Hereditary hemorrhagic telangiectasia may be the most morbid inherited bleeding disorder of women.

Hereditary hemorrhagic telangiectasia (HHT) is the second-most-common inherited bleeding disorder worldwide and remains without approved therapies. HHT causes serious mucosal bleeding resulting in severe iron deficiency anemia, major psychosocial complications, and visceral arteriovenous malformations in brain, lung, and liver that can cause life-threatening hemorrhagic complications. No study has examined the relative morbidity of HHT and von Willebrand disease (VWD), the most common inherited bleeding disorders in women. We performed an observational cohort study of women with HHT or VWD, comparing a representative sample of 100 randomly selected women with HHT to 100 randomly selected age-matched women with VWD. In HHT versus VWD, recurrent epistaxis and GI bleeding were more likely (OR [95% CI]=32.73 [13.81-71.80], P<0.0001 and 5.69 [2.59-12.89], P<0.0001) and heavy menstrual bleeding was less likely (OR 0.32 [0.18-0.57], P<0.0001). Iron deficiency anemia was significantly more likely, and lowest hemoglobin significantly lower, in HHT versus VWD. Odds of iron infusion dependence, requirement for red cell transfusion, and hemostatic surgical procedures were significantly higher-17-fold, 3-fold, and 8-fold higher, respectively-and hospital admissions to manage disease complications were both approximately 14 times more frequent in women with HHT versus VWD. In conclusion, much higher disease-related morbidity, mortality, and healthcare utilization was observed in women with HHT versus VWD, providing evidence that HHT may be the most clinically significant inherited bleeding disorder of women. Given the vast gap in research funding for HHT compared with both hemophilia (a disease primarily of men) and VWD, these findings have significant implications for gender equity in hematology.

Benzimidazolium quaternary ammonium salts: synthesis, single crystal and Hirshfeld surface exploration supported by theoretical analysis.

Owing to the broad applications of quaternary ammonium salts (QAS), we present the synthesis of benzimidazolium-based analogues with variation in the alkyl and alkoxy group at N-1 and N-3 positions. All the compounds were characterized by spectroscopic techniques and found stable to air and moisture both in the solid and solution state. Moreover, molecular structures were established through single-crystal X-ray diffraction studies. The crystal packing of the compounds was stabilized by numerous intermolecular interactions explored by Hirshfeld surface analysis. The enrichment ratio was calculated for the pairs of chemical species to acquire the highest propensity to form contacts. Void analysis was carried out to check the mechanical response of the compounds. Furthermore, theoretical investigations were also performed to explore the optoelectronic properties of compounds. Natural population analysis (NPA) has been conducted to evaluate the distribution of charges on the synthesized compounds, whereas high band gaps of the synthesized compounds by frontier molecular orbital (FMO) analysis indicated their stability. Nonlinear optical (NLO) analysis revealed that the synthesized QAS demonstrates significantly improved NLO behaviour than the standard urea.

Avatrombopag for adults with early versus chronic immune thrombocytopenia.

Avatrombopag is a newer thrombopoietin receptor agonist (TPO-RA) currently approved to treat chronic ITP (duration >12 months). No studies have yet evaluated the safety and effectiveness of avatrombopag in newly diagnosed ITP (duration <3 months) or persistent ITP (duration 3-12 months), and so its use in these populations is presently off-label worldwide. We hypothesize that avatrombopag has similar safety and effectiveness irrespective of ITP disease phase. To evaluate this, we performed a multicenter observational cohort study of adults with ITP treated with avatrombopag, comparing patient outcomes by disease phase (newly diagnosed/persistent versus chronic). Seventy-five patients were included, 23 with newly diagnosed/persistent ITP (17.7 patient-years of avatrombopag treatment) and 52 with chronic ITP (65.3 patient-years of avatrombopag treatment). On avatrombopag, 91% of newly diagnosed/persistent patients versus 96% of chronic patients (p = .58) achieved a platelet response (≥50 × 109 /L) and 86% versus 81% of patients (p = .78) achieved a complete response (≥100 × 109 /L). Median platelet counts on avatrombopag were similar between the two groups (165 × 109 /L vs. 129 × 109 /L, p = .57). Response durability was high and similar in both groups. No patients in the newly diagnosed/persistent group had a major bleeding event, thromboembolic event or avatrombopag discontinuation for adverse events, compared with 4, 1, and 2, respectively, in the chronic group. Thrombocytosis (platelets ≥400 × 109 /L) incidence was similar in the two groups. No other drug-related adverse events occurred in either group. Avatrombopag was safe and effective in patients with newly diagnosed and persistent ITP, with outcomes numerically, statistically, and clinically similar to patients receiving avatrombopag for chronic ITP.

