Correction to: Suprasternal approach for insertion of Impella 5.5 into the proximal right subclavian artery.

[This corrects the article DOI: 10.1007/s12055-024-01699-5.].

Real world predictors of response and 24-month survival in high-grade TP53-mutated myeloid neoplasms.

Current therapies for high-grade TP53-mutated myeloid neoplasms (≥10% blasts) do not offer a meaningful survival benefit except allogeneic stem cell transplantation in the minority who achieve a complete response to first line therapy (CR1). To identify reliable pre-therapy predictors of complete response to first-line therapy (CR1) and outcomes, we assembled a cohort of 242 individuals with TP53-mutated myeloid neoplasms and ≥10% blasts with well-annotated clinical, molecular and pathology data. Key outcomes examined were CR1 & 24-month survival (OS24). In this elderly cohort (median age 68.2 years) with 74.0% receiving frontline non-intensive regimens (hypomethylating agents +/- venetoclax), the overall cohort CR1 rate was 25.6% (50/195). We additionally identified several pre-therapy factors predictive of inferior CR1 including male gender (P = 0.026), ≥2 autosomal monosomies (P < 0.001), -17/17p (P = 0.011), multi-hit TP53 allelic state (P < 0.001) and CUX1 co-alterations (P = 0.010). In univariable analysis of the entire cohort, inferior OS24 was predicated by ≥2 monosomies (P = 0.004), TP53 VAF > 25% (P = 0.002), TP53 splice junction mutations (P = 0.007) and antecedent treated myeloid neoplasm (P = 0.001). In addition, mutations/deletions in CUX1, U2AF1, EZH2, TET2, CBL, or KRAS ('EPI6' signature) predicted inferior OS24 (HR = 2.0 [1.5-2.8]; P < 0.0001). In a subgroup analysis of HMA +/-Ven treated individuals (N = 144), TP53 VAF and monosomies did not impact OS24. A risk score for HMA +/-Ven treated individuals incorporating three pre-therapy predictors including TP53 splice junction mutations, EPI6 and antecedent treated myeloid neoplasm stratified 3 prognostic distinct groups: intermediate, intermediate-poor, and poor with significantly different median (12.8, 6.0, 4.3 months) and 24-month (20.9%, 5.7%, 0.5%) survival (P < 0.0001). For the first time, in a seemingly monolithic high-risk cohort, our data identifies several baseline factors that predict response and 24-month survival.

Dengue Fever Accompanied by Neurological Manifestations: Challenges and Treatment.

Dengue, commonly referred to as 'breakbone fever,' is a mosquito-borne arboviral infection transmitted by Aedes aegypti, featuring an average incubation period of approximately seven days. Key cytokines such as interferon-gamma (IFN-γ), tumor necrosis factor (TNF)-α, and interleukin (IL)-10 are pivotal in the pathogenesis of dengue. Travelers are particularly susceptible to contracting dengue fever, with disease severity often associated with CD8+ T cell response. Without proper hospitalization during severe cases like dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS), mortality rates can escalate to 50%. Dengue fever can lead to various complications, including neurological manifestations such as encephalopathy, encephalitis, cerebral venous thrombosis, myelitis, posterior reversible encephalopathy syndrome, strokes (both ischemic and hemorrhagic), immune-mediated neurological syndromes (such as mononeuropathy, acute transverse myelitis, Guillain-Barre syndrome, and acute disseminated encephalomyelitis), and neuromuscular complications. Treatment protocols typically involve assessing disease activity using composite indices, pursuing treatment objectives, and administering intravenous fluids according to symptomatology. Given the absence of specific antiviral treatment for dengue, supportive care, particularly hydration, remains paramount during the early stages. It is crucial to recognize that dengue viruses may contribute to the development of neurological disorders, particularly in regions where dengue is endemic. Furthermore, there is a necessity for well-defined criteria for specific neurological complications. Primary prevention strategies primarily revolve around vector control measures, which play a critical role in curtailing the spread of dengue.

Automated quantitative assessment of bone contusions and overlying articular cartilage following anterior cruciate ligament injury.

