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Over 90% of children with Autism Spectrum Disorders (ASD) demonstrate atypical sensory behaviors. In fact, hyper- or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment is now included in the DSM-5 diagnostic criteria.

Macitentan is a dual endothelin receptor antagonist (ERA) approved for treating pulmonary arterial hypertension (PAH). SOPRANO evaluated the efficacy and safety of macitentan versus placebo in pulmonary hypertension (PH) patients after left ventricular assist device (LVAD) implantation. SOPRANO was a phase 2, multicenter, double-blind, randomized, placebo-controlled, parallel-group study. Patients with an LVAD implanted within the prior 90 days who had persistent PH (i.e., mean pulmonary arterial pressure ≥25 mmHg, pulmonary artery wedge pressure [PAWP] ≤18 mmHg, and pulmonary vascular resistance [PVR] >3 Wood units [WU]) were randomized (1:1) to macitentan 10 mg or placebo once daily for 12 weeks. The primary endpoint was change in PVR. Secondary endpoints included change in right-heart catheterization hemodynamic variables, N-terminal prohormone of brain natriuretic peptide levels, World Health Organization functional class, and safety/tolerability. Fifty-seven patients were randomized to macitentan ( n  = 28) or placebo ( n  = 29). A statistically significant reduction in PVR from baseline to Week 12 was observed with macitentan versus placebo (placebo-corrected geometric mean ratio, 0.74; 95% confidence interval, 0.58-0.94; p  = .0158). No statistically significant differences were observed in secondary endpoints. In a post-hoc analysis, 66.7% of patients receiving macitentan achieved PVR <3 WU versus 40.0% receiving placebo ( p  = .0383). Macitentan was generally well tolerated; adverse events were consistent with those in previous PAH studies with macitentan. In conclusion, macitentan showed promising tolerability and significantly reduced PVR in PH patients with persistently elevated PVR after LVAD implantation. ClinicalTrials. gov identifier: NCT02554903., Competing Interests: Robert P. Frantz is receiving grants and research support from United Therapeutics, Medtronic, and Gossamer Bio, and is scientific medical advisor to Altavant, ShouTi, Liquidia Corporation, Merck, Tenax Therapeutics, and Janssen Pharmaceutical Companies of Johnson & Johnson. His institution has received funding from Bayer and Gossamer Bio. Shashank S. Desai has served on the speakers’ bureau for Abbott. Gregory Ewald is on the speakers’ bureau and is a consultant with Abbott. Veronica Franco's institution receives research support from Acceleron/Merck, Gossamer, Janssen, United Therapeutics, Aerovate Therapeutics, Respira, and Cereno Scientific. Antoine Hage is receiving grants and research support from United Therapeutics, Lung LLC, Arena, Reata, and Bayer, and is a stockholder in Johnson & Johnson and Pfizer. Evelyn M. Horn's institution has received funding from Gossamer, Acceleron/Merck, Abbott, and Cereno Scientific. Stacy Mandras is a speaker and consultant for United Therapeutics and Bayer Pharmaceuticals. Myung H. Park is a scientific medical advisor with AstraZeneca. Ashwin K. Ravichandran is consulting/speaking for Abbott, Medtronic and speaking for United Therapeutics, Janssen, and Bayer; he personally receives no grants from these companies, but his institution does. Ronald Zolty is a consultant for Janssen Pharmaceutical Companies of Johnson & Johnson, Bayer, United Therapeutics, and Alnylam. Mark A. Rocco, Mona Selej, and Carol Zhao were employees of Actelion Pharmaceuticals US, Inc., South San Francisco, CA (at the time of manuscript development) and are current stockholders of Johnson & Johnson. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 Actelion Pharmaceuticals US, Inc. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Background: The purpose of this study is to compare 30-day perioperative outcomes following treatment of intertrochanteric (IT) fractures with intramedullary nail (IMN), total hip arthroplasty (THA), or hemiarthroplasty (HA)., Methods: Using the National Surgical Quality Improvement Program database, we conducted a retrospective cohort study of patients who had sustained an IT fracture treated with primary IMN, THA, or HA between 2017 and 2020. International Classification of Diseases, 10th Revision codes S72.141-S72.146, subtypes A through C, were used to identify eligible patients and were cross-referenced to primary Current Procedural Terminology codes, used to identify the following procedure types: 27245: IMN; 27130: THA; and 27236: HA. Revision cases and patients who underwent arthroplasty for osteoarthritis were excluded. Outcomes of interest included reoperation, readmission, operative time, length of stay, and major and minor complications. Multivariate regression was used to evaluate differences in postoperative outcomes between groups., Results: There were 29,809 IT fractures treated with IMN (94.6%), 1493 treated with HA (4.7%), and 217 treated with THA (0.70%). There was a statistically significant increase in 30-day reoperation rates (adjusted odds ratio [aOR] = 1.99 [95% confidence interval = 1.51, 2.63], P < .001) when combining all arthroplasty patients compared to IMN. There was no statistically significant difference in the overall complication rate between IMN (13.58%) and HA (14.60%, aOR = 1.09, P  = .315) or THA (11.98%, aOR = 1.00, P  = .998). When compared to IMN (0.12%), there was a statistically significantly decreased need for transfusion in the HA group (aOR = 0.71 [95% confidence interval = 0.61, 0.80], P < .001)., Conclusions: Primary HA is associated with an increased 30-day reoperation rate and decreased need for blood transfusion, but there were no other significant differences in postoperative morbidity identified among IMN, THA, and HA in the treatment of IT fractures. Given the challenges and inferior outcomes associated with conversion arthroplasty, the lack of significant difference in morbidity between the 3 groups suggests that primary arthroplasty may be a safe and viable treatment option in selected patients with IT fractures. Comparative studies with longer clinical follow-up will be necessary to establish the appropriate indications and further evaluate the clinical outcomes of primary arthroplasty in the treatment of IT fractures., (© 2024 The Authors.)

