Nevin Manimala

Dig Dis Sci. 2025 Jan 13. doi: 10.1007/s10620-024-08828-5. Online ahead of print.

ABSTRACT

BACKGROUND: Pouchitis is common among patients with ulcerative colitis (UC) who have had colectomy with ileal pouch-anal anastomosis. Antibiotics are first-line therapy for pouch inflammation, increasing the potential for gut colonization with multi-drug resistant organisms (MDRO). Fecal microbial transplant (FMT) is being studied in the treatment of pouchitis and in the eradication of MDRO. Prior work using aerobic antibiotic culture disks suggests that some patients with chronic pouchitis may regain fluoroquinolone sensitivity after FMT. However, gut MDRO include anaerobic, fastidious organisms that are difficult to culture using traditional methods.

AIM: We aimed to assess whether FMT reduced the abundance of antibiotic resistance genes (ARG) or affected resistome diversity, evenness, or richness in patients with chronic pouchitis.

METHODS: We collected clinical characteristics regarding infections and antibiotic exposures for 18 patients who had previously been enrolled in an observational study investigating FMT as a treatment for pouchitis. Twenty-six pre- and post-FMT stool samples were analyzed using FLASH (Finding Low Abundance Sequences by Hybridization), a CRISPR/Cas9-based shotgun metagenomic sequence enrichment technique that detects acquired and chromosomal bacterial ARGs. Wilcoxon rank sum tests were used to assess differences in clinical characteristics, ARG counts, resistome diversity and ARG richness, pre- and post-FMT.

RESULTS: All 13 of the patients with sufficient stool samples for analysis had recently received antibiotics for pouchitis prior to a single endoscopic FMT. Fecal microbiomes of all patients had evidence of multi-drug resistance genes and ESBL resistance genes at baseline; 62% encoded fluoroquinolone resistance genes. A numerical decrease in overall ARG counts was noted post-FMT, but no statistically significant differences were noted (P = 0.19). Richness and diversity were not significantly altered. Three patients developed infections during the 5-year follow-up period, none of which were associated with MDRO.

CONCLUSION: Antibiotic resistance genes are prevalent among antibiotic-exposed patients with chronic pouchitis. FMT led to a numerical decrease, but no statistically significant change in ARG, nor were there significant changes in the diversity, richness, or evenness of ARGs. Further investigations to improve FMT engraftment and to optimize FMT delivery in patients with inflammatory pouch disorders are warranted.

PMID:39804518 | DOI:10.1007/s10620-024-08828-5

Langenbecks Arch Surg. 2025 Jan 13;410(1):37. doi: 10.1007/s00423-025-03605-y.

ABSTRACT

PURPOSE: The impact of body-cavity depth on open (OLR) and laparoscopic liver resection (LLR) of segment 7 remains unclear. Therefore, we investigated the influence of body-cavity depth at the upper-right portion of the abdomen on LLR and OLR of segment 7.

METHODS: In total, 101 patients who underwent segment-7 liver resection over 2010-2023 were included. Body-cavity depth was measured from the abdominal-wall surface to the deepest site on the right side of the liver. Patients were categorized into shallow (< 18.4 cm) and deep (≥ 18.4 cm) populations based on median body-cavity depth. We compared surgical outcomes between OLR and LLR in shallow and deep populations after propensity-score adjustments.

RESULTS: In OLR and LLR groups, 27 and 22 patients in the shallow population, respectively, and 26 and 26 patients were included in the deep population, respectively, were included. The OLR group in the deep population had significantly greater blood loss than the corresponding LLR group (difference: 144 mL, 95% confidence interval (CI): [50, 238], P = 0.004). Other surgical outcomes, including operative time, were similar between groups. In the shallow population, the OLR group had significantly shorter operative time (difference: – 54 mL, 95% CI: [-101, – 6], P = 0.028) and similar blood loss than the LLR group.

CONCLUSIONS: For segment-7 liver resection, LLR is likely favorable for patients with a deep body cavity, with similar operative time and lower blood loss compared to OLR. Body-cavity depth could be a useful indicator for determining the suitable surgical approach for segment-7 liver resection.

PMID:39804508 | DOI:10.1007/s00423-025-03605-y

CNS Neurosci Ther. 2025 Jan;31(1):e70198. doi: 10.1111/cns.70198.

ABSTRACT

OBJECTIVES: Parkinson’s disease (PD) is characterized by olfactory dysfunction (OD) and cognitive deficits at its early stages, yet the link between OD and cognitive deficits is also not well-understood. This study aims to examine the changes in the olfactory network associated with OD and their relationship with cognitive function in de novo PD patients.