Benchmarking computational methods to identify spatially variable genes and peaks.

Spatially resolved transcriptomics offers unprecedented insight by enabling the profiling of gene expression within the intact spatial context of cells, effectively adding a new and essential dimension to data interpretation. To efficiently detect spatial structure of interest, an essential step in analyzing such data involves identifying spatially variable genes. Despite researchers having developed several computational methods to accomplish this task, the lack of a comprehensive benchmark evaluating their performance remains a considerable gap in the field. Here, we present a systematic evaluation of 14 methods using 60 simulated datasets generated by four different simulation strategies, 12 real-world transcriptomics, and three spatial ATAC-seq datasets. We find that spatialDE2 consistently outperforms the other benchmarked methods, and Moran's I achieves competitive performance in different experimental settings. Moreover, our results reveal that more specialized algorithms are needed to identify spatially variable peaks.

Measuring the burden of cystic fibrosis: A scoping review.

BACKGROUND: Cystic fibrosis (CF) contributes a significant economic burden on individuals, healthcare systems, and society. Understanding the economic impact of CF is crucial for planning resource allocation. METHODS: We conducted a scoping review of literature published between 1990 and 2022 that reported the cost of illness, and/or economic burden of CF. Costs were adjusted for inflation and reported as United States dollars. RESULTS: A total of 39 studies were included. Direct healthcare costs (e.g., medications, inpatient and outpatient care) were the most frequently reported. Most studies estimated the cost of CF using a prevalence-based (n = 18, 46.2 %), bottom-up approach (n = 23, 59 %). Direct non-healthcare costs and indirect costs were seldom included. The most frequently reported direct cost components were medications (n = 34, 87.2 %), inpatient care (n = 33, 84.6 %), and outpatient care (n = 31, 79.5 %). Twenty-eight percent (n = 11) of studies reported the burden of CF from all three perspectives (healthcare system (payer), individual, and society). Indirect costs of CF were reported in approximately 20 % of studies (n = 8). The reported total cost of CF varied widely, ranging from $451 to $160,000 per person per year (2022 US$). The total cost depended on the number of domains and perspectives included in each study. CONCLUSIONS: Most studies only reported costs to the healthcare system (i.e., hospitalizations and healthcare encounters) which likely underestimates the total costs of CF. The wide range of costs reported highlights the importance of standardizing perspectives, domains and costs when estimating the economic burden of CF.

A retrospective record review of tuberculous infections in rheumatoid arthritis patients on biologics in Malaysia.

INTRODUCTION: The aim of this study was to analyse the clinical characteristics of patients with rheumatoid arthritis receiving biologics therapy and investigate the association between types of biologics and tuberculosis (TB) infections in 13 tertiary hospitals in Malaysia. MATERIALS AND METHODS: This was a retrospective study that included all RA patients receiving biologics therapy in 13 tertiary hospitals in Malaysia from January 2008 to December 2018. RESULTS: We had 735 RA patients who received biologics therapy. Twenty-one of the 735 patients were diagnosed with TB infection after treatment with biologics. The calculated prevalence of TB infection in RA patients treated with biologics was 2.9% (29 per 1000 patients). Four groups of biologics were used in our patient cohort: monoclonal TNF inhibitors, etanercept, tocilizumab, and rituximab, with monoclonal TNF inhibitors being the most commonly used biologic. The median duration of biologics therapy before the diagnosis of TB was 8 months. 75% of patients had at least one co-morbidity and all patients had at least one ongoing cDMARD therapy at the time of TB diagnosis. More than half of the patients were on steroid therapy with an average prednisolone dose of 5 mg daily. CONCLUSION: Although the study population and data were limited, this study illustrates the spectrum of TB infections in RA patients receiving biologics and potential risk factors associated with biologics therapy in Malaysia.

