Uncommon Sociodemographic Factors Are Associated With Racial Disparities in Length of Stay Following Oncologic Elective Colectomy.

INTRODUCTION: Although outcome disparities by race have been identified in colorectal cancer, these patterns are challenging to explain using variables that are commonly available in databases. In a single institution serving a diverse community, length of stay (LOS) varies by race following elective oncologic colectomy. We investigated previously unexplored variables that may explain the relationship between race and LOS following elective resection of colorectal neoplasms. METHODS: Retrospective, single institution cohort study from January 2015 to December 2020 for adult patients undergoing elective colorectal cancer resections. Baseline demographic variables and intraoperative factors were analyzed for changes in LOS following elective colorectal resection. Additional retrospective chart review was carried out to determine household member composition and distance from home to hospital. Bivariate analysis was conducted to determine which variables should be included in multivariable analyses. All analyses were conducted using SAS Academic. RESULTS: Most patients (n = 383) were Asian (40%), Black (12%), or Hispanic (26%). Race and LOS were associated with age (P = 0.001 and P < 0.001 for race and LOS, respectively), American Society of Anesthesiologists class (P = 0.004 and P < 0.001), enhanced recovery after surgery protocols (P = 0.006 and P < 0.001), household members (P = 0.009 and P = 0.002), and discharge disposition (P = 0.049 and P < 0.001). In multivariable analysis, household members (P = 0.021) independently remained associated with LOS after controlling for race (P = 0.008) and discharge disposition (P < 0.001). CONCLUSIONS: Household member composition varies with LOS, suggesting that level of support at home may influence decisions regarding discharge disposition, which lead to differences in LOS.

SAGES guidelines for the use of laparoscopy during pregnancy.

BACKGROUND: When pregnant patients present with nonobstetric pathology, the physicians caring for them may be uncertain about the optimal management strategy. The aim of this guideline is to develop evidence-based recommendations for pregnant patients presenting with common surgical pathologies including appendicitis, biliary disease, and inflammatory bowel disease (IBD). METHODS: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Guidelines Committee convened a working group to address these issues. The group generated five key questions and completed a systematic review and meta-analysis of the literature. An expert panel then met to form evidence-based recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation approach. Expert opinion was utilized when the available evidence was deemed insufficient. RESULTS: The expert panel agreed on ten recommendations addressing the management of appendicitis, biliary disease, and IBD during pregnancy. CONCLUSIONS: Conditional recommendations were made in favor of appendectomy over nonoperative treatment of appendicitis, laparoscopic appendectomy over open appendectomy, and laparoscopic cholecystectomy over nonoperative treatment of biliary disease and acute cholecystitis specifically. Based on expert opinion, the panel also suggested either operative or nonoperative treatment of biliary diseases other than acute cholecystitis in the third trimester, endoscopic retrograde cholangiopancreatography rather than common bile duct exploration for symptomatic choledocholithiasis, applying the same criteria for emergent surgical intervention in pregnant and non-pregnant IBD patients, utilizing an open rather than minimally invasive approach for pregnant patients requiring emergent surgical treatment of IBD, and managing pregnant patients with active IBD flares in a multidisciplinary fashion at centers with IBD expertise.

Enhanced Recovery After Surgery protocols mitigate the weekend effect on length of stay following elective colectomy.