Aims: Despite significant morbidity and mortality, recent advances in cardiogenic shock (CS) management have been associated with increased survival. However, little is known regarding the management of patients who survive CS with heart failure (HF) with reduced left ventricular ejection fraction (LVEF, HFrEF), and the utilization of guideline-directed medical therapy (GDMT) in these patients has not been well described. To fill this gap, we investigated the use of GDMT during an admission for CS and short-term outcomes using the Inova single-centre shock registry., Methods: We investigated the implementation of GDMT for patients who survived an admission for CS with HFrEF using data from our single-centre shock registry from January 2017 to December 2019. Baseline characteristics, discharge clinical status, data on GDMT utilization and 30 day, 6 month and 12 month patient outcomes were collected by retrospective chart review., Results: Among 520 patients hospitalized for CS during the study period, 185 (35.6%) had HFrEF upon survival to discharge. The median age was 64 years [interquartile range (IQR) 56, 70], 72% (n = 133) were male, 22% (n = 40) were Black and 7% (n = 12) were Hispanic. Forty-one per cent of patients (n = 76) presented with shock related to acute myocardial infarction (AMI), while 59% (n = 109) had HF-related CS (HF-CS). The median length of hospital stay was 12 days (IQR 7, 18). At discharge, the proportions of patients on beta-blockers, angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs)/angiotensin receptor/neprilysin inhibitors (ARNIs) and mineralocorticoid receptor antagonists (MRAs) were 78% (n = 144), 58% (n = 107) and 55% (n = 101), respectively. Utilization of three-drug GDMT was 33.0% (n = 61). Ten per cent of CS survivors with HFrEF (n = 19) were not prescribed any component of GDMT at discharge. Multivariable logistic regression adjusted for baseline GDMT use revealed that patients with lower LVEF and those who transferred to our centre from an outside hospital were more likely to experience GDMT addition (P < 0.05). Patients prescribed at least one additional class of GDMT during admission had higher odds of 6 month and 1 year survival (P < 0.01): On average, 6 month survival odds were 7.1 times greater [confidence interval (CI) 1.9, 28.5] and 1 year survival odds were 6.0 times greater than those who did not have at least one GDMT added (CI 1.9, 20.5)., Conclusions: Most patients who survived CS admission with HFrEF in this single-centre CS registry were not prescribed all classes or goal doses of GDMT at hospital discharge. These findings highlight an urgent need to augment multidisciplinary efforts to enhance the post-discharge medical management and outcomes of patients who survive CS with HFrEF., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Cardiogenic shock (CS) is a time-sensitive and hemodynamically complex syndrome with a broad spectrum of etiologies and clinical presentations. Despite contemporary therapies, CS continues to maintain high morbidity and mortality ranging from 35 to 50%. More recently, burgeoning observational research in this field aimed at enhancing the early recognition and characterization of the shock state through standardized team-based protocols, comprehensive hemodynamic profiling, and tailored and selective utilization of temporary mechanical circulatory support devices has been associated with improved outcomes. In this narrative review, we discuss the pathophysiology of CS, novel phenotypes, evolving definitions and staging systems, currently available pharmacologic and device-based therapies, standardized, team-based management protocols, and regionalized systems-of-care aimed at improving shock outcomes. We also explore opportunities for fertile investigation through randomized and non-randomized studies to address the prevailing knowledge gaps that will be critical to improving long-term outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor LC declared a past co-authorship with the authors CR, SD, MP., (© 2024 Mehta, Vavilin, Nguyen, Batchelor, Blumer, Cilia, Dewanjee, Desai, Desai, Flanagan, Isseh, Kennedy, Klein, Moukhachen, Psotka, Raja, Rosner, Shah, Tang, Truesdell, Tehrani and Sinha.)

One of the primary reasons behind the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL) is the deregulation of the transcription factor BCL11B . The exon 4 of BCL11B harbors several driver mutations, which abolishes its DNA-binding ability. The high frequency of C > T or G > A conversion in close vicinity of AID (Activation-induced cytidine deaminase)-hotspot motifs in the deregulated gene prompted us to investigate the role of AID in BCL11B mutagenesis. Our results reveal that AID is expressed in T-ALL patient-derived cells, binds to BCL11B fragile region (FR) in exon 4 of T cells in vivo, and generates a signature mutation pattern in this region. The mutation frequency in BCL11B FR could be modulated upon overexpression of the AID gene in the knockout background, further suggesting the involvement of AID in BCL11B mutagenesis. Importantly, various lines of experimentation reveal that BCL11B FR could fold into parallel G-quadruplex, triplex, and hairpin structures, which could act as a replication/transcription block, causing mutagenesis. Thus, our results suggest that AID binds to BCL11B exon 4 due to non-B DNA formation, causing U:G mismatches or replication blocks, which, when repaired erroneously, generates deleterious mutations, resulting in loss of functionality of BCL11B , and thus becomes the cause of T-ALL.

Background: The purpose of this study is to provide a systematic review of the literature pertaining to Patient-Reported Outcome Measurement Information System (PROMIS) validation and utilization as an outcomes metric in total knee arthroplasty (TKA) patients. This is the first systematic review on PROMIS use in total knee arthroplasty patients., Methods: A systematic search of the Pubmed/MEDLINE and Embase databases was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Study characteristics, patient demographics, psychometric properties (Pearson and Spearman correlation) with legacy patient-reported outcome measurement (PROM) instruments, floor and ceiling effects, responsiveness, and minimum clinically important difference (MCID) and PROMIS outcomes were recorded and analyzed., Results: Fifteen studies investigating PROMIS in 11,140 patients were included. The weighted-average Pearson correlation coefficient comparing PROMIS domains with legacy patient-reported outcome measurements in total knee arthroplasty patients was 0.62 [standard error (SE) = 0.06] and the weighted-average Spearman correlation comparing PROMIS domains with legacy patient-reported outcome measurements in total knee arthroplasty patients was 0.59 (SE = 0.06), demonstrating moderate-to-strong correlation and validity. There were no differences in weighted average floor [0.03% (SE = 3.1) versus 0% (SE = 0.1) versus 0.01% (SE = 1.1); p = 0.25] or ceiling effects [0.01% (SE = 0.7) versus 0.02% (SE = 1.4) versus 0.04% (SE = 3.5); p = 0.36] between PROMIS and legacy instruments. The weighted average for percentage of patients achieving MCID was 59.1% for global physical health (GPH), 26.0% for global mental health (GMH), 52.7% for physical function (PF), 67.2% for pain interference (PI), and 37.2% for depression., Conclusion: Notably, PROMIS global physical health, physical function, and pain interference were found to be significantly responsive, with PROMIS pain interference most effectively capturing clinical improvement as evidenced by the achievement of MCID., (© 2023. The Author(s).)