Quantitative methods to characterize bone contusions and associated cartilage injury remain limited. We combined standardized voxelwise normalization and 3D mapping to automate bone contusion segmentation post-anterior cruciate ligament (ACL) injury and evaluate anomalies in articular cartilage overlying bone contusions. Forty-five patients (54% female, 26.4 ± 11.8 days post-injury) with an ACL tear underwent 3T magnetic resonance imaging of their involved and uninvolved knees. A novel method for voxelwise normalization and 3D anatomical mapping was used to automate segmentation, labeling, and localization of bone contusions in the involved knee. The same mapping system was used to identify the associated articular cartilage overlying bone lesions. Mean regional T1ρ was extracted from articular cartilage regions in both the involved and uninvolved knees for quantitative paired analysis against ipsilateral cartilage within the same compartment outside of the localized bone contusion. At least one bone contusion lesion was detected in the involved knee within the femur and/or tibia following ACL injury in 42 participants. Elevated T1ρ (p = 0.033) signal were documented within the articular cartilage overlying the bone contusions resulting from ACL injury. In contrast, the same cartilaginous regions deprojected onto the uninvolved knees showed no ipsilateral differences (p = 0.795). Automated bone contusion segmentation using standardized voxelwise normalization and 3D mapping deprojection identified altered cartilage overlying bone contusions in the setting of knee ACL injury.

A New Community-to-Hospital Specialist Otology Pathway Using Telemedicine: A Pilot Study of 50 Patients.

INTRODUCTION: Pathway innovation using smartphone otoscopy and tablet-based audiometry technologies to deliver ear and hearing services via trained audiologists may improve efficiency of the service. An ENT-integrated-community-ear service (ENTICES-combining community audiology management, remote ENT review and novel technologies) was piloted. We aimed to assess the efficiency and safety of ENTICES. METHOD: ENTICES was a community-based and audiologist-led pathway. Patients with otological symptoms were self-referred to this service. Smartphone otoscopy and tablet-based audiograms were performed. Two otologists reviewed all decisions made in the community by audiologists based on video-otoscopy, hearing tests and chart reviews. Data on the first 50 consecutive new patients attending either consultant-led hospital otology clinics (HOC), audiologist-led hospital advanced audiology diagnostics (AAD) or ENTICES clinics were collected between 1 August 2021 and 31 December 2021. Data were collected through chart reviews and questionnaires to compare the three pathways with respect to efficiency, patient satisfaction, technology utility and safety. RESULTS: No audiology-led ENTICES decisions were amended by hospital otologists following remote review. Remote review of video-otoscopy with history was sufficient for a diagnosis in 80% of cases. Adding hearing tests and standardised history increased the diagnostic yield to 98%. Patient satisfaction scores showed 100% service recommendation. The cost per patient, per visit, was £83.36, £99.07 and £69.72 for AAD, HOC or ENTICES, respectively. CONCLUSION: ENTICES provides a safe ear and hearing service that patients rated highly. Thirty-two per cent of hospital otology patients were eligible for this service. For those patients, ENTICES is 20% more cost-effective and can reduce the number of clinic visits by up to 60% compared with HOC.

Association of Cannabis Use with Complications Among Patients with Gastroesophageal Reflux Disease: Insights from National Inpatient Sample.