METHODS: A total of 116 drug-naïve PD patients and 51 healthy controls (HCs) were recruited for this study. Graph theoretical approaches were employed to reveal the abnormalities of topological characteristics in the olfactory network. Network-based statistics (NBS) analysis was employed to identify the abnormal subnetworks within the olfactory network. Moreover, partial correlation analysis and mediation analysis were performed to examine the relationship between the abnormal network metrics, olfactory function, and cognitive function.

RESULTS: Graph theoretical approaches revealed reduced betweenness centrality of the left insula in PD patients with OD. NBS analysis identified a disrupted subnetwork with decreased functional connectivity, primarily involving limbic regions. The average functional connectivity of this subnetwork partially mediated the relationship between olfactory and cognitive performance. Higher-granularity network analysis further highlighted the insula’s key role and revealed reduced efficiency of information integration within the olfactory network.

CONCLUSIONS: OD was associated with specific changes in the functional olfactory network, which, in turn, affects cognitive function. These findings underscore the importance of assessing and addressing OD. Understanding the neural correlates of OD could provide novel insights into the management and comprehension of cognitive impairment in PD.

PMID:39803685 | DOI:10.1111/cns.70198

J Eval Clin Pract. 2025 Feb;31(1):e14304. doi: 10.1111/jep.14304.

ABSTRACT

AIMS AND OBJECTIVES: In this study, it was aimed to determine nursing students’ attitudes towards clinical practice and their perceptions of occupational risk.

METHOD: The research is descriptive and cross-sectional. The population of this study consisted of second-, third- and fourth-year students studying in the Department of Nursing affiliated to the Faculty of Health Sciences of a university located in Turkey. The analysis was conducted using JASP 0.19.1.0 and SPSS 25 software. Mann-Whitney U and Kruskal-Wallis tests were applied. The Bonferroni test was performed to identify the group causing the difference.

RESULTS: A significant positive correlation was found between nursing students’ perception of occupational risk and nursing students’ attitude toward clinical practice (r = 0.434, p = 0.000). The mean score of the nursing students’ perception of occupational risk in nursing students was 68.74 ± 15.04. The mean score of attitude towards clinical practice in nursing students was 100.04 ± 24.83. A statistically significant difference was found between the presence of attitude towards clinical practice in nursing students and perception of occupational risk in nursing students in the gender variable (p < 0.05), whereas a statistically significant difference was found between adequate information about the nursing profession and attitude towards clinical practice in nursing students (p < 0.05).

CONCLUSION: In the findings of the study, nursing students’ perception of occupational risk and attitudes towards clinical practice were found at a high level. A statistically significant difference was found between the presence of perception of occupational risk in nursing students and attitude towards clinical practice in nursing students in the gender variable. In addition, a statistically significant difference was found between adequate knowledge and nursing profession about the nursing profession and attitude towards clinical practice in nursing students.

PMID:39803679 | DOI:10.1111/jep.14304

Br J Clin Psychol. 2025 Jan 13. doi: 10.1111/bjc.12525. Online ahead of print.

ABSTRACT

INTRODUCTION: Compared to their exclusively gay/lesbian or heterosexual identifying peers, young people identifying as bisexual+ (e.g. bisexual, pansexual, asexual, queer or questioning) are at elevated risk for suicidal ideation (SI) and attempts (SA). The present study aimed to establish whether the prevalence of, and psychosocial risk factors for, SI and SA vary as a function of sexual identity.

METHODS: Young adults (N = 274; 18-29 years old) were recruited via online crowdsourcing. They completed questionnaires assessing adverse childhood experiences (ACEs), emotion dysregulation, impulsivity, depression symptoms and lifetime history of SI and SA. Spearman correlations, Kruskal-Wallis H-tests and binomial logistic regression models were used.

RESULTS: No variable was associated with SI. Bisexual+ individuals reported greater SA than the heterosexual group, though statistically similar to the gay/lesbian group. A similar pattern emerged for ACEs. The bisexual+ group reported greater depression symptoms than the gay/lesbian group. Impulsivity and emotion dysregulation did not vary by sexual identity. Controlling for these psychosocial and sociodemographic variables did not alter results: bisexual+ individuals were almost three times more likely to report SA than heterosexual individuals, OR = 2.93 95% CI [1.16, 7.44]; gay/lesbian and heterosexual individuals had a statistically similar likelihood of reporting SA, OR = 1.09, 95% CI [0.27, 4.37].

CONCLUSION: This is the first study to establish that young adults identifying as bisexual+ are at greater risk for SA after controlling for well-established psychosocial correlates; this was not the case for SI. Further work is needed to establish the aetiology of this risk.

