Shariant platform: Enabling evidence sharing across Australian clinical genetic-testing laboratories to support variant interpretation.

Sharing genomic variant interpretations across laboratories promotes consistency in variant assertions. A landscape analysis of Australian clinical genetic-testing laboratories in 2017 identified that, despite the national-accreditation-body recommendations encouraging laboratories to submit genotypic data to clinical databases, fewer than 300 variants had been shared to the ClinVar public database. Consultations with Australian laboratories identified resource constraints limiting routine application of manual processes, consent issues, and differences in interpretation systems as barriers to sharing. This information was used to define key needs and solutions required to enable national sharing of variant interpretations. The Shariant platform, using both the GRCh37 and GRCh38 genome builds, was developed to enable ongoing sharing of variant interpretations and associated evidence between Australian clinical genetic-testing laboratories. Where possible, two-way automated sharing was implemented so that disruption to laboratory workflows would be minimized. Terms of use were developed through consultation and currently restrict access to Australian clinical genetic-testing laboratories. Shariant was designed to store and compare structured evidence, to promote and record resolution of inter-laboratory classification discrepancies, and to streamline the submission of variant assertions to ClinVar. As of December 2021, more than 14,000 largely prospectively curated variant records from 11 participating laboratories have been shared. Discrepant classifications have been identified for 11% (28/260) of variants submitted by more than one laboratory. We have demonstrated that co-design with clinical laboratories is vital to developing and implementing a national variant-interpretation sharing effort. This approach has improved inter-laboratory concordance and enabled opportunities to standardize interpretation practices.

Assessment of the Impact of RNase in Patients With Severe Fatigue Related to Post-Acute Sequelae of SARS-CoV-2 Infection (PASC): A Randomized Phase 2 Trial of RSLV-132.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and RNA debris persist in viral reservoirs for weeks to months following infection, potentially triggering interferon production and chronic inflammation. RSLV-132 is a biologic drug composed of catalytically active human RNase1 fused to human IgG1 Fc and is designed to remain in circulation and digest extracellular RNA. We hypothesized that removal of SARS-CoV-2 viral RNA from latent reservoirs may improve inflammation, neuroinflammation, and fatigue associated with post-acute sequelae of SARS-CoV-2 infection (PASC). METHODS: This was a phase 2, double-blind, placebo-controlled randomized clinical trial in participants with a 24-week history of PASC and severe fatigue. The primary endpoint of the trial assessed the impact of 6 intravenous doses of RSLV-132 on the mean change from baseline at day 71 in the Patient-Reported Outcomes Measurement Information System Fatigue Short Form 7a (PROMIS Fatigue SF 7a). RESULTS: A statistically significant difference on day 71 was not observed with respect to the primary or secondary endpoints. This was likely due to a placebo response that increased during the trial. Statistically significant improvement in fatigue as measured by the PROMIS Fatigue SF 7a, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), and Physicians Global Assessment (PGA) instruments were observed earlier in the trial, with women demonstrating greater responses to RSLV-132 than men. CONCLUSION: While fatigue was not statistically significantly improved at Day 71, earlier timepoints revealed statistically significant improvement in fatigue and physician global assessment. The data suggest eliminating latent viral RNA by increasing serum RNase activity may improve fatigue in PASC patients. Women may respond better to this approach than men. Future studies will aim to confirm these findings.

Fitting fangs in a finite face: A novel fang accommodation strategy in a 280-million-year-old ray-finned fish.