BACKGROUND: This study aimed to determine the effect of Enhanced Recovery After Surgery (ERAS) protocols on the weekend effect after elective colectomies. METHODS: This was a retrospective study on all elective colorectal surgeries at a single institution in New York City between January 1, 2015, and December 31, 2020. The length of stay (LOS) by day of the week of surgery and the effect of ERAS using univariable and multivariable analyses were compared. RESULTS: A total of 605 patients were included in the study. Of note, 41 cases were performed on Mondays, 197 cases were performed on Tuesdays, 45 cases were performed on Wednesdays, 187 cases were performed on Thursdays, and 135 cases were performed on Fridays. Univariate analysis showed that, for patients who did not undergo ERAS, Monday and Tuesday were significantly associated with decreased LOS (P < .001). For patients who underwent ERAS, there was no statistically significant difference in LOS (P = .06) when operated on early in the week vs later. After controlling for age, race/ethnicity, comorbidities, complications, functional health status, operation type, duration of surgery, presence of ostomy, and albumin level, adhering to the ERAS protocol was significantly associated with a shorter LOS (P < .001). CONCLUSION: Our study demonstrated that ERAS can mitigate the weekend effect on LOS. ERAS protocols may provide more structure to the expected hospital course and allow patients to reach recovery milestones earlier, facilitating discharge even by covering teams.

Unmasking bias in artificial intelligence: a systematic review of bias detection and mitigation strategies in electronic health record-based models.

OBJECTIVES: Leveraging artificial intelligence (AI) in conjunction with electronic health records (EHRs) holds transformative potential to improve healthcare. However, addressing bias in AI, which risks worsening healthcare disparities, cannot be overlooked. This study reviews methods to handle various biases in AI models developed using EHR data. MATERIALS AND METHODS: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, analyzing articles from PubMed, Web of Science, and IEEE published between January 01, 2010 and December 17, 2023. The review identified key biases, outlined strategies for detecting and mitigating bias throughout the AI model development, and analyzed metrics for bias assessment. RESULTS: Of the 450 articles retrieved, 20 met our criteria, revealing 6 major bias types: algorithmic, confounding, implicit, measurement, selection, and temporal. The AI models were primarily developed for predictive tasks, yet none have been deployed in real-world healthcare settings. Five studies concentrated on the detection of implicit and algorithmic biases employing fairness metrics like statistical parity, equal opportunity, and predictive equity. Fifteen studies proposed strategies for mitigating biases, especially targeting implicit and selection biases. These strategies, evaluated through both performance and fairness metrics, predominantly involved data collection and preprocessing techniques like resampling and reweighting. DISCUSSION: This review highlights evolving strategies to mitigate bias in EHR-based AI models, emphasizing the urgent need for both standardized and detailed reporting of the methodologies and systematic real-world testing and evaluation. Such measures are essential for gauging models' practical impact and fostering ethical AI that ensures fairness and equity in healthcare.

Application of enzyme-linked immunosorbent assay to detect antimicrobial peptides in human intestinal lumen.

Intestinal transplantation is the definitive treatment for intestinal failure. However, tissue rejection and graft-versus-host disease are relatively common complications, necessitating aggressive immunosuppression that can itself pose further complications. Tracking intraluminal markers in ileal effluent from standard ileostomies may present a noninvasive and sensitive way to detect developing pathology within the intestinal graft. This would be an improvement compared to current assessments, which are limited by poor sensitivity and specificity, contributing to under or over-immunosuppression, respectively, and by the need for invasive biopsies. Herein, we report an approach to reproducibly analyze ileal fluid obtained through stoma sampling for antimicrobial peptide/protein concentrations, reasoning that these molecules may provide an assessment of intestinal homeostasis and levels of intestinal inflammation over time. Concentrations of lysozyme (LYZ), myeloperoxidase (MPO), calprotectin (S100A8/A9) and ß-defensin 2 (DEFB2) were assessed using adaptations of commercially available enzyme-linked immunosorbent assays (ELISAs). The concentration of α-defensin 5 (DEFA5) was assessed using a newly developed sandwich ELISA. Our data support that with proper preparation of ileal effluent specimens, precise and replicable determination of antimicrobial peptide/protein concentrations can be achieved for each of these target molecules via ELISA. This approach may prove to be reliable as a clinically useful assessment of intestinal homeostasis over time for patients with ileostomies.

Acute Appendicitis in the Epicenter of the COVID-19 Pandemic: A New York City Single-Center Experience.

