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.

Higher critical shoulder angle increases the risk of retear after rotator cuff repair.

BACKGROUND: No evaluation has been done on the relationship of the critical shoulder angle (CSA) with retear after rotator cuff repair. Our purpose was to evaluate whether a higher CSA is associated with retear after rotator cuff repair. METHODS: This was a retrospective review of 76 patients who had undergone rotator cuff repair with postoperative ultrasound examination. Ultrasound findings were graded no retear (NT), partial-thickness (PT) retear, or full-thickness (FT) retear. Preoperative radiographs were used to measure CSA, glenoid inclination, lateral acromion angle, and acromion index. RESULTS: Average age was 61.9 years (45.3-74.9 years). On ultrasound examination, 57 shoulders (74.0%) had NT, 11 (14.2%) had PT retears, and 8 (10.3%) had FT retears. There was no significant difference in retear rate by age, gender, or tension of repair. Average CSA was significantly lower for the NT group at 34.3° ± 2.9° than for the FT group at 38.6° ± 3.5° (P < .01). If CSA was >38°, the odds ratio of having an FT retear was 14.8 (P < .01). In addition, higher CSA inversely correlated with postoperative American Shoulder and Elbow Surgeons scores (P < .03). Average glenoid inclination was significantly lower in the NT group at 12.3° ± 2.7° compared with 17.3° ± 2.6° in the FT group (P < .01). If glenoid inclination was >14, the odds ratio of having a FT retear was 15.0 (P < .01). CONCLUSION: At short-term follow-up, higher CSA significantly increased the risk of an FT retear after rotator cuff repair. Also, increasing CSA correlated with worse postoperative American Shoulder and Elbow Surgeons scores. This radiographic marker may help manage expectations for rotator cuff tear patients.

Hyperlipidemia increases the risk of retear after arthroscopic rotator cuff repair.

BACKGROUND: Hyperlipidemia (HL) has been identified as a risk factor for rotator cuff tear, but no studies have evaluated its effects on healing. The purpose of this study was to evaluate the effect of HL and statin use on rotator cuff healing after arthroscopic repair. METHODS: This was a retrospective review of 85 patients (86 shoulders) who underwent arthroscopic rotator cuff repair with postoperative ultrasound evaluation. Ultrasound findings were graded no retear, partial-thickness retear (PT), or full-thickness retear (FT). RESULTS: Average age was 62.1 years (45.3-74.3 years). On ultrasound evaluation, 65 shoulders (75.5%) had no retear, 14 (16.3%) had PT, and 7 (8.1%) had FT. There was no significant difference in retear rate by age, technique, or tissue quality. There were 33 patients (38.8%) who had the diagnosis of HL, and all were taking a statin medication. Compared with patients without HL, patients with HL had significantly higher rates of FT (18.1% vs. 1.9%; P < .001) and PT (27.2% vs. 9.4%; P < .001). The total retear rate (PT and FT) for HL patients was significantly higher at 45.5% (15/33) compared with the patients without HL at 11.3% (6/53), with an odds ratio of 6.5 (P < .001). There was no difference in retear rate by dosage or type of statin mediation. CONCLUSION: After arthroscopic rotator cuff repair, HL was a risk factor for retear. Further investigation is warranted on this topic, and these results may help in managing expectations after surgery.

Causes of poor postoperative improvement after reverse total shoulder arthroplasty.

BACKGROUND: Although reverse total shoulder arthroplasty (RTSA) has been successful in improving pain and function in most patients, some patients fail to improve clinically. The present study used a large registry of RTSA patients to evaluate associations between patient-related factors and poor postoperative improvement after RTSA. MATERIALS AND METHODS: A prospectively collected shoulder arthroplasty registry was queried for consecutive patients who underwent RTSA from 2007 to 2013. Patients with baseline and minimum 2-year postoperative American Shoulder and Elbow Surgeons (ASES) scores were included. Poor postoperative improvement was defined as a change in the ASES of less than 12 points. Multivariate logistic regression analysis was used to identify independent risk factors. RESULTS: A total of 150 patients met inclusion and exclusion criteria. Logistic regression revealed that male sex (adjusted odds ratio [OR], 7.9; P = .004), presence of an intact rotator cuff at the time of surgery (adjusted OR, 4.8; P = .025), depression (adjusted OR, 11.2; P = .005), a higher baseline ASES score (P < .001), and higher total number of medical comorbidities (P = .035) were associated with poor postoperative improvement after RTSA. CONCLUSIONS: Surrogates for better preoperative function after RTSA, such as a higher baseline ASES score and intact rotator cuff at the time of surgery, correlated with poor postoperative improvement. In addition, male sex, depression, and total number of medical comorbidities also correlated with poor postoperative improvement. Interestingly, factors such as patient age and indication for surgery were not found to correlate with poor improvement after RTSA.

Exploring Predictive and Prognostic Biomarkers in Colorectal Cancer: A Comprehensive Review.

Colorectal cancer (CRC) remains the second leading cause of cancer-related mortality worldwide. While immune checkpoint inhibitors have significantly improved patient outcomes, their effectiveness is mostly limited to tumors with microsatellite instability (MSI-H/dMMR) or an increased tumor mutational burden, which comprise 10% of cases. Advancing personalized medicine in CRC hinges on identifying predictive biomarkers to guide treatment decisions. This comprehensive review examines established tissue markers such as KRAS and HER2, highlighting their roles in resistance to anti-EGFR agents and discussing advances in targeted therapies for these markers. Additionally, this review summarizes encouraging data on promising therapeutic targets and highlights the clinical utility of liquid biopsies. By synthesizing current evidence and identifying knowledge gaps, this review provides clinicians and researchers with a contemporary understanding of the biomarker landscape in CRC. Finally, the review examines future directions and challenges in translating promising biomarkers into clinical practice, with the goal of enhancing personalized medicine approaches for colorectal cancer patients.

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.

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.

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.

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.

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.

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.

A novel bacterium associated with lymphadenitis in a patient with chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a rare inherited disease of the phagocyte NADPH oxidase system causing defective production of toxic oxygen metabolites, impaired bacterial and fungal killing, and recurrent life-threatening infections. We identified a novel gram-negative rod in excised lymph nodes from a patient with CGD. Gram-negative rods grew on charcoal-yeast extract, but conventional tests could not identify it. The best 50 matches of the 16S rRNA (using BLAST) were all members of the family Acetobacteraceae, with the closest match being Gluconobacter sacchari. Patient serum showed specific band recognition in whole lysate immunoblot. We used mouse models of CGD to determine whether this organism was a genuine CGD pathogen. Intraperitoneal injection of gp91(phox -/-) (X-linked) and p47 (phox -/-) (autosomal recessive) mice with this bacterium led to larger burdens of organism recovered from knockout compared with wild-type mice. Knockout mouse lymph nodes had histopathology that was similar to that seen in our patient. We recovered organisms with 16S rRNA sequence identical to the patient's original isolate from the infected mice. We identified a novel gram-negative rod from a patient with CGD. To confirm its pathogenicity, we demonstrated specific immune reaction by high titer antibody, showed that it was able to cause similar disease when introduced into CGD, but not wild-type mice, and we recovered the same organism from pathologic lesions in these mice. Therefore, we have fulfilled Koch's postulates for a new pathogen. This is the first reported case of invasive human disease caused by any of the Acetobacteraceae. Polyphasic taxonomic analysis shows this organism to be a new genus and species for which we propose the name Granulobacter bethesdensis.

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.