Outcomes and factors associated with cryptococcal disease among cirrhotics: A study of the national inpatient sample 2005 to 2014.

BACKGROUND: Cryptococcal disease (CD) confers a higher mortality in cirrhotic patients compared to non-cirrhotic patients. Factor association for CD in cirrhotic patients is poorly understood. Our aim was to determine the incidence, demographic, and comorbidities associated with CD among cirrhotic patients in the United States (US). METHOD: Retrospective analysis of admissions of cirrhotic patients, with or without CD, using the National Inpatient Sample (NIS) database from 2005 to 2014. The number of admissions were reported in raw and weighted frequencies. The trends of CD among cirrhotic patients and overall CD were evaluated. Rao-Scott chi-square, t-tests, and multivariate logistic regressions were performed to evaluate variables and CD among cirrhotic patients. RESULTS: There were 886,962 admissions for cirrhosis, and 164 of these with CD. By adjusted odds ratio (AOR), CD was more often associated with cirrhosis in Southern (2.95; 95 % CI 1.24, 7.02) and Western regions (4.45; 95 % CI 1.91, 10.37), Hispanic patients (1.80; 95 % CI 1.01, 3.20), and patients with chronic kidney disease (CKD) (3.13; 95 % CI 2.09, 4.69). Of note, CD in cirrhotic patients was associated with higher inpatient mortality (AOR of 3.89, 95 % CI 2.53, 5.99), longer length of stay (9.87 vs. 4.88 days), and a higher total charge ($76,880 vs. $ 37,227) when compared to cirrhotic patients without CD. DISCUSSION: Patients with cirrhosis admitted with CD have a high inpatient mortality. The geographical location and CKD were important factors associated with CD among cirrhotic patients. Autoimmune liver diseases and immunosuppression did not appear to increase the risk of CD.

Preoperative Symptoms of Depression are Associated with Worse Capability 6-weeks and 6-months After Total Hip Arthroplasty for Osteoarthritis.

BACKGROUND: Symptoms of depression have been associated with greater incapability following total hip arthroplasty (THA). A brief, 2-question, measure of symptoms of depression - the Patient Health Questionnaire 2 (PHQ-2) - may be sufficient to measure associations with the magnitude of incapability during recovery from THA. This study investigated whether preoperative symptoms of depression (measured with the PHQ-2) correlated with levels of incapability 6 weeks and 6 months after THA, accounting for demographic and clinical factors. METHODS: We performed a prospective cohort study across 5 centers and recruited 101 patients undergoing THA, of whom 90 (89%) completed follow-up. Patients completed demographics, a pre-operative two-item (PHQ-2) measure of symptoms of depression, and the Hip Dysfunction and Osteoarthritis Outcome Score for Joint Replacement HOOS JR at 6-weeks and 6-months postoperatively. Negative binomial regression models determined factors associated with HOOS JR at 6 weeks and 6 months, accounting for potential confounders. RESULTS: Accounting for potential confounding factors, we found that higher preoperative PHQ-2 scores (reflecting greater symptoms of depression) were associated with lower HOOS JR scores (reflecting a greater level of hip disability) at both 6 weeks (Regression Coefficient (RC) = -0.67, P < 0.001) and 6 months (RC = -1.9, P < 0.001) after THA. CONCLUSION: Symptoms of depression on a 2-question pre-operative questionnaire are common, and greater symptoms of depression are associated with reduced capability within the first year following THA. These findings support the prioritization of routine mental health assessments before THA. Measuring mindset using relatively brief instruments will be important considering the current shift toward implementing self-reported measures of health status in clinical practice and incorporating them within alternative payment models.

Considering the cellular landscape in marrow stimulation techniques for cartilage repair.

