Risk of severe coronavirus disease 2019 despite vaccination in patients requiring treatment with immune-suppressive drugs: A nationwide cohort study of US Veterans.

BACKGROUND: Patients taking immune-suppressive drugs are at increased risk of severe coronavirus disease 2019 (COVID-19), not fully ameliorated by vaccination. We assessed the contributions of clinical and demographic factors to the risk of severe disease despite vaccination in patients taking immune-suppressive medications for solid organ transplantation (SOT), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), or psoriasis. METHODS: Veterans Health Administration electronic health records were used to identify patients diagnosed with RA, IBD, psoriasis, or SOT who had been vaccinated against severe acute respiratory syndrome coronavirus 2, were subsequently infected, and had received immune-suppressive drugs within 3 months before infection. The association of severe (defined as hypoxemia, mechanical ventilation, dexamethasone use, or death) versus non-severe COVID-19 with the use of immune-suppressive and antiviral drugs and clinical covariates was assessed by multivariable logistic regression. RESULTS: Severe COVID-19 was more common in patients with SOT (230/1011, 22.7%) than RA (173/1355, 12.8%), IBD (51/742, 6.9%), or psoriasis (82/1125, 7.3%). Age was strongly associated with severe COVID-19, adjusted odds ratio (aOR) of 1.04 (CI 1.03-1.05) per year. Comorbidities indicating chronic brain, heart, lung, or kidney damage were also associated with severity, aOR 1.35-2.38. The use of glucocorticoids was associated with increased risk (aOR 1.66, CI 1.39-2.18). Treatment with antivirals was associated with reduced severity, for example, aOR 0.28 (CI 0.13-0.62) for nirmatrelvir/ritonavir. CONCLUSION: The risk of severe COVID-19 despite vaccination is substantial in patients taking immune-suppressive drugs, more so in patients with SOT than in patients with inflammatory diseases. Age and severe comorbidities contribute to risk, as in the general population. Oral antivirals were very beneficial but not widely used.

Maintaining the Utility of Coronavirus Disease 2019 Pandemic Severity Surveillance: Evaluation of Trends in Attributable Deaths and Development and Validation of a Measurement Tool.

BACKGROUND: Death within a specified time window following a positive SARS-CoV-2 test is used by some agencies for attributing death to COVID-19. With Omicron variants, widespread immunity, and asymptomatic screening, there is cause to re-evaluate COVID-19 death attribution methods and develop tools to improve case ascertainment. METHODS: All patients who died following microbiologically confirmed SARS-CoV-2 in the Veterans Health Administration (VA) and at Tufts Medical Center (TMC) were identified. Records of selected vaccinated VA patients with positive tests in 2022, and of all TMC patients with positive tests in 2021-2022, were manually reviewed to classify deaths as COVID-19-related (either directly caused by or contributed to), focused on deaths within 30 days. Logistic regression was used to develop and validate a surveillance model for identifying deaths in which COVID-19 was causal or contributory. RESULTS: Among vaccinated VA patients who died ≤30 days after a positive test in January-February 2022, death was COVID-19-related in 103/150 cases (69%) (55% causal, 14% contributory). In June-August 2022, death was COVID-19-related in 70/150 cases (47%) (22% causal, 25% contributory). Similar results were seen among the 71 patients who died at TMC. A model including hypoxemia, remdesivir, and anti-inflammatory drugs had positive and negative predictive values of 0.82-0.95 and 0.64-0.83, respectively. CONCLUSIONS: By mid-2022, "death within 30 days" did not provide an accurate estimate of COVID-19-related death in 2 US healthcare systems with routine admission screening. Hypoxemia and use of antiviral and anti-inflammatory drugs-variables feasible for reporting to public health agencies-would improve classification of death as COVID-19-related.

The V-shaped subscapularis tenotomy for anatomic total shoulder arthroplasty.

