Accuracy of machine learning to predict the outcomes of shoulder arthroplasty: a systematic review.

BACKGROUND: Artificial intelligence (AI) uses computer systems to simulate cognitive capacities to accomplish goals like problem-solving and decision-making. Machine learning (ML), a branch of AI, makes algorithms find connections between preset variables, thereby producing prediction models. ML can aid shoulder surgeons in determining which patients may be susceptible to worse outcomes and complications following shoulder arthroplasty (SA) and align patient expectations following SA. However, limited literature is available on ML utilization in total shoulder arthroplasty (TSA) and reverse TSA. METHODS: A systematic literature review in accordance with PRISMA guidelines was performed to identify primary research articles evaluating ML's ability to predict SA outcomes. With duplicates removed, the initial query yielded 327 articles, and after applying inclusion and exclusion criteria, 12 articles that had at least 1 month follow-up time were included. RESULTS: ML can predict 30-day postoperative complications with a 90% accuracy, postoperative range of motion with a higher-than-85% accuracy, and clinical improvement in patient-reported outcome measures above minimal clinically important differences with a 93%-99% accuracy. ML can predict length of stay, operative time, discharge disposition, and hospitalization costs. CONCLUSION: ML can accurately predict outcomes and complications following SA and healthcare utilization. Outcomes are highly dependent on the type of algorithms used, data input, and features selected for the model. LEVEL OF EVIDENCE: III.

Switch to generic formulation of temozolomide results in statistically significant increase in grade 3 and 4 bone marrow toxicity in glioma patients in the province of Alberta.

Background: Temozolomide (TMZ) is an oral, systemic chemotherapy used chiefly for treating high-grade glioma. Due to the rising costs of systemic chemotherapy, many jurisdictions have replaced brand name with generic formulations. The aim of this study was to determine whether or not there was difference in the incidence of grade 3 or 4 bone marrow toxicity and median overall survival in patients treated with brand name versus generic TMZ in the province of Alberta, Canada. The province suspended the use of generic TMZ based on preliminary data pointing to excess toxicity. Methods: This multicenter, retrospective study included data from patients with newly diagnosed high-grade glioma that received treatment with TMZ in Alberta. Multivariate logistic regression analysis was performed to determine the association between grade 3 or 4 toxicity to generic versus brand name TMZ exposure, ECOG score, and age. Kaplan-Meier survival estimates and log-rank testing were used to determine differences in overall survival between the brand name and generic TMZ cohorts, as well as the cytopenic versus non-cytopenic patients. Furthermore, a screening analysis for grade 3 or 4 bone marrow toxicity was conducted on all de novo glioma patients treated with brand name TMZ after Alberta preemptively stopped generic TMZ. Results: Grade 3 or 4 neutropenia and thrombocytopenia were observed in 15% and 19% of patients treated with generic TMZ (n = 156) as compared to 3% and 5% of patients (n = 100) treated with brand name TMZ-treated patients; P= .003 and .001. A trend toward increased median overall survival in glioblastoma patients treated with generic TMZ (13.7 months) versus brand name (15.8 months, P = .178.) was also observed through meeting statistical significance. Based on these results, the province stopped the use of generic TMZ and reverted to the Merck TMZ. An initial review of all new glioma patients (n = 89) treated with Merck TMZ since the province stopped the generic drug demonstrated 3.4% and 10.1% grade 3 or 4 neutropenia, respectively. Conclusions: The statistically significant difference in toxicity profile has prompted the province of Alberta to replace generic TMZ with brand name TMZ in high-grade glioma patients pending more detailed analysis. Our study provides evidence supporting the importance of conducting prospective studies on long-term safety for generic chemotherapies.

Hip Arthroscopy Simulator Training With Immersive Virtual Reality Has Similar Effectiveness to Nonimmersive Virtual Reality.