BACKGROUND: Appendectomy is the gold standard for simple appendicitis. During the coronavirus-19 pandemic, it was estimated that appendectomies in the United States decreased by 24%. We aimed to describe trends in acute appendicitis management at a center located in one of the largest epicenters of the pandemic. METHODS: This is a retrospective cohort study in a single institution located in Queens, New York, of patients who presented with acute appendicitis. A pre-COVID time period, March-June 2019, was compared to peak-COVID, March-June 2020, and late-COVID, March-June 2021. RESULTS: Of the 382 patients admitted with appendicitis during the time periods, 164 were admitted pre-COVID. Appendicitis presentations decreased by 44% during peak-COVID and 23% in late-COVID. Patients were younger during peak-COVID compared to pre-COVID (39 vs 34 years old, P = .036). Incidence of complicated appendicitis in pre-, peak-, and late-COVID was equivalent (41% vs 46% vs 45%) and operative management was similar (85% vs 76% vs 79%). Non-operative patients had shorter lengths of stay (pre- vs peak-COVID: 4.6 vs 2.9 days, P = .006). Readmission rates were similar between the cohorts across time periods. CONCLUSIONS: During peak-COVID, there was a significant decrease in presentation of acute appendicitis but clinical presentation and outcomes remained similar between the cohorts. Patients who were managed non-operatively may be discharged earlier without increased rates of readmissions.

Development of SkinTracker, an integrated dermatology mobile app and web portal enabling remote clinical research studies.

Introduction: In-person dermatology clinical research studies often face recruitment and participation challenges due to travel-, time-, and cost-associated barriers. Studies incorporating virtual/asynchronous formats can potentially enhance research subject participation and satisfaction, but few mobile health tools are available to enable remote study conduct. We developed SkinTracker, a patient-facing mobile app and researcher-facing web platform, that enables longitudinal collection of skin photos, patient reported outcomes, and biometric health and environmental data. Methods: Eight design thinking sessions including dermatologists, clinical research staff, software engineers, and graphic designers were held to create the components of SkinTracker. Following iterative prototyping, SkinTracker was piloted across six adult and four pediatric subjects with atopic dermatitis (AD) of varying severity levels to test and provide feedback on SkinTracker for six months. Results: The SkinTracker app enables collection of informed consent for study participation, baseline medical history, standardized skin photographs, patient-reported outcomes (e.g., Patient Oriented Eczema Measure (POEM), Pruritus Numerical Rating Scale (NRS), Dermatology Life Quality Index (DLQI)), medication use, adverse events, voice diary to document qualitative experiences, chat function for communication with research team, environmental and biometric data such as exercise and sleep metrics through integration with an Apple Watch. The researcher web portal allows for management and visualization of subject enrollment, skin photographs for examination and severity scoring, survey completion, and other patient modules. The pilot study requested that subjects complete surveys and photographs on a weekly to monthly basis via the SkinTracker app. Afterwards, participants rated their experience in a 7-item user experience survey covering app function, design, and desire for participation in future studies using SkinTracker. Almost all subjects agreed or strongly agreed that SkinTracker enabled more convenient participation in skin research studies compared to an in-person format. Discussion: To our knowledge, SkinTracker is one of the first integrated app- and web-based platforms allowing collection and management of data commonly obtained in clinical research studies. SkinTracker enables detailed, frequent capture of data that may better reflect the fluctuating course of conditions such as AD, and can be modularly customized for different skin conditions to improve dermatologic research participation and patient access.

National Cancer Institute Collaborative Workshop on Shaping the Landscape of Brain Metastases Research: challenges and recommended priorities.

Brain metastases are an increasing global public health concern, even as survival rates improve for patients with metastatic disease. Both metastases and the sequelae of their treatment are key determinants of the inter-related priorities of patient survival, function, and quality of life, mandating a multidimensional approach to clinical care and research. At a virtual National Cancer Institute Workshop in September, 2022, key stakeholders convened to define research priorities to address the crucial areas of unmet need for patients with brain metastases to achieve meaningful advances in patient outcomes. This Policy Review outlines existing knowledge gaps, collaborative opportunities, and specific recommendations regarding consensus priorities and future directions in brain metastases research. Achieving major advances in research will require enhanced coordination between the ongoing efforts of individual organisations and consortia. Importantly, the continual and active engagement of patients and patient advocates will be necessary to ensure that the directionality of all efforts reflects what is most meaningful in the context of patient care.