t(8;14) translocation is the hallmark of Burkitt's lymphoma and results in c-MYC deregulation. During the translocation, c-MYC gene on chromosome 8 gets juxtaposed to the Ig switch regions on chromosome 14. Although the promoter of c-MYC has been investigated for its mechanism of fragility, little is known about other c-MYC breakpoint regions. We have analyzed the translocation break points at the exon 1/intron 1 of c-MYC locus from patients with Burkitt's lymphoma. Results showed that the breakpoint region, when present on a plasmid, could fold into an R-loop confirmation in a transcription-dependent manner. Sodium bisulfite modification assay revealed significant single-strandedness on chromosomal DNA of Burkitt's lymphoma cell line, Raji, and normal lymphocytes, revealing distinct R-loops covering up to 100 bp region. Besides, ChIP-DRIP analysis reveals that the R-loop antibody can bind to the breakpoint region. Further, we show the formation of stable parallel intramolecular G-quadruplex on non-template strand of the genome. Finally, incubation of purified AID in vitro or overexpression of AID within the cells led to enhanced mutation frequency at the c-MYC breakpoint region. Interestingly, anti-γH2AX can bind to DSBs generated at the c-MYC breakpoint region within the cells. The formation of R-loop and G-quadruplex was found to be mutually exclusive. Therefore, our results suggest that AID can bind to the single-stranded region of the R-loop and G4 DNA, leading to the deamination of cytosines to uracil and induction of DNA breaks in one of the DNA strands, leading to double-strand break, which could culminate in t(8;14) chromosomal translocation., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the content of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Solitary fibrous tumor (SFT) is a rare mesenchymal tumor of fibroblastic origin commonly occurring in pleura. It can occur at many extrapleural sites but is rare in orbit. Most cases are benign and recurrence is not unusual in the head and neck and orbit and is usually due to incomplete surgical excision. However, malignant transformation (MT) in orbital SFT is extremely unusual. We present a case of orbital SFT in adult male who developed recurrence with MT eight years after initial surgical excision. He underwent left orbital exenteration. The recurrent tumor revealed features of malignancy with areas exhibiting morphology typical of SFT. The immunochemistry confirmed the diagnosis of SFT with MT. The patient was given adjuvant radiation and was disease free for the last 18 months. Identification of malignancy in orbital SFT is important for the patient to receive appropriate postoperative treatment, as seen in the present case.

Background: Textbook knowledge and clinical dogma are often insufficient for effective evidence-based decision making when treating musculoskeletal injuries in American football players, given the variability in presentation and outcomes across different sports and different levels of competition. Key evidence can be drawn directly from high-quality published articles to make the appropriate decisions and recommendations for each athlete's unique situation., Purpose: To identify and analyze the 50 most cited articles related to football-related musculoskeletal injury to provide an efficient tool in the arsenal of trainees, researchers, and evidence-based practitioners alike., Study Design: Cross-sectional study., Methods: The ISI Web of Science and SCOPUS databases were queried for articles pertaining to musculoskeletal injury in American football. For each of the top 50 most cited articles, bibliometric elements were evaluated: citation count and density, decade of publication, journal, country, multiple publications by the same first author or senior author, article content (topic, injury area), and level of evidence (LOE)., Results: The mean ± SD number of citations was 102.76 ± 37.11; the most cited article, with 227 citations, was "Syndesmotic Ankle Sprains" published in 1991 by Boytim et al. Several authors served as a first or senior author on >1 publication, including J.S. Torg (n = 6), J.P. Bradley (n = 4), and J.W. Powell (n = 4). The American Journal of Sports Medicine published the majority of the 50 most cited articles (n = 31). A total of 29 articles discussed lower extremity injuries, while only 4 discussed upper extremity injuries. The majority of the articles (n = 28) had an LOE of 4, with only 1 article having an LOE of 1. The articles with an LOE of 3 had the highest mean citation number (133.67 ± 55.23; F = 4.02; P = .05)., Conclusion: The results of this study highlight the need for more prospective research surrounding the management of football-related injury. The low overall number of articles on upper extremity injury (n = 4) also highlights an area for further research., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: H.W.S. has received education payments from Medwest and Smith & Nephew. C.A.P. has received education payments from Arthrex. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. Ethical approval was not sought for the present study., (© The Author(s) 2023.)

Purpose: The purpose of this study was to compare patient-reported outcomes and return to play (RTP) rates following ulnar collateral ligament reconstruction (UCLR) in patients with and without posteromedial elbow impingement (PI) treated with concomitant arthroscopic posteromedial osteophyte resection., Methods: Baseball players who underwent UCLR performed by the senior surgeon with minimum follow-up of 2 years were surveyed in this retrospective cohort study. Primary outcomes included Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow (KJOC) score, Andrews-Timmerman score, and RTP rate. Secondary outcomes included patient satisfaction scores., Results: 35 baseball players were included. Eighteen had no preoperative impingement (mean age: 19.06 ± 3.28 years), while 17 had PI treated with concomitant arthroscopic osteophyte resection (mean age: 20.06 ± 2.68 years). Following surgery, there was no difference in mean Andrews-Timmerman score (no impingement = 91.67 ± 8.04 vs PI = 92.06 ± 7.92, P = .89) nor KJOC score (no impingement = 83.36 ± 11.72 vs PI = 79.88 ± 12.35, P = .40), but there was a decreased mean KJOC throwing control sub-score in the PI group (7.65 ± 2.40 vs 9.11 ± 1.32, P = .04). There was no difference in RTP rate between the groups (no impingement = 72.22%, PI = 94.12%, χ 2  = 1.28; P  = .26). There was significantly higher mean satisfaction score in the no impingement group (96.67 ± 4.58 vs 90.12 ± 11.91; P  = .04), and those patients were also more likely to pursue surgical treatment again (94.44% vs 52.94%, χ 2  = 7.88; P  = .005)., Conclusions: There was no difference in RTP rate following ulnar collateral ligament reconstruction in baseball players with and without posteromedial impingement treated with arthroscopic resection. Outcomes on the KJOC and Andrews-Timmerman scores were good to excellent in both groups. Players in the posteromedial impingement group were less satisfied with their outcome, however, and less likely to elect for surgery if they were to sustain the injury again. Additionally, players in the posteromedial impingement group were found to have decreased throwing control on the KJOC questionnaire, which may suggest that the presence of posteromedial osteophytes represent adaptive changes to stabilize the elbow while throwing., Level of Evidence: Level III, retrospective cohort study., (© 2023 The Authors.)

Introduction: Acute leukemia is a heterogeneous disease with distinct genotypes and complex karyotypes leading to abnormal proliferation of hematopoietic cells. According to GLOBOCAN reports, Asia accounts for 48.6% of leukemia cases, and India reports ~10.2% of all leukemia cases worldwide. Previous studies have shown that the genetic landscape of AML in India is significantly different from that in the western population by WES. Methods: We have sequenced and analyzed 9 acute myeloid leukemia (AML) transcriptome samples in the present study. We performed fusion detection in all the samples and categorized the patients based on cytogenetic abnormalities, followed by a differential expression analysis and WGCNA analysis. Finally, Immune profiles were obtained using CIBERSORTx. Results: We found a novel fusion HOXD11-AGAP3 in 3 patients, BCR-ABL1 in 4, and KMT2A-MLLT3 in one patient. Categorizing the patients based on their cytogenetic abnormalities and performing a differential expression analysis, followed by WGCNA analysis, we observed that in the HOXD11-AGAP3 group, correlated co-expression modules were enriched with genes from pathways like Neutrophil degranulation, Innate Immune system, ECM degradation, and GTP hydrolysis. Additionally, we obtained HOXD11-AGAP3-specific overexpression of chemokines CCL28 and DOCK2. Immune profiling using CIBRSORTx revealed differences in the immune profiles across all the samples. We also observed HOXD11-AGAP3-specific elevated expression of lincRNA HOTAIRM1 and its interacting partner HOXA2. Discussion: The findings highlight population-specific HOXD11-AGAP3, a novel cytogenetic abnormality in AML. The fusion led to alterations in immune system represented by CCL28 and DOCK2 over-expression. Interestingly, in AML, CCL28 is known prognostic marker. Additionally, non-coding signatures (HOTAIRM1) were observed specific to the HOXD11-AGAP3 fusion transcript which are known to be implicated in AML., Competing Interests: Authors AP, NO, and SJ are employed by HealthCare Global Enterprises Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Desai, Ravindran, Panchal, Ojha, Jadhav and Choudhary.)

