Poor Disease Research Articles

Development and biological evaluation of a novel CEACAM6-targeted PET tracer for distinguishing malignant nodules in early-stage lung adenocarcinoma.

Low-dose CT (LDCT) screening effectively reduces lung adenocarcinoma (LUAD) mortality. However, accurately evaluating the malignant potential of indeterminate lung nodules remains a challenge. Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6), a potential biomarker for distinguishing benign pulmonary nodules from LUAD, may be leveraged for noninvasive positron emission tomography (PET) imaging to aid LUAD diagnosis. This study utilized mRNA, protein, and survival datasets of LUAD patients, along with an animal model of malignant pulmonary nodules, to investigate CEACAM6 expression specificity and its correlation with LUAD. Targeting ligands for CEACAM6 were designed using the Rosetta platform, labeled with [68Ga]Ga, and screened through high-throughput PET imaging to identify the optimal tracer. CEACAM6 was found to be specifically overexpressed in LUAD and was significantly associated with poor prognosis and disease progression. In vivo, [68Ga]Ga-NODA-P3 demonstrated high specificity for delineating CEACAM6-positive A549 xenografts, a LUAD model, via PET imaging, achieving a highest target-to-background ratio of 7.68 ± 0.44. Region of interest (ROI) analysis showed significantly higher tracer uptake in A549 xenografts compared to CEACAM6-negative Huh7 xenografts (a hepatocellular carcinoma model) at 30min post-injection (1.81 ± 0.10%ID/g vs. 0.54 ± 0.06%ID/g). Pre-treatment with an excess of unlabeled NODA-P3 significantly reduced tumor uptake to 0.52 ± 0.07%ID/g. These preclinical findings indicate that [68Ga]Ga-NODA-P3 is a candidate radiotracer for the non-invasive visualization of CEACAM6-positive LUAD, demonstrating favorable imaging contrast. Although the current tumor uptake limits its immediate clinical application, ongoing optimization efforts are expected to improve its efficacy, enabling earlier and more accurate diagnosis of malignant pulmonary nodules in LUAD.

Tumor Lesion Uptake of [177Lu]Lu-DOTA-Rituximab in Skeletal and Splenic Disease in Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, and a sizable fraction of the DLBCL patients presents with advanced, relapsed, and refractory disease, demonstrating poor response to standard chemotherapy regimens. Radioimmunotherapy (RIT) has shown to be clinically effective in refractory DLBCL. We present the case of a patient with DLBCL with [18F]FDG-avid widespread skeletal as well as splenic involvement as poor prognostic extranodal disease on FDG PET/CT. RIT based on [177Lu]Lu-DOTA-rituximab was explored to study the biodistribution and dosimetry of [177Lu]Lu-DOTA-rituximab in CD20-positive lymphoma. An exceptionally high tracer concentration in skeletal and splenic disease was observed, supporting its potential RIT application in relapsed and refractory DLBCL patients in the future.

Coeliac disease: complications and comorbidities.

Coeliac disease is an autoimmune disease characterized by small intestinal villus atrophy and inflammation upon exposure to gluten. It has a global prevalence of approximately 1%. Although the gluten-free diet can be an effective treatment, this diet is burdensome with practical difficulties and frequent inadvertent gluten exposure. Moreover, there are a variety of potential complications and comorbidities of coeliac disease that might be related to malabsorption and/or chronic immune activation. Overall, individuals with coeliac disease have increased mortality compared with the general population, underscoring the severity of this common disease. Comorbidities and complications that have been associated with coeliac disease include poor growth, reproductive complications, kidney and liver diseases, respiratory disease (such as pneumonia) and infections (including sepsis). Furthermore, coeliac disease has been linked to other autoimmune disease and psychiatric disease, as well as certain cancers. Data suggest that mucosal healing on a gluten-free diet might protect against some, but not all, of these complications. In this Review, we present absolute and relative risks of coeliac-associated disorders. We discuss underlying mechanisms, the role of the gluten-free diet and mucosal healing, as well as implications for follow-up and non-dietary treatment of coeliac disease.

Job loss and reemployment of newly diagnosed people with epilepsy: A nationwide cohort study.