PURPOSE: To (1) compare the efficacy of immersive virtual reality (iVR) to nonimmersive virtual reality (non-iVR) training in hip arthroscopy on procedural and knowledge-based skills acquisition and (2) evaluate the relative cost of each platform. METHODS: Fourteen orthopaedic surgery residents were randomized to simulation training utilizing an iVR Hip Arthroscopy Simulator (n = 7; PrecisionOS) or non-iVR simulator (n = 7; ArthroS Hip VR; VirtaMed). After training, performance was assessed on a cadaver by 4 expert hip arthroscopists through arthroscopic video review of a diagnostic hip arthroscopy. Performance was assessed using the Objective Structured Assessment of Technical Skills (OSATS) and Arthroscopic Surgery Skill Evaluation Tool (ASSET) scores. A cost analysis was performed using the transfer effectiveness ratio (TER) and a direct cost comparison of iVR to non-iVR. RESULTS: Demographic characteristics did not differ between treatment arms or by training level, hip arthroscopy experience, or prior simulator use. No significant differences were observed in OSATS and ASSET scores between iVR and non-iVR cohorts (OSATS: iVR 19.6 ± 4.4, non-iVR 21.0 ± 4.1, P = .55; ASSET: iVR 23.7 ± 4.5, non-iVR 25.8 ± 4.8, P = .43). The absolute TER was 0.06 and there was a 132-fold cost difference of iVR to non-iVR. CONCLUSIONS: Hip arthroscopy simulator training with iVR had similar performance results to non-iVR for technical skill and procedural knowledge acquisition after expert arthroscopic video assessment. The iVR platform had similar effectiveness in transfer of skill compared to non-iVR with a 132 times cost differential. CLINICAL RELEVANCE: Due to the accessibility, effectiveness, and relative affordability, iVR training may be beneficial in the future of safe arthroscopic hip training.

Current Concepts in the Business of Orthopaedics.

Practice management within orthopaedic surgery demands a multifaceted skillset including clinical expertise, technical proficiency, and business acumen, yet the latter is rarely taught during orthopaedic training. As the healthcare system evolves in the United States, surgeons continue to face challenges such as decreasing reimbursements, increased regulatory burdens, and potential for practice acquisition. To remain competitive and provide exceptional care for patients, orthopaedic surgeons must cultivate a business-minded approach. This article highlights the growing significance of the business of orthopaedics and offers guidance on ambulatory surgical center ownership models, effective management of ancillary services, the effect of private equity in orthopaedic practice, real estate investment opportunities in medical office buildings, and the importance of brand recognition. By understanding these concepts, orthopaedic surgeons can exercise greater control over their practice's finances while providing quality care for their patients.

Mobile Critical Care Recovery Program for Survivors of Acute Respiratory Failure: A Randomized Clinical Trial.

Importance: Over 50% of Acute Respiratory Failure (ARF) survivors experience cognitive, physical, and psychological impairments that negatively impact their quality of life (QOL). Objective: To evaluate the efficacy of a post-intensive care unit (ICU) program, the Mobile Critical Care Recovery Program (m-CCRP) consisting of a nurse care coordinator supported by an interdisciplinary team, in improving the QOL of ARF survivors. Design, Setting, and Participants: This randomized clinical trial with concealed outcome assessments among ARF survivors was conducted from March 1, 2017, to April 30, 2022, with a 12-month follow-up. Patients were admitted to the ICU services of 4 Indiana hospitals (1 community, 1 county, 2 academic), affiliated with the Indiana University School of Medicine. Intervention: A 12-month nurse-led collaborative care intervention (m-CCRP) supported by an interdisciplinary group of clinicians (2 intensivists, 1 geriatrician, 1 ICU nurse, and 1 neuropsychologist) was compared with a telephone-based control. The intervention comprised longitudinal symptom monitoring coupled with nurse-delivered care protocols targeting cognition, physical function, personal care, mobility, sleep disturbances, pain, depression, anxiety, agitation or aggression, delusions or hallucinations, stress and physical health, legal and financial needs, and medication adherence. Main Outcomes and Measures: The primary outcome was QOL as measured by the 36-item Medical Outcomes Study Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS), with scores on each component ranging from 0-100, and higher scores indicating better health status. Results: In an intention-to-treat analysis among 466 ARF survivors (mean [SD] age, 56.1 [14.4] years; 250 [53.6%] female; 233 assigned to each group), the m-CCRP intervention for 12 months did not significantly improve the QOL compared with the control group (estimated difference in change from baseline between m-CCRP and control group: 1.61 [95% CI, -1.06 to 4.29] for SF-36 PCS; -2.50 [95% CI, -5.29 to 0.30] for SF-36 MCS. Compared with the control group, the rates of hospitalization were higher in the m-CCRP group (117 [50.2%] vs 95 [40.8%]; P = .04), whereas the 12-month mortality rates were not statistically significantly lower (24 [10.3%] vs 38 [16.3%]; P = .05). Conclusions and Relevance: Findings from this randomized clinical trial indicated that a nurse-led 12-month comprehensive interdisciplinary care intervention did not significantly improve the QOL of ARF survivors after ICU hospitalization. These results suggest that further research is needed to identify specific patient groups who could benefit from tailored post-ICU interventions. Trial Registration: ClinicalTrials.gov Identifier: NCT03053245.

