Nevin Manimala

Curr Urol. 2025 Mar;19(2):125-132. doi: 10.1097/CU9.0000000000000268. Epub 2025 Jan 27.

ABSTRACT

OBJECTIVES: The aim of this study was to evaluate the effects of the combination of bacteriophage therapy with antibiotics and bacteriophage treatment alone on relieving clinical symptoms of chronic recurrent cystitis caused by multidrug-resistant bacteria.

MATERIALS AND METHODS: This clinical trial compared the treatment methods of 217 female patients with chronic recurrent cystitis caused by multidrug-resistant bacteria, who were investigated from June 2020 to May 2023. Patients were allocated into 4 groups: group I: received bacteriophage (Sextaphage) therapy alone; group II: received a combination of bacteriophages (Sextaphage) and furazidin; group III: received a combination of bacteriophage (Sextaphage) and furazidin with cefixime; and group IV: received furazidin and cefixime (without bacteriophage). The primary outcome included changes in the acute cystitis symptom scale and the pain visual analog scale, which were completed on days 7 and 14 following treatment. Secondary outcome measures included bladder diary records of urinary symptoms, median voided volumes, level of bacteriuria, and degree of leukocyturia.

RESULTS: Initially, 217 female patients were presented during baseline visits. Those who did not meet the criteria inclusions were excluded, and 178 female patients were included in the final analysis. Statistically significant improvements from baseline in acute cystitis symptom scale scores for differential, typical symptoms, and quality of life domains were observed after 14 days of treatment in groups II, III, and IV. The pain level measured on the 14th day with the visual analog scale significantly decreased in groups II, III, and IV compared with group I. The patients of group I had a reduction of mean level bacteriuria of Escherichia coli from 10⁶ to 10² CFU/mL at 14 days of therapy. Significant improvement of voided volume from baseline was observed in groups II, III, and IV. Episodes of urinary frequency, both daytime and night-time, reduced significantly from baseline in all 4 groups only at 14 days of treatment.

CONCLUSIONS: Bacteriophage cocktail alone or with antibiotics may improve clinical symptoms in women with chronic recurrent cystitis caused by multidrug-resistant bacterial pathogens. In addition to improving clinical symptoms, the therapy with a phage cocktail may restore antibiotic sensitivity and increase the efficacy of antimicrobial agents.

PMID:40314011 | PMC:PMC12042198 | DOI:10.1097/CU9.0000000000000268

J Immunol Res. 2025 Apr 24;2025:5539590. doi: 10.1155/jimr/5539590. eCollection 2025.

ABSTRACT

Objective: This study aimed to analyze the relevant risk factors for nosocomial infection (NI) in patients who were admitted to an emergency department, explore the correlation between each influencing factor and the risk of NI, and evaluate the application value of immunological indicators on the patient prognosis, all of which can provide reference for clinical guidance. Methods: We prospectively enrolled 128 patients meeting the inclusion criteria who visited the emergency department of Dongzhimen Hospital, Beijing University of Chinese Medicine, from January 1 to December 31, 2019. Basic information and serum samples were collected from the patients, and flow cytometry was used. T lymphocyte subgroups, CD3⁺CD4⁺and CD3⁺CD8⁺, and natural killer (NK) cells were measured. Patients were divided into infection group and control group according to whether nosocomial infection occurred within 48 h of admission. Age, gender, type of disease, APACHE II score, Charlton score, T lymphocyte subtypes, and NK cell values were compared, and a logistic multivariate regression analysis was conducted. A multifactor regression analysis was performed on various risk factors. The nomogram website was used to draw a nomogram model of meaningful indicators, and the receiver-operating characteristic (ROC) curve was based on experimental results. Results: Logistics multivariate regression analysis showed the Charlton score and NK cell count were independent risk factors for nosocomial infection. Cell counts for subsets CD3⁺CD4⁺ and CD3⁺CD8⁺ were protective factors, and the OR value and 95% CI were 5.199 (1.933-13.983), 1.248 (1.055-1.475), 0.851 (0.790-0.916), and 0.832 (0.711-0.973), p < 0.05. respectively. Statistical significance was set at p < 0.05.The nomogram model suggested that the area under the curve for predicting the risk of nosocomial infection was 0.920 (0.872-0.967), p < 0.001. Conclusion: Patients with low CD3⁺CD4⁺ and CD3⁺CD8⁺ T lymphocyte or high NK cell count as well as high Charlton score are more likely to have nosocomial infection. Then, we speculate that the risk of nosocomial infection within 48 h is also high for patients with underlying diseases and immune function that is affected and suppressed on admission, regardless of whether infection occurs during hospitalization.