PURPOSE: Management of the subscapularis tendon during anatomic total shoulder arthroplasty (TSA) remains controversial. In our unit, subscapularis tenotomy is the preferred technique; however, the potential for tendon gapping and failure is recognised. The purpose of this study is to describe and provide early clinical results of a novel, laterally based V-shaped tenotomy (VT) technique hypothesised to provide greater initial repair strength and resistance to gapping than a transverse tenotomy (TT), with both clinically and radiologically satisfactory post-operative tendon healing and function. METHODS: A retrospective study of patients who underwent primary TSA with VT over a three year period was performed using shoulder and subscapularis-specific outcome scores, radiographs, and ultrasound. A separate cohort of patients who underwent TSA using a subscapularis sparing approach was also reviewed to provide comparative clinical outcomes of a group with TSA and an un-violated subscapularis. RESULTS: Eighteen patients were reviewed at mean 30.4 months (± 11.7). Constant (78.2 ± 12.3), UCLA (8.4 ± 1.5), pain VAS (2.3 ± 2.8), and strength in internal rotation were no different from the comparison group. Likewise, neither were the clinical outcomes of range-of-motion, belly-press, lift-off, and shirt-tuck tests. One patient (5.5%) was found to have a failed subscapularis repair on ultrasound. CONCLUSION: VT during TSA appears to provide healing rates at least equal to those reported for TT, and not dissimilar from those of lesser tuberosity osteotomy. Clinical outcomes are comparable to reported results in the literature for alternative techniques, and not different from those observed here in a comparison cohort with TSA performed without violating the subscapularis tendon. VT therefore potentially offers a more effective and secure tendon repair than a traditional TT, with at least comparable clinical outcomes.

Can Surgical Trainees Achieve Arthroscopic Competence at the End of Training Programs? A Cross-sectional Study Highlighting the Impact of Working Time Directives.

PURPOSE: To provide training guidance on procedure numbers by assessing how the number of previously performed arthroscopic procedures relate to both competent and expert performance in simulated arthroscopic shoulder tasks. METHODS: A cross-sectional study that assessed simulated shoulder arthroscopic performance was undertaken. A total of 45 participants of varying experience performed 2 validated tasks: a simple diagnostic task and a more complex Bankart labral repair task. All participants provided logbook numbers for previously performed arthroscopies. Performance was assessed with the Global Rating Scale and motion analysis. Receiver operating characteristic curve analyses were conducted to identify optimum cut points for task proficiency at both "competent" and "expert" levels. RESULTS: Increasing surgical experience resulted in significantly better performance for both tasks as assessed by Global Rating Scale or motion analysis (P < .0001). Receiver operating characteristic curve analyses demonstrated 52 previous arthroscopies were needed to perform to a competent level at the diagnostic task and 248 to be competent at the complex task. To perform at an expert level, 290 and 476 previous arthroscopies, respectively, were needed. CONCLUSIONS: This study provides quantified guidance for arthroscopic training and highlights the positive relationship between arthroscopic case load and arthroscopic competency. We have estimated that the number of arthroscopies required to achieve competency in a basic arthroscopic task exceed those recommended in some countries. These estimates provide useful guidance to those responsible for training program. CLINICAL RELEVANCE: The numbers to achieve competent arthroscopic performance in the assessed simulated tasks exceed what is recommended and what is possible during surgical training programs in some countries.

Severe COVID-19 in Vaccinated Adults With Hematologic Cancers in the Veterans Health Administration.