Though Paleozoic ray-finned fishes are considered to be morphologically conservative, we report a novel mode of fang accommodation (i.e., the fitting of fangs inside the jaw) in the Permian actinopterygian †Brazilichthys macrognathus, whereby the teeth of the lower jaw insert into fenestrae of the upper jaw. To better understand how fishes have accommodated lower jaw fangs through geologic time, we synthesize the multitude of ways living and extinct osteichthyans have housed large mandibular dentition. While the precise structure of fang accommodation seen in †Brazilichthys has not been reported in any other osteichthyans, alternate strategies of upper jaw fenestration to fit mandibular fangs are present in some extant ray-finned fishes-the needlejaws Acestrorhynchus and the gars of the genus Lepisosteus. Notably, out of our survey, only the two aforementioned neopterygians bear upper jaw fenestration for the accommodation of mandibular fangs. We implicate the kinetic jaws of neopterygians in this trend, whereby large mandibular fangs are more easily fit between the multitude of upper jaw and palatal bones. The restricted space available in early osteichthyan jaws may have led to a proliferation of novel ways to accommodate large dentition. We recommend a greater survey of Paleozoic actinopterygian jaw morphology, in light of these results and other recent reevaluations of jaw structure in early fossil ray-fins.

Adrenal venous sampling for lateralization of cortisol hypersecretion in patients with bilateral adrenal masses.

OBJECTIVE: The objective of this study was to evaluate the role of adrenal venous sampling (AVS) in guiding the management of patients with corticotropin (ACTH)-independent glucocorticoid secretory autonomy and bilateral adrenal masses. DESIGN AND PATIENTS: A cohort with 25 patients underwent AVS and surgical management. MEASUREMENTS: Cortisol was measured from the adrenal veins (AVs) and inferior vena cava (IVC). AV/IVC cortisol ratio and cortisol lateralization ratio (CLR) (dominant AV cortisol concentration divided by the nondominant AV cortisol concentration) were calculated. Posthoc receiver-operating characteristic curves were generated to determine the specificity of revised AV/IVC cortisol ratio and CLR in differentiating unilateral from bilateral disease. RESULTS: Patients underwent unilateral (n = 21) or bilateral (n = 4) adrenalectomy. The mean AV/IVC cortisol ratio for unilateral adrenalectomy was 12.1 ± 9.6 (dominant) and 4.7 ± 3.8 (contralateral) with a mean CLR of 3.6 ± 3.5. The mean AV/IVC cortisol ratio for bilateral adrenalectomy was 7.5 ± 2.1, with a mean CLR of 1.1 ± 0.6. At a mean follow-up of 22 months, one patient who underwent unilateral adrenalectomy for the predicted bilateral disease developed recurrent mild autonomous cortisol secretion. Posthoc analyses demonstrated a specificity of 95%-100% for unilateral disease with AV/IVC cortisol ratio >9 for one side, <2.0 for the opposite side and a CLR > 2.3. The specificity was 80%-90% for bilateral disease with AV/IVC cortisol ratio >5.1 bilaterally and a CLR < 1.1. CONCLUSIONS: Among patients with bilateral adrenal masses and ACTH-independent autonomous cortisol secretion, AVS can distinguish between unilateral and bilateral disease with high specificity and may guide surgical management.

Imaging of Bowel Ischemia: An Update, From the AJR Special Series on Emergency Radiology.

Acute mesenteric ischemia is a life-threatening condition that results from abrupt reduction in or cessation of blood flow to the bowel. Characterized by nonspecific abdominal symptoms, mesenteric ischemia is infrequently encountered and commonly misdiagnosed, with potentially catastrophic consequences. Prompt clinical diagnosis and early implementation of therapeutic interventions are critical to improving patient outcomes. Because cross-sectional imaging plays a key role in the diagnosis of mesenteric ischemia, radiologists must be familiar with the varied imaging manifestations of intestinal ischemia. Thus, the objectives of this article are to review the various types and common causes of mesenteric ischemia and to describe its spectrum of multimodality imaging findings, with special attention to novel imaging techniques and emerging diagnoses.

Endoscopic ultrasound-guided versus percutaneous drainage for the management of post-operative fluid collections after distal pancreatectomy.