PMID:40313971 | PMC:PMC12045693 | DOI:10.1155/jimr/5539590

Front Immunol. 2025 Apr 17;16:1576849. doi: 10.3389/fimmu.2025.1576849. eCollection 2025.

ABSTRACT

BACKGROUND: C-X-C motif chemokine ligand 9 (CXCL9) is induced by the interferon-γ response, and its receptor, C-X-C motif chemokine receptor 3, is a well-established marker of T-helper 1 (Th1) cells, which play an essential role in type 1 immune responses. CXCL9 expression is upregulated in patients with interstitial lung disease (ILD), COVID-19, and asthma. Although type 1 inflammation and CD8⁺ T cell activation are considered central to the inflammatory pathophysiology of chronic obstructive pulmonary disease (COPD), the relationship between blood levels of Th1 chemokines and this pathophysiology remains unclear. This study aimed to investigate the relationship between CXCL9 and chronic respiratory diseases.

METHODS: We conducted a retrospective cohort study. The serum levels of CXCL9, surfactant protein A (SP-A), Krebs von den Lungen-6 (KL-6), and C-reactive protein (CRP) were analyzed in 165 patients with ILD and COPD. COPD was diagnosed using pulmonary function tests according to the Global Initiative for Chronic Obstructive Lung Disease criteria. Statistical analyses included Fisher’s exact test, Steel-Dwass test, Mann-Whitney U, and Wilcoxon test. An unsupervised hierarchical cluster analysis using complete linkage and Euclidean distance was performed for data clustering.

RESULTS: CXCL9 levels were significantly higher in patients with COPD and interstitial ILD than in healthy smokers and non-smokers. The median serum CXCL9 levels in patients with ILD, COPD, healthy smokers, and healthy nonsmokers were 61.6, 69.3, 37.0, and 32.5pg/mL, respectively. CXCL9 levels in patients with COPD significantly correlated with KL-6, SP-A, blood eosinophil ratio, lactate dehydrogenase (LDH), and CRP levels, with correlation coefficients of 0.243, 0.381, 0.225, 0.369, and 0.293, respectively. Additionally, CXCL9 levels were negatively correlated with FEV₁%. Levels of LDH and KL-6 and the neutrophil ratio were significantly elevated in non-eosinophilic COPD patients with high CXCL9 levels.

CONCLUSIONS: Our results highlight the potential role of CXCL9 in the inflammatory pathophysiology of COPD.

PMID:40313944 | PMC:PMC12043484 | DOI:10.3389/fimmu.2025.1576849

Front Immunol. 2025 Apr 17;16:1542780. doi: 10.3389/fimmu.2025.1542780. eCollection 2025.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognosis, and its clinical management remains a significant challenge due to the high recurrence rates and limited treatment options. Despite advances in understanding the molecular mechanisms underlying ACC, no reliable biomarkers have been validated for routine clinical use.

METHODS: We analyzed RNA sequencing data from The Cancer Genome Atlas (TCGA) database (n=79) and Genotype Tissue Expression (GTEx) database (n=128) to investigate the expression of VGF in ACC and normal adrenal tissues. Gene expression levels of VGF were quantified and correlated with clinicopathological features and survival outcomes. Statistical methods included Cox proportional hazards models and Kaplan-Meier analysis, while Gene Set Enrichment Analysis (GSEA) was utilized to identify relevant biological pathways associated with VGF expression. Clinical data from 7 ACC patients from YANTAI YUHUANGDING Hospital were also analyzed. The expression of VGF in ACC and normal adrenal gland tissue was further validated through IHC experiments.

RESULTS: Our results demonstrate that VGF expression is elevated in ACC tissues compared to normal adrenal tissues and is significantly associated with advanced disease stages, lymph node involvement, metastasis and poor overall survival. VGF levels also correlate with immune cell infiltration, including Th2 cells, T helper cells, and Neutrophils. Importantly, our study establishes VGF as a potential prognostic biomarker for ACC and highlights its role in tumor progression and immune modulation. Additionally, GSEA analysis suggests that VGF is involved in cytokine receptor interaction and the P13K-Akt signaling pathway, possibly relating to tumor immunity.