Remission of Ectopic Cushing Syndrome Secondary to Medullary Thyroid Cancer With Vandetanib and Selpercatinib.

Medullary thyroid cancer (MTC) is a neuroendocrine tumor associated with activating mutations of the rearranged during transfection (RET) proto-oncogene. These tumors may rarely secrete adrenocorticotropin or corticotropin-releasing hormone, resulting in a paraneoplastic ectopic Cushing syndrome (ECS). Paraneoplastic ECS carries a high risk of mortality, and management is difficult due to the lack of response to antiadrenal therapies. We report on a 37-year-old man who was diagnosed with metastatic MTC and reported symptoms of cortisol excess with laboratory testing in keeping with ECS. He began treatment with vandetanib, a multitargeted tyrosine kinase inhibitor, which resulted in decreased tumor burden as well as clinical and biochemical resolution of ECS. Due to progressive structural disease 10 months later, he was switched to the selective RET inhibitor selpercatinib, which was followed by a rapid reduction of cortisol nearing the threshold of adrenal insufficiency. Tumor markers were also improved, and repeat imaging showed decreased tumor burden. Our case highlights the efficacy of tyrosine kinase inhibitors in the management of paraneoplastic ECS. Selective RET inhibitors may emerge as preferred targeted treatment options due to better efficacy and toxicity profiles compared to multitargeted inhibitors. Clinicians should monitor for adrenal insufficiency with the use of selective RET inhibitors.

Changes in the outcomes of patients with anaplastic thyroid carcinoma over the past two decades.

OBJECTIVE: To assess the changes in survival outcomes among patients with anaplastic thyroid carcinoma in the US over the past two decades. METHODS: Surveillance, Epidemiology, and End Results (SEER) database research data were reviewed, and patients with anaplastic thyroid carcinoma, who were diagnosed from 2004 to 2020 were evaluated. Kaplan-Meier survival estimates were conducted to examine differences in overall survival between three year-of-diagnosis groups (2004 to 2010; 2011 to 2016; and 2017 to 2020). Multivariable Cox regression analysis was then performed to explore the factors affecting overall survival. RESULTS: A total of 1804 patients with anaplastic thyroid carcinoma were included. Using Kaplan-Meier survival estimates, overall survival was better among patients diagnosed from 2017 to 2020 versus those diagnosed at earlier periods (P < 0.001). One-year survival estimates were 25% among patients diagnosed from 2017 to 2020 versus 15% for patients diagnosed from 2011 to 2016, and 19%, for patients diagnosed from 2004 to 2010. Using the multivariable Cox regression model, an earlier year of diagnosis was associated with worse overall survival compared to the diagnosis year 2017 to 2020 (HR for diagnosis 2004 to 2010 versus diagnosis 2017 to 2020: 1.170; 95% CI: 1.029 to 1.331, and HR for diagnosis 2011 to 2016 versus diagnosis 2017 to 2020: 1.251; 95% CI: 1.103 to 1.419). CONCLUSIONS: While anaplastic thyroid carcinoma remains a deadly cancer, survival seems to be improving for the last few years compared to earlier years. There is still additional work to be done to improve the outcomes of those patients.

Maternal risk factors for fetal alcohol spectrum disorders: Distal variables.