Osteoimmunology in Periodontitis and Orthodontic Tooth Movement.

PURPOSE OF REVIEW: To review the role of the immune cells and their interaction with cells found in gingiva, periodontal ligament, and bone that leads to net bone loss in periodontitis or bone remodeling in orthodontic tooth movement. RECENT FINDINGS: Periodontal disease is one of the most common oral diseases causing inflammation in the soft and hard tissues of the periodontium and is initiated by bacteria that induce a host response. Although the innate and adaptive immune response function cooperatively to prevent bacterial dissemination, they also play a major role in gingival inflammation and destruction of the connective tissue, periodontal ligament, and alveolar bone characteristic of periodontitis. The inflammatory response is triggered by bacteria or their products that bind to pattern recognition receptors that induce transcription factor activity to stimulate cytokine and chemokine expression. Epithelial, fibroblast/stromal, and resident leukocytes play a key role in initiating the host response and contribute to periodontal disease. Single-cell RNA-seq (scRNA-seq) experiments have added new insight into the roles of various cell types in the response to bacterial challenge. This response is modified by systemic conditions such as diabetes and smoking. In contrast to periodontitis, orthodontic tooth movement (OTM) is a sterile inflammatory response induced by mechanical force. Orthodontic force application stimulates acute inflammatory responses in the periodontal ligament and alveolar bone stimulated by cytokines and chemokines that produce bone resorption on the compression side. On the tension side, orthodontic forces induce the production of osteogenic factors, stimulating new bone formation. A number of different cell types, cytokines, and signaling/pathways are involved in this complex process. Inflammatory and mechanical force-induced bone remodeling involves bone resorption and bone formation. The interaction of leukocytes with host stromal cells and osteoblastic cells plays a key role in both initiating the inflammatory events as well as inducing a cellular cascade that results in remodeling in orthodontic tooth movement or in tissue destruction in periodontitis.

Progressive neuronal plasticity in primate visual cortex during stimulus familiarization.

The primate brain is equipped to learn and remember newly encountered visual stimuli such as faces and objects. In the macaque inferior temporal (IT) cortex, neurons mark the familiarity of a visual stimulus through response modification, often involving a decrease in spiking rate. Here, we investigate the emergence of this neural plasticity by longitudinally tracking IT neurons during several weeks of familiarization with face images. We found that most neurons in the anterior medial (AM) face patch exhibited a gradual decline in their late-phase visual responses to multiple stimuli. Individual neurons varied from days to weeks in their rates of plasticity, with time constants determined by the number of days of exposure rather than the cumulative number of presentations. We postulate that the sequential recruitment of neurons with experience-modified responses may provide an internal and graded measure of familiarity strength, which is a key mnemonic component of visual recognition.

Operative Management of Acute Appendicitis Was Safe During the COVID-19 Pandemic Shutdown.