BACKGROUND: Marrow stimulation is a common reparative approach to treat injuries to cartilage and other soft tissues (e.g., rotator cuff). It involves the recruitment of bone marrow elements and mesenchymal stem cells (MSCs) into the defect, theoretically initiating a regenerative process. However, the resulting repair tissue is often weak and susceptible to deterioration with time. The populations of cells at the marrow stimulation site (beyond MSCs), and their contribution to inflammation, vascularity, and fibrosis, may play a role in quality of the repair tissue. SUMMARY: In this review, we accomplish three goals: 1) systematically review clinical trials on the augmentation of marrow stimulation and evaluate their assumptions on the biological elements recruited; 2) detail the cellular populations in bone marrow and their impact on healing; and 3) highlight emerging technologies and approaches that could better guide these specific cell populations towards enhanced cartilage or soft tissue formation. KEY MESSAGES: We found that most clinical trials do not account for cell heterogeneity, nor do they specify the regenerative element recruited, and those that do typically utilize descriptions such as "clots", "elements", and "blood". Furthermore, our review of bone marrow cell populations demonstrates a dramatically heterogenous cell population, including hematopoietic cells, immune cells, fibroblasts, macrophages, and only a small population of MSCs. Finally, the field has developed numerous innovative techniques to enhance the chondrogenic potential (and reduce the anti-regenerative impacts) of these various cell types. We hope this review will guide approaches that account for cellular heterogeneity and improve marrow stimulation techniques to treat chondral defects.

Cerebrospinal fluid diversion from the cisterna magna in patients with idiopathic intracranial hypertension and slit ventricles: long-term effectiveness, revision rates, and clinical outcomes.

OBJECTIVE: Idiopathic intracranial hypertension (IIH) is a cerebrospinal fluid (CSF) disorder defect that is frequently treated with CSF shunts. Shunts utilizing the cisterna magna as a proximal reservoir have been described in literature, however, long-term outcomes are unknown. The present study aims to describe the long-term effectiveness, revision rates, and clinical outcomes of this shunt in 14 patients with IIH and slit ventricles. METHODS: A single-center retrospective review of 14 IIH patients treated by cisterna magna shunts was performed. Shunt histories, including revision rate and time until first shunt failure for ventricular, lumbar, and cisterna magna shunts were recorded. "Revision rate" was calculated as the total number of shunt revisions over years of total shunt placement. The average follow-up time was 12.08 years. RESULTS: The mean age at first cisterna magna shunt placement was 18.1 years (6.6 - 43.3 years) and all patients had radiological evidence of slit ventricles. Cisterna magna shunts improved or resolved clinical symptoms for all 14 patients and had a lower rate of revisions (0.42 revision/year) compared to ventricular (0.72 revision/year) and lumbar (1.30 revision/year) shunts. Of the 11 patients still requiring CSF diversion at the end of the study, eight had functioning shunts that utilized the cisterna magna. CONCLUSIONS: The cisterna magna shunt may be a suitable option for patients with IIH and slit ventricles. Further study is needed to understand the clinical utility of this shunt for the population in which it is indicated.

The Curious Case of a Painful Leg Ulcer.

Sickle cell disease is a condition that can involve numerous organ systems secondary to vascular occlusion. Herein, we present a case of a 21-year-old male with sickle cell disease requiring long-term hydroxyurea therapy. Upon migrating to the United States from Yemen, the patient developed a rapidly progressive, exquisitely painful ulcer on his right lower extremity. Given his country of origin, a broad differential, including select infectious diseases, was essential. Moreover, establishing the unequivocally correct diagnosis was crucial to determine proper and safe therapy. Ultimately, a lesional biopsy demonstrated numerous sickled red blood cells occluding blood vessels, leading to the diagnosis of sickle cell disease-related leg ulceration.

Targeting of lysosomal-bound protein mEAK-7 for cancer therapy.