BACKGROUND: A variety of maternal risk factors for fetal alcohol spectrum disorders (FASD) have been described in the literature. Here, we conducted a multivariate analysis of a large array of potential distal influences on FASD risk. METHODS: Interviews were conducted with 2515 mothers of first-grade students whose children were evaluated to assess risk for FASD. Topics included: physical/medical status, childbearing history, demographics, mental health, domestic violence, and trauma. Regression modeling utilized usual level of alcohol consumption by trimester and six selected distal variables (maternal head circumference, body mass index, age at pregnancy, gravidity, marital status, and formal years of education) to differentiate children with FASD from control children. RESULTS: Despite individual variation in distal maternal risk factors among and within the mothers of children with each of the common diagnoses of FASD, patterns emerged that differentiated risk among mothers of children with FASD from mothers whose children were developing typically. Case-control comparisons indicate that mothers of children with FASD were significantly smaller physically, had higher gravidity and parity, and experienced more miscarriages and stillbirths, were less likely to be married, reported later pregnancy recognition, more depression, and lower formal educational achievement. They were also less engaged with a formal religion, were less happy, suffered more childhood trauma and interpersonal violence, were more likely to drink alone or with her partner, and drank to deal with anxiety, tension, and to be part of a group. Regression analysis showed that the predictor variables explain 57.5% of the variance in fetal alcohol syndrome (FAS) diagnoses, 30.1% of partial FAS (PFAS) diagnoses, and 46.4% of alcohol-related neurodevelopmental disorder (ARND) diagnoses in children with FASD compared to controls. While the proximal variables explained most of the diagnostic variance, six distal variables explained 16.7% (1 /6 ) of the variance in FAS diagnoses, 13.9% (1 /7 ) of PFAS, and 12.1% (1 /8 ) of ARND. CONCLUSIONS: Differences in distal FASD risks were identified. Complex models to quantify risk for FASD hold promise for guiding prevention/intervention.

Increasing access to palliative care for patients with advanced cancer of African and Latin American descent: a patient-oriented community-based study protocol.

BACKGROUND: Cancer disparities are a major public health concern in Canada, affecting racialized communities of Latin American and African descent, among others. This is evident in lower screening rates, lower access to curative, and palliative-intent treatments, higher rates of late cancer diagnoses and lower survival rates than the general Canadian population. We will develop an Access to Palliative Care Strategy informed by health equity and patient-oriented research principles to accelerate care improvements for patients with advanced cancer of African and Latin American descent. METHODS: This is a community-based participatory research study that will take place in two Canadian provinces. Patients and community members representatives have been engaged as partners in the planning and design of the study. We have formed a patient advisory council (PAC) with patient partners to guide the development of the Access to Palliative Care Strategy for people of African and Latin American descent. We will engage100 participants consisting of advanced cancer patients, families, and community members of African and Latin American descent, and health care providers. We will conduct in-depth interviews to delineate participants' experiences of access to palliative care. We will explore the intersections of race, gender, socioeconomic status, language barriers, and other social categorizations to elucidate their role in diverse access experiences. These findings will inform the development of an action plan to increase access to palliative care that is tailored to our study population. We will then organize conversation series to examine together with community partners and healthcare providers the appropriateness, effectiveness, risks, requirements, and convenience of the strategy. At the end of the study, we will hold knowledge exchange gatherings to share findings with the community. DISCUSSION: This study will improve our understanding of how patients with advanced cancer from racialized communities in Canada access palliative care. Elements to address gaps in access to palliative care and reduce inequities in these communities will be identified. Based on the study findings a strategy to increase access to palliative care for this population will be developed. This study will inform ways to improve access to palliative care for racialized communities in other parts of Canada and globally.

Geographic Disparities in Access to Cancer Clinical Trials in Canada.

OBJECTIVE: This study aims to evaluate geographic disparities in access to cancer clinical trials across Canada. METHODS: Cancer clinical trial data recorded within the clinicaltrials.gov and reporting the conduct of any of these trials in Canada, 2005 to 2023 were reviewed. Frequency analyses of the number of clinical trials that were registered on clinicaltrials.gov for Canada, individual Canadian provinces, main Canadian urban centers, and different cancer types, according to the funding source (industry versus non-industry), as well as according to different periods (using 3-y intervals) were conducted. Moreover, a comparison of cancer clinical trials per 10,000 persons was done between Canada and the United States. RESULTS: The number of cancer clinical trials per 10,000 individuals (according to the 2021 census) in each province/territory varied between 6.79 (New Brunswick) to 0 (the 3 territories). The number of cancer clinical trials in relation to 1000 projected cancer cases for some of the common tumor types in Canada was then reviewed. The highest number was for lymphoma clinical trials (32.85), whereas the lowest number was for bladder cancer clinical trials (7.06). Most of the trials have industry funding (69%). Using 3-year intervals, the highest number of cancer clinical trials was observed from 2014 to 2016 (778 trials), and the lowest number was observed from 2020 to 2022 (633 trials). CONCLUSIONS: Access to clinical trials in Canada is not equitably distributed, with geographical and primary tumor site disparities. Moreover, access to cancer clinical trials has been negatively impacted during the time of the COVID-19 pandemic.