BACKGROUND: Post-operative pancreatic fluid collections (POPFCs) can be drained using percutaneous or endoscopic approaches. The primary aim of this study was to compare rates of clinical success between endoscopic ultrasound-guided drainage (EUSD) with percutaneous drainage (PTD) in the management of symptomatic POPFCs after distal pancreatectomy. Secondary outcomes included technical success, total number of interventions, time to resolution, rates of adverse events (AEs), and POPFC recurrence. METHODS: Adults who underwent distal pancreatectomy from January 2012 to August 2021 and developed symptomatic POPFC in the resection bed were retrospectively identified from a single academic center database. Demographic data, procedural data, and clinical outcomes were abstracted. Clinical success was defined as symptomatic improvement and radiographic resolution without requiring an alternate drainage modality. Quantitative variables were compared using a two-tailed t-test and categorical data were compared using Chi-squared or Fisher's exact tests. RESULTS: Of 1046 patients that underwent distal pancreatectomy, 217 met study inclusion criteria (median age 60 years, 51.2% female), of whom 106 underwent EUSD and 111 PTD. There were no significant differences in baseline pathology and POPFC size. PTD was generally performed earlier after surgery (10 vs. 27 days; p < 0.001) and more commonly in the inpatient setting (82.9% vs. 49.1%; p < 0.001). EUSD was associated with a significantly higher rate of clinical success (92.5% vs. 76.6%; p = 0.001), fewer median number of interventions (2 vs. 4; p < 0.001), and lower rate of POPFC recurrence (7.6% vs. 20.7%; p = 0.007). AEs were similar between EUSD (10.4%) and PTD (6.3%, p = 0.28), with approximately one-third of EUSD AEs due to stent migration. CONCLUSION: In patients with POPFCs after distal pancreatectomy, delayed drainage with EUSD was associated with higher rates of clinical success, fewer interventions, and lower rates of recurrence than earlier drainage with PTD.

Boutonniere Versus Pseudoboutonniere Deformities: Pathoanatomy, Diagnosis, and Treatment.

Finger injuries involving the proximal interphalangeal (PIP) joint are common, particularly among athletes. Injury severity is often underappreciated at initial presentation and may be dismissed broadly as a "jammed finger" injury. Delayed diagnosis and treatment of certain injuries can have an important impact on the patient's chance of regaining full function. Central slip and PIP volar plate injuries are frequently encountered injuries that, if left untreated, can lead to the permanent loss of function of the proximal interphalangeal joint. Despite the differing mechanisms of these 2 pathologies, volar plate hyperextension injuries often present with a PIP joint flexion contracture and mild distal interphalangeal joint hyperextension deformity. This is similar to a boutonniere deformity seen after an injury to the central slip, and thus, has been referred to as a "pseudo-boutonnière" deformity. Distinguishing these 2 diagnoses is important, as treatment differs, and highlights the importance of thoroughly understanding the anatomy and relevant clinical applications when evaluating PIP joint injuries.

Clinical outcomes and return to play in softball players following SLAP repair or biceps tenodesis.

BACKGROUND: Shoulder pain due to labral tears and biceps tendonitis is commonly found in softball players. Surgical options include labral repair and biceps tenodesis. Although past studies are limited by heterogeneous study groups from multiple sports, this is the first study that assesses clinical outcomes and return to play rates for fast-pitch softball players. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the clinical outcomes and return to play for fast-pitch softball players treated for a superior labrum anterior posterior (SLAP) tear and recalcitrant biceps tendonitis with a biceps tenodesis compared with a traditional SLAP repair. We hypothesized that the biceps tenodesis would have comparable outcomes with a faster return to play compared with SLAP repair. METHODS: We performed a retrospective analysis on fast-pitch softball players treated surgically for SLAP tear, recalcitrant biceps tendonitis, or a combination between 2001 and 2019 at our institution. Inclusion criteria were fast-pitch softball players who underwent biceps tenodesis or a SLAP repair with greater than 2-year follow-up. Exclusion criteria involved slow-pitch softball players, patients with less than 2-year follow-up, and patients who had undergone concomitant procedures on the ipsilateral shoulder at the time of SLAP repair or biceps tenodesis. Follow-up was either self-reported through OBERD, a patient-reported outcomes (PRO)-managing software, or achieved over the phone. Follow-up data included American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form score, Andrews Carson Score, Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow Score, Numeric Rating Scale for Pain, and our institution-specific return-to-play questionnaire. We statistically compared players who underwent biceps tenodesis or a SLAP repair, and compared pitchers with position players using Student t tests and Fisher exact test with statistical significance determined to be P < .05. RESULTS: From 60 eligible patients identified, follow-up outcome data were successfully captured for 47 (78%). Of the 18 SLAP repair patients, 17 (94%) returned to full competition at an average of 7.9 months. Of the 29 patients who underwent biceps tenodesis, 27 (93%) returned to full competition at an average of 7.1 months. Statistical analysis of PRO scores for each group found no significant differences between any of the measures used to evaluate patient outcomes, including no statistical difference in pitchers compared with position players. CONCLUSION: In conclusion, this study demonstrated comparable outcomes between SLAP repairs and biceps tenodesis procedures among our study group of fast-pitch softball players. There was no significant difference between RTP times between the 2 groups.