INTRODUCTION: In the spring of 2020, New York City was one of the first epicenters of the COVID outbreak. In this study, we evaluate the incidence and treatment of appendicitis in two New York City community hospitals during the COVID pandemic. METHODS: This retrospective study focused on the incidence and outcome of acute appendicitis in the adult population (>18 y old) during peak-COVID periods (March 16, 2020,-June 15, 2020) compared to pre-COVID and post-COVID periods. We compared the number of patients who underwent operative versus nonoperative management, patient demographics, length of stay (LOS), complications, and readmission rates within these time periods. Data are presented as mean ± standard deviation (analysis of variance). RESULTS: From January 1, 2020 to December 31, 2020, 393 patients presented with acute appendicitis and 321 (81.7%) were treated operatively, compared to 441 total and 366 treated operatively (83%) in 2019 (P = 0.88). During the COVID outbreak, fewer patients presented with appendicitis (mean 6.9 ± 1 pre-COVID case/week, 4.4 ± 2.4 peak-COVID cases/week and 7.6 ± 0.65 post-COVID cases/week, P = 0.018) with no significant difference in the pre-COVID and post-COVID period. There was no difference in LOS between the pre-, peak-, and post-COVID periods with a median of 1 for all the three, (interquartile range (IQR): 0.8-2, 0.6-2, 0.6-2, respectively, P = 0.43). Additionally, there was no difference in 30-day readmission rates (4.2%, 0%, 3.9%, P = 0.99) and postoperative complications (4.2%, 0%, 2.9%, P = 0.98). CONCLUSIONS: During peak-COVID, there was a significant reduction in the number of patients who presented with acute appendicitis without a post rebound increase in presentation. Those who presented during peak-COVID were able to undergo operative management safely, without affecting LOS or postoperative complications.

Outcomes of a Colorectal Enhanced Recovery After Surgery Protocol Modified for a Diverse and Urban Community.

INTRODUCTION: Enhanced recovery after surgery (ERAS) colorectal programs have been shown to improve the length of stay (LOS) without increasing hospital resource utilization at academic centers worldwide. A multidisciplinary ERAS protocol that includes preoperative, intraoperative, and postoperative management guidelines was recently implemented at our urban, racially diverse, and academically affiliated community hospital. A delivery option was provided to reduce barriers to care. Given our unique patient population, the objective of our study was to determine if improvements in outcomes were reproducible in our hospital. METHODS: This is a retrospective study of patients undergoing elective colectomy at New York-Presbyterian Queens Hospital between January 1, 2015, and December 31, 2020. Patient outcomes were compared between surgeries performed under standard practice (all colectomies prior to April 2017) and those performed after the implementation of the ERAS protocol. Demographic and perioperative data were abstracted from a prospectively derived database used to submit data to the National Surgical Quality Improvement Program. Additional data were obtained from chart review. RESULTS: Six hundred five elective colectomies were performed by 12 surgeons (range 1-228 cases) during the study period. Of these, 22 were performed open (41% followed ERAS), 467 were performed laparoscopically (57% followed ERAS), and 116 were performed robotically (74% followed ERAS). The average patient age was 64 y. Of which, 55% were male; 34% were Asian, 27% were non-Hispanic Caucasian, 27% were Hispanic, and 11% were Black or African American (all P-values > 0.05 for ERAS versus non-ERAS). Average duration of procedure was longer in the ERAS group (262 min versus 243 min, P = 0.04), although when stratified by procedure type, this relationship held true only for laparoscopic procedures. Hospital LOS was significantly shorter in the ERAS group (4.3 versus 5.4 d, P < 0.001) and this relationship held true for procedures performed both laparoscopically (4.2 versus 5.3 d, P = 0.01) and robotically (4.1 versus 5.1 d, P = 0.04). Of the ERAS group, patients who opted for delivery of ERAS components (n = 205) had the shortest LOS when compared to patients who picked up components (n = 91) or opted out of ERAS (n = 309) (4.1 versus 4.4 versus 5.2 d, P = 0.003). No significant differences were found for 30-d mortality, 30-d readmission, wound infection, or other postoperative complications (all P-values > 0.05). CONCLUSIONS: Implementation of an ERAS protocol in an urban, diverse, academically affiliated community hospital is associated with reductions in LOS for colectomies performed both laparoscopically and robotically. Facilitating ERAS compliance with a delivery option was also associated with improvements in hospital LOS. Preoperative nutrition supplementation was not associated with outcomes. No differences in mortality, readmission rates, or rates of postoperative complications were found.

Multi-society consensus conference and guideline on the treatment of gastroesophageal reflux disease (GERD).