Background/Objective: Cannabis, one of the most widely used recreational drug in the United States, has had a significant surge in usage following its legalization in 1996. In recent years, there has been research into the physiological effects of cannabis on the gastrointestinal (GI) system. Our study aims to systematically examine the association between cannabis use and complications of gastroesophageal reflux disease (GERD). Materials and Methods: We queried the 2016-2020 National Inpatient Sample database to identify patient encounters with GERD. Patients with eosinophilic esophagitis or missing demographics were excluded. We compared patient demographics, comorbidities, and complications among cannabis users and nonusers. Multivariate logistic regression analysis was used to investigate the relationship between cannabis use and complications of GERD. Results: A total of 27.2 million patient encounters were included in the analysis, out of which 507,190 were cannabis users. Majority of the cannabis users were aged between 45-64 years (46.6%), males (57.4%), White (63.84%), and belonged to the lowest income quartile (40.6%). Cannabis users demonstrated a higher prevalence of esophagitis compared to nonusers (6.11% vs. 3.23%, p<0.001). However, they exhibited a lower rates of esophageal stricture (0.6% vs. 0.8%, p<0.001) and esophageal cancer (0.2% vs. 0.24%, p<0.001). After adjusting for confounding factors, cannabis users were noted to have higher odds of esophagitis (adjusted odds ratio [aOR]: 1.34, 95% confidence interval [CI]: 1.30-1.39, p<0.001). A lower odds of esophageal stricture (aOR: 0.88, 95% CI: 0.81-0.96, p=0.02) and esophageal cancer (aOR: 0.48,95% CI: 0.42-0.57, p<0.001) were noted. Conclusion: Our cross-sectional study using the nationally available database indicates an association between cannabis use and higher odds of esophagitis, along with lower odds of esophageal stricture and cancer. While these findings suggest a potential relationship between cannabis use and esophageal complications, it is limited in establishing causality. Therefore, further long-term studies are warranted to understand the mechanism behind this association and to determine if cannabis use has an impact on esophagus.

Suprasternal approach for insertion of Impella 5.5 into the proximal right subclavian artery.

The Impella 5.5 (Abiomed) is a percutaneous, temporary left ventricular assist device (LVAD) that serves as an important method of treatment of acute cardiogenic shock refractory to medical management. The Impella 5.5 and 5.0 are commonly inserted through the right axillary artery; however, this may be limited by inadequate vessel diameter to accommodate the Impella and inadequate vessel quality. A central approach to Impella 5.5 incision has been described in the pediatric population, particularly via the innominate artery through a suprasternal and/or neck incision, with success. As an alternative to axillary Impella placement, we propose the usage of a limited suprasternal incision for Impella 5.5 insertion in the adult population, either through the proximal right subclavian artery or the distal innominate artery. This may offer multiple advantages, such as increased vessel diameter and quality of more proximal vessels, avoidance of partial sternotomy, avoidance of a second infraclavicular wound site if the patient progresses to require LVAD or transplant, avoidance of lymphatic and nerve injury through the axillary exposure, ease of manipulation for repositioning, and patient rehabilitation. Potential limitations include difficulty due to body habitus, potential risk of stroke with the innominate approach, and wound complications. A central approach is a reasonable alternative to axillary Impella placement in patients with inadequate axillary artery caliber, defined as less than 6-7 mm diameter, poor artery quality to accommodate anastomosis, and small body habitus, allowing for ease of exposure.

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 preoperative 2-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 = -0.67, P < .001) and 6 months (regression coefficient = -1.9, P < .001) after THA. CONCLUSIONS: Symptoms of depression on a 2-question preoperative 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.

Capability After Total Knee Arthroplasty for Osteoarthritis Is Strongly Associated With Preoperative Symptoms of Depression.

BACKGROUND: Primary total knee arthroplasty (TKA) aims to improve the level of capability (ability to perform valued life activities) associated with knee osteoarthritis (OA). However, some evidence suggests a substantial proportion of patients remain dissatisfied with their outcomes after this procedure. We sought to better understand the association between mental health, specifically symptoms of depression, with postoperative outcomes. Symptoms of depression are shown to be common among orthopaedic populations in general and can be briefly and conveniently evaluated using the Patient Health Questionnaire-2 (PHQ-2) in a less burdensome manner compared with longer mental health surveys. This study assesses the association between preoperative depressive symptoms (PHQ-2) and levels of capability at 6 weeks and 6 months after TKA. METHODS: We conducted a prospective cohort study involving 114 patients with knee OA across five clinics in California and Texas scheduled for TKA. Participants completed a preoperative PHQ-2 and Knee Injury and OA Outcome Score for Joint Replacement (KOOS JR) survey at 6 weeks and 6 months post-TKA. We analyzed these data using bivariate and multivariable regression. RESULTS: Preoperative PHQ-2 scores were significantly associated with lower KOOS JR scores at 6 weeks and 6 months post-TKA. Latino/Hispanic race was also associated with lower KOOS JR scores at 6 weeks. The association between preoperative depressive symptoms and level of capability after TKA were more pronounced at 6 months compared with 6 weeks. CONCLUSION: Preoperative symptoms of depression are strongly associated with reduced capability after TKA and can be screened for using the PHQ-2-a brief tool that can be feasibly incorporated into clinical workflows. User-friendly assessment of depressive symptoms can assist orthopaedic surgeons in identifying and addressing mental health at the outset during the management of knee OA.