mEAK-7 (mammalian EAK-7 or MTOR-associated protein, eak-7 homolog), is an evolutionarily conserved lysosomal membrane protein that is highly expressed in several cancer cells. Multiple recent studies have identified mEAK-7 as a positive activator of mTOR (mammalian/mechanistic target of rapamycin) signaling via an alternative mTOR complex, implying that mEAK-7 plays an important role in the promotion of cancer proliferation and migration. In addition, structural analyses investigating interactions between mEAK-7 and V-ATPase, a protein complex responsible for regulating pH homeostasis in cellular compartments, have suggested that mEAK-7 may contribute to V-ATPase-mediated mTORC1 activation. The C-terminal α-helix of mEAK-7 binds to the D and B subunits of the V-ATPase, creating a pincer-like grip around its B subunit. This binding undergoes partial disruption during ATP hydrolysis, potentially enabling other proteins such as mTOR to bind to the α-helix of mEAK-7. mEAK-7 also promotes chemoresistance and radiation resistance by sustaining DNA damage-mediated mTOR signaling through interactions with DNA-PKcs (DNA-dependent protein kinase catalytic subunit). Taken together, these findings indicate that mEAK-7 may be a promising therapeutic target against tumors. However, the precise molecular mechanisms and signal transduction pathways of mEAK-7 in cancer remain largely unknown, motivating the need for further investigation. Here, we summarize the current known roles of mEAK-7 in normal physiology and cancer development by reviewing the latest studies and discuss potential future developments of mEAK-7 in targeted cancer therapy.

Spatial mass cytometry-based single cell imaging reveals a disrupted epithelial-immune axis in prurigo nodularis.

Prurigo nodularis (PN) is a chronic, inflammatory skin condition that disproportionately affects African Americans and features intensely pruritic, hyperkeratotic nodules on the extremities and trunk. PN is understudied compared to other inflammatory skin diseases, with the spatial organization of the cutaneous infiltrate in PN yet to be characterized. In this work, we employ spatial imaging mass cytometry to visualize prurigo nodularis lesional skin inflammation and architecture with single cell resolution through an unbiased machine learning approach. PN lesional skin has increased expression of caspase 3, NFkB, and pSTAT3 as compared to healthy skin. Keratinocytes in lesional skin are subdivided into CD14+CD33+, CD11c+, CD63+, and caspase 3+ innate subpopulations. CD14+ macrophage populations expressing pERK1/2 correlate positively with patient-reported itch (p=0.006). Hierarchical clustering reveals a cluster of prurigo nodularis patients with greater atopy, increased NFkB+pSTAT3+pERK1/2+ MoDCs, and increased vimentin expression (p<0.05). Neighborhood analysis finds interactions between CD14+ macrophages, CD3+ T cells, MoDCs, and keratinocytes expressing innate immune markers. These findings highlight pERK+CD14+ macrophages as contributors to itch and suggest an epithelial-immune axis in prurigo nodularis pathogenesis.

Impact of aspirin use on rates of metastasis in patients with esophageal cancer: insights from the National Inpatient Sample.

Despite advancing treatment methods, esophageal cancer (EC) maintains a high mortality rate and poor prognosis. Through various mechanisms, aspirin has been suggested to have a chemopreventive effect on EC. However, the long-term impact, particularly regarding the rate of metastasis, needs to be further elucidated. NIS 2016-2020 was used to identify adult patients (age > 18 years) with EC using ICD-10 codes. Patients with missing demographics and mortality were excluded. Patients were stratified into two groups based on aspirin use. Data were collected on patient demographics, Elixhauser Comorbidity Index (ECI), and comorbidities (hypertension, chronic pulmonary disease, coronary artery disease (CAD), chronic kidney disease (CKD), congestive heart failure (CHF), coagulopathy, alcohol use, smoking, and obesity). The outcomes studied were rates of total metastasis, gastrointestinal (GI) metastasis, non-GI metastasis, and lymphoid metastasis. Multivariate logistic regression analysis was performed to evaluate the impact of aspirin use on various metastases after adjusting for patient demographics, comorbidities, and ECI. Out of 190,655 patients, 20,650 (10.8%) patients were aspirin users. Majority of the patients in the aspirin group were aged > 65 years (74.7%), males (82.1%), White race (84%), and had medicare insurance (71%). There was a higher incidence of diabetes, hypertension, chronic pulmonary disease, CAD, CKD, CHF, and smoking in aspirin users than non-aspirin users. Patients with aspirin users had a lower incidence of metastasis (28.9% vs. 38.7%, P < 0.001), GI metastasis (14.2% vs. 20.6%, P < 0.001), non-GI metastasis (15.1% vs. 22%, P < 0.001), and lymphoid metastasis (8.9% vs. 11.3%, P < 0.001) than non-aspirin users. After adjusting for confounding factors, patients with aspirin use had lower odds of having metastasis (aOR-0.73, 95% CI-0.70-0.77, P < 0.001). Our study noted that aspirin use is associated with a reduction in the rate of metastasis in patients with EC. These studies support the use of aspirin in patients with EC and suggest the need for further studies to understand the mechanism by which aspirin use reduces metastasis in patients with EC.