Cardiac Sarcoidosis and a Likely Pathogenic TTN Variant in a Patient Presenting With Ventricular Tachycardia.

Rare variants in TTN are the most common monogenic cause of early-onset atrial fibrillation and dilated cardiomyopathy. Whereas cardiac sarcoidosis is very underdiagnosed, a common presentation can be ventricular arrhythmias. This report presents a patient with a likely pathogenic TTN variant and cardiac sarcoidosis. (Level of Difficulty: Intermediate.).

Antithrombotic therapy for atrial fibrillation in hereditary hemorrhagic telangiectasia.

Antithrombotic therapy reduces stroke risk in patients with atrial fibrillation but at the cost of increased bleeding risk. Patients with hereditary hemorrhagic telangiectasia (HHT) are at increased bleeding risk due to fragile mucocutaneous telangiectasias and visceral arteriovenous malformations. These patients are simultaneously at elevated thrombotic risk due to the vascular abnormalities of HHT. Managing atrial fibrillation in patients with HHT represents an understudied and challenging clinical scenario. We present a retrospective cohort study investigating antithrombotic therapy in patients with HHT and atrial fibrillation. We found that antithrombotic therapy was poorly tolerated, leading to premature dose-reduction or discontinuation of therapy in a majority of patients and in a majority of treatment episodes. Five patients undergoing left atrial appendage procedures did well despite difficulties completing the prescribed course of post-procedure antithrombotic therapy. Left atrial appendage occlusion or simultaneous administration of systemic anti-angiogenic therapy may represent alternatives but require additional study in patients with HHT.

Anticoagulation and antiplatelet therapy in hereditary hemorrhagic telangiectasia: A scoping review.

INTRODUCTION: Data describing safety and tolerability of anticoagulation and antiplatelet therapy in hereditary hemorrhagic telangiectasia (HHT), the second-most-common inherited bleeding disorder, is limited. METHODS: We performed a scoping review, searching MEDLINE and EMBASE from inception to March 2023 for eligible studies reporting detailed clinical data describing antithrombotic use in HHT. Data extracted included study design, patient population, and characteristics and outcomes of antithrombotic therapy. RESULTS: Of 625 unique manuscripts identified through database search, 77 were included: 64 case reports/case series describing 65 patients and 13 cohort studies. Data were extracted on a total of 466 patients with HHT, covering 587 episodes of antithrombotic therapy. The most common reasons for antithrombotic therapy were venous thromboembolism (VTE) (44.6 %), atrial arrhythmias (17.8 %) and stroke (10.5 %). anticoagulation was used in in 356 episodes (61.9 %), antiplatelet therapy in 140 episodes (24.3 %), and both together in 50 episodes (8.7 %). Complications of therapy included worsened HHT-associated bleeding (primarily epistaxis and gastrointestinal bleeding) in 198 antithrombotic treatment episodes (38.9 %) and premature antithrombotic therapy discontinuation in 142 episodes (28.9 %). Bleeding-directed therapy (local ablative therapy and systemic therapies) were employed to address worsening bleeding in 14.6 % of episodes. No specific complications of therapy were reported in 322 total antithrombotic events (58.4 %). Rates of bleeding (8.3 % to 80 %), therapy discontinuation (14.3 % to 57.1 %), and other complications ranged considerably from study to study. CONCLUSION: Current publications vary widely on the outcomes and tolerability of antithrombotics in HHT, but confirm the clinical challenge of adequate antithrombotic therapy in this population. More formal studies are needed to better guide optimal antithrombotic use in HHT.