Background: Ulnar collateral ligament (UCL) reconstruction has received a unique level of attention in the press and social media. There has also been an increasing use of the internet by patients to seek medical information. Concern exists regarding the quality and comprehensibility of online information when used for patient education., Purpose: To evaluate the quality and comprehensibility of the most-viewed YouTube videos related to the diagnosis and management of UCL injuries. Based on our new evidence-based scoring rubrics, we hypothesized that the quality and comprehensibility of these videos would be poor., Study Design: Cross-sectional study., Methods: The YouTube platform was searched on September 7, 2021, with the terms "UCL injury," "ulnar collateral ligament injury," "UCL surgery," "ulnar collateral ligament surgery," and "Tommy John surgery," and the 50 most-viewed videos from each search were compiled, yielding 250 videos. After removal of duplicates and application of exclusion criteria, the 100 most-viewed videos remained. Basic attributes, including duration of video and number of views, were recorded. Each video was then analyzed by 2 independent reviewers and evaluated for 4 key parameters (quality of diagnostic content [QAR-D], quality of treatment content [QAR-T], presence of inaccurate information, and comprehensibility) and graded on a novel scale from 1 to 4 (4 being the most appropriate for patient education)., Results: The mean QAR-D was 4.83 ± 3.41 (fair quality), and the mean QAR-T was 2.76 ± 3.26 (poor quality). Physician-led educational videos had both the highest mean QAR-D (6.37) and the highest mean QAR-T (4.34). No correlation was observed between video quality and views/likes. A total of 12 videos included ≥1 inaccuracy. The mean comprehensibility score was 2.66 ± 1.12, with 39 videos falling below the acceptable comprehensibility threshold (score <3)., Conclusion: The overall quality of UCL injury-related YouTube content was low. In addition, the absence of correlation between video quality and views/likes suggests that patients are not preferentially utilizing the limited high-quality content that does exist on the YouTube platform. In addition, inaccurate videos were prevalent (12%), and almost half of all videos were deemed inappropriate for patient education in terms of comprehensibility, as defined by our comprehensibility parameter., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: C.A.P. has received education payments from Arthrex. C.S.A. has received consulting fees, nonconsulting fees, and royalties from Arthrex. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2023.)

Purpose: Robotic-assisted total knee arthroplasty typically necessitates use of tracking pins, which can vary in diameter. Complications such as infections and fractures at the pin-site have been observed, but clarification of the effect of pin diameter on complication is needed. The aim of this study is to compare the pin-related complication rates following robotic-assisted total knee arthroplasty between 4.5 mm and 3.2 mm diameter pins., Methods: In this retrospective cohort study, 90-day pin-site complication rates after robotic-assisted total knee arthroplasty were compared between 4.5 mm diameter and 3.2 mm diameter groups. In total, 367 patients were included: 177 with large pin diameter and 190 with small pin diameter. All four pin sites were evaluated using postoperative radiographs. Cases without orthogonal views or visualization of all four pin tracts were noted. Multivariate logistic regression was used to control for age, which differed between the two cohorts., Results: The rate of pin-site complications was 5.6% in the large pin diameter cohort and 2.6% in the small pin diameter cohort, with no statistically significant difference between the groups. The adjusted odds ratio for complications in small compared to large diameter group was 0.48, with a p-value of 0.18. The most common pin-site complication was infection/persistent drainage, found in 1.9% of patients, followed by intraoperative fracture of the second cortex in 1.4%. Intraoperative fracture could not be ruled out in 96 cases due to inadequate radiographic visualization of all pin sites. There was one postoperative pin-site fracture in the large diameter cohort, which required operative fixation., Conclusion: This study demonstrates no statistically significant difference in pin-site complication rates after robotic-assisted total knee arthroplasty between 4.5 mm and 3.2 mm pin diameter cohorts, although there was a trend towards increased intraoperative and postoperative pin-site fractures in the 4.5 mm group., (© 2023. The Author(s).)

Patient reported outcome measures (PROMs) are essential for clinical research and patient-centric care because they allow us to capture patient perspectives on their health condition. In knee arthroplasty, PROMs are frequently used to assess the risks and benefits of new interventions, surgical approaches, and other management strategies. A few examples of PROMs used in total knee arthroplasty (TKA) include the Oxford Knee Score (OKS), Knee Injury and Osteoarthritis Outcome Score (KOOS), and the Forgotten Joint Score (FJS) (collectively referred to as "legacy" PROMs). More recently, attention has been brought to another PROM called the Patient-Reported Outcomes Measurement Information System (PROMIS). PROMIS was developed by the National Institute of Health (NIH) and has over 300 domains assessing various aspects of patient health, including pain, physical function, and mental health. With the use of PROMIS increasing in TKA literature, there is a need to review the advancements being made in understanding and applying PROMIS for this population. Thus, the purpose of this study is to provide insight on the utilization, advantages, and disadvantages of PROMIS within the field of knee arthroplasty and to provide a comparison to legacy PROMs., (© 2023. The Author(s).)

Chromosomal translocations are considered as one of the major causes of lymphoid cancers. RAG complex, which is responsible for V(D)J recombination, can also cleave non-B DNA structures and cryptic RSSs in the genome leading to chromosomal translocations. The mechanism and factors regulating the illegitimate function of RAGs resulting in oncogenesis are largely unknown. Upon in silico analysis of 3760 chromosomal translocations from lymphoid cancer patients, we find that 93% of the translocation breakpoints possess adjacent cryptic nonamers (RAG binding sequences), of which 77% had CpGs in proximity. As a proof of principle, we show that RAGs can efficiently bind to cryptic nonamers present at multiple fragile regions and cleave at adjacent mismatches generated to mimic the deamination of CpGs. ChIP studies reveal that RAGs can indeed recognize these fragile sites on a chromatin context inside the cell. Finally, we show that AID, the cytidine deaminase, plays a significant role during the generation of mismatches at CpGs and reconstitute the process of RAG-dependent generation of DNA breaks both in vitro and inside the cells. Thus, we propose a novel mechanism for generation of chromosomal translocation, where RAGs bind to the cryptic nonamer sequences and direct cleavage at adjacent mismatch generated due to deamination of meCpGs or cytosines., Competing Interests: The authors have declared that no competing interests exist.