CONCLUSIONS: VGF could serve as a valuable marker for patient stratification, monitoring disease progression, and predicting responses to immunotherapies. Future studies should focus on investigating circulating VGF levels as a non-invasive biomarker for ACC to improve clinical management and treatment outcomes.

PMID:40313932 | PMC:PMC12043488 | DOI:10.3389/fimmu.2025.1542780

J Parasitol Res. 2025 Apr 23;2025:5596158. doi: 10.1155/japr/5596158. eCollection 2025.

ABSTRACT

Intestinal parasitic infections (IPIs) remain a significant global health burden, disproportionately affecting developing nations. This cross-sectional study aimed to determine the prevalence and associated risk factors of IPIs among patients visiting Kidus Harvey Health Center in North Wollo, Ethiopia, from February to April 2023. Stool samples and questionnaire data were collected from 404 voluntary participants. Data were analyzed using SPSS version 20, employing descriptive statistics and logistic regression. The overall prevalence of IPIs was 41.09% (166/404). E. histolytica/dispar (16.34%) and A. lumbricoides (7.2%) were the predominant parasitic species. Significant risk factors identified included marital status (married: AOR = 3.536, 95%CI = 1.515-8.250, p = 0.003), occupation (farmers: AOR = 2.447, 95%CI = 0.816-7.337, p = 0.04), family size (> 9 members: AOR = 2.860, 95%CI = 0.619-13.206, p = 0.008), infrequent handwashing before meals, infrequent shoe wearing, contact with water bodies, untreated water sources, and raw meat consumption. The high prevalence of IPIs underscores the need for targeted public health interventions. These interventions should prioritize promoting personal and environmental sanitation, reducing raw meat consumption, and preventing unprotected contact with soil and water. Comprehensive public health campaigns delivering specific hygiene education to high-risk groups, emphasizing handwashing, shoe wearing, and safe water practices, are essential to mitigate the burden of IPIs in this population.

PMID:40313928 | PMC:PMC12043435 | DOI:10.1155/japr/5596158

Prostate. 2025 May 1. doi: 10.1002/pros.24902. Online ahead of print.

ABSTRACT

BACKGROUND: This study investigates the association between thromboembolic events (TE) and castration-resistant prostate cancer (CRPC) patients receiving oral androgen receptor pathway inhibitors (ARPi) compared to those undergoing chemotherapy, both with and without a pre-existing history of cardiovascular disease (CVD).

METHODS: A total of 2779 men diagnosed with CRPC were identified using the Surveillance, Epidemiology, and End Results (SEER) Medicare Linked Database from 2012 to 2016. Patients were stratified based on their CVD history. Within each CVD stratum (pre-existing CVD vs. no pre-existing CVD), patients were further categorized into two treatment groups: those receiving oral ARPi and those undergoing chemotherapy. Unadjusted and inverse probability treatment weight (IPTW)-adjusted proportional hazards models, using Fine and Gray’s method, were applied to evaluate the potential association between ARPi treatment and TE.

RESULTS: Patients with pre-existing CVD treated with ARPi exhibited a significantly lower crude hazard ratio (HR) for TE compared to chemotherapy (HR 0.39, 95% CI 0.27-0.58, p < 0.001). However, after adjustment using IPTW, this association was no longer significant (adjusted hazard ratio [AHR] 1.00, 95% CI 0.75-1.32, p = 0.99). For patients without CVD, ARPi use was also associated with a reduced risk of TE in the crude analysis (HR 0.53, 95% CI 0.32-0.87, p = 0.01), but this effect was not statistically significant after IPTW adjustment (HR 0.99, 95% CI 0.69-1.41, p = 0.94).

CONCLUSION: ARPi demonstrated no significant effect on TE risk compared to chemotherapy, regardless of pre-existing CVD status. Similarly, when excluding patients with a prior history of TE, ARPi use remained non-significantly associated with new TE in the IPTW-adjusted competing risk analysis, highlighting the need for further investigation.

PMID:40312772 | DOI:10.1002/pros.24902

Stem Cell Res Ther. 2025 May 1;16(1):215. doi: 10.1186/s13287-025-04316-3.