Importance: With SARS-CoV-2 transforming into an endemic disease and with antiviral treatments available, it is important to establish which patients remain at risk of severe COVID-19 despite vaccination. Objective: To quantify the associations of clinical and demographic variables with odds of severe COVID-19 among patients with hematologic cancers. Design, Setting, and Participants: This case-control study included all patients with hematologic malignant neoplasms in the national Veterans Health Administration (VHA) who had documented SARS-CoV-2 infection after vaccination. Groups of patients with severe (cases) vs nonsevere (controls) COVID-19 were compared. Data were collected between January 1, 2020, and April 5, 2023, with data on infection collected between January 1, 2021, and September 30, 2022. All patients with diagnostic codes for hematologic malignant neoplasms who had documented vaccination followed by documented SARS-CoV-2 infection and for whom disease severity could be assessed were included. Data were analyzed from July 28 to December 30, 2023. Exposures: Clinical (comorbidities, predominant viral variant, treatment for malignant neoplasm, booster vaccination, and antiviral treatment) and demographic (age and sex) variables shown in prior studies to be associated with higher or lower rates of severe COVID-19. Comorbidities included Alzheimer disease or dementia, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, heart failure, and peripheral vascular disease. Main Outcome and Measures: The main outcome was severe COVID-19 compared with nonsevere SARS-CoV-2 infection. Severe COVID-19 was defined as death within 28 days, mechanical ventilation, or hospitalization with use of dexamethasone or evidence of hypoxemia or use of supplemental oxygen. Multivariable logistic regression was used to estimate the associations of demographic and clinical variables with the odds of severe COVID-19, expressed as adjusted odds ratios (aORs) with 95% CIs. Results: Among 6122 patients (5844 [95.5%] male, mean [SD] age, 70.89 [11.57] years), 1301 (21.3%) had severe COVID-19. Age (aOR per 1-year increase, 1.05; 95% CI, 1.04-1.06), treatment with antineoplastic or immune-suppressive drugs (eg, in combination with glucocorticoids: aOR, 2.32; 95% CI, 1.93-2.80), and comorbidities (aOR per comorbidity, 1.35; 95% CI, 1.29-1.43) were associated with higher odds of severe disease, whereas booster vaccination was associated with lower odds (aOR, 0.73; 95% CI, 0.62-0.86). After oral antiviral drugs became widely used in March 2022, 20 of 538 patients (3.7%) with SARS-CoV-2 infection during this period had progression to severe COVID-19. Conclusions and Relevance: In this case-control study of patients with hematologic cancers, odds of severe COVID-19 remained high through mid-2022 despite vaccination, especially in patients requiring treatment.

Matching Patients to Accelerate Clinical Trials (MPACT): Enabling Technology for Oncology Clinical Trial Workflow.

Clinical trial enrollment is impeded by the significant time burden placed on research coordinators screening eligible patients. With 50,000 new cancer cases every year, the Veterans Health Administration (VHA) has made increased access for Veterans to high-quality clinical trials a priority. To aid in this effort, we worked with research coordinators to build the MPACT (Matching Patients to Accelerate Clinical Trials) platform with a goal of improving efficiency in the screening process. MPACT supports both a trial prescreening workflow and a screening workflow, employing Natural Language Processing and Data Science methods to produce reliable phenotypes of trial eligibility criteria. MPACT also has a functionality to track a patient's eligibility status over time. Qualitative feedback has been promising with users reporting a reduction in time spent on identifying eligible patients.

Factors Associated With Severe COVID-19 Among Vaccinated Adults Treated in US Veterans Affairs Hospitals.