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.

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.

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

Fiber-reinforcement approaches have been used to replace aligned tissues with engineered constructs after injury or surgical resection, strengthening soft biomaterial scaffolds and replicating anisotropic, load-bearing properties. However, most studies focus on the macroscale aspects of these scaffolds, rarely considering the cell-biomaterial interactions that govern remodeling and extracellular matrix organization toward aligned neo-tissues. As initial cell-biomaterial responses within fiber-reinforced microenvironments likely influence the long-term efficacy of repair and regeneration strategies, here we elucidate the roles of spatial orientation, substrate stiffness, and matrix remodeling on early cell-fiber interactions. Bovine mesenchymal stromal cells (MSCs) were cultured in soft fibrin gels reinforced with a stiff 100 µm polyglycolide-co-caprolactone fiber. Gel stiffness and remodeling capacity were modulated by fibrinogen concentration and aprotinin treatment, respectively. MSCs were imaged at 3 days and evaluated for morphology, mechanoresponsiveness (nuclear Yes-associated protein [YAP] localization), and spatial features including distance and angle deviation from fiber. Within these constructs, morphological conformity decreased as a function of distance from fiber. However, these correlations were weak (R2 = 0.01043 for conformity and R2 = 0.05542 for nuclear YAP localization), illustrating cellular heterogeneity within fiber-enforced microenvironments. To better assess cell-fiber interactions, we applied machine-learning strategies to our heterogeneous dataset of cell-shape and mechanoresponsive parameters. Principal component analysis (PCA) was used to project 23 input parameters (not including distance) onto 5 principal components (PCs), followed by agglomerative hierarchical clustering to classify cells into 3 groups. These clusters exhibited distinct levels of morpho-mechanoresponse (combination of morphological conformity and YAP signaling) and were classified as high response (HR), medium response (MR), and low response (LR) clusters. Cluster distribution varied spatially, with most cells (61%) closest to the fiber (0-75 µm) belonging to the HR cluster, and most cells (55%) furthest from the fiber (225-300 µm) belonging to the LR cluster. Modulation of gel stiffness and fibrin remodeling showed differential effects for HR cells, with stiffness influencing the level of mechanoresponse and remodeling capacity influencing the location of responding cells. Together, these novel findings demonstrate early trends in cellular patterning of the fiber-reinforced microenvironment, showing how spatial orientation, substrate biophysical properties, and matrix remodeling may guide the amplitude and localization of cellular mechanoresponses. These trends may guide approaches to optimize the design of microscale scaffold architecture and substrate properties for enhancing organized tissue assembly at the macroscale.

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.

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 with 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 PN lesional skin inflammation and architecture with single-cell resolution through an unbiased machine learning approach. PN lesional skin has increased expression of caspase 3, NF-kB, and phosphorylated signal transducer and activator of transcription 3 compared with healthy skin. Keratinocytes in lesional skin are subdivided into CD14+CD33+, CD11c+, CD63+, and caspase 3-positive innate subpopulations. CD14+ macrophage populations expressing phosphorylated extracellular signal-regulated kinase 1/2 correlate positively with patient-reported itch (P = .006). Hierarchical clustering reveals a cluster of patients with PN with greater atopy, increased NF-kB+ signal transducer and activator of transcription 3-positive phosphorylated extracellular signal-regulated kinase 1/2-positive monocyte-derived myeloid dendritic cells, and increased vimentin expression (P < .05). Neighborhood analysis finds interactions between CD14+ macrophages, CD3+ T cells, monocyte-derived myeloid dendritic cells, and keratinocytes expressing innate immune markers. These findings highlight phosphorylated extracellular signal-regulated kinase-positive CD14+ macrophages as contributors to itch and suggest an epithelial-immune axis in PN pathogenesis.

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.

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.

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.

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.

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.