Mechanical thrombectomy is associated with shorter length of hospital stay and lower readmission rates compared with conservative therapy for acute submassive pulmonary embolism: a propensity-matched analysis.

PURPOSE: To determine if mechanical thrombectomy (MT) for submassive pulmonary embolism (PE) positively impacts length of hospital stay (LOS), intensive care unit stay (ICU LOS), readmission rate, and in-hospital mortality compared with conservative therapy. METHODS: This was a retrospective review of all patients with submassive PE who either underwent MT or conservative therapy (systemic anticoagulation and/or inferior vena cava filter) between November 2019 and October 2021. Pediatric patients (age <18) and those with low-risk and massive PEs were excluded from the study. Patient characteristics, comorbidities, vitals, laboratory values (cardiac biomarkers, hospital course, readmission rates, and in-hospital mortality) were recorded. A 2:1 propensity score match was performed on the conservative and MT cohorts based on age and the PE severity index (PESI) classification. Fischer's exact test, Pearson's χ2 test, and Student's t-tests were used to compare patient demographics, comorbidities, LOS, ICU LOS, readmission rates, and mortality rates, with statistical significance defined as P < 0.05. Additionally, a subgroup analysis based on PESI scores was assessed. RESULTS: After matching, 123 patients were analyzed in the study, 41 in the MT cohort and 82 in the conservative therapy cohort. There was no significant difference in patient demographics, comorbidities, or PESI classification between the cohorts, except for increased incidence of obesity in the MT cohort (P = 0.013). Patients in the MT cohort had a significantly shorter LOS compared with the conservative therapy cohort (5.37 ± 3.93 vs. 7.76 ± 9.53 days, P = 0.028). However, ICU LOS was not significantly different between the cohorts (2.34 ± 2.25 vs. 3.33 ± 4.49, P = 0.059). There was no significant difference for in-hospital mortality (7.31% vs. 12.2%, P = 0.411). Of those that were discharged from the hospital, there was significantly lower incidence of 30-day readmission in the MT cohort (5.26% vs. 26.4%, P < 0.001). A subgroup analysis did not demonstrate that the PESI score had a significant impact on LOS, ICU LOS, readmission, or in-hospital mortality rates. CONCLUSION: MT for submassive PE can reduce the total LOS and 30-day readmission rates compared with conservative therapy. However, in-hospital mortality and ICU LOS were not significantly different between the two groups.

Safety, tolerability, and effectiveness of anticoagulation and antiplatelet therapy in hereditary hemorrhagic telangiectasia.

BACKGROUND: Antithrombotic therapy (anticoagulation and antiplatelet therapy) is frequently needed in patients with hereditary hemorrhagic telangiectasia (HHT); however, data describing and guiding its use are very limited. OBJECTIVES: To investigate the safety, tolerability, and effectiveness of antithrombotic therapy in HHT in a cohort large enough to compare agents, evaluate for baseline predictors of premature discontinuation, and evaluate hematologic support requirements and healthcare utilization before and after antithrombitc therapy initiation. METHODS: We performed a multicenter observational cohort study characterizing the outcomes of antithrombic therapy in adults with HHT. RESULTS: A total of 119 patients with HHT with 187 discrete antithrombotic therapy episodes were included. Of these, 59 patients (50%) dose-reduced and/or prematurely discontinued therapy (including 52 patients [44%] who discontinued) due to worsened bleeding complications. Initiation at reduced dose intensity had a similar premature discontinuation rate (49%) as initiation at standard dose intensity (43%). In a multivariable logistic model, a history of gastrointestinal bleeding was associated with 3.25-fold odds of discontinuation (p = .001). Hemoglobin was significantly lower (10.8 g/dL vs 12.2 g/dL, p < .001), and the need for hematologic support (intravenous iron and/or red blood cell transfusion) was significantly higher (29 patients vs 12 patients, p = .004) in the 3 months after antithrombotic therapy initiation vs the 3 months before; emergency department visits and hospital admissions due to bleeding also increased. The rates of dose-reduction and/or premature discontinuation were similar regardless of the anticoagulant class (warfarin, 46%; heparin-based, 48%; direct oral anticoagulants, 44%) or with multiple simultaneous agents (44%) but were slightly lower with single-agent antiplatelet therapy (37%). Thromboembolism despite receiving antithrombotic therapy was common (18 patients, 15%) with varying outcomes. CONCLUSION: Antithrombotic therapy is challenging in HHT, resulting in objectively higher morbidity and health care utilization from worsened bleeding. Discontinuation rates approached 50% regardless of the dose intensity at initiation or type of antithrombotic agent used and were higher in patients with a gastrointestinal bleeding history.

