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.

The Comparative Effect of Age on Clinical Outcomes Following Anatomic Total Shoulder Arthroplasty and Reverse Total Shoulder Arthroplasty.

At many institutions, the pendulum has swung toward reverse total shoulder arthroplasty (RTSA). Good results have been reported for patients older than 65 years with glenohumeral osteoarthritis with an intact rotator cuff, leading to questioning of the role of anatomic total shoulder arthroplasty (TSA) in the elderly. The purpose of this study was to compare outcome measures between TSA and RTSA patients using minimal clinically important difference (MCID) and substantial clinical benefit (SCB) as a function of age. Primary TSA or RTSA patients with American Shoulder and Elbow Surgeons (ASES) scores at 2-year follow-up were retrospectively identified from a prospective database. Patients with a diagnosis of inflammatory arthritis, infection, proximal humerus fracture, or revision TSA were excluded. Patients were stratified by age as younger than 65 years, 65 to 74 years, and 75 years or older. A total of 659 TSA and 172 RTSA patients were included. Total shoulder arthroplasty had a larger improvement in ASES scores compared with RTSA in patients aged 65 to 74 years and 75 years and older (P=.04 and P<.01, respectively). In patients aged 75 years or older, the percentages of patients achieving MCID were similar (93.1% TSA and 92.3% RTSA; P=.53); however, a higher percentage of TSA patients achieved SCB vs RTSA patients (90.5% vs 76.9%; P=.01). This study highlights the importance of indications and a shared decision-making model to ensure patient satisfaction. The results support a trend that primary RTSA is a viable option for low-demand patients aged 75 years or older; however, appropriately indicated TSA offers a potential for greater improvement in ASES scores and is more successful at achieving SCB compared with RTSA at 2-year follow-up. [Orthopedics. 2021;44(4):e600-e606.].

Lung Histopathology in Coronavirus Disease 2019 as Compared With Severe Acute Respiratory Sydrome and H1N1 Influenza: A Systematic Review.

BACKGROUND: Patients with severe coronavirus disease 2019 (COVID-19) have respiratory failure with hypoxemia and acute bilateral pulmonary infiltrates, consistent with ARDS. Respiratory failure in COVID-19 might represent a novel pathologic entity. RESEARCH QUESTION: How does the lung histopathology described in COVID-19 compare with the lung histopathology described in SARS and H1N1 influenza? STUDY DESIGN AND METHODS: We conducted a systematic review to characterize the lung histopathologic features of COVID-19 and compare them against findings of other recent viral pandemics, H1N1 influenza and SARS. We systematically searched MEDLINE and PubMed for studies published up to June 24, 2020, using search terms for COVID-19, H1N1 influenza, and SARS with keywords for pathology, biopsy, and autopsy. Using PRISMA-Individual Participant Data guidelines, our systematic review analysis included 26 articles representing 171 COVID-19 patients; 20 articles representing 287 H1N1 patients; and eight articles representing 64 SARS patients. RESULTS: In COVID-19, acute-phase diffuse alveolar damage (DAD) was reported in 88% of patients, which was similar to the proportion of cases with DAD in both H1N1 (90%) and SARS (98%). Pulmonary microthrombi were reported in 57% of COVID-19 and 58% of SARS patients, as compared with 24% of H1N1 influenza patients. INTERPRETATION: DAD, the histologic correlate of ARDS, is the predominant histopathologic pattern identified in lung pathology from patients with COVID-19, H1N1 influenza, and SARS. Microthrombi were reported more frequently in both patients with COVID-19 and SARS as compared with H1N1 influenza. Future work is needed to validate this histopathologic finding and, if confirmed, elucidate the mechanistic underpinnings and characterize any associations with clinically important outcomes.

Radiographic and clinical characteristics associated with a positive PART (Prone Apprehension Relocation Test): a new provocative exam to elicit hip instability.

Hip instability due to mild dysplasia can be a diagnostic challenge. The physical exam is an important adjunct to radiographic evaluation for the clinical diagnosis of hip instability. Herein, we describe a new maneuver to replicate hip instability pain, called the PART (Prone Apprehension Relocation Test). We retrospectively identified patients in our institution's hip preservation registry who presented for evaluation of hip pain. We divided patients into 'positive' or 'negative' PART and analyzed associated clinical and radiographic findings. Ninety patients (159 hips) were included, 83 female and 7 male, average age 27.3 ± 9.1 years. Thirty-four hips (21.4%) had a positive PART. There were no significant differences in hip range of motion, lateral center edge angle, or in acetabular depth. There was, however, a significant difference in acetabular version at 3 o'clock between the two test groups (18.5 ± 6.9° in negative, 21.2 ± 4.9° in positive, P = 0.045). There was no association between PART and previously described anterior apprehension testing. Historical methods of diagnosing hip dysplasia may not adequately identify patients with clinical hip instability. We describe a new provocative exam, the PART, which may be helpful in replicating hip instability symptoms in patients with anterior acetabular undercoverage. PART positive patients had significantly more acetabular anteversion at the 3 o'clock position, which is measured on computed tomography and is not visible on standard anteroposterior (AP) pelvis or false profile radiographs. We believe that the PART is a valuable supplement to clinical examination and radiographic measurements to identify patients with symptomatic hip instability.