As the informatics community grows in its ability to address health disparities, there is an opportunity to expand our impact by focusing on the disability community as a health disparity population. Although informaticians have primarily catered design efforts to one disability at a time, digital health technologies can be enhanced by approaching disability from a more holistic framework, simultaneously accounting for multiple forms of disability and the ways disability intersects with other forms of identity. The urgency of moving toward this more holistic approach is grounded in ethical, legal, and design-related rationales. Shaped by our research and advocacy with the disability community, we offer a set of guidelines for effective engagement. We argue that such engagement is critical to creating digital health technologies which more fully meet the needs of all disabled individuals., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: To identify and analyze the 50 most-cited articles in patellar tendon injury research., Methods: The ISI Web of Science and SCOPUS databases were used to conduct a search for articles pertaining to patellar tendon injury. For the top 50 most-cited articles, bibliometric data (title, first and senior author, citation count, journal, publication year, citation density, country of origin, Level of Evidence [LOE]) and topic of article were recorded., Results: The mean number of citations was 172.0 ± 88.2 (range 101-546). There was a statistically significant correlation between publication year and citation density (r = 0.61, P < .01). The earliest article was the third most-cited article (362 citations), published by Blazina et al. in 1973, which discussed the epidemiology of patellar tendinopathy. The first and second most-cited articles (546 and 466 citations, respectively) covered surgical outcomes of patellar tendinopathy and prevalence of patellar tendinopathy among elite athletes. A total of 14 articles (28%) discussed nonoperative management, whereas only 5 articles discussed surgical management (10%). The most frequent LOE category was a LOE of IV (n = 18, 36%), but 19 studies (38%) were LOE I or LOE II., Conclusions: Among the top 50 most-cited studies regarding patellar tendon injury, a relatively high number were of a high LOE (19 Level I or II, 38%), affirming that these articles in patellar tendon injury research are not only influential, but also of high-quality evidence., Clinical Relevance: This bibliometric analysis provides an efficient tool for educators, researchers, and evidence-based practitioners to identify and evaluate the most influential articles in patellar tendon injury research., (© 2022 The Authors.)

Background: Though once considered an integral part of professional hockey, fighting carries significant health risks to players. Fighting has remained legal in the National Hockey League (NHL) due to its purported economic and entertainment value. However, fights per game have diminished over the past 20 years, challenging the necessity of fighting to promote fan attendance., Hypothesis: Despite decreasing fighting rates, attendance has been stable and is negatively associated with fights per game., Methods: Two public databases were reviewed to determine attendance, fighting majors, goals scored, and games played for each NHL team from 2000 to 2020 and averaged on a per game basis. Univariate analysis was used to evaluate relationships between attendance and fights, attendance and goals, as well as goals and fights., Results: Fights per game decreased from a peak of 0.64 in 2002 to a low of 0.18 in 2020, while average attendance increased from a low of 16,549 in 2004 to a peak of 17,768 in 2013, before settling between 17,400 and 17,500 during the final three seasons of the study period. A significant negative correlation was found between attendance and fights per game ( R = -0.6617, p = 0.0020). There was a positive, but not significant correlation between attendance and goals per game ( R = 0.2457, p = 0.3105). A significant inverse correlation existed between goals per game and fights per game ( R = -0.521, p = 0.0222)., Conclusions: NHL fighting rates have diminished during the past two decades, while fan attendance has increased. A significant negative correlation exists between fan attendance and fights per game, casting doubt on fighting's entertainment value. Meanwhile, a significant inverse correlation was noted between goals per game and fights per game. Taken together, these findings suggest fans may prefer higher scoring and less violent competitions. We conclude by suggesting that prohibiting fights in the NHL could improve player safety without negatively impacting fan attendance., Competing Interests: CP is a team physician for USA Hockey and a member of the USA Hockey Safety and Protective Equipment Committee. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fortney, Tedesco, Kopydlowski, Korzelius, Desai and Popkin.)

Background: Traumatic ankle injuries are commonly complicated by persistent symptoms and the development of chronic ankle instability., Purpose: To describe the epidemiology of ankle injuries in the National Football League (NFL) and investigate the effects that ankle injuries have on performance metrics in the years after injury., Study Design: Descriptive epidemiologic study., Methods: Ankle injuries sustained by NFL players during the 2015-2016, 2016-2017, and 2017-2018 seasons were identified using the Pro Football Reference database. Cumulative incidence was calculated, and demographic identifiers were collected for each injury. The return-to-play (RTP) rate was also recorded. For each player who met inclusion for the performance analysis, power rating (PR) was calculated for the preinjury season (Y-1) and 2 postinjury seasons (Y+1 and Y+2) as follows: PR = ( offensive yards /10) + ( total touchdowns × 6) + ( combined tackle s) + ( sacks × 2) + ( interceptions × 2). Mean PRs were calculated for each season as well as the percentage change and mean difference in PR between Y-1 and Y+1 (ΔPR 1 %, ΔPR 1 ) and between Y-1 and Y+2 (ΔPR 2 %, ΔPR 2 ). Subgroup analyses of PR were performed by player position, injury type, and years of experience., Results: Overall, 668 ankle injuries were identified, with an average cumulative incidence across the 3 seasons of 11.2% and RTP rate of 91%. Of those injuries, 159 met inclusion criteria for the PR analysis. The mean overall PR (96.95 in Y-1) declined 22% in Y+1 to 76.10 (-20.85 [95% CI, -13.82 to -27.89]; P < .001) and 27% in Y+2 to 70.93 (-26.02 [95% CI, -18.04 to -34.00]; P < .001). The mean PR per game played (6.70 in Y-1) decreased 14% in Y+1 to 5.75 (-0.95 [95% CI, -0.56 to -1.34]; P < .001) and 17% in Y+2 to 5.54 (-1.16 [95% CI, -0.63 to -1.62]; P < .001)., Conclusion: It was found that ankle injuries hampered the performance of NFL players, even multiple years after the injury occurred, despite a relatively high RTP rate. There was a decrease in total games played after ankle injuries as well as a decreased performance output per game played., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: P.R.A. has received education payments from Southern Edge Orthopaedics. C.A.P. has received education payments from Arthrex. A.A.A. has received education payments from Arthrex; consulting fees from Arthrex, Medline Industries, and Vilex; speaking fees from Arthrex and Medline Industries; honoraria from Paragon 28; and hospitality payments from Smith & Nephew and Stryker. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2022.)