Urinoma formation following renal mass cryoablation treated with nephroureteral stent placement.

Renal cryoablation (CA) has become an accepted treatment option for patients with small renal tumors and co-morbidities that make them less favorable for surgical intervention. Complications from renal CA have been previously reported and are generally associated with increasing size and central location of the tumor. Ureteral injury from renal CA, although rare, can be difficult to manage and may require complex surgeries in patients who are poor surgical candidates to begin with. We report a case of a renal mass CA complicated by proximal ureteral necrosis and transection, treated with multiple minimally invasive procedures ultimately resulting in successful bridging of the necrotic segment with nephroureteral stent and thus avoiding major surgery.

Outcomes Following Primary Anterior Cruciate Ligament Reconstruction Using a Partial Transphyseal (Over-the-Top) Technique in Skeletally Immature Patients.

Background: The incidence of anterior cruciate ligament (ACL) injuries in skeletally immature patients is increasing, with ACL reconstruction preferred in this population due to reported chondroprotective benefits. Due to concerns with growth disturbance following ACL reconstruction in skeletally immature patients, various physealsparing and partial transphyseal techniques have been developed. Currently, there is no consensus on the most effective ACL reconstruction technique in skeletally immature patients. The purpose of the current study was to report the outcomes of a partial-transphyseal over-the-top (OTT) ACL reconstruction in a cohort of skeletally immature patients. Methods: All patients with radiographic evidence of open tibial and femoral physes that underwent primary ACL reconstruction using a partial-transphyseal OTT technique between 2009-2018 at a single tertiary-care institution with at least twelve months of clinical follow-up were retrospectively reviewed. Patient demographics, physical examination findings, graft ruptures, return to sport, and Tegner activity levels were analyzed. Statistical significance was defined as p<0.05. Results: Overall, 11 males and 1 female (12 knees) with a mean age of 12.8±1.8 (range: 10-16) years were included in the study. The mean postoperative follow-up of the cohort was 2.3±1.2 (range: 1.1-5.2) years. All ACLs were reconstructed with hamstring autograft with allograft augmentation utilized in a single patient. There were two cases of ACL graft rupture (16.7%). All patients were able to return to the same or higher level of sporting activity at an average of 7.4+2.7 months. There were no cases of clinically significant longitudinal or angular growth disturbance. Conclusion: Partial transphyseal ACL reconstruction using a transphyseal tibial tunnel and an extra-articular OTT technique on the femur in skeletally immature patients affords minimal risk of growth disturbance with a graft rupture rate consistent with what has been reported in this high-risk population. All patients were able to return to sport at the same or higher level. Level of Evidence: IV.

Utilization of Arthroscopy During Ankle Fracture Fixation Among Early Career Surgeons: An Evaluation of the American Board of Orthopaedic Surgery Part II Oral Examination Database.

