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Neonatal brachial plexus injuries may cause critical limitations of upper extremity function. The optimal surgical approach to address neonatal brachial plexus injuries has not been defined. In this systematic review, we compare clinical results after spinal accessory to suprascapular nerve transfer and nerve graft techniques among patients with neonatal brachial plexus injury. [ Orthopedics . 2022;45(1):7–12.]

Extensor carpi ulnaris tendon subluxation can be a challenging diagnosis as a cause of wrist pain. The tendon is stabilized by a tough subsheath. This subsheath is vulnerable to tears in acute wrist movements, especially those combining supination, flexion, and ulnar deviation. The patient presenting acutely may experience swelling, tenderness, and pain. In a chronic setting, the complaint is often an unstable wrist. The diagnosis can be made with a thorough examination, and ultrasonography can be used to evaluate the dynamics of the tendon. Surgical repair with a flap of extensor retinaculum to re-create the tendon's stabilizing subsheath is recommended.

Purpose To determine whether functional vision and visual function improvements after voretigene neparvovec (VN; Luxturna [Spark Therapeutics, Inc]) administration in patients with biallelic RPE65 mutation-associated inherited retinal disease are maintained at 3 to 4 years and to review safety outcomes. Design Open-label, randomized, controlled phase 3 trial. Participants Thirty-one individuals were enrolled and randomized 2:1 to intervention (n = 21) or control (n = 10). One participant from each group withdrew before, or at, randomization. Methods Patients in the original intervention (OI) group received bilateral subretinal VN injections. Delayed intervention (DI) patients served as control participants for 1 year then received VN. Main Outcome Measures Change from injection baseline in bilateral performance on the multiluminance mobility test (MLMT), a measure of ambulatory navigation, and change from injection baseline in full-field light sensitivity threshold white light, visual field (VF), and visual acuity (VA). Results Mean bilateral MLMT change scores at year 4 for OI patients and year 3 for DI patients were 1.7 and 2.4, respectively, with 71% of patients with a year 3 visit able to pass MLMT at the lowest light level. Mean change in full-field light sensitivity threshold white light, averaged over both eyes at year 4 for OI patients and year 3 for DI patients, was −1.90 log10(cd.s/m2) and −2.91 log10(cd.s/m2), respectively. Mean change in Goldmann kinetic VF III4e sum total degrees, averaged across both eyes, was 197.7 at year 4 for OI patients and 157.9 at year 3 for DI patients. Mean change in VA (Holladay scale), averaged across both eyes, was –0.003 logarithm of the minimum angle of resolution (logMAR) at year 4 for OI patients and −0.06 logMAR at year 3 for DI patients. One OI patient experienced retinal detachment at approximately year 4 that impacted VA for the OI group. No product-related serious adverse events (AEs) occurred, nor did any deleterious immune responses. Conclusions Improvements in ambulatory navigation, light sensitivity, and VF were consistent in both intervention groups. Overall, improvements were maintained up to 3 to 4 years, with ongoing observation. The safety profile of VN was consistent with vitrectomy and the subretinal injection procedure and was similar between intervention groups, with no product-related serious AEs reported.

BACKGROUND: Gastrointestinal dysfunction is a frequent and disabling manifestation of autoimmune polyendocrine syndrome type 1 (APS-1), a rare monogenic multi-organ autoimmune disease caused by the loss of central AIRE-controlled immune tolerance. OBJECTIVE: We aimed to understand the role of the gut microbiome in APS-1 symptoms and potentially alleviate common gastrointestinal symptoms by probiotic intervention. METHODS: We characterized the fecal microbiomes of 28 APS-1 patients and searched for associations with gastrointestinal symptoms, circulating anti-cytokine autoantibodies and tryptophan-related metabolites. We additionally administered daily doses of the probiotic Lactobacillus rhamnosus GG for three months. RESULTS: Of 581 metagenomic operational taxonomic units (mOTUs) characterized in total, 14 were significantly associated with APS-1 compared to healthy controls, with six mOTUs depleted and eight enriched in APS-1 patients. Four overabundant mOTUs were significantly associated with severity of constipation. We observed phylogenetically conserved microbial associations with autoantibodies against cytokines. After the three-month intervention with the probiotic L. rhamnosus GG, a subset of gastrointestinal symptoms were alleviated. L. rhamnosus GG abundance was increased post-intervention and corresponded with decreased abundances of Alistipes onderdonkii and Collinsella aerofaciens, two species positively associated with severity of diarrhea in APS-1 patients. CONCLUSION: The APS-1 microbiome correlates with several APS-1 symptoms, some of which are alleviated after a three-month L. rhamnosus GG intervention. Autoantibodies against cytokines appear to shape the gut microbiome by positively correlating with a taxonomically consistent group of bacteria. CLINICAL IMPLICATIONS: Administration of L. rhamnosus GG appears to alleviate certain gastrointestinal symptoms of APS-1.

Background Multi-cancer early detection (MCED) next-generation-sequencing blood tests represent a potential paradigm shift in screening. Methods We estimated the impact of screening in the US and UK. We used country-specific parameters for uptake, and test-specific sensitivity and false-positive rates for current screening: breast, colorectal, cervical and lung (US only) cancers. For the MCED test, we used cancer-specific sensitivities by stage. Outcomes included the true-positive:false-positive (TP:FP) ratio; and the cost of diagnostic investigations among screen positives, per cancer detected (Diagcost). Outcomes were estimated for recommended screening only, and then when giving the MCED test to anyone without cancer detected by current screening plus similarly aged adults ineligible for recommended screening. Results In the US, current screening detects an estimated 189,498 breast, cervical, colorectal and lung cancers. An MCED test with 25–100% uptake detects an additional 105,526–422,105 cancers (multiple types). The estimated TP:FP (Diagcost) was 1.43 ($89,042) with current screening but only 1:1.8 ($7060) using an MCED test. For the UK the corresponding estimates were 1:18 (£10,452) for current screening, and 1:1.6 (£2175) using an MCED test. Conclusions Adding an MCED blood test to recommended screening can potentially be an efficient strategy. Ongoing randomised studies are required for full efficacy and cost-effectiveness evaluations.

With the development of newer techniques for symptomatic neuroma treatment, such as regenerative peripheral nerve interface and targeted muscle reinnervation, transposition and coverage techniques often have been referred to as "passive techniques." In spite of its negative connotation, these passive techniques yield positive results in a majority of patients treated. The experienced surgeon has more options than ever before in the prevention and management of problematic neuromas. Critical appraisal of the current literature reveals no single, optimal standard of care. Instead, surgeons have a plethora of useful techniques that can be implemented on a case-by-case basis to optimize outcomes.

Introduction Geographic access to novel oncology therapies, and the extent to which it may vary by potential sites of care, regions, and population characteristics, is poorly understood. We examined how expanding access to chimeric antigen receptor (CAR) T cell therapy administration sites impacts patient travel distances and time. Methods We used geographic information system techniques to calculate shortest travel distance and time between patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) and the nearest CAR T cell therapy administration site in three scenarios: academic hospitals; academic and community multispecialty hospitals; and academic and community multispecialty hospitals plus nonacademic specialty oncology network centers. Main outcome measures were differences in travel distance and time among the scenarios and the relationship between travel time and socioeconomic status, race, rural–urban areas, and non-Hodgkin lymphoma clusters. Non-Hodgkin lymphoma incidence, socioeconomic status, and administration centers were derived from governmental/publicly available data sources. Results Of 3922 patients eligible for CAR T cell therapy, more than 37% had to travel more than 1 h to the nearest academic hospital. Average travel time and distance were significantly reduced by 23% and 30% (P

Repetitive stress on the lumbosacral spine during sporting activity places the athletic patient at risk of developing symptomatic pars defect. Clinical history, physical examination, and diagnostic imaging are important to distinguish spondylolysis from other causes of lower back pain. Early pars stress reaction can be identified with advanced imaging, before the development of cortical fracture or vertebral slip progression to spondylolisthesis. Conservative management is first-line for low-grade injury with surgical intervention indicated for refractory symptoms, severe spondylolisthesis, or considerable neurologic deficit. Prompt diagnosis and management of spondylolysis leads to good outcomes and return to competition for most athletes.