Genomic analyses in Cornelia de Lange Syndrome and related diagnoses: Novel candidate genes, genotype-phenotype correlations and common mechanisms.

Cornelia de Lange Syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder characterized by highly variable manifestations of growth and developmental delays, upper limb involvement, hypertrichosis, cardiac, gastrointestinal, craniofacial, and other systemic features. Pathogenic variants in genes encoding cohesin complex structural subunits and regulatory proteins (NIPBL, SMC1A, SMC3, HDAC8, and RAD21) are the major pathogenic contributors to CdLS. Heterozygous or hemizygous variants in the genes encoding these five proteins have been found to be contributory to CdLS, with variants in NIPBL accounting for the majority (>60%) of cases, and the only gene identified to date that results in the severe or classic form of CdLS when mutated. Pathogenic variants in cohesin genes other than NIPBL tend to result in a less severe phenotype. Causative variants in additional genes, such as ANKRD11, EP300, AFF4, TAF1, and BRD4, can cause a CdLS-like phenotype. The common role that these genes, and others, play as critical regulators of developmental transcriptional control has led to the conditions they cause being referred to as disorders of transcriptional regulation (or "DTRs"). Here, we report the results of a comprehensive molecular analysis in a cohort of 716 probands with typical and atypical CdLS in order to delineate the genetic contribution of causative variants in cohesin complex genes as well as novel candidate genes, genotype-phenotype correlations, and the utility of genome sequencing in understanding the mutational landscape in this population.

Geographic Disparities in Case Fatality and Discharge Disposition Among Patients With Primary Intracerebral Hemorrhage.

Background We evaluate nationwide trends and urban-rural disparities in case fatality (in-hospital mortality) and discharge dispositions among patients with primary intracerebral hemorrhage (ICH). Methods and Results In this repeated cross-sectional study, we identified adult patients (≥18 years of age) with primary ICH from the National Inpatient Sample (2004-2018). Using a series of survey design Poisson regression models, with hospital location-time interaction, we report the adjusted risk ratio (aRR), 95% CI, and average marginal effect (AME) for factors associated with ICH case fatality and discharge dispositions. We performed a stratified analysis of each model among patients with extreme loss of function and minor to major loss of function. We identified 908 557 primary ICH hospitalizations (overall mean age [SD], 69.0 [15.0] years; 445 301 [49.0%] women; 49 884 [5.5%] rural ICH hospitalizations). The crude ICH case fatality rate was 25.3% (urban hospitals: 24.9%, rural hospitals:32.5%). Urban (versus rural) hospital patients had a lower likelihood of ICH case fatality (aRR, 0.86 [95% CI, 0.83-0.89]). ICH case fatality is declining over time; however, it is declining faster in urban hospitals (AME, -0.049 [95% CI, -0.051 to -0.047]) compared with rural hospitals (AME, -0.034 [95% CI, -0.040 to -0.027]). Conversely, home discharge is increasing significantly among urban hospitals (AME, 0.011 [95% CI, 0.008-0.014]) but not significantly changing in rural hospitals (AME, -0.001 [95% CI, -0.010 to 0.007]). Among patients with extreme loss of function, hospital location was not significantly associated with ICH case fatality or home discharge. Conclusions Improving access to neurocritical care resources, particularly in resource-limited communities, may reduce the ICH outcomes disparity gap.

The clinical and molecular spectrum of the KDM6B-related neurodevelopmental disorder.