PMID:39803671 | DOI:10.1111/bjc.12525

Am J Cancer Res. 2024 Dec 15;14(12):5909-5920. doi: 10.62347/MUCQ4129. eCollection 2024.

ABSTRACT

The combination of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAb) and doublet chemotherapy is the standard first-line treatment for patients with wild-type RAS/BRAF metastatic colorectal cancer (mCRC). Some patients may require secondary resection after first-line treatment. However, it remains unclear whether targeted therapy should be continued after liver resection. To investigate whether targeted therapy can be spared after secondary resection, we retrospectively analyzed data from the Taiwan National Health Insurance Research Database for patients with wild-type KRAS mCRC who received first-line anti-EGFR mAb plus doublet chemotherapy. Between 2013 and 2018, 5694 mCRC patients were screened, with 174 meeting the eligibility criteria and being enrolled in this study. Among them, 153 patients continued anti-EGFR mAb after secondary resection. These patients demonstrated a significant improvement in overall survival (OS) but not in time to treatment failure. Postresection anti-EGFR mAb conferred OS benefits compared to no anti-EGFR mAb (43.17 vs. 31.41 months; P = 0.0064). When stratified by assessment period, OS was longer in patients assessed between 2016 and 2018 than in those assessed between 2012 and 2015 (not reached vs. 39.87 months; P = 0.1819). However, no significant difference was observed in time to treatment failure when stratified by assessment period or primary tumor location. A multivariate analysis revealed that postresection anti-EGFR mAb was an independent predictor of prolonged OS. In conclusion, for mCRC patients who have undergone secondary resection after first-line anti-EGFR mAb plus doublet chemotherapy, continuing anti-EGFR mAb may significantly extend OS, regardless of the primary tumor location.

PMID:39803663 | PMC:PMC11711520 | DOI:10.62347/MUCQ4129

Am J Cancer Res. 2024 Dec 15;14(12):5717-5733. doi: 10.62347/SSPI9013. eCollection 2024.

ABSTRACT

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated cancer, and immune checkpoint inhibitors (ICIs) have shown efficacy in its treatment. The combination of chemotherapy and ICIs represents a new trend in the standard care for metastatic NPC. In this study, we aim to clarify the immune cell profile and related prognostic factors in the ICI-based treatment of metastatic NPC. Programmed cell death ligand 1 (PD-L1) expression was measured in 81 metastatic tissue samples that had not received prior ICI treatment. The combined positive score (CPS) was positive in 58.0% of the samples, with a statistically significant correlation to median overall survival (OS) (CPS ≥ 1 vs. CPS < 1: 28 vs. 16 months, P = 0.004). For the combination treatment of metastatic NPC, 62 patients were enrolled in a retrospective analysis, yielding a median OS of 39.3 months. The objective response rate for this combination therapy was 71%, with a complete response rate of 45.2%. With a cutoff value of 4.8 for the pre-treated neutrophil-lymphocyte ratio (NLR) in peripheral blood (PB), the difference in median OS was statistically significant (P = 0.021). Thirty-seven patients received local treatment following the combination therapy of ICIs and chemotherapy, which provided additional survival benefits. Most hyper-responders exhibited a prolonged low NLR (< 3), a high total lymphocyte count, and an undetectable or stable EBV DNA load in PB during treatment. Peripheral blood mononuclear cells (PBMCs) from most patients receiving the combination treatment were rich in PD-1+CD8+ lymphocytes, which showed high expression of both IFN-γ and Granzyme B, demonstrating the ability to kill the EBV-positive NPC cell line and xenografts in vitro and in vivo. Responders also displayed increased levels of CD4+CD45RA-CCR7-CD28+CD57- cells (effector memory cell subset) in peripheral blood. These results indicate that in the context of combined chemotherapy and ICIs, high PD-L1 expression in pre-treated metastatic tumor tissue, a low NLR before treatment, a decrease in NLR after treatment, and local treatment can provide significant benefits for patients with metastatic NPC.

PMID:39803661 | PMC:PMC11711527 | DOI:10.62347/SSPI9013

Am J Cancer Res. 2024 Dec 15;14(12):5851-5862. doi: 10.62347/ZWAM1063. eCollection 2024.

ABSTRACT

OBJECTIVE: To analyze the clinical characteristics and molecular biomarkers of adult T-cell lymphoblastic lymphoma (T-LBL) to identify prognostic factors, and to evaluate the efficacy of different chemotherapy regimens, providing a basis for optimizing treatment strategies for T-LBL.

METHODS: A total of 89 Patients aged 18-72 years with T-LBL, confirmed via histopathological examination of lymph nodes, extranodal tissues, or bone marrow, were retrospectively included. Clinical data, treatment details, and mutational profiles were collected. Prognostic factors were assessed based on clinical and molecular characteristics, and the efficacy and safety of two chemotherapy regimens were compared. Descriptive statistics were used to analyze the disease spectrum.