Objectives Cancer diagnoses at later stages are associated with a decrease in health-related quality of life (HRQOL). Health state utility values (HSUVs) reflect preference-based HRQOL and can vary based on cancer type, stage, treatment, and disease progression. Detecting and treating cancer at earlier stages may lead to improved HRQOL, which is important for value assessments. We describe published HSUVs by cancer type and stage. Methods A systematic review was conducted using Embase, MEDLINE®, EconLit, and gray literature to identify studies published from January 1999 to September 2019 that reported HSUVs by cancer type and stage. Disutility values were calculated from differences in reported HSUVs across cancer stages. Results From 13,872 publications, 27 were eligible for evidence synthesis. The most frequent cancer types were breast (n = 9), lung (n = 5), colorectal (n = 4), and cervical cancer (n = 3). Mean HSUVs decreased with increased cancer stage, with consistently lower values seen in stage IV or later-stage cancer across studies (e.g., − 0.74, − 0.44, and − 0.51 for breast, colorectal, and cervical cancer, respectively). Disutility values were highest between later-stage (metastatic or stage IV) cancers compared to earlier-stage (localized or stage I–III) cancers. Conclusions This study provides a summary of HSUVs across different cancer types and stages that can inform economic evaluations. Despite the large variation in HSUVs overall, a consistent decline in HSUVs can be seen in the later stages, including stage IV. These findings indicate substantial impairment on individuals’ quality of life and suggest value in early detection and intervention.

Background Opioids are commonly prescribed for postoperative pain following total joint arthroplasty. Despite widespread use, few studies have examined the dose-dependent effect of perioperative opioid use on postoperative complications following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Therefore, we examined the dose-dependent relationship between opioid use and postoperative complications following primary THA and TKA. Methods We queried the Premier Healthcare Database to identify adult patients who underwent primary elective THA or TKA from 2004 to 2014, and quantified opioid consumption within the first 3 postoperative days. Opioid consumption was standardized to morphine milligram equivalents (MMEs). Patients were divided into quintiles on the basis of MME exposure: 172 MMEs. Primary outcomes included postoperative periprosthetic joint infection, pulmonary embolism, deep venous thrombosis, and pulmonary complications. Secondary outcomes included wound infection, wound dehiscence, and readmission within 30 and 90 days postoperatively. Univariate and multivariate analyses were performed to compare differences between groups and to account for confounders. Results A total of 1,525,985 patients were identified. The mean age was 65.7 ± 10.8 years, 598,320 patients (39.2%) were male, and 1,174,314 patients (77.0%) were Caucasian. On multiple logistic regression analysis, increasing MME exposure was associated with a dose-dependent increased risk of postoperative complications. Compared with patients receiving 172 MMEs was associated with greater odds of periprosthetic joint infection (adjusted odds ratio [aOR], 1.37; 95% confidence interval [CI], 1.33 to 1.42), deep venous thromboembolism (aOR, 1.34; 95% CI, 1.30 to 1.38), pulmonary embolism (aOR, 1.29; 95% CI, 1.25 to 1.34), and pulmonary complications (aOR, 1.06; 95% CI, 1.05 to 1.08). Exposure to >172 MMEs was associated with increased risk of wound infection (aOR, 1.37; 95% CI, 1.33 to 1.41), wound dehiscence (aOR, 1.24; 95% CI, 1.19 to 1.31), and readmission within 30 (aOR, 1.21; 95% CI, 1.20 to 1.22) and 90 days (aOR, 1.20; 95% CI, 1.19 to 1.21). Conclusions Increasing opioid use within the early postoperative period following THA or TKA was associated with a dose-dependent increased risk of periprosthetic joint infection and venous thromboembolic events. Level of evidence Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Background IgG4-related disease (IgG4-RD) is an immune-mediated disease that may present as a tumefactive lesion in nearly any organ. These mass lesions often resemble malignancy both clinically and radiologically, and some patients undergo surgical resection which could possibly be avoided with early recognition of IgG4-RD. We performed a retrospective single-center study examining how many patients with IgG4-RD were initially believed to have malignancy, with particular attention to those who underwent potentially avoidable surgical procedures. Methods Sixty-three patients with biopsy confirmed IgG4-related disease were included. Clinical, laboratory, radiological, and histological data were collected and analyzed. Results Over 60% of patients (38/63) were initially thought to have a malignancy when they initially presented with symptomatic IgG4-RD. The most common types of malignancy suspected were lymphoma (18/38) and pancreatic cancer (11/38). Of the 38 patients with suspected malignancy, 14 underwent an invasive intervention either to alleviate the severity of their symptoms or as treatment for their presumed malignancy. These included Whipple resection/attempted Whipple (3), nephrectomy (3), bile duct resection and reconstruction (1), removal of other abdominal/retroperitoneal masses (3), and stenting of obstructed organs (4). Conclusion IgG4-RD should be on the differential diagnosis of patients with mass lesions, in particular those with pancreatic masses and obstructive jaundice, extensive lymphadenopathy, or retroperitoneal masses. Oncologists and other physicians involved in cancer care should be aware of the various manifestations and diagnostic approach to IgG4-RD in order to provide accurate diagnosis and minimize unnecessary invasive procedures. While some procedures in this study, such as stenting of obstructed organs, were required regardless of diagnosis, others could have potentially been avoided or attenuated with early recognition of IgG4-RD. Patients with mass lesions suspicious for IgG4-RD should have serum protein electrophoresis, IgG subclass measurement, and, where possible, tissue biopsy before undergoing major surgical resection. Consultation with a physician experienced in IgG4-RD is recommended.

Surgical registries have provided reliable, generalizable, and applicable clinical data that have shaped many fields. Broad collection of defined data can answer clinical questions with greater numbers of patients and more ability to generalize to routine clinical care than randomized trials. National hand surgical registries exist outside the United States. Before the pursuit of a registry, the focus of such an effort must be defined to ensure that registry goals are feasible. This article presents the consensus process conducted by the American Society for Surgery of the Hand's Registry Task Force exploring potential diagnoses for a hand registry.

SUMMARY The ambiguity of medical finances, both to the patient and to the provider, has direct effects on the quality of care that is delivered to the patient. To encourage transparency in health care, physician reimbursement is a process that must be understood to ensure patient satisfaction, a physician's willingness to deliver care, and the success of health care facilities. Furthermore, physicians should be aware of the effects that legislative action, such as the Patient Protection and Affordable Care Act, has on their income. As a field that encompasses both cosmetic and reconstructive surgery, plastic surgeons must know this process intimately to ensure efficient services and appropriate reimbursement. In particular, plastic surgeons should be familiar with how the Affordable Care Act affects their income, practice, and the patient's access to care. As Medicare and Medicaid continue to increase health care access for many Americans, specialists such as plastic surgeons will need to reinforce the value of the specialty in the continuum of care. As the health care industry moves away from a fee-for-service system to one of value-based care, plastic surgeons need to be at the forefront of this transition to ensure that they are delivering quality care, and receiving appropriate reimbursement. The authors have provided data from the University of Michigan to demonstrate the reimbursement patterns seen in plastic surgery. This Special Topic article provides insight into the reimbursement process in the era of the Affordable Care Act and the various challenges that may be encountered within this field.