Epilepsy has negative socioeconomic impacts on those affected, resulting not only from actual disability but also from social stigma. However, longitudinal studies examining occupational consequences following an epilepsy diagnosis are limited. We aimed to investigate the occupational outcomes of newly diagnosed epilepsy among Korean employees. We conducted a nationwide population-based retrospective cohort study using the Korean National Health Insurance Service database. We included newly diagnosed people with epilepsy (PWE) aged 25 to 54 years, identified by diagnostic codes and antiseizure medication (ASM) prescriptions, who were employed at diagnosis between 2004 and 2018. The employment status of PWE was determined based on their enrollment in the employer-provided health insurance scheme. We analyzed the rates of job loss and reemployment, associated factors, and income changes following diagnosis. Among the 13 122 newly diagnosed PWE, the overall first-year job loss rate across the study period was 21.7%, which was 1.62-2.54 times higher than that of the general population for each year. The excesses of job loss among PWE in safe occupations were comparable to those in safety-sensitive occupations. Central nervous system illness (adjusted hazard ratio [aHR] = 1.12), psychiatric disease (aHR = 1.19), ≥2 emergency room visits or hospitalizations (aHR = 3.00), and ≥4 ASM attempts (aHR = 1.26) increased the risk of job loss. Among individuals who lost their job during the first year, 22.4% were reemployed within 1 year, with similar risk factors hindering reemployment. The income distribution of regained jobs showed a downward shift compared to previous jobs. Newly diagnosed PWE were at risk of job loss, irrespective of the occupational hazards related to seizures. Poor disease control and comorbidities partially contributed to unemployment. Alongside active seizure management, guidance for suitable occupations and the implementation of tailored restrictions based on occupational risk stratification are imperative to improve the job security of PWE.

P0557 Multiomics analysis identifies key pathways associated with severe disease course in children with IBD: a prospective study

Abstract Background Identifying biological pathways that are associated with poor disease course in IBD may improve early risk stratification and guide targeted therapeutic approaches. We therefore aimed to integrate multiomics data determined at disease onset to explore pathways associated with disease course in pediatric IBD, focusing on both microbial and host-derived signals. Methods Children with IBD were enrolled at disease onset and followed prospectively for18 months. Samples for whole exome sequencing (WES), serum metabolomics, stool metabolomics, and microbiome were analyzed using MaAsLin2 for differential expression and Random Forest for outcome prediction for single-omic. A late integration approach with Support Vector Machine was applied for multi-omics prediction. Severe outcome was defined as steroid-dependency, early or multiple biologics, or IBD-related hospitalizations/surgeries. Pathway enrichment analyses for each omic were assessed using Fisher’s exact test and odd ratio (OR) was calculated to asses the enrichment magnitude. Results Altogether, 182 children were enrolled (123 with CD (28% severe course) and 59 UC (39% severe course). Several pathways were differentially enriched in the severe group (Figure 1). Shared pathways across CD and UC included AGE-RAGE signaling, implicated in oxidative stress and inflammation (OR=36 [95%CI 3-459] in CD and OR=92 [7-1121] in UC), and choline metabolism in cancer, associated with lipid signaling, inflammation, and fibrosis (OR=37 [95%CI 4-382] and OR=66 [3-475]). CD-specific pathways included sphingolipid metabolism (OR=30 [95%CI 2-393]), linked to barrier dysfunction and chronic inflammation, glycerolipid metabolism (OR=11 [95%CI 1-160]), and fat digestion and absorption (OR=16 [95%CI 3-167]), highlighting disruptions in nutrient absorption and inflammation. UC-specific pathways included pathways in cancer (OR=23 [95%CI 3-263]), reflecting tissue remodeling and neoplasia risk, inflammatory regulation of TRP channels (OR=14 [95%CI 1-143]), contributing to colonic inflammation, sensory perception and purine metabolism (OR=5 [95%CI 0.4-58]). Random Forest machine learning models showed modest to no predictive performance of the different omics (area under ROC curve ranged between 0.41-0.67 in CD, and 0.38-0.72 in UC; Table 1). Conclusion Key biological pathways were identified in association with severity of disease course in pediatric IBD, utilizing large datasets of genetics, metabolomics and microbiome. The findings offer insights into mechanisms underlying pediatric IBD and highlight potential therapeutic targets as well as biomarkers for early intervention.