Does Having a Rotator Cuff Repair Before Total Shoulder Arthroplasty Influence Outcomes?

BACKGROUND: The number of rotator cuff repairs (RCRs) is increasing each year. Total shoulder arthroplasty (TSA) is a successful treatment option for patients with glenohumeral osteoarthritis with a functioning rotator cuff. PURPOSE/HYPOTHESIS: The purposes of this study were to report the outcomes of TSA in patients with ipsilateral RCR and determine whether patients with a history of ipsilateral RCR who subsequently underwent TSA had differences in outcomes compared with matched controls who underwent TSA with no history of RCR. We hypothesized that patients with prior RCR will have significant improvements in clinical outcome scores, with no difference in outcomes after TSA compared with those with no prior RCR. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Patients eligible for inclusion were those with a history of prior RCR who underwent TSA at a single institution with a minimum 2-year follow-up between 2000 and 2015. Outcomes for this group, including American Shoulder and Elbow Surgeons (ASES) scores, were reported and then compared with a matched control group of patients who underwent TSA with no history of prior RCR. Controls were matched based on age, sex, and preoperative ASES score. RESULTS: Overall, 14 patients (64% males; mean ± SD age, 65.1 ± 11.1 years) underwent prior ipsilateral RCR before TSA. ASES scores significantly improved from 42.9 to 78.5 at 2 years and to 86.6 at 5 years. When compared with 42 matched control patients (matched 1:3) who underwent TSA with no history of RCR, there was no significant difference in ASES scores at 2 years (78.5 vs 85.3; P = .19) and 5 years (86.6 vs 90.9; P = .72) between the prior RCR and no RCR groups. CONCLUSION: TSA in patients with a history of prior ipsilateral RCR led to significant improvements in clinical outcomes. No difference in clinical outcomes at 2 or 5 years after TSA was found between patients with and without a history of prior ipsilateral RCR.

Characterization of version in the dysplastic hip and the need for subsequent femoral derotational osteotomy after periacetabular osteotomy.

Hip dysplasia is a three-dimensional pathomechanical condition that is often more complex than the standard method of measuring lateral center edge angle (CEA) can quantify. Yet there is a paucity of literature examining the differences in version seen between dysplastic and non-dysplastic femoroacetabular impingement (FAI) hips, the relationship of acetabular and femoral version (FV) within dysplastic hips and the contribution of each of these factors to symptoms and outcomes of dysplasia treatment. We sought to describe the acetabular version (AcetV) and FV in dysplastic hips and quantify how these measurements compared with non-dysplastic FAI hips. We also sought to analyze the association of these factors with patient-reported outcomes (PROs) after periacetabular osteotomy (PAO) and determine the need for subsequent femoral derotational osteotomy after PAO. A total of 113 dysplastic patients who underwent PAO (92% female, mean age 24) were compared with 1332 (45% female, mean age 25) non-dysplastic FAI (CEA > 25°) patients. We found that dysplastic hips had a statistically higher AcetV and FV than non-dysplastic FAI hips. There was a very weak correlation between AcetV and FV in dysplastic hips, suggesting that patients with higher AcetV did not necessarily have higher FV. There was no association with AcetV or FV and patient outcomes in our very limited analysis of PROs after PAO, and only 5% of patients with excessive FV (>20°) required subsequent femoral derotational osteotomy, suggesting that in a majority of patients with hip dysplasia, FV may not impact the post-operative clinical course.

Sarcopenia and Cardiac Dysfunction.

Although muscle loss is part of the natural course of human aging, sarcopenia has been associated with an increased risk of physical disability and mortality in older patients. Many heart failure patients concomitantly develop deficits in muscle mass and strength, resulting in decreased quality of life and exercise capacity. An underlying state of inflammation is central to the development of sarcopenia and muscle wasting in heart failure; however, additional research in human models is needed to further delineate the pathophysiology of muscle wasting in these patients. Previous studies have shed light on many of the potential targets for therapeutic intervention of sarcopenia in heart failure; however, physical exercise remains the prominent beneficial intervention. Future research must explore other therapeutic interventions in randomized, double-blind clinical trials, which may help to supplement exercise regimens. Sarcopenia shows promise as an easily measured predictor of outcomes after transcatheter aortic valve replacement.