Purpose To evaluate factors that predict the use of electrodiagnostic testing (EDS) for patients undergoing carpal tunnel release (CTR). Methods In this cohort study, we analyzed 553 patients who underwent primary CTR from 8 practices between July 1, 2019 and December 1, 2019 by 32 surgeons in the Michigan Collaborative Hand Initiative for Quality in Surgery (M-CHIQS). The M-CHIQS is a collaborative initiative aimed at improving quality in hand surgery. Demographic and clinical characteristics were collected, including the 6-item carpal tunnel symptoms scale (CTS-6) scores and EDS timing. Multilevel logistic regression was used to assess practice and surgeon variation in EDS use related to clinical diagnostic criteria. Results Of the 553 patients who underwent CTR during the study period, 461 (83.3%) received preoperative EDS. After controlling for patient clinical and demographic characteristics, CTS-6 scores were not associated with receiving any preoperative EDS (lower probability of CTS: odds ratio [OR], 0.94; 95% confidence interval [95% CI], 0.59–1.51), preconsultation EDS (low probability of CTS: OR, 1.00; 95% CI, 0.73–1.38), or postconsultation EDS (low probability of CTS, OR, 1.10; 95% CI, 0.77–1.60). For use of any EDS, 9.3% of the variation in testing was explained at the practice level and 31.1% of the variation in testing was explained at the surgeon level. Conclusions Variation in EDS use is explained primarily at the practice and surgeon levels and is not related to patient clinical criteria. We recommend that providers and practices assess their use of preoperative EDS and limit its use to patients with an unclear clinical CTS diagnosis, as stated in current clinical practice guidelines. Likewise, providers should be encouraged to use the CTS-6 before prescribing EDS. Clinical relevance Limiting the use of EDS to patients with an unclear clinical diagnosis of CTS will reduce costs and improve patient care by eliminating the discomfort and time associated with this test.

BACKGROUND Management of suspected scaphoid fractures includes repeated evaluation and casting in symptomatic patients with nondiagnostic radiographs. In this systematic review and meta-analysis, the authors compare the diagnostic accuracy of clinical examinations for scaphoid fractures and create a decision guide using Bayesian statistics. METHODS The MEDLINE, Embase, and Cumulative Index to Nursing and Allied Health Literature databases were queried for studies that evaluated clinical index tests and their diagnostic accuracies for scaphoid fracture. Summary estimates were achieved by a bivariate random effects model and used in Bayes' theorem. The authors varied the scaphoid fracture prevalence for sensitivity analysis. RESULTS Fourteen articles with 22 index tests and 1940 patients were included. Anatomical snuffbox pain/tenderness (11 studies, 1363 patients), pain with axial loading (eight studies, 995 patients), and scaphoid tubercle tenderness (five studies, 953 patients) had sufficient data for pooled analysis. Anatomical snuffbox pain/tenderness was the most sensitive test (0.93; 95 percent CI, 0.87 to 0.97), and pain with axial loading was the most specific test (0.66; 95 percent CI, 0.41 to 0.85), but all three tests had lower estimated specificities compared with sensitivities. In the base case, the probability of fracture was approximately 60 percent when a patient presented with all three findings after acute wrist injury. CONCLUSIONS The posttest probability of scaphoid fracture was sensitive to both prevalence and diagnostic accuracy of individual clinical index tests. In a population with a fracture prevalence of 20 percent, patients presenting with concurrent anatomical snuffbox pain/tenderness, pain on axial loading, and scaphoid tubercle tenderness may benefit from early advanced imaging to rule out scaphoid fractures if initial radiographs are nondiagnostic. CLINICAL QUESTION/LEVEL OF EVIDENCE Diagnostic, II.

Background Immunoglobulin G4-related disease (IgG4-RD) and systemic sclerosis (SSc) are rare autoimmune diseases characterized by the presence of CD4+ cytotoxic T cells in the blood as well as inflammation and fibrosis in various organs, but they have no established etiologies. Similar to other autoimmune diseases, the gut microbiome might encode disease-triggering or disease-sustaining factors. Methods The gut microbiomes from IgG4-RD and SSc patients as well as healthy individuals with no recent antibiotic treatment were studied by metagenomic sequencing of stool DNA. De novo assembly-based taxonomic and functional characterization, followed by association and accessory gene set enrichment analysis, were applied to describe microbiome changes associated with both diseases. Results Microbiomes of IgG4-RD and SSc patients distinctly separated from those of healthy controls: numerous opportunistic pathogenic Clostridium and typically oral Streptococcus species were significantly overabundant, while Alistipes, Bacteroides, and butyrate-producing species were depleted in the two diseases compared to healthy controls. Accessory gene content analysis in these species revealed an enrichment of Th17-activating Eggerthella lenta strains in IgG4-RD and SSc and a preferential colonization of a homocysteine-producing strain of Clostridium bolteae in SSc. Overabundance of the classical mevalonate pathway, hydroxyproline dehydratase, and fibronectin-binding protein in disease microbiomes reflects potential functional differences in host immune recognition and extracellular matrix utilization associated with fibrosis. Strikingly, the majority of species that were differentially abundant in IgG4-RD and SSc compared to controls showed the same directionality in both diseases. Compared with multiple sclerosis and rheumatoid arthritis, the gut microbiomes of IgG4-RD and SSc showed similar signatures; in contrast, the most differentially abundant taxa were not the facultative anaerobes consistently identified in inflammatory bowel diseases, suggesting the microbial signatures of IgG4-RD and SSc do not result from mucosal inflammation and decreased anaerobism. Conclusions These results provide an initial characterization of gut microbiome ecology in fibrosis-prone IgG4-RD and SSc and reveal microbial functions that offer insights into the pathophysiology of these rare diseases.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis, particularly for patients with metastatic disease. Treatment for oligometastatic presentation has been reported in recent literature, but the role of intraperitoneal chemotherapy for patients with peritoneal metastases (PM) remains unclear. We performed a systematic literature search of the PubMed, Cochrane and Embase databases in order to identify clinical trials and case-series reporting on the safety and efficacy of intraperitoneal chemotherapy in patients with PDAC-derived PM. Eight publications reporting on 85 patients were identified, using three different therapeutic strategies. First, 37 patients received cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for PDAC with PM. Grade 3 and 4 complications occurred in 37.8% of patients, without perioperative mortality. Median disease-free survival and overall survival (OS) rates varied from 4 to 36 months and 4 to 62 months, respectively. Secondly, 40 patients with resectable PDAC without PM received prophylactic HIPEC following pancreatic resection, with postoperative morbidity and mortality rates of 30% and 5%, and 5-year OS rates of 23-24%. Finally, eight patients with PDAC-derived peritoneal disease were converted to resectable disease after receiving neoadjuvant intraperitoneal chemotherapy and operated on with curative intent, achieving a median OS of 27.8 months. In conclusion, CRS with HIPEC for PDAC-derived PM appears to be safe, conferring the same postoperative morbidity and mortality as reported on non-pancreatic malignancies. In highly selected patients, it could be considered for short-term disease control. However, long-term survival remains poor. The addition of prophylactic HIPEC for resectable PDAC cannot be recommended.

Despite the use of various factors to measure hospital quality, most measures have not resulted in long-term improvements in patient outcomes. This study's purpose is to determine the effect of a previously unassessed measure of quality of care-a hospital's preventable hospitalization rate-on 30-day mortality at both the hospital and individual levels after three major cardiovascular surgery procedures. This is a population-based study using Taiwan's National Health Insurance database. We retrieved data from 2001 to 2014 for patients who had undergone abdominal aortic aneurysm (AAA) repair, coronary artery bypass graft, or aortic valve replacement (AVR). Preventable hospitalizations are hospitalizations for 11 chronic conditions that are considered preventable with effective primary care. The outcome was 30-day surgical mortality. Our dataset contained 65,863 patients who had undergone surgery for one of the three cardiovascular procedures. Preventable hospitalization rate was significantly associated with higher hospital mortality rates for all procedures. At the patient level, the adjusted odds of mortality after AAA repair were increased 55% (P0.01) for every 2% increase in the preventable hospitalization rate. For coronary artery bypass graft, preventable hospitalization was not a significant predictor of mortality, but rather patient factors and surgeon factors were significant. For AVR, the adjusted odds of mortality were increased 7% (P0.01) for every 1% increase in preventable hospitalization rate. High preventable hospitalization rate may serve as a hospital quality measure that could signal increased odds of mortality for selected cardiovascular procedures, especially for higher risk-lower volume procedures such as AAA repair and AVR.