Background: Rotational ankle fractures are common injuries associated with high rates of intra-articular injury. Traditional ankle fracture open reduction and internal fixation (ORIF) techniques provide limited capacity for evaluation of intra-articular pathology. Ankle arthroscopy represents a minimally invasive technique to directly visualize the articular cartilage and syndesmosis while aiding with reduction and allowing joint debridement, loose body removal, and treatment of chondral injuries. The purpose of this study was to evaluate temporal trends in concomitant ankle arthroscopy during ankle fracture ORIF surgery amongst early-career orthopaedic surgeons while examining the influence of subspecialty fellowship training on utilization. Methods: The American Board of Orthopaedic Surgery (ABOS) Part II Oral Examination database was queried to identify all candidates performing at least one ankle fracture ORIF from examination years 2010 to 2019. All ORIF cases were examined to identify those that carried a concomitant CPT code for ankle arthroscopy. Concomitant ankle arthroscopy cases were categorized by candidates self-reported fellowship training status and examination year. Descriptive statistics were performed to report relevant data and linear regression analyses were utilized to assess temporal trends in concomitant ankle arthroscopy with ORIF for ankle fractures. Statistical significance was defined as p<0.05. Results: During the study period, there were 36,113 cases of ankle fracture ORIF performed of which 388 cases (1.1%) were performed with concomitant ankle arthroscopy. Ankle fracture ORIF was most frequently performed by trauma fellowship trained ABOS Part II candidates (n=8,888; 24.6%), followed by sports medicine (n=7,493; 20.8%) and foot and ankle (n=6,563; 18.2%). Arthroscopy was most frequently utilized by foot and ankle fellowship trained surgeons (293/6,270 cases; 4.5%) followed by sports medicine (29/7,464 cases; 0.4%) and trauma (4/8,884 cases; 0.1%). With respect to arthroscopic cases, 293 cases (75.5%) were performed by foot and ankle fellowship trained surgeons, 29 (7.5%) sports medicine, and 4 (1.0%) trauma. Ankle arthroscopy utilization significantly increased from 3.65 cases per 1,000 ankle fractures in 2010 to 13.91 cases per 1,000 ankle fractures in 2019 (p=0.010). Specifically, foot and ankle fellowship trained surgeons demonstrated a significant increase in arthroscopy utilization during ankle fracture ORIF over time (p<0.001; OR: 1.101; CI: 1.054-1.151). Conclusion: Ankle arthroscopy utilization during ankle fracture ORIF has increased over the past decade. Foot and ankle fellowship trained surgeons contribute most significantly to this trend. Level of Evidence: IV.

Systemic bevacizumab as salvage therapy for persistent severe bleeding and anemia in heyde syndrome following aortic valve replacement.

Heyde syndrome is characterized by the co-occurrence of aortic stenosis and bleeding gastrointestinal angiodysplasias, often with acquired von Willebrand syndrome. Current management for bleeding includes hematologic support with red cell transfusion and intravenous iron and correction of aortic stenosis with valve replacement. However, persistent Heyde syndrome after valve replacement occurs in a significant minority of cases, and there is no accepted therapy for these patients. Given that the pathophysiology of angiodysplasia formation in Heyde syndrome involves dysregulated angiogenesis, targeting angiogenesis may be an effective therapeutic option. We describe two cases of persistent Heyde syndrome with severe bleeding and anemia in patients following aortic valve replacement who were treated with systemic bevacizumab, a monoclonal antibody directed against vascular endothelial growth factor. In both cases, treatment was successful, with resolution of bleeding, liberation from hematologic support, and normalization of hemoglobin. In addition to responding to therapy, neither patient had treatment-related adverse events (and both had recurrent anemia upon treatment discontinuation, further evidence of the therapeutic impact of bevacizumab). Additional investigation into the use of systemic antiangiogenic therapy for treatment of Heyde syndrome is warranted.

Gastroduodenal artery embolization for peptic ulcer hemorrhage refractory to endoscopic intervention: A single-center experience.