Clinical outcomes of osteochondritis dissecans lesions of the capitellum treated with arthroscopy with a mean follow-up period of 8.3 years.

BACKGROUND AND HYPOTHESIS: Although numerous studies exist evaluating the short-term clinical outcomes of patients who have undergone elbow arthroscopy for osteochondritis dissecans (OCD) of the capitellum, the literature on minimum 2-year clinical outcomes in a large cohort of patients is limited. We hypothesized that the clinical outcomes of patients treated arthroscopically for OCD of the capitellum would be favorable, with improved postoperative subjective functional and pain scores and with an acceptable return-to-play rate. METHODS: A retrospective analysis of a prospectively collected surgical database was performed to identify all patients treated surgically for OCD of the capitellum at our institution from January 2001 to August 2018. The inclusion criteria for this study included a diagnosis of OCD of the capitellum treated arthroscopically with a minimum 2-year follow-up period. The exclusion criteria included any prior surgical treatment on the ipsilateral elbow, missing operative reports, and cases in which any portion of the surgical procedure was performed in an open manner. Follow-up was performed by telephone using multiple patient-reported outcome questionnaires: American Shoulder and Elbow Surgeons-Elbow (ASES-e), Andrews-Carson, and Kerlan-Jobe Orthopaedic Clinic Shoulder and Elbow Score (KJOC) questionnaires and our institution-specific return-to-play questionnaire. RESULTS: After the inclusion and exclusion criteria were applied to our surgical database, 107 eligible patients were identified. Of these, 90 were successfully contacted, for a follow-up rate of 84%. The mean age was 15.2 years, and the mean follow-up time was 8.3 years. A subsequent revision procedure was performed in 11 patients, for a 12% failure rate in these patients. The ASES-e pain score was an average of 4.0 on a maximum pain scale of 100, the ASES-e function score was an average of 34.5 of a maximum of 36, and the surgical satisfaction score was an average of 9.1 of 10. The average Andrews-Carson score was 87.1 of 100, and the average KJOC score for overhead athletes was 83.5 of 100. Additionally, of the 87 patients evaluated who played sports at the time of their arthroscopy, 81 (93%) returned to play. CONCLUSION: This study demonstrated an excellent return-to-play rate and satisfactory subjective questionnaire scores with a 12% failure rate following arthroscopy for OCD of the capitellum with a minimum 2-year follow-up period.

DiceCT for fishes: recommendations for pairing iodine contrast agents with µCT to visualize soft tissues in fishes.