Distal radius fractures with severe displacement or concomitant triangular fibrocartilage complex tears may be accompanied by distal radioulnar joint instability. Clinicians should examine the distal radioulnar joint closely when managing wrist fractures and treat coexisting instability appropriately. Chronic instability from distal radius malunion may require osteotomy or radioulnar ligament reconstruction. With proper management, most patients recover forearm stability and rotational motion after distal radius fracture.

Low-dose aspirin is recommended by the U.S. Preventive Services Task Force for primary prevention of colorectal cancer in certain individuals. However, broader implementation will require improved precision prevention approaches to identify those most likely to benefit. The major urinary metabolite of PGE2, 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), is a biomarker for colorectal cancer risk, but it is unknown whether PGE-M is modifiable by aspirin in individuals at risk for colorectal cancer. Adults (N = 180) who recently underwent adenoma resection and did not regularly use aspirin or NSAIDs were recruited to a double-blind, placebo-controlled, randomized trial of aspirin at 81 or 325 mg/day for 8–12 weeks. The primary outcome was postintervention change in urinary PGE-M as measured by LC/MS. A total of 169 participants provided paired urine samples for analysis. Baseline PGE-M excretion was 15.9 ± 14.6 (mean ± S.D, ng/mg creatinine). Aspirin significantly reduced PGE-M excretion (−4.7 ± 14.8) compared with no decrease (0.8 ± 11.8) in the placebo group (P = 0.015; mean duration of treatment = 68.9 days). Aspirin significantly reduced PGE-M levels in participants receiving either 81 (−15%; P = 0.018) or 325 mg/day (−28%; P < 0.0001) compared with placebo. In 40% and 50% of the individuals randomized to 81 or 325 mg/day aspirin, respectively, PGE-M reduction reached a threshold expected to prevent recurrence in 10% of individuals. These results support that aspirin significantly reduces elevated levels of PGE-M in those at increased colorectal cancer risk to levels consistent with lower risk for recurrent neoplasia and underscore the potential utility of PGE-M as a precision chemoprevention biomarker. The ASPIRED trial is registered as NCT02394769.

BACKGROUND Lateral epicondylitis is a common overuse injury affecting approximately 1 to 3 percent of the population. Although symptoms may disappear spontaneously within 1 year, the clinical guidelines for conservative treatment are not clear. The authors' objective was to examine the outcomes of nonsurgical treatments for lateral epicondylitis through a meta-analysis and provide a treatment recommendation using the available evidence. METHODS The authors searched the PubMed, EMBASE, Scopus, and Web of Science databases to identify primary research articles studying conservative treatments (electrophysiotherapy, physical therapy, and injections) for lateral epicondylitis. The authors included randomized controlled trials published in peer-reviewed journals. Data related to outcomes (pain, grip strength, Patient-Rated Tennis Elbow Evaluation score, and Disabilities of the Arm, Shoulder and Hand score) and complications were extracted. RESULTS Fifty-eight randomized controlled trials were included in the meta-analysis. Electrophysiotherapy was effective in improving pain [mean difference, -10.0 (95 percent CI, -13.8 to -6.1)], Patient-Rated Tennis Elbow Evaluation score [mean difference, -10.7 (95 percent CI, -16.3 to -5.0)], and Disabilities of the Arm, Shoulder and Hand score [mean difference, -11.9 (95 percent CI, -15.8 to -7.9)]; and physical therapy improved pain [mean difference, -6.0 (95 percent CI, -9.7 to -2.3)] and Patient-Rated Tennis Elbow Evaluation scores [mean difference, -7.5 (95 percent CI, -11.8 to -3.2)] compared to placebo. Injections did not improve any outcome measures. Patients who received electrophysiotherapy and injections reported higher adverse effects than physical therapy patients. CONCLUSIONS Patients who received electrophysiotherapy and physical therapy reported statistically and clinically improved scores in pain and function compared to placebo. Injections may put patients at higher risk for adverse effects compared to other conservative treatments. When managing lateral epicondylitis conservatively, electrophysiotherapy and physical therapy should be prioritized before other interventions. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, I.

Upper extremity infections are common. Most infections can be effectively treated with minor surgical procedures and/or oral antibiotics; however, inappropriate or delayed care can result in significant, long-term morbidity. The basic principles of treating hand infections were described more than a century ago and most remain relevant today. Immunosuppressant medications, chronic health conditions such as diabetes and human immunodeficiency virus, and public health problems like intravenous drug use, have changed the landscape of hand infections and provide new challenges in treatment.

BACKGROUND Evidence-based practices in medicine are linked with a higher quality of care and lower health care cost. For trigger finger, identifying patient factors associated with nonadherence to evidence-based practices will aid physicians in treatment decisions. The objectives were to (1) determine patient factors associated with treatment nonadherence, (2) examine the success rates of steroid injections, and (3) evaluate the economic consequences of nonadherence to treatment recommendations. METHODS The authors used data from the Clinformatics DataMart database from 2010 to 2017 to conduct a population-based analysis of patients with single-digit trigger finger. The authors calculated rates of steroid injection success and examined associations between injection success and patient factors using chi-square tests. In addition, the authors analyzed differences in the cost to the insurer, the cost to the patient, and total cost. RESULTS A total of 29,722 patients were included in this analysis. Injection success rates were similar for diabetic (72 percent) and nondiabetic patients (73 percent), women (73 percent), and men (73 percent). Nonetheless, diabetics (OR, 1.4; 95 percent CI, 1.4 to 1.5; p < 0.001) and women (OR, 1.2; 95 percent CI, 1.1 to 1.2; p < 0.001) were significantly more likely to receive nonadherent treatment. In total, $23 million (U.S. dollars) were spent on nonadherent trigger finger care. CONCLUSIONS Diabetics and women have increased odds of having surgery without a prior steroid injection, despite similar success rates of steroid injections compared to nondiabetics and men. Because performing surgical release before any steroid injections may represent a higher cost treatment option, providers should provide steroid injections before surgery for all patients regardless of diabetes status or sex to minimize overtreatment. CLINICAL QUESTION/LEVEL OF EVIDENCE Risk, III.

Background Previous studies of the relationship between dietary factors and risk of diverticulosis have yielded inconsistent results. We therefore sought to investigate the association between consumption of fruit and vegetables and prevalent diverticulosis. Methods Our study population included participants in the Gastrointestinal Disease and Endoscopy Registry (GIDER), a colonoscopy-based longitudinal cohort at the Massachusetts General Hospital, who provided comprehensive information on dietary intake and lifestyle factors using validated questionnaires prior to colonoscopy. Information on presence and location of diverticula was obtained from the endoscopist at the end of each procedure. We used Poisson regression modeling to calculate the prevalence ratios (PRs) and 95% confidence intervals (CIs). Results Among 549 participants with a mean age of 61 years enrolled in GIDER, we confirmed diverticulosis in 245 (44.6%). The prevalence of diverticulosis appeared to decrease with higher consumption of fruit and vegetables (Ptrend = 0.007 for fruit and 0.008 for vegetables, respectively). Compared to participants with less than five servings of vegetables per week, the multivariable-adjusted PRs of diverticulosis were 0.84 (95% CI, 0.60–1.17) with five to seven servings per week and 0.62 (95% CI, 0.44–0.89) with greater than one serving per day. Similarly, compared to participants with less than five servings per week of fruit, the multivariable-adjusted PR of diverticulosis was 0.60 (95% CI, 0.41–0.87) with greater than one serving per day. These associations were not modified by age, BMI, smoking, or red meat intake (All Pinteraction > 0.055). Conclusion In a colonoscopy-based longitudinal cohort study, we show that higher consumption of fruit and vegetables is associated with lower risk of prevalent diverticulosis.