De novo variants are a leading cause of neurodevelopmental disorders (NDDs), but because every monogenic NDD is different and usually extremely rare, it remains a major challenge to understand the complete phenotype and genotype spectrum of any morbid gene. According to OMIM, heterozygous variants in KDM6B cause "neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities." Here, by examining the molecular and clinical spectrum of 85 reported individuals with mostly de novo (likely) pathogenic KDM6B variants, we demonstrate that this description is inaccurate and potentially misleading. Cognitive deficits are seen consistently in all individuals, but the overall phenotype is highly variable. Notably, coarse facies and distal skeletal anomalies, as defined by OMIM, are rare in this expanded cohort while other features are unexpectedly common (e.g., hypotonia, psychosis, etc.). Using 3D protein structure analysis and an innovative dual Drosophila gain-of-function assay, we demonstrated a disruptive effect of 11 missense/in-frame indels located in or near the enzymatic JmJC or Zn-containing domain of KDM6B. Consistent with the role of KDM6B in human cognition, we demonstrated a role for the Drosophila KDM6B ortholog in memory and behavior. Taken together, we accurately define the broad clinical spectrum of the KDM6B-related NDD, introduce an innovative functional testing paradigm for the assessment of KDM6B variants, and demonstrate a conserved role for KDM6B in cognition and behavior. Our study demonstrates the critical importance of international collaboration, sharing of clinical data, and rigorous functional analysis of genetic variants to ensure correct disease diagnosis for rare disorders.

Patterns of emergency department visits before diagnosis with digestive neuroendocrine neoplasms.

OBJECTIVE: To evaluate the patterns of emergency department visits before diagnosis with digestive neuroendocrine neoplasms (NENs). METHODS: Linked administrative databases from the province of Alberta, Canada, were examined, and patients diagnosed with digestive NENs from 2004 to 2019 were reviewed. Incidents of emergency department visits in the 3 months before histological diagnosis were reviewed. Multivariable logistic regression analyses were used to examine factors associated with at least one emergency department (ED) visit as well as factors associated with more than one ED visit. The impact of pre-diagnosis ED visits on overall survival was further assessed in a multivariable Cox regression model, which included (in addition to ED visits), age at diagnosis, sex, histology, Charlson comorbidity index, and stage. RESULTS: A total of 2120 patients were considered eligible for the study, and they were included in the analysis (including 1041 patients (49.1%) with at least one ED visit in the 3 months before diagnosis). The following factors were associated with a higher likelihood of an ED visit prior to diagnosis: younger age (OR with increasing age: 0.983; 95% CI: 0.977-0.989), higher comorbidity index (OR: 1.332; 95% CI: 1.215-1.460), female sex (OR: 1.292; 95% CI: 1.084-1.540), and stage IV (OR: 1.515; 95% CI: 1.106-2.075). Likewise, the following factors were associated with more than one ED visit within 3 months before diagnosis: younger age (OR with increasing age: 0.985; 95% CI: 0.979-0.992), higher comorbidity index (OR: 1.280; 95% CI: 1.167-1.405), and female sex (OR: 1.516; 95% CI: 1.230-1.868). Using multivariable Cox regression modeling, the following factors were associated with worse overall survival (higher risk of death): older age (HR: 1.050; 95% CI: 1.043-1.056), higher comorbidity index (HR: 1.280; 95% CI: 1.209-1.356), stage IV (HR: 3.163; 95% CI: 2.562-3.905), neuroendocrine carcinoma histology (HR: 1.645; 95% CI: 1.350-2.003), pre-diagnosis ED visit (HR: 1.784; 95% CI: 1.529-2.083). CONCLUSION: Almost one-half of patients with NENs visit the ED within 3 months before diagnosis. ED visits were associated with younger age, female sex, advanced disease, and higher comorbidity. Moreover, pre-diagnosis ED visit(s) were associated with worse overall survival in the current cohort.

Midcarpal Instability.

Midcarpal instability (MCI) of the wrist represents multiple distinct clinical entities that all have in common abnormal force transmission across the midcarpal joint. This can be asymptomatic but can also result in painful wrist motion, a characteristic catch-up clunk, and symptoms of instability. The carpus is stabilized by numerous extrinsic and intrinsic ligaments. Dynamic joint reactive forces between the proximal and distal carpal rows help create reciprocal motion, which results in smooth, physiologic wrist mechanics. Diagnosis of MCI requires a thorough history, physical examination, and adequate imaging. MCI can be managed nonsurgically with activity modification, physical therapy, specialized orthotics, medications, and corticosteroid injections. A variety of surgical treatment options exists to treat symptomatic MCI. These include arthroscopic thermal capsulorrhaphy, ligament repair or reconstruction, radial osteotomies, and limited radiocarpal or intercarpal fusions. Capsulorrhaphy or ligament repair is favored for mild to moderate cases; osteotomies can be used for the correction of bony deformities contributing to instability, whereas partial wrist arthrodesis is indicated for severe or recurrent instability and fixed deformities.