Computed tomography (CT) scanning and other high-throughput three-dimensional (3D) visualization tools are transforming the ways we study morphology, ecology and evolutionary biology research beyond generating vast digital repositories of anatomical data. Contrast-enhanced chemical staining methods, which render soft tissues radio-opaque when coupled with CT scanning, encompass several approaches that are growing in popularity and versatility. Of these, the various diceCT techniques that use an iodine-based solution like Lugol's have provided access to an array of morphological data sets spanning extant vertebrate lineages. This contribution outlines straightforward means for applying diceCT techniques to preserved museum specimens of cartilaginous and bony fishes, collectively representing half of vertebrate species diversity. This study contrasts the benefits of using either aqueous or ethylic Lugol's solutions and reports few differences between these methods with respect to the time required to achieve optimal tissue contrast. It also explores differences in minimum stain duration required for different body sizes and shapes and provides recommendations for staining specimens individually or in small batches. As reported by earlier studies, the authors note a decrease in pH during staining with either aqueous or ethylic Lugol's. Nonetheless, they could not replicate the drastic declines in pH reported elsewhere. They provide recommendations for researchers and collections staff on how to incorporate diceCT into existing curatorial practices, while offsetting risk to specimens. Finally, they outline how diceCT with Lugol's can aid ichthyologists of all kinds in visualizing anatomical structures of interest: from brains and gizzards to gas bladders and pharyngeal jaw muscles.

Association of Cirrhosis and Other Patient and Procedural Characteristics With Postembolization Syndrome After Bland Hepatic Artery Embolization for Hepatic Malignancy.

BACKGROUND. Patients who undergo bland hepatic artery embolization (HAE) for the treatment of hepatic malignancy may undergo routine overnight postprocedure hospitalization to monitor for postembolization syndrome (PES) given the potential for ischemic injury from HAE to lead to rapid onset of PES. In our experience, PES after HAE is more frequent in patients without cirrhosis. OBJECTIVE. The purpose of this study was to investigate the utility of cirrhosis and other patient and procedural characteristics in predicting the development of PES after bland HAE performed for the treatment of hepatic malignancy. METHODS. This retrospective study included 167 patients (122 men and 45 women; mean age, 63.5 ± 13.1 [SD] years) who underwent a total of 248 bland HAE procedures to treat primary or secondary hepatic malignancy. All patients were hospitalized for 24 hours of observation after HAE to monitor for and manage PES symptoms. PES severity was graded using the Southwest Oncology Group's toxicity coding scale. Patient and procedural characteristics were recorded. Associations with the development of PES were explored. A risk model to predict the risk of PES was constructed using independent predictors of PES in multivariable analysis. RESULTS. PES developed after 51.2% (127/248) of procedures; 23 cases were mild, 50 were moderate, and 54 were severe. PES developed in 32.1% (45/140) of patients with cirrhosis versus 75.9% (82/108) of patients without cirrhosis, whereas severe PES developed in 10.0% (14/140) versus 37.0% (40/108) of such patients, respectively. In multivariable analysis (which controlled for primary versus secondary malignancy, comorbidities, pre-procedure laboratory values, size and multiplicity of treated lesions, lobar vs segmental embolization, embolized artery, and embolic material used), independent predictors of lower likelihood of PES were older age (OR = 0.95 [95% CI, 0.92-0.99]), cirrhosis (OR = 0.26 [95% CI, 0.11-0.64]), and primary hepatic malignancy (OR = 0.34 [95% CI, 0.13-0.93]); the only independent predictor of a higher likelihood of PES was embolization of 50% or more of liver volume (OR = 4.29 [95% CI, 1.89-10.18]). A risk model using these factors had sensitivity of 75.6% and specificity of 76.0% for predicting PES. CONCLUSION. Cirrhosis was associated with a decreased risk of PES after bland HAE performed for the treatment of hepatic malignancy. A risk model combining cirrhosis and other factors had good performance in predicting the risk of PES. CLINICAL IMPACT. These findings may be applied to the selection of patients for early discharge after bland HAE, to avoid the need for overnight inpatient monitoring.

Cellular Augmentation of Anterior Cruciate Ligament Surgery Is Not Currently Evidence Based: A Systematic Review of Clinical Studies.