BACKGROUND: Optimal treatment for distal radius fractures (DRFs) in older adults remains uncertain. No randomized trials comparing the most frequently used treatments in this population have been conducted. Surgical treatment rates vary widely, though the sustained benefits of surgery are uncertain. METHODS: The Wrist and Radius Injury Surgical Trial (WRIST), randomized, multicenter trial, enrolled 304 adults age 60 years and older with isolated, unstable DRFs at 24 institutions. Patients who wanted surgery (n=187) were randomized to internal fixation with volar plate (VLPS), external fixation (EFP), or percutaneous pinning; patients who preferred conservative management (n=117) received casting. The primary outcome was the 12-month Michigan Hand Outcomes Questionnaire (MHQ) Summary score. Secondary outcomes included MHQ domain scores and radiographic parameters. RESULTS: At 12 months, there were no differences by treatment in primary or the majority of secondary outcomes. Twelve-month MHQ Summary scores differed between VLPS and EFP by 3 points (97.5% CL: −6.0, 11.5) and between VLPS and pinning by −0.14(−9.2,8.9). However, at 6 weeks, mean MHQ Summary score for VLPS was greater than EFP by 19(p

We investigated whether genetic susceptibility to tuberculosis (TB) influences lung adenocarcinoma development among never-smokers using TB genome-wide association study (GWAS) results within the Female Lung Cancer Consortium in Asia. Pathway analysis with the adaptive rank truncated product method was used to assess the association between a TB-related gene-set and lung adenocarcinoma using GWAS data from 5512 lung adenocarcinoma cases and 6277 controls. The gene-set consisted of 31 genes containing known/suggestive associations with genetic variants from previous TB-GWAS. Subsequently, we followed-up with Mendelian Randomization to evaluate the association between TB and lung adenocarcinoma using three genome-wide significant variants from previous TB-GWAS in East Asians. The TB-related gene-set was associated with lung adenocarcinoma (p = 0.016). Additionally, the Mendelian Randomization showed an association between TB and lung adenocarcinoma (OR = 1.31, 95% CI: 1.03, 1.66, p = 0.027). Our findings support TB as a causal risk factor for lung cancer development among never-smoking Asian women.

Hand surgery leadership in the United States must identify and define what quality care means for its patients. To achieve this, the surgical team needs a standardized framework to track and improve quality. This is necessary not only in our value-based health care system but also in light of considerable provider variation in the management of common hand conditions and the ongoing need for evidence-based guidelines to inform decision-making. Building a national registry for the field of hand surgery could be the solution and warrants serious consideration. A registry designed by hand surgery experts can collect data on process and outcome measures that are meaningful and specific to patients with hand conditions. These data inform the surgical team regarding where to focus their efforts for improvement. Existing methods of quality measurement are not compatible with hand surgery, a field with an ambulatory setting and rare incidence of mortality. Patient-reported outcomes, such as health-related quality of life, represent a more useful measure of quality for hand surgery and are just one example of the type of data that could be tracked using a national registry. An investment in a large-scale registry could seamlessly integrate patient preferences, values, and expectations into clinical practice so that desired outcomes can be delivered consistently across the nation.

Background Potentially preventable hospitalizations (PPH) are defined as unplanned hospital admissions which could potentially have been prevented with the provision of effective, timely outpatient care. To better understand and ultimately reduce rates of PPH, a means of identifying those which are actually preventable is required. The Preventability Assessment Tool (PAT) was designed for use by hospital clinicians to assess the preventability of unplanned admissions for chronic conditions. Objective The present study examined the ability of the PAT to distinguish between those unplanned admissions which are preventable and those which are not, compared to the assessments of an Expert Panel. Methods Data were collected between November 2014 and June 2017 at three hospitals in NSW, Australia. Participants were community-dwelling patients with unplanned hospital admissions for congestive heart failure, chronic obstructive pulmonary disease, diabetes complications or angina pectoris. A nurse and a doctor caring for the patient made assessments of the preventability of the admission using the PAT. Expert Panels made assessments of the preventability of each admission based on a comprehensive case report and consensus process. Results There was little concordance between the hospital doctors and nurses regarding the preventability of admissions, nor between the assessments of the Expert Panel and the hospital nurse or the Expert Panel and the hospital doctor. Conclusions The PAT demonstrated poor concurrent validity and is not a valid tool for assessing the preventability of unplanned hospital admissions. The use of Expert Panels provides a more rigorous approach to assessing the preventability of such admissions.

Hand trauma surgical treatment and perioperative therapy are often lacking in low- and middle-income countries resulting in high rates of patient morbidity following injury. Providing education through a multifaceted approach including in-person teaching, written resources, videos, and Internet and social media platforms and facilitating skill acquisition through simulation permits local providers to gain expertise in hand trauma care and thus benefits patients. This article outlines challenges faced by low- and middle-income countries in caring for hand trauma patients and possible implementable solutions.

Background As many as 34 percent of nonfatal firearm injuries involve the upper extremity. Although not lethal, these injuries cause substantial morbidity. The authors conducted an epidemiologic study characterizing upper extremity firearm-related injuries presenting to U.S. trauma centers over a 10-year period. Methods The authors used the National Trauma Databank from 2007 to 2017 to identify isolated upper extremity firearm-related injuries. Descriptive statistics were performed to characterize patient demographic data, firearm type, extremity injury patterns, treatments received, hospital length of stay, and regional variation. Results The authors identified 48,254 upper extremity firearm-related injuries. The patients were largely male patients (85 percent), and over half were between the ages of 20 and 39 years. Handguns (34 percent) were the most frequently used firearm. Shoulder and upper arm were the most frequently injured areas (54 percent); however, 18 percent of patients injured two or more areas. Patients were most often treated at university hospitals (59 percent) with Level I or II trauma designation. Seventy percent were admitted and/or taken directly to the operating room. The mean hospital length of stay was 3 days. Payer mix among these patients was variable: Medicaid, 20 percent; private insurance, 20 percent; and self-pay, 29 percent. Conclusions Upper-extremity firearm injuries are resource intensive, with three-quarters of patients requiring operative intervention and/or hospitalization. Level I and II trauma centers were the site of care for the majority of patients. Targeted gun policy reform and prevention measures directed toward at-risk groups have the potential to limit the unnecessary morbidity and costs associated with these injuries.

To examine the extent of the evaluation required to achieve diagnostic resolution and the test performance characteristics of a targeted methylation cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test, ~6200 participants ≥50 years with (cohort A) or without (cohort B) ≥1 of 3 additional specific cancer risk factors will be enrolled in PATHFINDER (NCT04241796), a prospective, longitudinal, interventional, multi-center study. Plasma cfDNA from blood samples will be analyzed to detect abnormally methylated DNA associated with cancer (i.e., cancer “signal”) and a cancer signal origin (i.e., tissue of origin). Participants with a “signal detected” will undergo further diagnostic evaluation per guiding physician discretion, those with a “signal not detected” will be advised to continue guideline-recommended screening. The primary objective will be to assess the number and types of subsequent diagnostic tests needed for diagnostic resolution. Based on microsimulations (using estimates of cancer incidence and dwell times) of the typical risk profiles of anticipated participants, the median (95% CI) number of participants with a “signal detected” result is expected to be 106 (87–128). Subsequent diagnostic evaluation is expected to detect 52 (39–67) cancers. The positive predictive value of the MCED test is expected to be 49% (39–58%). PATHFINDER will evaluate the integration of a cfDNA-based MCED test into existing clinical cancer diagnostic pathways. The study design of PATHFINDER is described here.