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most common diseases in North America and globally. The aim of this guideline is to provide evidence-based recommendations regarding the most utilized and available endoscopic and surgical treatments for GERD. METHODS: Systematic literature reviews were conducted for 4 key questions regarding the surgical and endoscopic treatments for GERD in adults: preoperative evaluation, endoscopic vs surgical or medical treatment, complete vs partial fundoplication, and treatment for obesity (body mass index [BMI] ≥ 35 kg/m2) and concomitant GERD. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. Recommendations for future research were also proposed. RESULTS: The consensus provided 13 recommendations. Through the development of these evidence-based recommendations, an algorithm was proposed for aid in the treatment of GERD. Patients with typical symptoms should undergo upper endoscopy, manometry, and pH-testing; additional testing may be required for patients with atypical or extra-esophageal symptoms. Patients with normal or abnormal findings on manometry should consider undergoing partial fundoplication. Magnetic sphincter augmentation or fundoplication are appropriate surgical procedures for adults with GERD. For patients who wish to avoid surgery, the Stretta procedure and transoral incisionless fundoplication (TIF 2.0) were found to have better outcomes than proton pump inhibitors alone. Patients with concomitant obesity were recommended to undergo either gastric bypass or fundoplication, although patients with severe comorbid disease or BMI > 50 should undergo Roux-en-Y gastric bypass for the additional benefits that follow weight loss. CONCLUSION: Using the recommendations an algorithm was developed by this panel, so that physicians may better counsel their patients with GERD. There are certain patient factors that have been excluded from included studies/trials, and so these recommendations should not replace surgeon-patient decision making. Engaging in the identified research areas may improve future care for GERD patients.

Local features drive identity responses in macaque anterior face patches.

Humans and other primates recognize one another in part based on unique structural details of the face, including both local features and their spatial configuration within the head and body. Visual analysis of the face is supported by specialized regions of the primate cerebral cortex, which in macaques are commonly known as face patches. Here we ask whether the responses of neurons in anterior face patches, thought to encode face identity, are more strongly driven by local or holistic facial structure. We created stimuli consisting of recombinant photorealistic images of macaques, where we interchanged the eyes, mouth, head, and body between individuals. Unexpectedly, neurons in the anterior medial (AM) and anterior fundus (AF) face patches were predominantly tuned to local facial features, with minimal neural selectivity for feature combinations. These findings indicate that the high-level structural encoding of face identity rests upon populations of neurons specialized for local features.

The State of Preclinical Modeling for Early Phase Cancer Trials Using Molecularly Targeted Agents with Radiation.

Preclinical studies inform and guide the development of novel treatment combination strategies that bridge the laboratory with the clinic. We aimed to evaluate approaches cancer researchers used to justify advancing new combinations of molecularly targeted agents and radiation treatment into early-phase human clinical trials. Unsolicited early phase clinical trial proposals submitted to the National Cancer Institute's Cancer Therapy Evaluation Program between January 2016 and July 2020 were curated to quantify key characteristics and proportion of preclinical data provided by trialists seeking to conduct molecularly targeted agent-radiation combination studies in cancer patients. These data elucidate the current landscape for how the rationale for a molecularly targeted agent-radiation combination therapy is supported by preclinical research and illustrate unique challenges faced in translation at the intersection of precision medicine and radiation oncology.

Demographic and Clinical Factors Associated with Patient-Reported Remission in Psoriatic Arthritis.