Challenges in Diagnosis and Treatment of Pancreatic Exocrine Insufficiency among Patients with Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is the most common malignancy of the pancreas and is associated with an extremely poor prognosis. Many PDAC patients suffer from profound nutritional complications such as nutrient deficiencies, weight loss, malnutrition, and cancer cachexia. These complications cause barriers to effective anticancer treatments, gravely influence their quality of life, and decrease their overall survival. Pancreatic exocrine insufficiency (PEI) is defined as impaired digestion due to inadequate secretion of pancreatic enzymes and is a common cause of malnutrition in PDAC. This review first summarizes the existing literature around malnutrition in PDAC, with a particular focus on PEI and its management with pancreatic enzyme replacement therapy (PERT). Second, we summarize existing guidelines and recommendations for the management of PEI among patients with PDAC. Lastly, we highlight potential gaps of knowledge of PEI among healthcare providers resulting in underdiagnosis and treatment, which may have implications for the quality of life and overall survival of PDAC patients.

Impact of Patient Characteristics on the Outcomes of Patients with Gastrointestinal Cancers Treated with Immune Checkpoint Inhibitors.

Gastrointestinal (GI) cancers are a group of malignancies that globally account for a significant portion of cancer incidence and cancer-related death. Survival outcomes for esophageal, gastric, pancreatic, and hepatobiliary cancers remain poor, but new treatment paradigms are emerging with the advent of immune checkpoint inhibitor (ICI) therapy. This review characterizes patient-related prognostic factors that influence the response to ICI therapy. We performed an analysis of the landmark randomized clinical trials in esophageal, gastric, colorectal, hepatocellular, pancreatic, and biliary tract cancers in terms of patient demographic factors. A literature review of smaller retrospective studies investigating patient-related factors was completed. The immunological bases for these associations were further explored. The key predictive factors identified include age, sex, performance status, geography, body mass index, sarcopenia, gut microbiome, various biochemical factors, and disease distribution.

Impact of Time From Diagnosis to Treatment Start on the Outcomes of Patients With Nonmetastatic Anal Squamous Cell Carcinoma.

OBJECTIVE: To assess the impact of time from diagnosis to treatment on the survival outcomes of patients with nonmetastatic anal squamous cell carcinoma, controlling for other clinicopathological features. METHODS: Surveillance, Epidemiology, and End Results research plus database was accessed, and patients with nonmetastatic anal squamous cell carcinoma were reviewed. Factors associated with longer time to treatment were evaluated through multivariable logistic regression analysis. Kaplan-Meier survival estimates were used to examine survival differences according to time to treatment (≤2 vs. >2 mo), and multivariable Cox regression analysis was used to examine factors associated with worse overall and cancer-specific survival. RESULTS: A total of 13,032 patients were considered eligible and they were included in this study. The following factors were associated with longer time to treatment (>2 mo): male sex (odds ratio [OR]: 1.503; 95% CI, 1.292 to 1.749), and non-White race (OR for Black vs. White patients: 1.846; 95% CI, 1.488 to 2.290; OR for American Indian vs. White patients: 2.414; 95% CI, 1.197 to 4.872; OR for Asian-Pacific Islanders vs. White patients: 2.182; 95% CI, 1.440 to 3.309). Using Kaplan-Meier survival estimates, longer time to treatment was associated with worse overall survival (median OS for >2 mo=109 mo; for ≤2 mo=164 mo P <0.0001). Using multivariable Cox regression analysis, the following factors were associated with worse overall survival: older age (hazard ratio [HR]: 1.037; 95% CI, 1.034 to 1.039), male sex (HR: 1.650; 95% CI, 1.548 to 1.758), Black race (HR: 1.341; 95% CI, 1.210 to 1.487), advanced stage (HR for regional vs. localized stage: 1.596; 95% CI, 1.500 to 1.698), and longer time to treatment (HR: 1.385; 95% CI, 1.222 to 1.571). CONCLUSIONS: Time from diagnosis to treatment longer than 2 months is associated with worse survival outcomes among patients with nonmetastatic anal squamous cell carcinoma.