DOP086 Burden of depression and anxiety among patients with pediatric-onset Inflammatory Bowel Diseases: A nationwide study from the epi-IIRN

Abstract Background Data regarding burden of depression and anxiety in pediatric-onset inflammatory bowel diseases (PIBD) are limited. We aimed to study the prevalence of depression and anxiety in a nationwide cohort of PIBD Methods Data were retrieved from the epi-IIRN, a nationwide cohort of the 4 Israeli Health Maintenance Organizations covering 98% of the population from 2005. We matched PIBD children to non-IBD controls for calculating time to depression/anxiety. Patients with depression/anxiety prior to IBD diagnosis were excluded. Poor disease course (PDC) was defined as IBD-related surgery, steroid-dependency, or need for more than one biologic class. A time-dependent Cox-proportional-hazard-ratio model was fit to examine predictors of the development of depression/anxiety over time. Inverse probability weights (IPW) were calculated to estimate the probability that an individual will develop depression at each time point within an individual follow up period Results In total, 4,960 PIBD cases were included [mean age 13.4±3.8 years; 3,304 (67%) with Crohn's disease (CD) and 1,656 (33%) ulcerative colitis (UC)], translating into 32,700 person-years of follow-up. These were individually matched to 4,806 non-IBD children. In a univariable Cox proportional regression model, PIBD was associated with overall anxiety/depression compared to controls (HR=1.9 95%CI 1.7-2.2). The probability of depression/anxiety was higher in PIBD patients vs controls at 3 (6% vs 2.5%) and 10 years (17.5% vs 10.2%; p<0.001, Figure 1). There were no differences in the probability of depression/anxiety between patients with UC and CD (HR=0.96 95%CI 0.81-1.1, p=0.62). In multivariable Cox proportional regression model in patients with CD; perianal disease [HR=1.5 (95%CI 1.3-2)], need for >1 biologic class, [HR=1.6 (95%CI 1.03-2.63)], and hospitalizations [HR=1.4 (95%CI 1.1-1.9)] were associated with developing anxiety/depression. Risk for anxiety/depression was lower among patients after CD related surgery compared with those who did not undergo surgery [HR 0.5 (95%CI 0.28-0.99)]. For patients with UC, steroid dependency was associated with anxiety/depression [HR 1.5, (95%CI 1.05-2.1)]. Figure 1 (Depression free survival probability) Conclusion Our study highlights the substantial burden of depression/anxiety in PIBD and identifies risk factors for these conditions. These findings emphasize the need for mental health monitoring and early intervention in this vulnerable population

P0248 Insomnia as a determinant of poor IBD disease course

Abstract Background Insomnia is one of the most common sleep disorders, affecting up to 30% of the adult population worldwide. Sleep disorders can have a marked impact on immune functions and inflammation, including in patients with inflammatory bowel diseases (IBD) in both active and inactive disease states. Whether insomnia preceding IBD flares affects clinical outcomes is unknown. We examined the association between insomnia and IBD-related outcomes in adults diagnosed with of Crohn’s disease (CD) or ulcerative colitis (UC). Methods A retrospective, real-world, cohort study utilizing the Lynx MD’s electronic medical record dataset, provided by a US-based community gastroenterology practice. Deidentified patient charts were analyzed to identify patients with a confirmed diagnosis of IBD (either CD or UC). Eligibility criteria included: ≥3 diagnoses of IBD, ≥1 diagnoses of IBD and: histopathologic diagnosis of IBD; or IBD related surgery; or ≥ 3 months of treatment with standard accepted therapies for IBD; and ≥3 years of follow-up. IBD-related events of hospitalization and/or surgery were recorded. The cohort was classified into two groups based on insomnia diagnosis, prior to IBD related hospitalizations or surgeries. We implemented Cox Proportional Regression models to estimate Hazard Ratios for the IBD-related outcomes. Results Among 20,011 patients with IBD, 10,775 (54%) were women, at a mean age of 48.2 ± 18.2 years old, 11,842 (59%) were diagnosed with UC and 8,169 (41%) with CD. Over 3,100 patients (16%) were diagnosed with insomnia prior to the first IBD related hospitalization or surgery. In an unadjusted model, insomnia was significantly associated with IBD-related hospitalizations - hazard ratio (HR) of 1.43 (95% CI 1.28, 1.59) and IBD related surgeries - HR of 1.42 (95% CI 1.12, 1.81). After adjustment for age, sex, race, body mass index, anxiety and type of IBD (CD vs. UC), IBD-affected patients with insomnia had a higher HR of hospitalization and surgery: HR of 1.35 (95% CI 1.2,1.51) and 1.29 (95% CI 1.01,1.66), respectively, compared to those without insomnia. Conclusion In a large real-life dataset of patients with IBD, we found higher rates of IBD-related hospitalizations and surgeries among patients with comorbid insomnia, suggesting that insomnia may be associated with a more severe course of IBD.