Predicting dental anxiety in young adults: classical statistical modelling approach versus machine learning approach.

OBJECTIVES: To predict and identify the key demographic and clinical exposure factors associated with dental anxiety among young adults, and to compare if the traditional statistical modelling approach provides similar results to the machine learning (ML) approach in predicting factors for dental anxiety. METHODS: A cross-sectional study of Western Illinois University students. Three survey instruments (sociodemographic questionnaire, modified dental anxiety scale (MDAS), and dental concerns assessment tool (DCA)) were distributed via email to the students using survey monkey. The dependent variable was the mean MDAS scores, while the independent variables were the sociodemographic and dental concern assessment variables. Multivariable analysis was done by comparing the classical statistical model and the machine learning model. The classical statistical modelling technique was conducted using the multiple linear regression analysis and the final model was selected based on Akaike information Criteria (AIC) using the backward stepwise technique while the machine learining modelling was performed by comparing two ML models: LASSO regression and extreme gradient boosting machine (XGBOOST) under 5-fold cross-validation using the resampling technique. All statistical analyses were performed using R version 4.1.3. RESULTS: The mean MDAS was 13.73 ± 5.51. After careful consideration of all possible fitted models and their interaction terms the classical statistical approach yielded a parsimonious model with 13 predictor variables with Akaike Information Criteria (AIC) of 2376.4. For the ML approach, the Lasso regression model was the best-performing model with a mean RMSE of 0.617, R2 of 0.615, and MAE of 0.483. Comparing the variable selection of ML versus the classical statistical model, both model types identified 12 similar variables (out of 13) as the most important predictors of dental anxiety in this study population. CONCLUSION: There is a high burden of dental anxiety within this study population. This study contributes to reducing the knowledge gap about the impact of clinical exposure variables on dental anxiety and the role of machine learningin the prediction of dental anxiety. The predictor variables identified can be used to inform public health interventions that are geared towards eliminating the individual clinical exposure triggers of dental anxiety are recommended.

Bridging the Gap: A Strategic Approach to Upscale Knowledge Among Diverse Healthcare Providers for Effective Tuberculosis Management in Gujarat, India.

INTRODUCTION: Tuberculosis (TB) remains a global health challenge, particularly in low- and middle-income countries. Knowledge gaps among healthcare providers (HCPs) significantly impact TB management, hindering timely care-seeking and effective interventions. OBJECTIVE: The primary objective was to assess knowledge gaps among 3086 HCPs engaged in the National Tuberculosis Elimination Program (NTEP) implementation in Gujarat, India. The study provided a platform to develop and implement cadre-specific training modules to address identified knowledge deficiencies and enhance TB management. METHODOLOGY: The study was conducted in two phases. Phase one was designed as a cross-sectional assessment to identify the knowledge gaps. Phase two involved the development of cadre-specific training modules based on identified deficiencies in the knowledge, crafted with collaboration from an expert panel. The training impact will be evaluated after completion of the training of all cadres through a comprehensive assessment. RESULTS: Out of 3086 assessed HCPs, 26% scored below the passing benchmark, revealing significant knowledge gaps. The variations were observed among and within the same cadres, with the accredited social health activists (ASHAs) and community health workers showing higher proficiency while pharmacists and medical officers showed lower proficiency. The cadre-specific training modules and training cascade were designed to address these gaps and improve TB-related knowledge and skills. CONCLUSION: The study underscores the critical need for targeted interventions to address knowledge gaps among HCPs involved in TB control. The customized HCP-specific training programs are recommended to enhance knowledge, improve TB management, and contribute to national TB elimination goals.