INTRODUCTION: Achievement of remission in psoriatic arthritis is a key goal for patients and clinicians, yet definitions of remission may vary. Previous efforts have utilized multidomain measures such as minimal disease activity that assess the status of joints, skin, and function to determine current level of psoriatic arthritis (PsA) disease activity. The goal of this study is to identify factors associated with patient-reported psoriatic arthritis remission. METHODS: The National Psoriasis Foundation conducted a cross-sectional study using an online survey of a random stratified sample of 1570 individuals with psoriatic disease in the USA. Participants were asked about a provider diagnosis of psoriasis and/or psoriatic arthritis, comorbid conditions, and psoriatic arthritis impact and disease activity, and demographic questions. All participants reporting a physician-given diagnosis of psoriatic arthritis were asked if they felt their psoriatic arthritis was in remission ("Do you feel your psoriatic arthritis is in remission?" Yes/No/Unsure) and, if so, length of remission. Individuals with psoriasis and psoriatic arthritis reporting a body surface area impacted by psoriasis 3% or less were asked if they felt their psoriasis was in remission. Psoriatic arthritis disease activity and impact was assessed using the nine-question Psoriatic Arthritis Impact of Disease (PsAID-9) instrument and a global PsA-related quality of life question. PsAID-9 scores ≤ 4 were used to indicate acceptable disease state. Multivariate logistic regression was used to identify factors associated with patient-perceived PsA remission. RESULTS: Of 834 participants with PsA, including 76 (4.8%) with PsA without skin involvement ever, 144 (17.3%) felt their psoriatic arthritis was in remission, with an average remission duration of 43 months. Of those in remission, 116 (78.4%) reported currently using a treatment for their PsA, with most (75.7%) reporting using a biologic therapy for their PsA in the past 12 months. Multivariate logistic regression revealed that patient-perceived psoriatic arthritis remission was independently associated with experiencing acceptable disease state (PsAID-9 ≤ 4), perception of psoriasis remission, lower impact of PsA on global quality of life, and non-white race. Age, sex, body mass index, or biologic use in the last 12 months were not associated with patient-reported PsA remission. CONCLUSION: Overall, patient perception of PsA remission was most strongly associated with patient-reported psoriasis remission.

TNF-alpha inhibitors and ustekinumab for the treatment of psoriasis: therapeutic utility in the era of IL-17 and IL-23 inhibitors.

Psoriasis is a chronic inflammatory condition for which eleven FDA-approved biologic therapies are approved. Over the past decade, studies have documented the higher efficacy of IL-17 and IL-23 inhibitors for the treatment of psoriasis compared to the TNF-alpha inhibitors and ustekinumab, an IL-12/23 inhibitor. Despite this, there remains an important role for the use of TNF-alpha inhibitors and ustekinumab in the treatment of psoriasis. Here, we review how considerations of infection and malignancy risk, patient demographics, treatment resistance, and co-morbidities may make certain TNF-alpha inhibitors or ustekinumab an excellent choice for therapy in particular patient subgroups.

Single Cell Transcriptome and Surface Epitope Analysis of Ankylosing Spondylitis Facilitates Disease Classification by Machine Learning.

Ankylosing spondylitis (AS) is an immune-mediated inflammatory disorder that primarily affects the axial skeleton, especially the sacroiliac joints and spine. This results in chronic back pain and, in extreme cases, ankylosis of the spine. Despite its debilitating effects, the pathogenesis of AS remains to be further elucidated. This study used single cell CITE-seq technology to analyze peripheral blood mononuclear cells (PBMCs) in AS and in healthy controls. We identified a number of molecular features associated with AS. CD52 was found to be overexpressed in both RNA and surface protein expression across several cell types in patients with AS. CD16+ monocytes overexpressed TNFSF10 and IL-18Rα in AS, while CD8+ TEM cells and natural killer cells overexpressed genes linked with cytotoxicity, including GZMH, GZMB, and NKG7. Tregs underexpressed CD39 in AS, suggesting reduced functionality. We identified an overrepresented NK cell subset in AS that overexpressed CD16, CD161, and CD38, as well as cytotoxic genes and pathways. Finally, we developed machine learning models derived from CITE-seq data for the classification of AS and achieved an Area Under the Receiver Operating Characteristic (AUROC) curve of > 0.95. In summary, CITE-seq identification of AS-associated genes and surface proteins in specific cell subsets informs our understanding of pathogenesis and potential new therapeutic targets, while providing new approaches for diagnosis via machine learning.