Background: Little is known about clinical characteristics, hospital course, and longitudinal outcomes of patients with cardiogenic shock (CS) related to heart failure (HF-CS) compared to acute myocardial infarction (AMI; CS related to AMI [AMI-CS])., Methods: We examined in-hospital and 1-year outcomes of 520 (219 AMI-CS, 301 HF-CS) consecutive patients with CS (January 3, 2017-December 31, 2019) in a single-center registry., Results: Mean age was 61.5±13.5 years, 71% were male, 22% were Black patients, and 63% had chronic kidney disease. The HF-CS cohort was younger (58.5 versus 65.6 years, P <0.001), had fewer cardiac arrests (15.9% versus 35.2%, P <0.001), less vasopressor utilization (61.8% versus 82.2%, P <0.001), higher pulmonary artery pulsatility index (2.14 versus 1.51, P <0.01), lower cardiac power output (0.64 versus 0.77 W, P <0.01) and higher pulmonary capillary wedge pressure (25.4 versus 22.2 mm Hg, P <0.001) than patients with AMI-CS. Patients with HF-CS received less temporary mechanical circulatory support (34.9% versus 76.3% P <0.001) and experienced lower rates of major bleeding (17.3% versus 26.0%, P= 0.02) and in-hospital mortality (23.9% versus 39.3%, P <0.001). Postdischarge, 133 AMI-CS and 229 patients with HF-CS experienced similar rates of 30-day readmission (19.5% versus 24.5%, P =0.30) and major adverse cardiac and cerebrovascular events (23.3% versus 28.8%, P =0.45). Patients with HF-CS had lower 1-year mortality (n=123, 42.6%) compared to the patients with AMI-CS (n=110, 52.9%, P =0.03). Cumulative 1-year mortality was also lower in patients with HF-CS (log-rank test, P =0.04)., Conclusions: Patients with HF-CS were younger, and despite lower cardiac power output and higher pulmonary capillary wedge pressure, less likely to receive vasopressors or temporary mechanical circulatory support. Although patients with HF-CS had lower in-hospital and 1-year mortality, both cohorts experienced similarly high rates of postdischarge major adverse cardiovascular and cerebrovascular events and 30-day readmission, highlighting that both cohorts warrant careful long-term follow-up., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03378739.

RAG1 and RAG2 genes generate diversity in immunoglobulin and TCR genes by initiating the process of V-D-J recombination. RAGs recognize specific sequences (heptamer-nonamer) to generate a diversity of immunoglobulins. RAG expression is limited to early B and T cell developmental stages. Aberrant expression of RAG can lead to double strand breaks and translocations as observed in leukemia and lymphoma. The expression of RAG is tightly regulated at the transcriptional and posttranscriptional levels. MicroRNAs (miRNAs) are small non-coding RNAs that are involved in the post-transcriptional regulation of gene expression. This study aimed to identify and catalog RAG regulation by miRNA during normal development and cancer. NGS data from normal B-cell and T-cell developmental stages and blood cancer samples have been analyzed for the expression of miRNAs against RAG1 (1,173 against human RAG1 and 749 against mouse RAG1). The analyzed data has been organized to retrieve the miRNA and mRNA expression of various RAG regulators (10 transcription factors and interacting partners) in normal and diseased states. The database allows users to navigate through the human and mouse RAG regulators, visualize and plot expression. miRAGDB is freely available and can be accessed at http://52.4.112.252/shiny/miragdb/., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Desai, Whadgar, Raghavan and Choudhary.)

Background: Anatomic total shoulder arthroplasty is typically performed through the deltopectoral approach followed by either a subscapularis tenotomy, tendon peel, or lesser tuberosity osteotomy to provide adequate exposure. These subscapularis-takedown methods have been associated with incomplete subscapularis healing, however, and as a result often lead to functional deficits and complications. Subscapularis-sparing approaches have been introduced to mitigate these complications, but thus far have either been limited to hemiarthroplasty or resulted in residual inferior humeral head osteophytes and humeral component size mismatch. The present technique demonstrates the possibility for surgeons to capitalize on the improved patient outcomes that are afforded by subscapularis-sparing approaches, while still utilizing the deltopectoral interval to perform a total glenohumeral joint arthroplasty., Methods: This article describes in detail the placement of a stemless anatomic TSA with the use of angled glenoid instruments through a subscapularis-sparing deltopectoral approach. Postoperatively, patients are placed in a sling but are instructed to remove as tolerated, as early as the 1st postoperative week. Physical therapy is started at week 1 with a 4-phase progression., Conclusions: This technique using a TSA system with a polyaxial glenoid reamer and angled pegs on the backside of the glenoid allows the potential for maintenance of the strong postoperative radiographic and patient-reported outcomes that are achieved using traditional TSA approaches, with the advantage of accelerated rehabilitation protocols and decreased risk of subscapularis insufficiency that result from the use of subscapularis-sparing approaches., (© 2022. The Author(s).)

Head and neck squamous cell carcinomas (HNSCC) include heterogeneous group of tumors, classified according to their anatomical site. It is the sixth most prevalent cancer globally. Among South Asian countries, India accounts for 40% of HNC malignancies with significant morbidity and mortality. In the present study, we have performed exome sequencing and analysis of 51 Head and Neck squamous cell carcinoma samples. Besides known mutations in the oncogenes and tumour suppressors, we have identified novel gene signatures differentiating buccal, alveolar, and tongue cancers. Around 50% of the patients showed mutation in tumour suppressor genes TP53 and TP63. Apart from the known mutations, we report novel mutations in the genes AKT1, SPECC1, and LRP1B, which are linked with tumour progression and patient survival. A highly curated process was developed to identify survival signatures. 36 survival-related genes were identified based on the correlation of functional impact of variants identified using exome-seq with gene expression from transcriptome data (GEPIA database) and survival. An independent LASSO regression analysis was also performed. Survival signatures common to both the methods led to identification of 4 dead and 3 alive gene signatures, the accuracy of which was confirmed by performing a ROC analysis (AUC=0.79 and 0.91, respectively). Also, machine learning-based driver gene prediction tool resulted in the identification of IRAK1 as the driver (p-value = 9.7 e-08) and also as an actionable mutation. Modelling of the IRAK1 mutation showed a decrease in its binding to known IRAK1 inhibitors., Competing Interests: Authors AS and VR are employed by HealthCare Global Enterprises Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Desai, K, Jain, Bawa, Dutta, Atre, Subhash, Rao, J, Srinivasan and Choudhary.)