ABSTRACT

BACKGROUND: Preliminary phase I clinical trial results revealed that autologous umbilical cord blood-derived mononuclear cells (UCB-MNCs) preserved right ventricular cardiac function. To establish the efficacy of intramyocardial injections of an autologous UCB-MNC product at the time of stage II palliation surgery in patients with hypoplastic left heart syndrome (HLHS).

METHODS: A phase IIb, multicenter, open-label, nonrandomized study was conducted. Ninety-five children (fifty treated and forty-five controls) with HLHS and its variants, a history of stage I palliation surgery, and planned stage II palliation surgery at less than thirteen months were enrolled. We assessed coprimary efficacy endpoints for changes in right ventricular cardiac function through fractional area changes and longitudinal and circumferential strain, both in the short term (three months) and long term (twelve months). Second, we assessed changes in biomarkers of cardiac injury. Safety endpoints included severe adverse events (SAEs), changes in overall health through vital signs, and cumulative hospitalization.

RESULTS: Assessment of our coprimary efficacy endpoints revealed an unfavorable change in longitudinal cardiac strain in the treatment group compared with an improvement in strain in the control group (unadjusted p =.032) in the short term. No differences were observed between the groups in terms of other coprimary efficacy endpoints in the short or long term. A secondary assessment of biomarkers of cardiac injury revealed higher troponin T levels in the treatment group at three and six hours postsurgery. Regarding safety, no deaths related to the administered product or delivery procedure were reported. The treatment group presented a greater incidence (20%) of at least one SAE than the control group at three months (p =.048). Additionally, no statistically significant differences were found for the other safety endpoints.

CONCLUSION: Intramyocardial injections of autologous UCB-MNC products into the right ventricular myocardium during stage II palliation surgery failed to enhance cardiac function in patients with hypoplastic left heart syndrome. REGISTERED ON CLINICALTRIALS.GOV: Registered on ClinicalTrials.gov (NCT03779711) on 12/04/2018; URL: https://clinicaltrials.gov/ct2/show/NCT0377971 .

PMID:40312733 | DOI:10.1186/s13287-025-04316-3

Glob Health Res Policy. 2025 May 1;10(1):20. doi: 10.1186/s41256-025-00403-3.

ABSTRACT

BACKGROUND: As a newly emerging collaborative platform to boost regional growth and prosperity, the Belt and Road Initiative (BRI) has great potential to promote global health development. However, the overall health status of BRI countries remains unclear. We analyzed the health patterns and its geographical distribution in 149 BRI countries from 1990 to 2021.

METHODS: Using the Global Burden of Disease 2021 (GBD 2021) online database, we examined time trends, country and income variations in death rate and disability-adjusted life years (DALY) rate, and compared the trends and projected 2030 values for ten key health-related Sustainable Development Goals (SDGs) indicators among the 149 BRI countries.

RESULTS: The number of deaths and DALYs of BRI countries represented 62.9-66.0% of global deaths and 64.8-66.8% of global DALYs between 1990 and 2021, and both the overall age-standardized death rate and DALY rate continued to be higher in BRI countries than in non-BRI countries throughout the time period studied. Great variations existed across the 149 BRI countries for both level of and changes in age-standardized death rate and DALY rate. The 2030 targets for six health-related SDGs indicators will not be reached in over 70% of BRI countries according to the previous changing speed trajectory.

CONCLUSIONS: Our findings demonstrate that BRI countries face a heavy burden of disease that varies across countries, although health outcomes have improved since 1990. Progress toward 2030 targets for six key health-related SDGs indicators in most BRI countries was slow. These findings support calls for more health collaborations, aid programs, and other health service to reduce health disparities across the BRI countries.

PMID:40312730 | DOI:10.1186/s41256-025-00403-3

BMC Public Health. 2025 May 1;25(1):1609. doi: 10.1186/s12889-025-22865-3.

ABSTRACT

BACKGROUND: The present study aims to investigate the association of smoking behaviors and cardiovascular-kidney-metabolic (CKM) syndrome with incident cardiovascular disease (CVD), and to evaluate whether the cardiovascular benefits of smoking cessation vary across different CKM conditions.