Safety and tolerability of macitentan in the management of pulmonary arterial hypertension: an update.

Macitentan is a medication in the endothelin receptor antagonist class, approved for treatment of pulmonary arterial hypertension in 2013 based on the results of the pivotal SERAPHIN Trial (Study with an Endothelin Receptor Antagonist in Pulmonary arterial Hypertension to Improve cliNical outcome). Macitentan was shown in initial trials to reduce the likelihood of a morbidity/mortality event. Real-world use of this medication additionally reveals a reduced risk of hospitalizations related to pulmonary arterial hypertension, improved health-related quality of life scores, potential clinical utility in other conditions (such as chronic thromboembolic pulmonary hypertension and pulmonary hypertension related to congenital heart disease), and has a similar safety profile as demonstrated in initial trials.

PROMIS physical function underperforms psychometrically relative to American Shoulder and Elbow Surgeons score in patients undergoing anatomic total shoulder arthroplasty.

BACKGROUND: The purpose of this study was to evaluate the psychometric properties of the Patient-Reported Outcomes Measurement Information System (PROMIS) physical function computer adaptive test (PF-CAT) relative to the American Shoulder and Elbow Surgeons (ASES) score in patients with glenohumeral osteoarthritis undergoing primary anatomic total shoulder arthroplasty (TSA). METHODS: A retrospective study of an institutional TSA registry was performed. Preoperative PROMIS PF-CAT and ASES scores were collected. Floor and ceiling effects were determined, and convergent validity was established through Pearson correlations. Rasch partial credit modeling was used for psychometric analysis of the validity of PF-CAT and ASES question items. Person-item maps were generated to characterize the distribution of question responses along the latent dimension of shoulder disability. RESULTS: Responses from 179 patients (184 shoulders) were included. PF-CAT had a moderate correlation to ASES (r = 0.487; P < .001), with no floor or ceiling effects; ASES had a 1.1% floor effect and no ceiling effect. With iterative Rasch model item-reduction analysis eliminating poorly fitting question items, all possible PF-CAT items were eliminated after 6 iterations. With ASES, just 1 function question item was dropped. Person-item maps showed ASES to be superior to PROMIS PF-CAT psychometrically, with sequential and improved coverage of the latent dimension of shoulder disability. CONCLUSION: Despite moderate correlation with ASES, PROMIS PF-CAT demonstrated inferior validity and psychometric properties in patients undergoing TSA. PF-CAT should not replace the ASES in this population of patients.

The Shoulder Self-Administered Motion Evaluation Has Excellent Patient Reliability and Reproducibility on Both Physician and Repeat Follow-up Testing.

Long-term clinical evaluation is becoming more important, yet difficulties exist because there are substantial patient costs for extended follow-up. The goal of this study was to validate whether a new shoulder motion evaluation is reproducible and reliable with physician examination. Consecutive patients were administered a shoulder motion assessment during their clinic visit. Patients completed the same evaluation 2 weeks after their visit to determine test-retest reliability. Exact and approximate (within 20° or 4 spinal levels) agreements between patient and physician measurements were calculated. A total of 112 patients (224 shoulders) with an average age of 56.7 years were evaluated. The most common diagnoses were osteoarthritis (33.0%) and rotator cuff tear (32.1%). All motion questions had greater than 50% exact patient-physician agreement and greater than 70% approximate agreement. When agreement was off, patients more often underestimated their motion. There was substantial clinician-patient agreement for all questions and almost perfect agreement for forward elevation (intraclass correlation coefficient, 0.78) and internal rotation (intraclass correlation coefficient, 0.77). On test-retest reliability testing, patient-patient agreement was substantial for external rotation at the side (intraclass correlation coefficient, 0.71). There was near perfect agreement for internal rotation (intraclass correlation coefficient, 0.83) and abduction (intraclass correlation coefficient, 0.81) testing. This shoulder assessment tool had both good agreement to physician examination and substantial agreement on correlation testing. There was substantial agreement between follow-up visits, suggesting excellent reproducibility. This motion assessment shows effectiveness with most shoulder pathologies. It is recommended as a good screening tool for both clinical and research purposes requiring long-term follow-up in which in-person clinical examinations may be costly and time consuming. [Orthopedics. 2018; 41(6):e820-e826.].