PURPOSE: To perform a systematic review of clinical outcome studies exploring cellular augmentation of anterior cruciate ligament (ACL) surgery, including stem cell techniques. METHODS: A systematic search was performed according to the Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines using the Cochrane, PubMed, MEDLINE, SPORTDiscus, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases from 2000 to 2019. The inclusion criteria were clinical studies that reported on ACL surgery augmented with stem cells or cellular therapy and patient-reported outcome measures or graft healing. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomized clinical trials, and nonrandomized trials were assessed using the Methodological Items for Non-randomized Studies (MINORS) tool. Methodologic assessment was performed according to the Modified Coleman Methodology Score. RESULTS: Four studies were found: 2 randomized clinical trials, 1 cohort study with a matched historical control group, and 1 case series. The mean Modified Coleman Methodology Score in these studies was 59, and there was a low risk of bias in 1 study. One study reported outcomes of augmented ACL repair, and 3 studies reported the results of augmented ACL reconstruction. Cellular therapies varied and included concentrated bone marrow aspirate, collagenase/centrifuge processed adipose, and marrow stimulation combined with platelet-rich plasma, as well as cells cultured from allograft bone marrow aspirate. The concentrated bone marrow aspirate and adipose tissue study results did not support their use. The marrow stimulation technique combined with repair led to promising clinical results. The use of allograft cultured cells improved patient-reported outcomes and postoperative radiographic findings. CONCLUSIONS: Augmentation of ACL surgery with cellular therapy is not supported by clinical evidence at this time. LEVEL OF EVIDENCE: Level IV.

Successful Outcomes and Return to Sport After Arthroscopic Bankart Repair in National Collegiate Athletic Association and National Football League Football Players.

OBJECTIVE: To characterize recurrent instability, return to sport (RTS), and patient-reported outcomes (PROs) after arthroscopic Bankart repair for acute traumatic anterior shoulder instability in National Collegiate Athletic Association (NCAA) and National Football League (NFL) football players. DESIGN: Case series. SETTING: Orthopaedic and sports medicine clinic. PARTICIPANTS: National Collegiate Athletic Association and NFL football athletes with traumatic anterior shoulder instability who underwent arthroscopic shoulder stabilization at a single institution with at least 2-year follow-up. INTERVENTIONS OR ASSESSMENT OF RISK FACTORS OR INDEPENDENT VARIABLES: Arthroscopic Bankart repair. MAIN OUTCOME MEASURES: Recurrent instability, RTS, patient satisfaction, the visual analog scale (VAS) for pain, American Shoulder and Elbow Surgeons (ASES) score, and Rowe score. RESULTS: Thirty-three players were included with a mean age of 23.8 years (range, 18-33 years) and a mean follow-up of 6.3 years (range, 4.1-9.3 years). One shoulder (3.0%) had a postoperative subluxation event, and 1 shoulder (3.0%) required revision surgery for issues other than instability; 93.3% of players were able to RTS at the same level or higher for at least 1 season. Mean satisfaction was 8.9 ± 2.3. Mean VAS was 1.0 ± 1.7, and mean ASES and Rowe scores were 90.7 ± 18.5 and 89.7 ± 15.2, respectively. CONCLUSION: Arthroscopic Bankart repair is an effective surgical intervention for traumatic anterior shoulder instability in NCAA and NFL football players. At a mean 6-year follow-up, surgery restored stability in 97% of cases and 93.3% returned to their preinjury level of sport.

Lean mass, grip strength, and hospital-associated disability among older adults in Health ABC.

INTRODUCTION: Older adults with cognitive impairment, including those with Alzheimer's disease and related dementias, are particularly at risk for hospitalization and hospital-associated disability. Understanding of key risk factors for hospital-associated disability is limited. Sarcopenia, age-related declines in muscle mass and strength, is common in older adults with cognitive impairment and may be an important risk factor for hospital-associated disability. METHODS: Using data from the Health ABC Study, we examined associations of pre-hospitalization appendicular lean mass (ALM) and grip strength with the development of a new activity of daily living (ADL) disability at the next annual assessment after hospitalization. RESULTS: Grip strength, but not ALM, was negatively associated with increased risk of hospital-associated ADL disability, and this association was greater among those with cognitive impairment compared to those without. DISCUSSION: Lower grip strength may be an important risk factor for hospital-associated ADL disability in older adults, particularly those with cognitive impairment.