Importance: With a large proportion of the US adult population vaccinated against SARS-CoV-2, it is important to identify who remains at risk of severe infection despite vaccination. Objective: To characterize risk factors for severe COVID-19 disease in a vaccinated population. Design, Setting, and Participants: This nationwide, retrospective cohort study included US veterans who received a SARS-CoV-2 vaccination series and later developed laboratory-confirmed SARS-CoV-2 infection and were treated at US Department of Veterans Affairs (VA) hospitals. Data were collected from December 15, 2020, through February 28, 2022. Exposures: Demographic characteristics, comorbidities, immunocompromised status, and vaccination-related variables. Main Outcomes and Measures: Development of severe vs nonsevere SARS-CoV-2 infection. Severe disease was defined as hospitalization within 14 days of a positive SARS-CoV-2 diagnostic test and either blood oxygen level of less than 94%, receipt of supplemental oxygen or dexamethasone, mechanical ventilation, or death within 28 days. Association between severe disease and exposures was estimated using logistic regression models. Results: Among 110 760 patients with infections following vaccination (97 614 [88.1%] men, mean [SD] age at vaccination, 60.8 [15.3] years; 26 953 [24.3%] Black, 11 259 [10.2%] Hispanic, and 71 665 [64.7%] White), 10 612 (9.6%) had severe COVID-19. The strongest association with risk of severe disease after vaccination was age, which increased among patients aged 50 years or older with an adjusted odds ratio (aOR) of 1.42 (CI, 1.40-1.44) per 5-year increase in age, such that patients aged 80 years or older had an aOR of 16.58 (CI, 13.49-20.37) relative to patients aged 45 to 50 years. Immunocompromising conditions, including receipt of different classes of immunosuppressive medications (eg, leukocyte inhibitor: aOR, 2.80; 95% CI, 2.39-3.28) or cytotoxic chemotherapy (aOR, 2.71; CI, 2.27-3.24) prior to breakthrough infection, or leukemias or lymphomas (aOR, 1.87; CI, 1.61-2.17) and chronic conditions associated with end-organ disease, such as heart failure (aOR, 1.74; CI, 1.61-1.88), dementia (aOR, 2.01; CI, 1.83-2.20), and chronic kidney disease (aOR, 1.59; CI, 1.49-1.69), were also associated with increased risk. Receipt of an additional (ie, booster) dose of vaccine was associated with reduced odds of severe disease (aOR, 0.50; CI, 0.44-0.57). Conclusions and Relevance: In this nationwide, retrospective cohort of predominantly male US Veterans, we identified risk factors associated with severe disease despite vaccination. Findings could be used to inform outreach efforts for booster vaccinations and to inform clinical decision-making about patients most likely to benefit from preexposure prophylaxis and antiviral therapy.

A Mouse Model to Investigate the Role of Cancer-associated Fibroblasts in Tumor Growth.

Cancer-associated fibroblasts (CAFs) can play an important role in tumor growth by creating a tumor-promoting microenvironment. Models to study the role of CAFs in the tumor microenvironment can be helpful for understanding the functional importance of fibroblasts, fibroblasts from different tissues, and specific genetic factors in fibroblasts. Mouse models are essential for understanding the contributors to tumor growth and progression in an in vivo context. Here, a protocol in which cancer cells are mixed with fibroblasts and introduced into mice to develop tumors is provided. Tumor sizes over time and final tumor weights are determined and compared among groups. The protocol described can provide more insight into the functional role of CAFs in tumor growth and progression.

Early computerized tomography accurately determines the presence or absence of scaphoid and other fractures.

OBJECTIVE: To validate the use of early CT in predicting scaphoid fracture and other fractures in patients with suspected scaphoid fracture. METHOD: A prospective observational study of adult patients with a diagnosis of clinical scaphoid fracture presenting to a regional ED. Patients were immobilized in a scaphoid plaster and had a CT (wrist and carpals) same or next day. The gold standard used was the diagnosis on Day 10 with clinical examination and X-rays, with MRI performed in patients with persistent tenderness but normal X-rays. RESULTS: Forty-seven patients completed the study protocol from September 2004 until February 2006. For all fractures, early CT had a 96.8% negative predictive value and 100% positive predictive value (94.4% sensitive, 100% specific). No scaphoid fracture was missed by early CT. One patient had a trapezium fracture on CT, with a coexistent subtle capitate fracture only detected on MRI. CONCLUSION: Early CT scans show promise in the diagnosis of scaphoid and other fractures of the wrist and carpals. Further study is warranted to validate early CT in clinical scaphoid fracture as an alternative to other early advanced imaging, or plaster immobilization and 2 week review.

Complications of posterolateral corner injuries of the knee and how to avoid them.

Knee dislocations and in particular posterolateral corner injuries to the knee are severe injuries demanding an organized approach and technically challenging surgery. Complications include unrecognized vascular or neurological injury and failure to reconstruct appropriately. During reconstruction, performing an inappropriate operation (failure to recognize malalignment) or technical error with tunnel or hardware placement can lead to delayed problems. Wound infection and wound breakdown is common as in arthrofibrosis often from overconstraint of the knee. Attention to principles and expertise in technique can minimize these complications.