P0443 Prognosis of primary sclerosing cholangitis (PSC) in Hungary is independent of coexisting inflammatory bowel disease (IBD) and prognostic ability of the currently used PSC risk scores are limited

Abstract Background Primary sclerosing cholangitis (PSC) is a rare, chronic disorder of the intra- and extrahepatic biliary tree characterized by cholestasis, periductal inflammation and fibrosis. Currently, there is very limited epidemiological data from the Central-Eastern European region. We assessed disease characteristics and natural history of PSC in a bicentre Hungarian cohort and compared its outcome with respect to co-existing inflammatory bowel disease (IBD). Methods Imaging, laboratory and clinical data including presence of IBD, variant syndrome, disease course and outcome were prospectively collected in two large Hungarian Clinical Centre Patients were followed on a yearly basis. Median diseases follow-up (FUP) time was 8.82 (IQR: 5.2-13.5) years. A wide range of clinical scoring systems were applied. Poor disease outcome was defined as orthotopic liver transplantation (LT) and/or liver-related death during the FUP. Results Of 135 patients (57.8% males; median age at diagnosis: 31 [IQR: 20-47] yrs) with confirmed PSC, 73 (54.1%) had coexisting IBD. Nineteen patients already had cirrhosis at diagnosis and 31 more developed it during the FUP. A total of 21 (15.6%) patients died of which 85.7% were liver-related deaths. Twenty-five patients (18.5%) underwent liver transplantation (LT). Twenty-three (17%) patients developed malignancy (9 cholangiocarcinoma, 3 hepatocellular carcinoma, 6 colorectal carcinoma and 6 non-gastrointestinal malignancy) during the FUP. Patients with IBD were younger and had higher Mayo and Amsterdam-Oxford scores at diagnosis compared to those without, however there was no difference in disease outcomes in these groups (p=0.133). Clinical scores at diagnosis had moderate prognostic ability for poor disease outcome (AUROC [95%CI], Mayo score: 0.637 [0.521-0.753]; p=0.018; Amsterdam-Oxford: 0.687 [0.576-0.798]; p=0.002; p<0.001; UK-long: 0.695 [0.588-0.803]; p<0.001), except UK-short PSC risk score (0.745 [0.643-0.847]). Persistent alkaline phosphatase (ALP) increase, despite ursodeoxycholic acid (UDCA) treatment, especially within the first two years of diagnosis had good prognostic ability (AUROC [95%C], at diagnosis: 0.656 [0.556-0.757], p= 0.006; after one year: 0.724 [0.602-0.847], p<0.001; after two years: 0.746 [0.617-0.875], p<0.001). Conclusion Prognosis of PSC is independent of coexisting IBD in our large Hungarian prospective PSC cohort. Prognostic ability of the currently used PSC risk scores is limited. The UK-short PSC risk score and early ALP response to UDCA treatment showed to have the best accuracy.

P0380 Mild Hyperemia in the Absence of Bowel Wall Thickening on Intestinal Ultrasound is Associated with Biochemical Disease Activity and Worse Disease Outcomes in Patients with Crohn’s Disease and Ulcerative Colitis

Abstract Background Bowel wall thickness (BWT) and hyperemia measured by intestinal ultrasound (IUS) predict endoscopic disease activity in Inflammatory Bowel Disease (IBD). The clinical significance of mild hyperemia (mLim1) without BWT is unknown. We previously described the short-term predictive value of mLim1 without BWT. Here we compare biochemical disease activity and longer-term outcomes in IBD pts with mLim1 to those with normal IUS. Methods We reviewed index IUS exams of pts with IBD at the University of Chicago from 7/18/2022 to 5/7/2024 and included pts with normal BWT (≤3.0mm) + mLim1 and compared them to pts with normal BWT + no hyperemia (mLim0). We excluded pts with mLim2 or 3, BWT>3mm anywhere on index IUS or pts with mLim1 at surgical anastomoses only. Clinical Harvey-Bradshaw Index (HBI) or Simple Clinical Colitis Activity Index (SCCAI)) and biochemical disease activity (faecal calprotectin (FCP) or C-reactive protein (CRP)) were assessed at the time of index IUS. Clinical remission was defined as HBI of <5 or SCCAI of ≤2, FCP<150 μg/g, CRP<5 mg/L. Primary analysis was poor disease outcome (PDO) within 12 mo of follow-up, defined as: IBD medication change/escalation, prescription of corticosteroids, IBD-related surgery, or IBD-related hospitalization. Results 45 pts with mLim1 (38 Crohn’s disease (CD), 7 Ulcerative colitis (UC)) and 61 pts with mLim0 (52 CD, 9 UC) at index IUS were included (Table 1). At baseline IUS, mLim1 pts had elevated median FCP but normal median HBI/SCCAI, while mLim0 pts had normal median FCP and HBI/SCCAI (Table 1). Of mLim1 CD pts, 14/38 (36.8%) had a PDO within 3 months (mo), 18/38 (47.4%) within 6 mo, and 18/30 (60%) within 12 mo, with median time to PDO of 37 d (IQR 28.5-112.5). Of the mLim0 CD pts, 5/52 (9.6%) had a PDO within 3 mo, 9/46 (19.6%) within 6 mo, and 14/45 (31.1%) within 12 mo, with median time to PDO of 91 d (IQR 93-184). Rates of PDO between mLim1 and mLim0 in CD pts at 12 mo were statistically significant (stat sig), p = 0.013. Of the mLim1 UC pts, 3/7 (42.9%) had a PDO within 3 mo and 2/3 (66.7%) had a PDO within 12 mo, with a median time to PDO of 139 d (IQR 93-184). Of the mLim0 UC pts, one had a PDO at 3 mo with no further events noted at 6 mo (0/8) or 12 mo (0/4). Rates of PDO between mLim1 and mLim0 in UC pts at 12 mo were not stat sig, (p = 0.270). Conclusion Mild hyperemia without BWT is associated with biochemical disease activity in both CD and UC and predicts PDO in CD. Although PDO in UC was numerically higher in mLim1 compared to mLim0, this was not stat sig likely due to small cohort size. These findings support the consideration of treatment adjustments when this isolated parameter is identified and inform future IUS treat-to-target strategies.