Background  Mammography has been established as the key modality in the detection and diagnosis of breast cancers. Digital breast tomosynthesis (DBT) has emerged as a mammographic technique which allows improved visualization of abnormalities by reducing the effect of overlapping breast tissue. Purpose  This article is a pictorial essay which highlights the advantages of DBT with two-dimensional (2D) synthesized mammography (2DSM) images, its clinical applications, and its role in breast imaging. Materials and Methods  Selenia Dimensions HD mammography machine performs DBT which acquires a series of low-dose digital mammographic images of the compressed breast followed by full-field digital mammography. Software using specialized algorithms helps to create a 2DSM image reconstructed from the DBT data set. The images are interpreted on a dedicated work station on high-resolution monitors by the radiologist. American College of Radiology Breast Imaging-Reporting and Data System (BI-RADS) lexicon is used for reporting. High-resolution breast ultrasound which includes evaluation of the axilla is done for all cases. Conclusion  DBT improves detection and better characterization of lesions which thereby increases confidence of interpretation of mammograms and assigning BI-RADS categories for further management., Competing Interests: Conflict of Interest There are no conflicts of interest., (Indian Radiological Association. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background  Lobular carcinoma in situ (LCIS) is a noninvasive neoplasm that is known to have an increased relative risk for developing subsequent invasive breast carcinoma. Pure LCIS is usually an incidental finding on histopathological examination (HPE) of tissue samples. However, in the recent years, there has been an increasing trend seen in the diagnosis of LCIS. Purpose  This article aims to bring out the spectrum of appearances on breast imaging in confirmed cases of pure LCIS on HPE and immunohistochemical. Materials and Methods  Cases that were confirmed as pure LCIS on HPE from core or excision biopsy were retrospectively analyzed for abnormalities on breast imaging. Digital breast tomosynthesis mammography was performed with high-resolution ultrasound with elastography for all cases. Magnetic resonance imaging (MRI) was performed in cases wherever indicated, with dynamic postcontrast imaging after injecting intravenous gadolinium. Conclusion  LCIS is recognized as an intermediate risk factor for the development of breast cancer. Pure LCIS has varied histology and imaging patterns on mammography, high-resolution ultrasound, and MRI. It is important to recognize the imaging appearances of these lesions to enable the radiologist to detect LCIS early for proper management., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Indian Radiological Association. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Variable definitions and an incomplete understanding of the gradient of reverse cardiac remodeling following continuous flow left ventricular assist device (LVAD) implantation has limited the field of myocardial plasticity. We evaluated the continuum of LV remodeling by serial echocardiographic imaging to define 3 stages of reverse cardiac remodeling following LVAD., Methods: The study enrolled consecutive LVAD patients across 4 study sites. A blinded echocardiographer evaluated the degree of structural (LV internal dimension at end-diastole [LVIDd]) and functional (LV ejection fraction [LVEF]) change after LVAD. Patients experiencing an improvement in LVEF ≥40% and LVIDd ≤6.0 cm were termed responders, absolute change in LVEF of ≥5% and LVEF <40% were termed partial responders, and the remaining patients with no significant improvement in LVEF were termed nonresponders., Results: Among 358 LVAD patients, 34 (10%) were responders, 112 (31%) partial responders, and the remaining 212 (59%) were nonresponders. The use of guideline-directed medical therapy for heart failure was higher in partial responders and responders. Structural changes (LVIDd) followed a different pattern with significant improvements even in patients who had minimal LVEF improvement. With mechanical unloading, the median reduction in LVIDd was -0.6 cm (interquartile range [IQR], -1.1 to -0.1 cm; nonresponders), -1.1 cm (IQR, -1.8 to -0.4 cm; partial responders), and -1.9 cm (IQR, -2.9 to -1.1 cm; responders). Similarly, the median change in LVEF was -2% (IQR, -6% to 1%), 9% (IQR, 6%-14%), and 27% (IQR, 23%-33%), respectively., Conclusions: Reverse cardiac remodeling associated with durable LVAD support is not an all-or-none phenomenon and manifests in a continuous spectrum. Defining 3 stages across this continuum can inform clinical management, facilitate the field of myocardial plasticity, and improve the design of future investigations.

Background: We evaluated the imaging and functional outcomes of anatomic stemless shoulder arthroplasty (ECLIPSE) in elderly patients with primary osteoarthritis of the glenohumeral joint in Asian developing countries., Methods: Thirty patients were treated using stemless TSA in 26 months period (years 2017 and 2019), and were followed for a minimum of 24 months. Functional outcomes were assessed using Constant and ASES scores. Radiolucent lines and osteopenia were analyzed on radiographs., Results: Pre-surgery Constant and ASES scores improved from 27.33(21-38) and 29.67(22-38) to 68(54-78) and 71(71.4(56-79) at final follow up. Around the humeral component, one patient had calcar thinning and a radiolucent line thicker than 2 mm, while six patients had radiolucent lines less than 2 mm. The mean glenoid radiolucency score was 2± 1.1., Conclusion: In our setting, stemless total shoulder arthroplasty demonstrated significant improvement in functional scores at short- to mid-term follow-up. Radiographic findings did not correlate with functional scores.

Background: Free flap transfer is a standard practice in reconstruction of oral defects. Fasciocutaneous flaps are commonly used for reconstruction of soft tissue defects. Replacement of oral mucosa with skin often causes discomfort, foreign body sensation, dysgeusia, problems with skin hair and morbidity at the donor site. Morbidity at the donor site may interfere with physical activity among manual labourers., Materials and Methods: We prospectively analysed nine cases of oral cavity defects reconstructed with free gastro-omental flap over 4 months from March to July 2019. A free gastric flap based on right and left gastric artery and vascular arcade was harvested from the body of stomach. Feasibility, technical aspects, advantages and disadvantages of the flap are reviewed., Results: Flap survival was 100%. No re-exploration for salvage was required. Flap was monitored for viability by colour change and capillary refill. All the nine cases healed well. One patient required readmission for bleeding from the raw area exposed at the margins of the flap. Patient satisfaction and quality of life was satisfactory. Long pedicle length, rich submucosal vascular network, dual pedicles available for anastomosis, like to like mucosal tissue replacement and low donor site morbidity make it a reliable option in the armamentarium of oral reconstruction., Conclusion: Free gastro-omental flap is a feasible and reliable tissue available for reconstruction of oral soft tissue defects., (© Indian Association of Surgical Oncology 2021.)

Sensory processing dysfunction (SPD) is characterized by a behaviorally observed difference in the response to sensory information from the environment. While the cerebellum is involved in normal sensory processing, it has not yet been examined in SPD. Diffusion tensor imaging scans of children with SPD ( n = 42) and typically developing controls (TDC; n = 39) were compared for fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) across the following cerebellar tracts: the middle cerebellar peduncles (MCP), superior cerebellar peduncles (SCP), and cerebral peduncles (CP). Compared to TDC, children with SPD show reduced microstructural integrity of the SCP and MCP, characterized by reduced FA and increased MD and RD, which correlates with abnormal auditory behavior, multisensory integration, and attention, but not tactile behavior or direct measures of auditory discrimination. In contradistinction, decreased CP microstructural integrity in SPD correlates with abnormal tactile and auditory behavior and direct measures of auditory discrimination, but not multisensory integration or attention. Hence, altered cerebellar white matter organization is associated with complex sensory behavior and attention in SPD, which prompts further consideration of diagnostic measures and treatments to better serve affected individuals., Competing Interests: MR, MG, and EM were employed by Cortica Healthcare. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Narayan, Rowe, Palacios, Wren-Jarvis, Bourla, Gerdes, Brandes-Aitken, Desai, Marco and Mukherjee.)