Introduction The Michigan Hand Outcomes Questionnaire (MHQ) is a patient-reported outcome measure previously validated in patients with rheumatoid arthritis (RA) using classical test theory. Rasch analysis is a more rigorous method of questionnaire validation that has not been used to test the psychometric properties of the MHQ in patients with RA. The objective of this study is to evaluate the validity and reliability of the MHQ for measuring outcomes in patients with RA with metacarpophalangeal joint deformities. Methods We performed a Rasch analysis using baseline data from the Silicone Arthroplasty in Rheumatoid Arthritis (SARA) prospective cohort study. All domains were tested for threshold ordering, item fit, targeting, differential-item functioning, unidimensionality, and internal consistency. Results The Function and Work domains showed excellent fit to the Rasch model. After making adjustments, the Pain, Activities of Daily Living (ADL) and Satisfaction domains also fulfilled all Rasch model criteria. The Aesthetics domain met the majority of Rasch criteria, but could not be tested for unidimensionality. Conclusions After collapsing disordered thresholds and removing misfitting items, the MHQ demonstrated reliability and validity for assessing outcomes in patients with RA with metacarpophalangeal joint deformities. These results suggest that interpreting individual domain scores may provide more insight into a patient’s condition rather than analyzing an overall MHQ summary score. However, more Rasch analyses are needed in other RA populations before making adjustments to the MHQ.

Importance Distal radius fractures (DRFs) are common injuries among older adults and can result in substantial disability. Current evidence regarding long-term outcomes in older adults is scarce. Objective To compare outcomes across treatment groups at 24 months among adults with DRFs who participated in the WRIST trial. Design, Setting, and Participants The Wrist and Radius Injury Surgical Trial (WRIST) randomized, international, multicenter trial was conducted from April 1, 2012, through December 31, 2016. Participants were adults aged 60 years or older with isolated, unstable DRFs at 24 health systems in the US, Canada, and Singapore. Data analysis was performed from March 2019 to March 2021. Interventions Participants were randomized to open reduction and volar locking plate system (VLPS), external fixation with or without supplementary pinning (EFP), and percutaneous pinning (CRPP). The remaining participants chose closed reduction and casting. Main Outcomes and Measures The primary outcome was the 24-month Michigan Hand Outcomes Questionnaire (MHQ) summary score. Secondary outcomes were scores on the MHQ subdomains hand strength and wrist motion. Results A total of 304 adults were recruited for the study, and 187 were randomized to undergo surgery, 65 to VLPS, 64 to EFP, and 58 to CRPP; 117 participants opted for closed reduction and casting. Assessments were completed at 24 months for 182 participants (160 women [87.9%]; mean [SD] age, 70.1 [8.5] years). Mean MHQ summary scores at 24 months were 88 (95% CI, 83-92) for VLPS, 83 (95% CI, 78-88) for EFP, 85 (95% CI, 79-90) for CRPP, and 85 (95% CI, 79-90) for casting, with no clinically meaningful difference across groups after adjusting for covariates (χ23 = 1.44; P = .70). Pain scores also did not differ across groups at 24 months (χ23 = 2.64; P = .45). MHQ summary scores changed from 82 (95% CI, 80-85) to 85 (95% CI, 83-88) (P = .12) between 12 and 24 months across groups. The rate of malunion was higher in the casting group (26 participants [59.1%]) than in the other groups (4 participants [8.0%] for VLPS, 8 participants [17.0%] for EFP, and 4 participants [9.8%] for CRPP; χ23 = 43.6; P

STUDY DESIGN This is a retrospective cohort study of consecutive patients undergoing lumbar spinal fusion (LSF) within the PearlDiver Humana research database from 2010 to 2018. OBJECTIVE The aim of this study was to determine if timing of total hip arthroplasty (THA) affects LSF outcomes. SUMMARY OF BACKGROUND DATA In patients with both spine and hip pathology, outcomes of THA have been shown to be affected by the timing of THA relative to LSF. However, few studies have assessed postoperative outcomes following LSF in this clinical scenario. MATERIALS AND METHODS A national database was queried for patients undergoing lumbar fusion and divided into 4 groups: (1) those who underwent LSF without THA (No THA); (2) those who underwent THA at least 2 years before LSF (>2 Prior THA); (3) those who underwent THA in the 2 years before LSF (0-2 Prior THA); and (4) those who underwent THA after LSF (THA After). We assessed lumbar-specific outcomes, including pseudarthrosis, revision, mechanical failure, and adjacent segment disease (ASD); as well as systemic complications. Controlling for age, sex, and Charlson comorbidity index, complication rates between all groups were assessed using univariate and multivariate logistic regression analysis. Post hoc comparisons were performed using the Fisher exact test with Bonferroni correction to account for multiple pairwise comparisons, resulting in an adjusted threshold for statistical significance of P

Key Points Question Can deep convolutional neural networks (DCNNs) detect occult scaphoid fractures not visible to human observers? Findings In this diagnostic study of 11 838 scaphoid radiographs, the DCNN trained to distinguish scaphoid fractures from scaphoids without fracture achieved an overall sensitivity and specificity of 87.1% and 92.1%, respectively, with an area under the receiver operating curve (AUROC) of 0.955; a second DCNN, which examined negative cases from the first DCNN, achieved a sensitivity and specificity of 79.0% and 71.6% with an AUROC of 0.810. This 2-stage DCNN model correctly identified 90% of occult fractures. Meaning These findings suggest that DCNNs can be trained to reliably detect fractures of small bones, such as scaphoids, and may be able to assist with radiographic detection of occult fractures that are not visible to human observers., This diagnostic study develops and validates a deep convolutional neural network to detect both apparent and occult scaphoid fractures from radiographic images., Importance Scaphoid fractures are the most common carpal fracture, but as many as 20% are not visible (ie, occult) in the initial injury radiograph; untreated scaphoid fractures can lead to degenerative wrist arthritis and debilitating pain, detrimentally affecting productivity and quality of life. Occult scaphoid fractures are among the primary causes of scaphoid nonunions, secondary to delayed diagnosis. Objective To develop and validate a deep convolutional neural network (DCNN) that can reliably detect both apparent and occult scaphoid fractures from radiographic images. Design, Setting, and Participants This diagnostic study used a radiographic data set compiled for all patients presenting to Chang Gung Memorial Hospital (Taipei, Taiwan) and Michigan Medicine (Ann Arbor) with possible scaphoid fractures between January 2001 and December 2019. This group was randomly split into training, validation, and test data sets. The images were passed through a detection model to crop around the scaphoid and were then used to train a DCNN model based on the EfficientNetB3 architecture to classify apparent and occult scaphoid fractures. Data analysis was conducted from January to October 2020. Exposures A DCNN trained to discriminate radiographs with normal and fractured scaphoids. Main Outcomes and Measures Area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity. Fracture localization was assessed using gradient-weighted class activation mapping. Results Of the 11 838 included radiographs (4917 [41.5%] with scaphoid fracture; 6921 [58.5%] without scaphoid fracture), 8356 (70.6%) were used for training, 1177 (9.9%) for validation, and 2305 (19.5%) for testing. In the testing test, the first DCNN achieved an overall sensitivity and specificity of 87.1% (95% CI, 84.8%-89.2%) and 92.1% (95% CI, 90.6%-93.5%), respectively, with an AUROC of 0.955 in distinguishing scaphoid fractures from scaphoids without fracture. Gradient-weighted class activation mapping closely corresponded to visible fracture sites. The second DCNN achieved an overall sensitivity of 79.0% (95% CI, 70.6%-71.6%) and specificity of 71.6% (95% CI, 69.0%-74.1%) with an AUROC of 0.810 when examining negative cases from the first model. Two-stage examination identified 20 of 22 cases (90.9%) of occult fracture. Conclusions and Relevance In this study, DCNN models were trained to identify scaphoid fractures. This suggests that such models may be able to assist with radiographic detection of occult scaphoid fractures that are not visible to human observers and to reliably detect fractures of other small bones.

