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 criteria. Each study was queried for demographics, lesion classification, surgical treatment, patient-reported outcome scores, revision arthroscopy, and conversion to total hip arthroplasty (THA). A qualitative subanalysis 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 4 included studies reported the modified Harris Hip Score, and all 3 of these studies reported statistically significant improvement in the modified Harris Hip Score at final follow-up (P < .001) with mean preoperative values ranging from 44.5 to 62.8 and mean postoperative values ranging from 78.8 to 95.8. Two of the 4 studies compared patients treated with AMIC to microfracture alone. In these 2 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%). CONCLUSIONS: Patients who underwent hip arthroscopy and AMIC for the treatment of femoroacetabular impingement syndrome and acetabular chondral lesions demonstrated improved patient-reported outcomes and low rates of secondary surgeries at short-term follow-up. STUDY DESIGN: Level IV, systematic review of Level III and IV studies.

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.

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.

Patients Undergoing Revision Hip Arthroscopy With Labral Reconstruction or Augmentation Demonstrate Favorable Patient Reported Outcomes: A Systematic Review.

PURPOSE: To review current literature evaluating patient-reported outcomes (PROs) and survivorship in patients undergoing revision hip arthroscopy with labral reconstruction or augmentation. METHODS: A systematic review was performed with the following key words: (revision) AND (hip OR femoroacetabular impingement) AND (arthroscopy OR arthroscopic) AND (reconstruction OR augmentation OR irreparable). PubMed, Cochrane Trials, and Scopus were queried in October 2022 using the criteria established in the Preferred Reporting Items for Systematic Reviews and Meta-analyses. Studies were included if they involved patients undergoing revision hip arthroscopy with labral reconstruction or augmentation and reported preoperative and postoperative PROs at minimum 2-year follow-up. Only original research articles were included. Survivorship was defined as a nonconversion to total hip arthroplasty. Outcomes present in 3 or more studies underwent further statistical analysis with forest plots. Heterogeneity of studies was evaluated using the I2 statistic. RESULTS: Five studies were reviewed, including 359 revision hip arthroscopies (335 with complete follow-up) with a follow-up that ranged from 2.2 to 5.2 years. Four studies reported on outcomes after revision labral reconstruction and 1 study reported on labral augmentation. Two out of 5 included studies evaluated for statistical significance between preoperative and postoperative outcomes. Three out of 5 studies reported a rate of at least 70% for achieving minimal clinically important difference in at least 1 PRO. At minimum 2-year follow-up, survivorship ranged from 93.5% to 100%. CONCLUSIONS: Patients that underwent revision hip arthroscopy with labral reconstruction or augmentation demonstrated improvement in PROs with mixed rates of achieving clinical benefit and rates of survivorship at minimum 2-year follow-up ranging from 93.5% to 100%. LEVEL OF EVIDENCE: Level IV, systematic review of level III to IV studies.

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.

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.

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.

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.

Complete and Immediate Resolution of See-Saw Nystagmus Following Pituitary Macroadenoma Resection: Case Report and Review of the Literature.

See-saw nystagmus (SSN) is a rare form of nystagmus characterised by alternating elevation with incyclotorsion of one eye and concomitant depression with excyclotorsion of the other eye, often due to abnormalities involving the midbrain and parasellar region. Herein, we highlight a rare case of pendular SSN, which demonstrated complete resolution following resection of a pituitary macroadenoma. A patient in their 40s was identified to have SSN and was diagnosed with a pituitary macroadenoma. They underwent an endoscopic endonasal transsellar approach for resection of the pituitary adenoma. Their nystagmus resolved immediately after surgery. From a review of the literature, resolution and/or significant improvement in SSN occurred in 74% of cases following treatment, with 100%, 86% and 50% following treatment for medication-induced, neurological infarcts, and mass-effect aetiologies of SSN, respectively. SSN is a rare entity with a wide array of aetiologies. Identification of the causative aetiology and appropriate treatment can lead to significant improvement or resolution of the nystagmus in most cases.

A giant armoured skink from Australia expands lizard morphospace and the scope of the Pleistocene extinctions.

There are more species of lizards and snakes (squamates) alive today than any other order of land vertebrates, yet their fossil record has been poorly documented compared with other groups. Here, we describe a gigantic Pleistocene skink from Australia based on extensive material that includes much of the skull and postcranial skeleton, and spans ontogenetic stages from neonate to adult. Tiliqua frangens substantially expands the known ecomorphological diversity of squamates. At approximately 2.4 kg, it was more than double the mass of any living skink, with an exceptionally broad, deep skull, squat limbs and heavy, ornamented body armour. It probably filled the armoured herbivore niche that land tortoises (testudinids), absent from Australia, occupy on other continents. Tiliqua frangens and other giant Plio-Pleistocene skinks suggest that small-bodied groups that dominate vertebrate biodiversity might have lost their largest and often most morphologically extreme representatives in the Late Pleistocene, expanding the scope of these extinctions.