METHODS: This study included 242,636 white European participants from the UK Biobank who were classified as CKM syndrome Stages 0 to 3 and free of CVD at baseline. Covariates adjusted Cox proportional hazards models were employed to evaluate the associations of CKM syndrome with the risks of total CVD, stroke, coronary heart disease (CHD), major adverse cardiovascular events (MACE), and 13 CVD subtypes. The impact of smoking behavior across different CKM stages and the joint effect of smoking and CKM syndrome on CVD risk were also evaluated. To investigate the potential effect modification by CKM syndrome, we examined the multiplicative scale by interaction terms in Cox models, and quantified the additive scale using statistics such as the relative excess risk due to interaction (RERI).

RESULTS: The risk of total CVD, stroke, and CHD increased progressively with advancing CKM stages, with Stage 3 associated with hazard ratios (HRs) of 3.38 (95% CI: 3.05-3.74), 3.01 (2.49-3.64), and 3.65 (3.25-4.10), respectively (P for trend < 0.001). The time required to reduce CVD risk to a level not significantly different from that of never smokers tends to be longer for individuals with advancing CKM stage: smokers at Stages 0-1 achieved this after approximately 10 years of cessation, whereas those at Stages 2-3 required more than 25 years. Compared with never smokers at CKM Stage 0, current smokers at CKM Stage 3 had substantially higher risk of total CVD (HR = 4.14, 95% CI: 3.54-4.83) and several subtypes, particularly abdominal aortic aneurysm (HR = 17.68, 95% CI: 6.33-49.43) and peripheral vascular disease (HR = 10.53, 95% CI: 6.79-16.34). CKM syndrome appeared to act as a positive additive effect modifier in smoking-related risk of total CVD (RERI = 0.20, 95% CI: 0.05-0.32), as well as several CVD subtypes, suggesting that the combined effect of smoking and CKM progression exceeds the sum of their individual effects.

CONCLUSIONS: Our finding emphasizes the importance of smoking cessation among individuals with advanced CKM syndrome, as they face heightened CVD risk. However, compared to those at earlier CKM stages, the short-term benefits of smoking cessation may be less pronounced in this population. Interventions that combine smoking cessation promotion with CKM syndrome management may yield greater reductions in the risk of several CVD outcomes.

PMID:40312716 | DOI:10.1186/s12889-025-22865-3

BMC Prim Care. 2025 May 1;26(1):139. doi: 10.1186/s12875-025-02831-z.

ABSTRACT

BACKGROUND: Cancer is increasing worldwide. Palliative care can help reduce the suffering of patients with cancer. Providing palliative care with a primary health care (PHC) approach can lead to greater patient access to palliative services. Given the lack of studies in this area, the present study aimed to determine the impact of community-based palliative care integrated with PHC on outcomes of terminally ill cancer patients.

METHODS: This was a randomized controlled trial. Research population included 120 cancer patients in Khorramabad in 2023. A convenience sampling method was conducted, and then subjects were allocated to the intervention and control groups through randomization blocks with size of four. Subjects in the intervention group received PHC-integrated community-based palliative support for two months, while their control peers received their routine health care programs during the same period. The data were gathered using the Palliative Care Outcome Scale before and two months after the intervention and then were analyzed using SPSS 22 software and descriptive and inferential statistics.

RESULTS: The mean scores of all dimensions of palliative outcomes, including physical, psychological, emotional, and social, as well as the overall palliative care outcome, improved after the intervention in the experimental group, and these changes were statistically significant (p < 0.001). Before the intervention, the mean score of overall palliative care outcome was 22.21 ± 2.89 in the intervention group and 21.88 ± 2.55 in the control group (P = 0.51), While after the intervention, the mean scores in the experimental and control groups changed to 17.98 ± 2.88 and 21.83 ± 2.69, respectively, and this difference was statistically significant (p < 0.001). The mean changes in the overall palliative outcome score before and after the intervention in the experimental and control groups were 4.23 ± 2.83 and 0.5 ± 0.72, respectively, and this difference was statistically significant (p < 0.001).

CONCLUSION: The community-based palliative care integrated into the PHC structure could positively affect all aspects of palliative care. It is recommended that policymakers create conditions where cancer patients can receive care through the PHC structure. More studies are required to designate the strengths and weaknesses of this care approach.

TRIAL REGISTRATION NUMBER: IRCT20180721040540N5, 2023-06-07, Registered on June 7,2023. https://irct.behdasht.gov.ir/user/trial/68288/view .

PMID:40312691 | DOI:10.1186/s12875-025-02831-z