P1320 Oral highly-virulent pathogenic isolates aggravated colitis through gut microbiota-equol-ERβ axis

Abstract Background We isolated potential oral pathogens from IBD patients saliva and analyzed their virulence differences, hoping to elucidate the mechanism of different disease patterns in IBD patients. Methods A series of in vitro and in vivo experiments, whole-genome sequencing, 16S rRNA sequencing and non-targeted metabolomics sequencing were used to explore the pathogenicity of Streptococcus mutans (S.m) isolates. Results Our previous study indicated that the abundance of streptococcus in ulcerative colitis (UC) patients saliva was higher than healthy people. After over 1 year follow-up, we found that UC patients with poor disease state had higher proportion of S.m in saliva, and 31 S.m strains were further isolated from 25 UC saliva. Whole-genome sequencing showed that the virulence genes of S.m strains were related to immunity, metabolism and exotoxins. 9 strains with greater pro-inflammatory effects and barrier destroying ability were obtained based on microbe-cell co-culture. Subsequent animal experiments suggested that pro-inflammatory S.m strains significantly exacerbated intestinal inflammation of DSS mice, while non-pro-inflammatory S.m strains didn’t induce above effects. The pro-inflammatory effects of pro-inflammatory S.m strains on DSS mice disappeared after the depletion of gut microbiota by antibiotics, and fecal bacteria transplantation (FMT) found that the intestinal inflammation of DSS mice transplanted with pro-inflammatory strains groups feces was more severe than that of non-proinflammatory mice, suggesting that intestinal microbiota is essential for the proinflammatory effects of S.m strains. 16S rRNA sequencing showed that α diversity of intestinal microbiota of pro-inflammatory strains groups mice was lower than that of non-proinflammatory mice. The level of equol was lower in pro-inflammatory groups compared to non-pro-inflammatory groups through non-targeted metabolomics sequencing. Subsequently, we further confirmed S-equol/R-equol both ameliorated DSS mice colitis, while estrogen receptor β (ERβ) antagonist inhibited the protective effect of equol partially. Molecular docking also confirmed the combination of equol and ERβ protein, of which the binding sites were GLU-305, Ph-356 and HIE-475. Conclusion This study found for the first time that the pro-inflammatory effects of S.m isolates are different, which may be related to gut microbiota-equol-ERβ axis.

Update on the Progress of Musashi-2 in Malignant Tumors.

Since the discovery of the Musashi (MSI) protein, its ability to affect the mitosis of Drosophila progenitor cells has garnered significant interest among scientists. In the following 20 years, it has lived up to expectations. A substantial body of evidence has demonstrated that it is closely related to the development, metastasis, migration, and drug resistance of malignant tumors. In recent years, research on the MSI protein has advanced, and many novel viewpoints and drug resistance attempts have been derived; for example, tumor protein p53 mutations and MSI-binding proteins lead to resistance to protein arginine N-methyltransferase 5-targeted therapy in lymphoma patients. Moreover, the high expression of MSI2 in pancreatic cancer might suppress its development and progression. As a significant member of the MSI family, MSI2 is closely associated with multiple malignant tumors, including hematological disorders, common abdominal tumors, and other tumor types (e.g., glioblastoma, breast cancer). MSI2 is highly expressed in the majority of tumors and is related to a poor disease prognosis. However, its specific expression levels and regulatory mechanisms may differ based on the tumor type. This review summarizes the research progress related to MSI2 in recent years, including its occurrence, migration mechanism, and drug resistance, as well as the prospect of developing tumor immunosuppressants and biomarkers.