Revealing Early Spatial Patterns of Cellular Responsivity in Fiber-Reinforced Microenvironments.

Due to responses to reviewer comments, we are slightly above the word limit for the abstract. The revised version is included in the main manuscript text. Please let us know if this is an issue, and we can revise to try to get under the word limit. Thank you.

The impact of Clostridioides difficile infection on outcomes among kidney transplant recipients.

BACKGROUND: Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality among hospitalized patients, particularly those who are immunosuppressed. We aim to assess the outcomes of CDI among kidney transplant (KT) recipients. METHODS: Nationwide Inpatient Sample from 2016 to 2020 was used to identify patients with KT and stratify based on the presence of CDI. Data were collected regarding demographics and comorbidities. Outcomes included in-hospital mortality, acute kidney injury, intensive care unit admission, transplant rejection, transplant failure, length of stay, and total hospitalization charges. The relationships between variables of interest and outcomes were analyzed using multivariate regression. RESULTS: A total of 557,635 KT recipients were included. CDI prevalence was 2.4%. The majority of patients in the CDI group were age >65 (43.6%), female (51%), White (55.3%), and had Medicare insurance (74.9%). On multivariate regression analysis, CDI was associated with increased odds of acute kidney injury (aOR 2.06, p < 0.001), intensive care unit admission (aOR 2.47, p < 0.001), and mortality (aOR 1.90, p < 0.001). CDI was also associated with longer length of stay (9.35 days vs 5.42 days, p < 0.001) and higher total hospitalization charges ($110,063 vs $100,006, p < 0.001). There was no difference in transplant rejection, complication, failure, or infection among KT recipients with CDI and those without. CONCLUSIONS: We found that CDI was associated with worse outcomes and higher costs. KT patients should be monitored closely for signs of CDI in order to initiate appropriate management.

Kaposi's Sarcoma Cases Manifesting as Non-Specific "Edema".

Kaposi sarcoma can have a myriad cutaneous presentation, but an underrecognized one is an initial manifestation of simply edema. Herein, we highlight a series of cases where edema was the presenting feature of Kaposi Sarcoma and emphasize the importance of recognizing this finding as a possible sign of KS. Keywords: Kaposi Sarcoma, HIV, edema.

Recent technological development of penile prosthesis: a literature review.

Background and Objective: In contemporary Urology, the gold standard for treatment of erectile dysfunction refractory to medical therapy has been implantation with a penile prosthesis. The past 40 years has witnessed evolutions in technology and surgical techniques, which have led to increased patient satisfaction rates and decreased complication and infection rates. This review is an update to a prior review article that evaluates these advancements in the context of patient satisfaction and different rates of complications following surgeries. In addition, the review compares malleable and inflatable prostheses with regard to infection rate, mechanical failure rate, and erosion rate. Methods: A literature search was conducted using Medline and Google Scholar to examine papers from 1973 to the present day. Keywords, such as, "penile prosthesis surgery", "malleable penile prosthesis", "inflatable penile prosthesis", "two-piece Inflatable Penile Prosthesis (IPP)", and "three-piece IPP" were utilized during the search. A total of 76 papers were included, and all were in English. Key Content and Findings: Studies on the latest models of each of the three prostheses (malleable, two-piece IPP, three-piece IPP) revealed patient satisfaction ratings at or above 75%. Both types of IPPs were associated with greater satisfaction and lower erosion rates while malleable prostheses were associated with lower mechanical failure rates. Although no significant differences in infection rates were noted between the prosthesis types, a history of diabetes, obesity, and smoking were predictive of infection events. Conclusions: The three-piece IPP, if indicated for a suitable patient, is generally accepted as the best type of prosthesis given its biological mimicry to an erect human penis.

Comprehensive geriatric assessment predicts listing for kidney transplant in patients with end-stage renal disease: a retrospective cohort study.