This article reviews the impact of the most cited works on distal radius fractures. Judged by the most cited works in this field, distal radius fracture research has followed other paradigm shifts in the history of science. Landmark papers showed that restoring premorbid anatomy led to better outcomes, and a plurality of fixation strategies emerged. A breakthrough in technology came with volar plating, and the new paradigm emerged: precise anatomic reduction is achieved typically with volar plates, unless fragment-specific approaches are needed. This paradigm is being challenged as the association among malunion, arthritis, and function continues to be understood. The best treatment of distal radius fractures in the elderly has also evolved through time.

The critical role of the gut microbiome in microscopic colitis (MC) is evident by the observation that fecal diversion is associated with resolution of mucosal inflammation while restoration of fecal stream is associated with recurrence of disease.1 Characterization of the composition and function of the gut microbiome in MC therefore could provide insights into disease pathogenesis.

Identifying individuals with hereditary syndromes allows for improved cancer surveillance, risk reduction, and optimized management. Establishing criteria for assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provide recommendations for the assessment and management of patients with high-risk colorectal cancer syndromes. These NCCN Guidelines Insights focus on criteria for the evaluation of Lynch syndrome and considerations for use of multigene testing in the assessment of hereditary colorectal cancer syndromes.

Most pancreatic neuroendocrine tumors (PNETs) do not produce excess hormones and are therefore considered ‘non-functional’1–3. As clinical behaviors vary widely and distant metastases are eventually lethal2,4, biological classifications might guide treatment. Using enhancer maps to infer gene regulatory programs, we find that non-functional PNETs fall into two major sub-types whose epigenomes and transcriptomes partially resemble islet alpha and beta cells. Transcription factors ARX and PDX1 specify these normal cells, respectively5,6, and 84% of 142 non-functional PNETs expressed one or the other factor, occasionally both. Among 103 cases, distant relapses occurred almost exclusively in patients with ARX+PDX1− tumors and, within this sub-type, in cases with alternative lengthening of telomeres (ALT). These markedly different outcomes belied similar clinical presentations and histology and, in one cohort, occurred irrespective of MEN1 mutation. This robust molecular stratification provides insight into cell lineage correlates of non-functional PNETs, accurately predicts disease course, and can inform post-operative clinical decisions.

Acute and chronic injuries to the finger extensor mechanism can result in swan neck and boutonniere deformities. Loss of coordination between the multiple, specialized components of the extensor mechanism results in tendon imbalances leading to altered interphalangeal joint flexion and extension forces. Treatments include corrective splinting and operative interventions. Swan neck deformities are functionally limiting. Surgical correction generally results in functional benefit. Boutonniere deformities are functional but aesthetically displeasing; proximal interphalangeal (PIP) joint flexion and the ability to make a fist are maintained. Surgical improvement can be attempted with caution. Attempts to improve PIP extension can impede flexion, resulting in a poor functional outcome.

Thin soft tissue covering extensor tendons make them prone to injury. The extensor mechanism achieves a delicate balance with the flexor system. Inappropriate management in the acute setting can lead to long-term deformity and dysfunction. Acute extensor tendon injuries are usually managed with splinting and/or primary repair of the tendon. In cases of tendon length loss, tendon graft or flap may be necessary for reconstruction. This article presents a series of cases illustrating the appropriate management of traumatic extensor tendon injuries.

Objective To explore the intrinsic role of inhibitor of DNA binding 1 (ID‐1) in rheumatoid arthritis (RA) fibroblast‐like synoviocytes (FLS) and to investigate whether ID‐1 is citrullinated and autoantigenic in RA. Methods RA patient serum ID‐1 levels were measured before and after infliximab treatment. RA FLS were transfected with a clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR‐associated protein 9 construct targeting ID‐1 to examine the effects of ID‐1 deletion. RA synovial fluid (SF) and homogenized synovial tissue (ST) were immunoprecipitated for ID‐1 and measured for citrullinated residues using an enzyme‐linked immunosorbent assay and Western blotting. Liquid chromatography tandem mass spectrometry (LC‐MS/MS) was performed on in vitro–citrullinated recombinant human ID‐1 (cit–ID‐1) to localize the sites of citrullination. Normal and RA sera and SF were analyzed by immunodot blotting for anti–citrullinated protein antibodies (ACPAs) to cit–ID‐1. Results RA patient serum ID‐1 levels positively correlated with several disease parameters and were reduced after infliximab treatment. RA FLS displayed reduced growth and a robust increase in interleukin‐6 (IL‐6) and IL‐8 production upon deletion of ID‐1. ID‐1 immunodepletion significantly reduced the levels of citrullinated residues in RA SF, and citrullinated ID‐1 was detected in homogenized RA ST (n = 5 samples; P < 0.05). Immunodot blot analyses revealed ACPAs to cit–ID‐1 but not to native ID‐1, in RA peripheral blood (PB) sera (n = 30 samples; P < 0.001) and SF (n = 18 samples; P < 0.05) but not in normal PB sera. Following analyses of LC‐MS/MS results for citrullination sites and corresponding reactivity in immunodot assays, we determined the critical arginines in ID‐1 for autoantigenicity: R33, R52, and R121. Conclusion Novel roles of ID‐1 in RA include regulation of FLS proliferation and cytokine secretion as well as autoantigenicity following citrullination.

BACKGROUND Decisions made to undergo contralateral prophylactic mastectomy, in women at low risk for bilateral disease, are often attributed to a lack of knowledge. This study examines the role knowledge plays in determining surgical treatment for unilateral breast cancer made by laywomen and surgeons for themselves or loved ones. METHODS The study cohort had three groups: (1) laywomen in the general population, (2) breast surgeons, and (3) plastic surgeons. Laywomen were recruited using Amazon Mechanical Turk Crowd Sourcing. Breast and plastic surgeons from nine states were sent electronic surveys. Demographic and contralateral prophylactic mastectomy-specific data on decisions and knowledge were collected and analyzed. RESULTS Surveys from 1333 laywomen, 198 plastic surgeons, and 142 breast surgeons were analyzed. A significantly greater proportion of laywomen in the general population favored contralateral prophylactic mastectomy (67 percent) relative to plastic (50 percent) and breast surgeons (26 percent) (p < 0.0001). Breast surgeons who chose contralateral prophylactic mastectomy were younger (p = 0.044) and female (0.012). On assessment of knowledge, 78 percent of laywomen had a low level of breast cancer knowledge. Laywomen with higher levels of breast cancer knowledge had lower odds of choosing contralateral prophylactic mastectomy (OR, 0.37; 95 percent CI, 0.28 to 0.49). CONCLUSIONS Fewer women are likely to make decisions in favor of contralateral prophylactic mastectomy with better breast cancer-specific education. A knowledge gap likely explains the lower rates with which surgeons choose contralateral prophylactic mastectomy for themselves or loved ones; however, some surgeons who were predominantly young and female favor contralateral prophylactic mastectomy. Improving patient education on surgical options for breast cancer treatment is critical, with well-informed decisions as the goal.