Production and marketing challenges of tomato (Solanum lycopersicum L.) in Ethiopia. Review

Tomato is one of the most important and widely grown vegetables in the world. The aim is to review the key challenges on tomato production and marketing in Ethiopia. In Ethiopia, tomato production is concentrated in river, valleys and lakes, especially in Awash Valley and around Lake Ziway for favorable growing conditions, good access to market outlets and better infrastructure. Tomato production is commercially important for fresh fruit market and processing. Some of tomato varieties that have been in use by farmers are used for processing and for fresh marketing. However, several constraints caused inconsistent of tomato production and low yielding’s are; the shortages of improved varieties, inadequate transport, poor marketing system, poor cultural practices, unreliable rainfall, price fluctuation, product nature (perishability), post-harvest losses, pest and diseases. Lack of market linkages, post-harvest losses, low institutional support, lack inputs and transportation are the key challenges. Small-scale producers are struggling to gain market access, but due to listed challenges the farmers are not selling their produce in an organized system and not getting the right shares. Therefore, critical attentions in harvesting and postharvest operations are very important to reduce losses, to keep quality and market standards. Moreover, addressing both production and market-related challenges are essential to minimize the losses, to access quality goods and to ensure the right shares for producers, distributors, processors and traders.

Association between patient perception of disease status and different components of the Minimal Disease Activity (MDA) criteria in psoriatic arthritis.

The aim of this analysis was to evaluate the relationship between the criteria met of the Minimal Disease Activity (MDA) score for psoriatic arthritis (PsA) and patient-perceived disease status. We analysed data from the ReFlaP study (NCT03119805), a cross-sectional international study of adult patients with PsA. Patients self-reported if they felt their PsA was in remission (REM), low disease activity (LDA) or neither. The relationship between patient-reported status and MDA domains met was analysed using point biserial correlation, chi-square test (Χ2), odds ratio, and specificity. 88.4% of study patients who met MDA reported good disease status (REM/LDA). Pain was the most commonly missed domain for these patients. A moderate to strong correlation was found between meeting more MDA domains and patient-reported good status irrespective of domain missed. On individual domain testing, MDA state and patient-reported REM/LDA were significantly associated irrespective of domain missed with the exception of enthesitis. Specificity of the MDA score irrespective of domain missed was above 90%. The odds of MDA patients reporting poor disease status was significant only for when pain < 1 was the unmet domain. This significance was not supported by sensitivity analysis. This study suggests strong agreement between MDA status and patient-reported good status irrespective of domain missed. Pain < 1 or 2 on a 0-10 numerical rating scale was the hardest domain to meet. The high specificity regardless of the unmet domain suggests patients who feel their disease is active are minimally misclassified by the score.

Novel combination therapy targeting oncogenic signaling kinase P21 activated Kinase-1 and chemotherapeutic drugs against triple negative breast cancer.

Most of the triple negative phenotype or basal-like molecular subtypes of breast cancers are associated with aggressive clinical behaviour and show poor disease prognosis. Current treatment options are constrained, emphasizing the need for novel combinatorial therapies for this particular tumor subtype. Our group has demonstrated that functionally active p21 activated kinase 1 (PAK1) exhibits significantly higher expression levels in clinical triple negative breast cancer (TNBC) samples compared to other subtypes, as well as adjacent normal tissues. Low PAK1 expression in TNBC was significantly linked to better prognosis, with improved overall survival (OS, p=0.00236) and relapse-free survival (RFS, p=0.0314), as shown by GOBO analysis. To confirm the role of PAK1 as a therapeutic target and to discover novel synergistic chemotherapy drug combinations, we conducted a drug combination screen using triple negative breast cancer cell lines and a mouse metastatic tumor cell line. We identified the combined inhibition of PAK1 inhibitor, NVS-PAK1 with doxorubicin/paclitaxel/methotrexate as a synergistic novel therapeutic approach for treating metastatic TNBC to improve overall survival. This study also indicated a reduction in the effective dosage of the chemotherapeutic drug when combined with NVS-PAK1. Our study demonstrates that combining NVS-PAK1 with each of the chemotherapeutic drugs' doxorubicin, paclitaxel, and methotrexate resulted in decreased colony formation, reduced wound healing capability, and diminished migratory and invasive potential in both TNBC cell lines and 4T1 in vitro. These findings were further validated in orthotopic mouse mammary tumors, confirming that simultaneous PAK1 inhibition alongside chemotherapy significantly enhanced anti-tumor efficacy and reduced metastasis.