Return to Play Among Elite Basketball Players After Osteochondral Allograft Transplantation of Full-Thickness Cartilage Lesions.

BACKGROUND: Osteochondral allograft transplantation (OCA) is a recognized option for full-thickness articular cartilage defects of the knee, especially in the setting of large lesions or those involving the subchondral bone. Previous heterogenous studies of athletes have shown a 75% to 79% rate of return to play after the procedure. PURPOSE: To define return-to-play rates in a cohort of elite collegiate and professional basketball players following osteochondral allograft of the knee. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Prospectively collected data from an institutional cartilage repair registry were retrospectively reviewed. Patients were eligible for inclusion if they were collegiate or professional basketball players at the time of surgery. Patient demographics, lesion size and location, and surgical details were collected. Postoperative magnetic resonance imaging scans were scored with the OCAMRISS system. Time to return to play and pre- versus postoperative player performance were determined with publicly available internet resources. RESULTS: Eleven athletes (4 professional, 7 collegiate) with a total of 14 treated lesions (1 to the medial femoral condyle, 6 to the lateral femoral condyle, 5 to the trochlea, and 2 to the patella) were eligible for study inclusion. Mean lesion size was 509 mm2. All patients underwent OCA through an arthrotomy, with fresh grafts. The overall rate of return to play at the same level of competition was 80%. Median time to return to play was 14 months (range, 6-26 months). Among players with available statistics, there was no significant reduction in any performance category. CONCLUSION: OCA in elite basketball players results in an 80% return to previous level of competition, which is consistent with previous reports of athletes playing other sports. Osteochondral allografting is a reasonable option to consider for full-thickness cartilage lesions of the knee, even for elite jumping athletes.

Return to Work After Anatomic Total Shoulder Arthroplasty for Patients 55 Years and Younger at Average 5-Year Follow-up.

As the number of anatomic total shoulder arthroplasties performed on younger patients continues to grow, return to work after surgery becomes increasingly important. The purpose of this study was to evaluate the ability of anatomic total shoulder arthroplasty to return patients 55 years or younger to work postoperatively. A retrospective review was performed of consecutive anatomic total shoulder arthroplasty patients. Inclusion criteria were age 55 years or younger at surgery, greater than 2 years of follow-up, and employment within 3 years of surgery. Employment was stratified by intensity of work (sedentary, light, moderate, or heavy). Return to work status and time out of work were also evaluated. Fifty-two patients worked before surgery. Average age was 48.4 years, with average follow-up of 5.4 years. Seventy-three percent were male, and average body mass index was 28.0 kg/m2. Average visual analog scale score improved from 5.5 to 0.9 (P<.0001) and American Shoulder and Elbow Society score improved from 39.9 to 88.3 (P<.0001). Forty-eight (92%) of 52 returned to work postoperatively after an average of 2.1 months. When stratified by intensity, all patients with sedentary, light, or moderate work returned, whereas 64% returned to heavy work (P<.01). Eighty-seven percent were satisfied to very satisfied after surgery. In summary, most patients (92%) who undergo anatomic total shoulder arthroplasty at 55 years or younger return to work, on average, 2.1 months after surgery. [Orthopedics. 2018; 41(3):e310-e315.].

Clinical Outcomes After Reverse Shoulder Arthroplasty With and Without Subscapularis Repair: The Importance of Considering Glenosphere Lateralization.

INTRODUCTION: Recent biomechanical data suggests that repairing the subscapularis during reverse shoulder arthroplasty (RSA) can increase the force required by the posterior rotator cuff and deltoid to elevate the arm. METHODS: We retrospectively studied patients who underwent primary RSA and had baseline and minimum 2-year postoperative American Shoulder and Elbow Surgeons (ASES) shoulder scores, stratified them according to subscapularis management, then subgrouped them according to lateralization of the glenosphere component. RESULTS: Patients with subscapularis repair and a lateralized glenosphere had significantly less improvement in ASES scores than did those without lateralization (P = 0.016) and patients without subscapularis repair (P = 0.006). Individually, subscapularis management (P = 0.163) and glenosphere lateralization (P = 0.847) had no significant effect on the change in ASES score but in combination did have a significant effect on the change in ASES score (P = 0.002). DISCUSSION: The combination of subscapularis repair and glenosphere implant lateralization in RSA translates to significantly less clinical improvement. CONCLUSIONS: Patients who underwent both subscapularis repair and glenosphere lateralization had significantly less improvement in ASES scores. LEVEL OF EVIDENCE: Level III.