Purpose: To identify and evaluate the top 50 most-cited articles pertaining to SLAP tears., Methods: The ISI Web of Knowledge database was used to conduct a query for articles pertaining to SLAP tears. Our query was conducted in April 2020 with multiple Boolean operative combinations performed by 2 independent reviewers. Articles on the final list were further reviewed to extract the following data: manuscript title, first author, total citation count, year of publication, citation density since publication, current citation rate since 2013, journal, country of origin, and level of evidence., Results: Our initial search yielded 2,597 articles. Within this cohort, the top 50 publications pertaining to SLAP tears were identified that met our search criteria. The top article was cited 802 times while the 50th ranked article was cited 46 times. The average number of citations per publication was 131, whereas the average citation density since year of publication was 7.3. No strong correlations were found between citation density and year published. Twelve journals published articles pertaining to SLAP tears, with Arthroscopy accounting for the greatest number (15 articles, 30%). Most articles were graded with a level of evidence (LOE) of IV (n = 24, 48%), followed by review articles without LOE (n = 8, 16%). Only 2 articles achieved an LOE of I (4%). Articles typically addressed the arthroscopic management (n = 11, 22%), whereas anatomy/classification (n =10, 20%), and outcomes (n = 9, 18%) also were reported., Conclusions: This review provides a quantitative analysis of the most-referenced literature pertaining to SLAP tears. This body of knowledge helps surgeons search for literature regarding these injuries and identify trends regarding SLAP tear research., Clinical Relevance: This research provides practitioners with an easily accessible and comprehensive collection of the major contributions regarding SLAP tears and offers insight into future areas for research., (© 2020 by the Arthroscopy Association of North America. Published by Elsevier Inc.)

We provide the South Asian Declaration, containing the consensus guidelines for coronavirus disease 2019 (COVID-19) vaccination in cancer patients., Competing Interests: Conflict of Interest None declared., (MedIntel Services Pvt Ltd. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Calcaneal fractures are the most common fracture of the tarsal bones and represent 1% to 2% of all fractures. Roughly 75% of these fractures include intra-articular involvement of the posterior facet of the calcaneus. Intra-articular calcaneal fractures are challenging injuries to manage for both patients and surgeons given their association with both early and late complications. This article aims to review the management, classification systems, surgical approaches, and care regarding intra-articular calcaneal fractures. A review of the current literature yielded treatment strategies that aim to reduce complications such as soft tissue injury or loss of articular reduction while maintaining satisfactory clinical outcomes. The purpose of this article is to review these current concepts in the management of intra-articular calcaneal fractures. Level of Evidence: Level V, expert opinion., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. ICMJE forms for all authors are available online., (© The Author(s) 2020.)

Background: A prospective study of motor milestones achieved in severe clubfeet treated by Ponseti method and comparison between unilateral and bilateral clubfoot will help us gain further insight of motor milestones in these children., Methods: Prospective study of 150 consecutive children with idiopathic clubfoot who were treated by Ponseti method and in whom percutaneous tendoachilles tenotomy was performed. The gross motor milestones recorded were: rolls from back to stomach, sitting without support, standing with assistance, walks with assistance, standing alone, walking alone. This was compared with published regional and World Health Organization (WHO) normal data., Result: 15 patients were excluded due to non-compliance and recurrence. Children with unilateral clubfoot (80 children) and bilateral clubfoot (55 children) showed a delay of 0.2-2.1 months in various milestones, and this was statistically significant when compared with both normal data. 95% children with unilateral clubfoot had independent ambulation by 17 months and in bilateral ambulation by 17.8 months. There was also a statistically significant difference in unilateral and bilateral clubfeet in all variables except sitting without support and walking with support., Conclusion: There is a delay in achievement in all children with clubfoot, with more delay in bilateral clubfoot as compared to unilateral clubfoot. The probable reasons could be plaster treatment, possible weakness due to tendoachilles tenotomy, use of orthosis or the inherent pathology associated with clubfeet. Parents hence need to be explained about this delay., Competing Interests: Conflict of interestThe authors declare no conflicts of interest., (© Indian Orthopaedics Association 2020.)

Background: The objective of this study was to define the volume (mLs) needed for a positive saline load challenge test in anterolateral (AL), anteromedial (AM), posterolateral (PL), or posteromedial (PM) ankle arthrotomy wounds using normal saline (NS) and methylene blue (MB). Another objective was to evaluate the use of fluoroscopy and iodinated contrast in the diagnosis of ankle arthrotomies., Methods: Four cadaveric ankle specimens underwent standardized arthrotomy creation in either the AL, AM, PL, or PM portion of each specimen. An 18-gauge needle was used to inject fluid into each ankle, and the volumes needed for positive fluid challenges were recorded. All 4 ankles were tested 10 times (n = 40) with NS and 10 times using MB (n = 40). A fifth cadaveric ankle was injected with radiopaque contrast solution, and an arthrotomy was simulated and imaged with fluoroscopy.Statistical analyses compared the volumes of NS and MB needed for a positive test. In addition, the 25th, 50th, 75th, 90th, and 95th percentiles of volumes needed for a positive test was calculated., Results: The volume of fluid necessary to detect 25%, 50%, 75%, 90%, and 95% of ankle arthrotomies from any site was 2.0 mL, 4.5 mL, 9.0 mL, 10 mL, and 10 mL, respectively. Anterior arthrotomies required less fluid (2.1 mL ± 0.5) than posterior arthrotomies (9.0 mL ± 1.2) for a positive test ( P < .0001). There was no difference between the amount of NS (5.5 mL ± 3.6) vs MB (5.6 mL ± 3.7) needed for a positive challenge test ( P = .739)., Conclusion: Ninety-five percent of ankle arthrotomies could be diagnosed with 10 mL of injected fluid; there was no difference between the volume of NS vs MB needed. Fluoroscopy assisted with needle placement and can be combined with radiopaque contrast solution to diagnose ankle arthrotomies., Clinical Relevance: The findings of this study may improve sensitivity and efficiency in the diagnosis of traumatic ankle arthrotomies, for which there is currently a paucity of literature., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. ICMJE forms for all authors are available online., (© The Author(s) 2020.)

DNA, the fundamental unit of human cell, generally exists in Watson-Crick base-paired B-DNA form. Often, DNA folds into non-B forms, such as four-stranded G-quadruplexes. It is generally believed that ionizing radiation (IR) induces DNA strand-breaks in a random manner. Here, we show that regions of DNA enriched in G-quadruplex structures are less sensitive to IR compared with B-DNA in vitro and inside cells. Planar G-quartet of G4-DNA is shielded from IR-induced free radicals, unlike single- and double-stranded DNA. Whole-genome sequence analysis and real-time PCR reveal that genomic regions abundant in G4-DNA are protected from radiation-induced breaks and can be modulated by G4 stabilizers. Thus, our results reveal that formation of G4 structures contribute toward differential radiosensitivity of the human genome., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)