Development and External Validation of the Hidradenitis Suppurativa Cutaneous Abscess Prediction Score-2 (HSCAPS-2): A Clinical Decision Support Tool for Diagnosis of Hidradenitis Suppurativa over Cutaneous Abscess.

Patients with hidradenitis suppurativa (HS) experience a 10-year diagnosis delay, on average. Accordingly, time to diagnosis represents one of the greatest unmet needs in HS, which to date has not been adequately addressed. A general lack of awareness about HS in the medical community and a notable heterogeneity in clinical presentation, which is most often confused with cutaneous abscess (CA), forms the basis of poor disease recognition and diagnosis delay. Our objective was to develop and validate a prediction model for diagnosis of HS versus site-specific cutaneous abscess (CA). We performed a cross-sectional study in which the model was developed using a large clinical database and externally validated using a sample of clinical records at Penn State Health. Prediction model discrimination and calibration were evaluated using the c-statistic, calibration intercept/slope, and a flexible calibration curve. Variable selection identified 15 predictors, 7 of which remained after model simplification. The following characteristics were predictive of HS relative to site-specific CA: female sex, increasing age up to 44 years, African American race, race other than White or African American, increasing body mass index, polycystic ovarian syndrome, and acne. The c-statistics of the 7-variable model in validation was 0.77 (95% CI 0.73-0.80). Calibration intercept and slope were 0.29 (95% CI 0.14, 0.43) and 1.09 (95% CI 0.90, 1.28). Clinical characteristics can predict diagnosis of HS over CA in practice without reliance on a specialty-specific examination to identify disease and potentially reduce diagnosis delay.

Socioeconomic status has direct impact on asthma control: Turkish adult asthma registry.

Asthma is one of the most common causes of chronic respiratory disease, and countries with low socioeconomic status have both a high prevalence of asthma and asthma-related death. In this study, we aimed to determine socioeconomic levels of asthmatic patients according to a national database and investigate the effects of social markers on disease control in our region. This is an analysis of data from 2053 adult asthma patients from a multicentre chart study in Turkey. Socioeconomic status (SES) data were collected from questionnaires and this form was sent to the patients via e-mail. Parameters related to social status and poor disease control were analyzed. Illiteracy (OR:2.687 [95% CI: 1.235-5.848]; p=0.013) and lower household income (OR:1,76 [95% CI: 1.002-3.09]; p=0.049) were found as independent risk factors for hospitalization in the multivariate logistic regression analysis. Therewithal, being aged between 40 and 60 (OR: 1.435 [95% CI: 1.074-1.917]; p=0.015), illiteracy (OR: 2.188 [95% CI: 1.262-3.795]; p=0.005) and being employed (OR: 1.466 [95% CI: 1.085-1.847]; p=0.011) were considered as independent risk factors for systemic corticosteroid use at least 3days within last 1year. As a result of our national database, education level, household income and working status briefly socioeconomic status have impacts on asthma control. Identification of social markers in asthma and better recognition of risk factors based on the population gives us clues to provide better asthma control in the future.

Serum BAFF levels are associated with the prognosis of idiopathic membranous nephropathy

Objective High serum levels of B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) have been observed in patients with idiopathic membranous nephropathy (iMN); however, their relationships with disease severity and progression remain unclear. Methods Patients with iMN diagnosed via renal biopsy were enrolled in this study. The concentrations of BAFF and APRIL were determined using ELISA kits. Proteinuria remission, including complete remission (CR) and partial remission (PR), and renal function deterioration were defined as clinical events. The Cox proportional hazards method was used to analyze the relationship between cytokine levels and disease progression. Results Seventy iMN patients were enrolled in this study, with a median follow-up time of 24 months (range 6–72 months). The serum levels of BAFF and APRIL were higher in iMN patients than in healthy controls but lower than those in minimal change disease (MCD) patients. The serum BAFF level was positively correlated with the serum APRIL level, serum anti-phospholipase A2 receptor (anti-PLA2R) antibody level, and 24-h proteinuria and negatively correlated with the serum albumin (ALB) level. However, no significant correlation was observed between the serum APRIL level and clinical parameters. According to the multivariate Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure (SBP), estimated glomerular filtration rate (eGFR), immunosuppressive agent use, 24-h proteinuria, APRIL level, and anti-PLA2R antibody, only the serum BAFF level was identified as an independent predictor of PR (HR, 0.613; 95% CI, 0.405–0.927; p = 0.021) and CR of proteinuria (HR, 0.362; 95% CI, 0.202–0.648; p < 0.001). Conclusions A high serum BAFF level is associated with severe clinical manifestations and poor disease progression in patients with iMN.