BACKGROUND: Comprehensive geriatric assessment (CGA) involves a formal broad approach to assess frailty and creating a plan for management. However, the impact of CGA and its components on listing for kidney transplant in older adults has not been investigated. METHODS: We performed a single-center retrospective study of patients with end-stage renal disease who underwent CGA during kidney transplant candidacy evaluation between 2017 and 2021. All patients ≥ 65 years old and those under 65 with any team member concern for frailty were referred for CGA, which included measurements of healthcare utilization, comorbidities, social support, short physical performance battery, Montreal Cognitive Assessment (MoCA), and Physical Frailty Phenotype (FPP), and estimate of surgical risk by the geriatrician. RESULTS: Two hundred and thirty patients underwent baseline CGA evaluation; 58.7% (135) had high CGA ("Excellent" or "Good" rating for transplant candidacy) and 41.3% (95) had low CGA ratings ("Borderline," "Fair," or "Poor"). High CGA rating (OR 8.46; p < 0.05), greater number of CGA visits (OR 4.93; p = 0.05), younger age (OR 0.88; p < 0.05), higher MoCA scores (OR 1.17; p < 0.05), and high physical activity (OR 4.41; p < 0.05) were all associated with listing on transplant waitlist. CONCLUSIONS: The CGA is a useful, comprehensive tool to help select older adults for kidney transplantation. Further study is needed to better understand the predictive value of CGA in predicting post-operative outcomes.

Hydroxyapatite deposition disease, an overlooked differential diagnosis in the emergency department: a case series and review of literature.

Hydroxyapatite crystal deposition disease (HADD) poses diagnostic challenges in the emergency department (ED) as it may clinically present similarly to infection and other musculoskeletal conditions. Misdiagnosis often leads to unnecessary treatments and resource over-utilization. This review article provides an overview of HADD in seven patients who presented to the ED secondary to an acute presentation of this disease process. HADD is a prevalent pathology, which commonly involves the shoulder, followed by the hip, elbow, wrist, and knee. Predisposing risk factors, such as diabetes and certain genetic factors, have also been identified. Clinical history and imaging, particularly radiographs, play a vital role in diagnosing HADD, with characteristic calcification patterns observed in different stages of the disease. Conservative nonsurgical therapy is the mainstay of treatment, providing effective symptom relief in over 90% of cases. By recognizing HADD as a crucial differential diagnosis for patients with acute or chronic pain, healthcare resource utilization can be optimized, leading to improved patient care in the ED.

Single-Cell RNA Sequencing Reveals Dysregulated POSTN+WNT5A+ Fibroblast Subclusters in Prurigo Nodularis.

Prurigo nodularis (PN) is an intensely pruritic, inflammatory skin disease with a poorly understood pathogenesis. We performed single-cell transcriptomic profiling of 28,695 lesional and nonlesional PN cells. Lesional PN has increased dysregulated fibroblasts (FBs) and myofibroblasts. FBs in lesional PN were shifted toward a cancer-associated FB-like phenotype, with POSTN+WNT5A+ cancer-associated FBs increased in PN and similarly so in squamous cell carcinoma. A multicenter cohort study revealed an increased risk of squamous cell carcinoma and cancer-associated FB-associated malignancies (breast and colorectal) in patients with PN. Systemic fibroproliferative diseases (renal sclerosis and idiopathic pulmonary fibrosis) were upregulated in patients with PN. Ligand-receptor analyses demonstrated an FB neuronal axis with FB-derived WNT5A and periostin interactions with neuronal receptors melanoma cell adhesion molecule and ITGAV. These findings identify a pathogenic and targetable POSTN+WNT5A+ FB subpopulation that may predispose cancer-associated FB-associated malignancies in patients with PN.

Phenotype Systemic Lupus Erythematosus Patients from EPIC Cosmos.

Systemic Lupus Erythematosus (SLE) is a widespread autoimmune disease for which early diagnosis is paramount in improving clinical outcomes. In this project, we used the de-identified patients from Epic Cosmos to retrieve the ICD code for SLE, checked data quality based on the EULAR/ACR classification systems, created an approach to determine the SLE patients, and performed statistical analyses on lab tests and clinical characteristics. Our preliminary results showed that clinical notes must be reviewed to improve the completeness, as structured EHR data fields provide limited information in determining if a patient meets the established classification criteria.