Patency rates of hepatic arterial resection and revascularization in locally advanced pancreatic cancer.

BACKGROUND: Arterial resection (AR) for pancreatic adenocarcinoma is increasingly considered at specialized centers. We aimed to examine the incidence, risk factors, and outcomes of hepatic artery (HA) occlusion after revascularization. METHODS: We included patients undergoing HA resection with interposition graft (IG) or primary end-to-end anastomoses (EE). Complete arterial occlusion (CAO) was defined as "early" (EO) or "late" (LO) before/after 90 days respectively. Kaplan-Meier and change-point analysis for CAO was performed. RESULTS: HA resection was performed in 108 patients, IG in 61% (66/108) and EE in 39% (42/108). An equal proportion (50%) underwent HA resection alone or in combination with celiac and/or superior mesenteric artery. CAO was identified in 18% of patients (19/108) with arterial IG least likely to occlude (p=0.019). Hepatic complications occurred in 42% (45/108) and correlated with CAO, symptomatic patients, venous resection, and postoperative portal venous patency. CAO-related operative mortality was 4.6% and significantly higher in EO vs LO (p = 0.046). Median CAO occlusion was 126 days. With change-point analysis, CAO was minimal beyond postoperative day 158. CONCLUSION: CAO can occur in up to 18% of patients and the first 5-month post-operative period is critical for surveillance. LO is associated with better outcomes compared to EO unless there is inadequate portal venous inflow.

GATA2 deficiency syndrome: A decade of discovery.

GATA2 deficiency syndrome (G2DS) is a rare autosomal dominant genetic disease predisposing to a range of symptoms, of which myeloid malignancy and immunodeficiency including recurrent infections are most common. In the last decade since it was first reported, there have been over 480 individuals identified carrying a pathogenic or likely pathogenic germline GATA2 variant with symptoms of G2DS, with 240 of these confirmed to be familial and 24 de novo. For those that develop myeloid malignancy (75% of all carriers with G2DS disease symptoms), the median age of onset is 17 years (range 0-78 years) and myelodysplastic syndrome is the first diagnosis in 75% of these cases with acute myeloid leukemia in a further 9%. All variant types appear to predispose to myeloid malignancy and immunodeficiency. Apart from lymphedema in which haploinsufficiency seems necessary, the mutational requirements of the other less common G2DS phenotypes is still unclear. These predominantly loss-of-function variants impact GATA2 expression and function in numerous ways including perturbations to DNA binding, protein structure, protein:protein interactions, and gene transcription, splicing, and expression. In this review, we provide the first expert-curated ACMG/AMP classification with codes of published variants compatible for use in clinical or diagnostic settings.

Transpapillary gallbladder stent placement for long-term therapy of acute cholecystitis.

BACKGROUND AND AIMS: Select patients with acute cholecystitis (AC) are poor candidates for cholecystectomy. ERCP-guided transpapillary gallbladder (GB) drainage (ERGD) is one modality for nonoperative management of AC in these patients. Our primary aim was to evaluate long-term success of destination ERGD. Secondary aims were the rate of technical and clinical success, number of repeat procedures, rate of adverse events, and risk factors for recurrent AC. METHODS: Consecutive patients with AC who were not candidates for cholecystectomy underwent ERGD with attempted transpapillary GB plastic double-pigtail stent placement at a tertiary hospital from January 2008 to December 2019. Long-term success was defined as no AC after ERGD until 6 months, death, or reintervention. Technical success was defined as placement of at least 1 transpapillary stent into the GB and clinical success as resolution of AC symptoms with discharge from the hospital. RESULTS: Long-term success was achieved in 95.9% of patients (47/49), technical success in 96% (49/51), and clinical success 100% in those with technical success. Mild adverse events occurred in 5.9% (n = 3). Mean follow-up was 453 days after ERGD (range, 18-1879). A trend toward longer time to recurrence of AC was seen in patients with 2 rather than 1 GB stent placed (P = .13), and more repeat procedures were performed when a single stent was placed (P = .045). CONCLUSIONS: ERGD with transpapillary GB double-pigtail stent placement is a safe and effective long-term therapy for poor surgical candidates with AC. Risk factors for recurrence include stent removal and single-stent therapy. Double-stent therapy is not always technically feasible but may salvage failed single-stent therapy or recurrence after elective stent removal and may therefore be the preferred treatment modality.