Effects of Maize Lethal Necrosis (MLN) Disease on Maize Output and Food Security Among Smallholder Farmers in Bomet County, Kenya

Maize is one of the leading cereals produced and consumed in Kenya and is very vital to food security. In the recent past, maize production has encountered many problems including poor input use, drought, pests, and diseases. Maize production in Kenya has been particularly devastated by Maize Lethal Necrosis (MLN), a viral disease which unexpectedly infested the maize crops in 2011. The disease has caused major economic and social losses to maize farmers and has spread to other neighbouring countries. Data on 3368 households was collected using a two-stage stratified cluster sampling method. The estimation procedure involves the use of propensity score matching to determine the effect of MLN on household food security and maize output. The results of this study indicate that MLN disease reduces household food security by about 16.6 percent, while it reduces maize output by about 10 (90 kgs.) bags per acre. The study therefore recommends that the government and stakeholders design appropriate policies for restoring plant health which include maize-resistant varieties, training of smallholder farmers on good agronomic practices and growing of alternative crops in order to break the disease cycle thus ensuring food security

Fulvestrant Monotherapy After CDK4/6 Inhibitors in Metastatic Breast Cancer Patients: A Real-Life Experience.

Background: The treatment of hormone receptor positive (HR+), HER-2 negative metastatic breast cancer (MBC) has radically changed over the last few years. CDK4/6 inhibitors combined with endocrine therapy have become the standard of care as a front-line therapeutic approach, conferring a significant improvement in progression-free survival and overall survival compared to traditional endocrine therapy (ET) alone. However, the wide administration of these drugs in clinical practice paved the way for the emergence of new intrinsic and acquired mechanisms of resistance that seem to compromise second-line treatment effectiveness. In this context, fulvestrant monotherapy appears disqualified. Materials and Methods: we evaluated a population of 30 women currently treated in our oncology unit with HR+/HER2- metastatic breast cancer, receiving fulvestrant 500 mg every 28 days after progression to first-line therapy with CDK 4/6 inhibitors combined with aromatase inhibitors. Results: Of 30 patients observed, 23 progressed to fulvestrant with a median PFS of 3.7 months (range 1-9.7 months). Conclusions: our real-life experience suggests that second-line fulvestrant monotherapy confers very poor disease control and is quite an inadequate therapeutic option. CDK4/6i administration beyond progression could possibly be considered as more valid option, in the absence of targetable mutations or newer, more effective drugs.

The importance of Naples prognostic score in predicting long-term mortality in heart failure patients

Background Heart failure (HF) remains a significant health problem despite advances in diagnosis and treatment options. Malnutrition and increased inflammation predict poor disease prognosis. The parameters of the Naples prognostic score (NPS) include albumin, total cholesterol, neutrophil-lymphocyte ratio (NLR), and lymphocyte-monocyte ratio (LMR). We aimed to assess the potential of NPS as a predictor of long-term mortality in patients with HF. Methods A total of 1728 patients with HF who applied to our center between 2018 and 2022 were included in this study. The NPS was computed and the patients were divided into three groups according to their NPS values as follows: NPS = 0 (Group 1), NPS = 1–2 (Group 2), and NPS = 3–4 (Group 3). We also evaluated the association between NPS value and HF mortality. Results The patients were followed for a mean follow-up duration of 30 months. The mortality rate was 8.3% (145 patients). We carried out Model-1 and -2 Cox regression analyses to identify long-term mortality determinants. Model-2 was constructed by adding NPS to Model-1. NPS was significantly associated with HF mortality (Hazard Ratio: 2.194, 95% Confidence Interval: 1.176–4.091, p = 0.014). According to the Kaplan-Meier plot and log-rank analyses, there was a statistically significant difference in the long-term mortality of patients with HF and their NPS values for the entire cohort. Conclusion Based on our findings, NPS showed promise as an independent predictor of long-term mortality in individuals with HF.