Extracellular matrix (ECsM) bioscaffolds have been successfully used to treat five esophageal adenocarcinoma (EAC) patients following resection of neoplastic mucosal tissue. The present study evaluated the in vitro effect of ECM harvested from nonmalignant, decellularized tissue on EAC cell phenotype to understand the molecular mechanisms underlying the clinical findings. Nonmalignant (Het-1A), metaplastic (CP-A), and neoplastic (SK-GT-4, OE33) esophageal epithelial cells were exposed to ECM degradation products (250 μg/mL) prepared from heterologous urinary bladder tissue or homologous esophageal mucosa tissue, and evaluated for cell morphology, cell function, and EAC signaling pathways. Both the ECM sources downregulated neoplastic cell phenotype, but had distinctive tissue-specific effects. Urinary bladder ECM decreased OE33 and SK-GT-4 metabolism and increased CP-A apoptosis. Esophageal ECM decreased SK-GT-4, CP-A, and Het-1A proliferation; robustly downregulated PI3K-Akt-mTOR, cell cycle/DNA replication signaling, and upregulated autophagy signaling in OE33 cells; and increased cell cycle/DNA replication signaling in Het-1A cells. Both ECM sources decreased OE33 proliferation and phosphorylated AKT in OE33 cells, and in contrast, increased phosphorylated AKT in Het-1A cells. The results support the concept that the biochemical signals in nonmalignant ECM can downregulate neoplastic cell phenotype with minimal, and sometimes opposite, effects on normal cells. PI3K-Akt signaling has been implicated in EAC progression and these ECM-mediated effects may be favorable for an esophageal therapy following cancer resection. IMPACT STATEMENT: Extracellular matrix (ECM) biomaterials were used to treat esophageal cancer patients after cancer resection and promoted regrowth of normal mucosa without recurrence of cancer. The present study investigates the mechanisms by which these materials were successful to prevent the cancerous phenotype. ECM downregulated neoplastic esophageal cell function (proliferation, metabolism), but normal esophageal epithelial cells were unaffected in vitro, and suggests a molecular basis (downregulation of PI3K-Akt, cell cycle) for the promising clinical results. The therapeutic effect appeared to be enhanced using homologous esophageal ECM. This study suggests that ECM can be further investigated to treat cancer patients after resection or in combination with targeted therapy.

Objectives The small intestine is the primary site for absorption of dietary zinc. Intestinal transplant recipients are at high risk for zinc deficiency because of the long process of posttransplant adaptation. We initiated an intestinal transplant program in Taiwan in 2007. In this study, we aimed to retrospectively investigate the incidence of zinc deficiency in recipients after intestinal transplantation. Methods Twenty-one isolated intestinal transplants were performed in 20 patients with 1 retransplantation. The level of serum zinc was monitored periodically, and zinc supplements were administered when zinc level was below 700 ng/mL. Twelve patients with graft above 1-year survival and with available related data were enrolled for the analysis of zinc deficiency. The levels of serum zinc were tracked, and the protocol of zinc supplementation is discussed herein. Results The survival rates of 20 transplant recipients for 1 year, 3 years, and 5 years were 85%, 75%, and 65%, respectively. In the 12 grafts that survived longer than 1 year, we found that zinc deficiency was highest during the third (41.7%) to sixth (50%) month after transplantation. Sustained supplementation of zinc was required for over 70% of patients throughout the 3-year period to maintain their zinc level around the lower normal limit. Conclusion The outcome of isolated small bowel transplantation is promising. Periodical monitoring and sufficient dosing of zinc supplements should be considered into the posttransplant protocol to prevent zinc deficiency after intestinal transplantation.

Spasticity of the hand profoundly limits an individual's independent ability to accomplish self-care and activities of daily living. Surgical procedures should be tailored to patients' needs and functional ability, and even patients with severe cognitive injuries and poor upper extremity function may benefit from surgery to improve appearance and hygiene. Careful preoperative examination and planning are needed, and consideration is given to the potential unintended detrimental effect of a surgical procedure on hand function.

Background Patients with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) metastatic colorectal cancer (mCRC) show a significant response to checkpoint inhibitor therapies, but the economic impact of these therapies is unknown. A decision analytic model was used to explore the effectiveness and cost burden of MSI-H/dMMR mCRC treatment. Methods The treatment of hypothetical patients with MSI-H/dMMR mCRC was simulated in 2 treatment scenarios: a third-line treatment and an exploratory first-line treatment. The treatments compared were nivolumab, ipilimumab and nivolumab, trifluridine and tipiracil (third-line treatment), and mFOLFOX6 and cetuximab (first-line treatment). Disease progression, drug toxicity, and survival rates were based on the CheckMate 142, study of TAS-102 in patients with metastatic colorectal cancer refractory to standard chemotherapies (RECOURSE), and Cancer and Leukemia Group B/Southwest Oncology Group 80405 trials. The analyzed outcomes included survival (life-years), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Results Ipilimumab with nivolumab was the most effective strategy (10.69 life-years and 9.25 QALYs for the third line; 10.69 life-years and 9.44 QALYs for the first line) in comparison with nivolumab (8.21 life-years and 6.76 QALYs for the third line; 8.21 life-years and 7.00 QALYs for the first line), trifluridine and tipiracil (0.74 life-years and 0.07 QALYs), and mFOLFOX6 and cetuximab (2.72 life-years and 1.63 QALYs). However, neither checkpoint inhibitor therapy was cost-effective in comparison with trifluridine and tipiracil (nivolumab ICER, $153,000; ipilimumab and nivolumab ICER, $162,700) or mFOLFOX6 and cetuximab (nivolumab ICER, $150,700; ipilimumab and nivolumab ICER, $158,700). Conclusions This modeling analysis found that both single and dual checkpoint blockade could be significantly more effective for MSI-H/dMMR mCRC than chemotherapy, but they were not cost-effective, largely because of drug costs. Decreases in drug pricing and/or the duration of maintenance nivolumab could make ipilimumab and nivolumab cost-effective. Prospective clinical trials should be performed to explore the optimal duration of maintenance nivolumab.

AimsThis study reports the outcomes of a technique of soft-tissue coverage and Chopart amputation for severe crush injuries of the forefoot.Patients and MethodsBetween January 2012 to December 2016, 12 patients (nine male; three female, mean age 38.58 years; 26 to 55) with severe foot crush injury underwent treatment in our institute. All patients were followed-up for at least one year. Their medical records, imaging, visual analogue scale score, walking ability, complications, and functional outcomes one year postoperatively based on the American Orthopedic Foot and Ankle Society (AOFAS) and 36-Item Short-Form Health Survey (SF-36) scores were reviewed.ResultsThe mean length of follow-up was 18.6 months (13 to 28). Two patients had a local infection, flap necrosis was seen in one patient, and one patient experienced a skin graft wound healing delay. Of the 12 patients, one had persistent infection and eventually required below-knee amputation, but pain-free walking was achieved in all the other patients. The mean one-year postoperative AOFAS and SF-36 scores were 75.6 (68 to 80) and 82 (74 to 88), respectively.ConclusionAlthough our sample size was small, we believe that this treatment method may be a valuable alternative for treating severe foot crush injuries. Cite this article: Bone Joint J 2018;100-B:1359–63.

BACKGROUND Nonsteroidal antiinflammatory drugs are useful alternatives to narcotics for analgesia. However, concerns remain regarding their safety. The authors evaluated ketorolac use and complications. We hypothesized that no association between ketorolac and morbidity exists in patients undergoing body contouring. METHODS Truven MarketScan claims database was analyzed for patients undergoing breast and body contouring surgery. Patients selected received ketorolac and were enrolled a minimum of 90 days. The authors performed a multivariable logistic regression to calculate risk of morbidity, adjusting for clinical and sociodemographic factors. RESULTS Among the 106,279 patients enrolled, 4924 (4.6 percent) received postoperative ketorolac. In multivariable regression analysis, ketorolac was not associated with hematoma (OR, 1.20; 95 percent CI, 0.99 to 1.46; p > 0.05). There was an increased rate of reoperation within 72 hours (OR, 1.22; 95 percent CI, 1.00 to 1.49; p < 0.05; number needed to harm, 262 patients). Ketorolac was associated with fewer readmissions (OR, 0.76; 95 percent CI, 0.62 to 0.93; p < 0.05; number needed to treat, 87 patients), with a reduction in the rate of pain as a readmission diagnosis (0.6 percent versus 4.3 percent; p = 0.021). Ketorolac was associated with seroma, but this association may not be causal (OR, 1.28; 95 percent CI, 1.05 to 1.57; p < 0.05; number needed to harm, 247 patients). Ketorolac provided an estimated savings of $157 per patient. CONCLUSIONS The benefits of ketorolac likely outweigh the risks after surgery. Absolute differences in reoperation rates were low, and improved rates of hospital admission impact cost savings. The authors advocate postoperative ketorolac once the wound is hemostatic. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, III.