Knee Kinetics in Baseball Hitting and Return to Play after ACL Reconstruction.

The purpose of this study was to describe the knee kinetics of baseball hitting, develop a tool to predict knee kinetics from easily obtainable measures, and to compare knee kinetics to other exercises along the rehabilitation continuum to determine a timeline for when hitting may resume after ACL reconstruction. Nineteen high school baseball athletes (16.3±0.8 yrs, 180.6±5.7 cm, 78.4±10.8 kg) participated. Participants took ten swings off a tee. Kinetic data were recorded using an electromagnetic tracking system. Data from swings with the top three exit velocities were averaged for analysis. Linear regressions were used to determine if predictors of height, mass, age and exit velocity could predict the following torques: bilateral knee net, extension, internal and external rotation, valgus and varus torque; and anterior force. Backwards regression models revealed independent variables could significantly predict front knee net, internal and external rotation, extension, and varus torque, and anterior force; and back knee net and valgus torque. Based on the kinetics of baseball hitting compared to those of rehabilitation exercises, if the involved knee is the front, we suggest tee hitting may be initiated at 13 weeks after ACL reconstruction. If the involved knee is the back, we suggest tee hitting may initiated at 17 weeks after ACL reconstruction.

Biceps Tendon Changes and Pitching Mechanics in Youth Softball Pitchers.

With the lack of pitch count regulation, youth softball pitchers are experiencing unremitting high stresses on the anterior shoulder. The purpose of this study was to examine the association of acute changes in the long head of the biceps tendon with pitching kinematics and kinetics in youth softball pitchers following an acute bout of pitching. Twenty-three softball pitchers (12.17±1.50 yrs.; 160.32±9.41 cm; 60.40±15.97 kg) participated. To investigate the association between biceps tendon changes and kinematic and kinetic changes from pre- to post-simulated game, each biceps tendon measure was split into those whose biceps tendon thickness, width, and/or area increased pre- to post-simulated game, and those whose did not. There were significant differences in biceps tendon longitudinal thickness (Z=- 2.739, p=0.006) and pitch speed; as well as a difference between groups in biceps tendon transverse thickness and the amount of change in trunk rotation at the start of the pitching motion (p=0.017) and the amount of change in trunk flexion at ball release (p=0.030). This study illustrates the association of trunk and lower extremity kinematics and shoulder kinetics with morphologic changes in the biceps tendon with an acute bout of windmill softball pitching.

Lower Extremity Pain and Pitching Kinematics and Kinetics in Collegiate Softball Pitchers.

The primary aims of the study were (1) to examine kinematics and kinetics of those pitching with and without lower extremity pain in collegiate softball pitchers, and (2) to determine if there was an association between the lower extremity pain and lower extremity kinematics, trunk kinematics, and shoulder kinetics in collegiate softball pitchers. Thirty-seven NCAA Division I female collegiate softball pitchers (19.8±1.3 yrs,173.7±7.7 cm, 79.0±12.4 kg) participated. Participants were divided into two groups, those who were currently experiencing lower extremity pain and those who were not. Participants threw three rise ball pitches. Kinematic data were collected at 100 Hz using an electromagnetic tracking system. Mann-Whitney U tests revealed no significant kinematic or kinetic differences between pitchers with and without lower extremity pain. Additionally, there were no significant correlations between pain and recorded kinematic and kinetic variables. Considering there were no biomechanical differences observed between pitchers, coaches and athletic trainers should take caution with athlete assessment since athletes may not display altered biomechanics. Further examination into the duration and degree of pain is needed in an attempt to fully understand the implication of pain and pitching mechanics.