Objective: To determine the efficacy of gastroduodenal artery embolization (GDAE) for bleeding peptic ulcers that failed endoscopic intervention. To identify incidence and risk factors for failure of GDAE. Materials and Methods: A retrospective review of patients who underwent GDAE for hemorrhage from peptic ulcer disease refractory to endoscopic intervention were included in the study. Refractory to endoscopic intervention was defined as persistent hemorrhage following at least two separate endoscopic sessions with two different endoscopic techniques (thermal, injection, or mechanical) or one endoscopic session with the use of two different techniques. Demographics, comorbidities, endoscopic and angiographic findings, significant post-embolization pRBC transfusion, and index GDAE failure were collected. Failure of index GDAE was defined as the need for re-intervention (repeat embolization, endoscopy, or surgery) for rebleeding or mortality within 30 days after GDAE. Multivariate analyzes were performed to identify independent predictors for failure of index GDAE. Results: There were 70 patients that underwent GDAE after endoscopic intervention for bleeding peptic ulcers with a technical success rate of 100%. Failure of index GDAE rate was 23% (n = 16). Multivariate analysis identified ≥2 comorbidities (odds ratio [OR]: 14.2 [1.68-19.2], P = 0.023), days between endoscopy and GDAE (OR: 1.43 [1.11-2.27], P = 0.028), and extravasation during angiography (OR: 6.71 [1.16-47.4], P = 0.039) as independent predictors of index GDAE failure. Endoscopic Forrest classification was not a significant predictor for the failure of index GDAE (P > 0.1). Conclusion: The study demonstrates safety and efficacy of GDAE for hemorrhage from PUD that is refractory to endoscopic intervention. Days between endoscopy and GDAE, high comorbidity burden, and extravasation during angiography are associated with increased risk for failure of index GDAE.

Reconstruction of full-length LINE-1 progenitors from ancestral genomes.

Sequences derived from the Long INterspersed Element-1 (L1) family of retrotransposons occupy at least 17% of the human genome, with 67 distinct subfamilies representing successive waves of expansion and extinction in mammalian lineages. L1s contribute extensively to gene regulation, but their molecular history is difficult to trace, because most are present only as truncated and highly mutated fossils. Consequently, L1 entries in current databases of repeat sequences are composed mainly of short diagnostic subsequences, rather than full functional progenitor sequences for each subfamily. Here, we have coupled 2 levels of sequence reconstruction (at the level of whole genomes and L1 subfamilies) to reconstruct progenitor sequences for all human L1 subfamilies that are more functionally and phylogenetically plausible than existing models. Most of the reconstructed sequences are at or near the canonical length of L1s and encode uninterrupted ORFs with expected protein domains. We also show that the presence or absence of binding sites for KRAB-C2H2 Zinc Finger Proteins, even in ancient-reconstructed progenitor L1s, mirrors binding observed in human ChIP-exo experiments, thus extending the arms race and domestication model. RepeatMasker searches of the modern human genome suggest that the new models may be able to assign subfamily resolution identities to previously ambiguous L1 instances. The reconstructed L1 sequences will be useful for genome annotation and functional study of both L1 evolution and L1 contributions to host regulatory networks.

Study of Deep Vein Thrombosis Screening by using Ultrasound Doppler in Patients with Pelvic and Acetabulum Fractures Requiring Operative Intervention.

Introduction: Pelvic and acetabulum fractures are commonly caused by high impact injuries, increasing the risk of patients developing thromboembolic diseases such as deep vein thrombosis (DVT) and pulmonary embolism (PE). Therefore, this study was performed to determine the incidence of lower extremity DVT in patients with pelvic and acetabulum fractures and the importance of preoperative screening with Doppler ultrasound prior to surgical intervention. Materials and methods: This retrospective study involved 78 patients with pelvic and acetabulum fractures requiring surgical intervention from January 2015 until December 2019. Patients who underwent surgical interventions were screened pre-operatively with Doppler ultrasound to detect lower limb DVT and later compared with the incidence of lower limb DVT post-operatively. Descriptive statistical analysis was performed using IBM SPSS Statistics Version 24. Results: The participants of this study consisted of 30.8% females and 69.2% males. Pre-operative screening with Doppler ultrasound showed that three patients (3.8%) were diagnosed with lower limb DVT, whereas one of them (1.3%) was symptomatic and diagnosed with PE. Postoperatively, one patient developed DVT, and one patient developed PE. Both patients were negative for DVT preoperatively. Conclusion: The incidence of DVT in patients with pelvic and acetabulum fractures requiring operative intervention was significant despite the initiation of mechanical and pharmacological thromboprophylaxis upon admission. Despite the low incidence of DVT in our study, it has a high impact on patients' morbidity and mortality; thus, preoperative screening is important for early detection and the subsequent reduction of the risk of developing PE. The compulsory use of Doppler ultrasound of bilateral lower limbs as a part of pre-operative screening is highly recommended because it is cost-effective, efficient and readily available in most tertiary hospitals nationwide.

Left aorto-ventricular tunnel: A differential diagnosis to aortic regurgitation.

Left aorto-ventricular tunnel is a rare congenital heart disorder. A then 19-year-old young lady was referred to our clinic for chronic rheumatic heart disease with aortic regurgitation. However, because of an almost continuous murmur, and an unusual transthoracic echo, she underwent various investigations, finally revealing a rare type 2 left aorto-ventricular tunnel. She had been variously diagnosed as chronic rheumatic heart disease with aortic regurgitation, bicuspid aortic valve with aortic regurgitation, and then possibly coronary arterial (cameral) fistula (based on 2D transthoracic echo) and finally left aorto-ventricular tunnel. This is the first case described in South East Asia who is asymptomatic, apart from a murmur, and her long journey to this final diagnosis illustrates the need to "chase shadows" on echoes, to come to a proper conclusion for the patient.

Resident Participation During Revision Total Knee Arthroplasty Is Not Associated With Increased Risk of 30-Day Postoperative Complication.

Background: Academic teaching institutions perform approximately one third of all orthopedic procedures in the United States. Revision total knee arthroplasty (rTKA) is a complex and challenging procedure that requires expertise and extensive planning, however the impact of resident involvement on outcomes is poorly understood. The aim of the study was to investigate whether resident involvement in rTKA impacts postoperative complication rates, operative time, and length of hospital stay (LOS). Methods: The American College of Surgeons National Surgical Quality Improvement Program registry was queried to identify patients who underwent rTKA procedures from 2006-2012 using CPT codes 27486 and 27487. Cases were classified as resident involved or attending only. Demographics, comorbidities, and 30-day postoperative complications were analyzed. Multiple logistic regression analysis was performed to identify independent risk factors for increased 30-day postoperative complications. Wilcoxon rank sum tests were performed to determine the impact of resident involvement on operative time and LOS with significance defined as p<0.05. Results: In total, 2,396 cases of rTKA were identified, of which 972 (40.6%) involved residents. The two study groups were similar, however the resident involved cohort had more patients with hypertension and ASA class 3 (p=0.02, p=0.04). There was no difference in complications between the cohorts (No Resident vs Resident-involved: 7.0% vs 6.7%, p=0.80). Multivariate analysis identified obesity (OR: 1.81, 95% CI: 1.18-2.79, p=0.01), morbid obesity (OR: 1.66, 95% CI: 1.09-2.57, p=0.02), congestive heart failure (OR: 5.97, 95% CI: 1.19-24.7, p=0.02), and chronic prosthetic joint infection (OR: 3.16, 95% CI: 2.184.56, p<0.01), as independent risk factors for 30-day complications after rTKA. However, resident involvement was not associated with complications within 30-days following rTKA (OR: 0.91, 95% CI: 0.65-1.26, p=0.57). Resident involvement was associated with increased operative time (p<0.001) and LOS (P<0.001). Conclusion: Resident involvement in rTKA cases is not associated with an increased risk of 30-day postoperative complications. However, resident operative involvement was associated with longer operative time and length of hospital stay. Level of Evidence: III.