RESULTS: Most patients (84.00%) presented with advanced disease (stages III-IV). Mediastinal invasion was observed in 63 patients (70.80%), and 59 patients (66.30%) exhibited B symptoms. Bone marrow involvement occurred in 19 patients (21.20%), and bulky mediastinum (>10 cm) was present in 50 patients (56.18%). Mutations were detected in 29 patients, with NOTCH1 being the most frequently mutated gene, followed by PHF-6, JAK-1, JAK-3, IL-7R, and TP53. The complete response (CR) rate was 51.69%. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 74.9% and 58.80%, respectively. Multivariate analysis identified female sex, lack of CR, and elevated lactate dehydrogenase (LDH) levels (>2× normal) as independent predictors of poor OS (58.25%). Chemotherapy regimens, LDH levels, and sex were independent prognostic factors for PFS (21.24%).

CONCLUSION: T-LBL is characterized by high-frequency gene mutations across multiple signaling pathways. Mediastinal invasion (70.80%) and extranodal involvement (39.33%) were prevalent in Chinese patients and were associated with poor prognosis. Combined assessment of clinical and molecular features allows for improved prognostic stratification and facilitates the development of targeted therapies for high-risk patients.

PMID:39803658 | PMC:PMC11711535 | DOI:10.62347/ZWAM1063

Am J Cancer Res. 2024 Dec 15;14(12):5628-5643. doi: 10.62347/ILIJ7959. eCollection 2024.

ABSTRACT

Breast cancer is one of the malignant tumors that seriously threaten women’s health, and early diagnosis and detection of breast cancer are crucial for effective treatment. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is an important diagnostic tool that allows for the dynamic observation of blood flow characteristics of breast tumors, including small lesions within the affected tissue. Currently, it is widely used in clinical practice and has been shown promising prospects. This study included a total of 1,987 patients who underwent breast surgery at Huangpu Branch, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine from January 1, 2019 to December 31, 2019. Comprehensive patient information was collected, including ultrasound, mammography findings, physical examination details, age, family history, and pathological diagnoses. The least absolute shrinkage and selection operator (LASSO) algorithm was employed to assign values to the x variables, facilitating the construction and validation of the LASSO model group. Receiver operating characteristic curves were generated using support vector machines to determine the area under the curve (AUC), as well as to assess sensitivity and specificity. There were no statistically significant differences (P>0.05) in average age, body mass index, tumor location, or tumor benignity/malignancy between the training and test sets. The AUC, sensitivity, and specificity of mammography for predicting the benignity or malignancy of breast tumors were 0.83, 86.96%, and 76%, respectively. In comparison, the AUC, sensitivity, and specificity of DCE-MRI for the same predictions were 0.91, 91.3%, and 88%, respectively. The predictive performance of DCE-MRI was significantly higher than that of mammography (P<0.05). In conclusion, both mammography and DCE-MRI demonstrated high AUC, sensitivity, and specificity in predicting the benignity or malignancy of breast tumors. However, DCE-MRI showed superior predictive performance, making it a valuable tool for the early detection of clinical breast cancer with potential for broader clinical application.

PMID:39803643 | PMC:PMC11711528 | DOI:10.62347/ILIJ7959

Heart Rhythm O2. 2024 Oct 5;5(12):951-956. doi: 10.1016/j.hroo.2024.09.018. eCollection 2024 Dec.

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) has a significant impact on health and quality of life. The relationship of AF burden and temporal patterns of AF on patient symptoms, outcomes, and healthcare utilization is unknown. Insertable cardiac monitors (ICMs) are a strategic and as yet untapped, tool to investigate these relationships.

OBJECTIVE: The DEFINE Atrial Fibrillation (DEFINE AFib) study will evaluate how AF burden and patterns are associated with changes in AF-related healthcare utilization (AFHCU) and patient-reported quality of life.

METHODS: This is a prospective, observational, multicenter study with a unique design that supports a complete method of assessing AF as a multifactorial disease. Patients with AF implanted with an ICM will be enrolled in the study and managed through an app-based research platform on their smartphone. Patients will be remotely monitored and patient-reported outcomes will be collected via the app. AFHCU will be confirmed via the participant’s medical record.

RESULTS: The primary analysis will evaluate whether summary and episodic measurements collected by ICMs are associated with changes in AFHCU. Secondary analyses will determine the relationship between AF characteristics and quality of life, timing and severity of AF-related complications, patient engagement, reliability of patient-reported outcomes, data from other digital rhythm detectors, and heterogeneity in care quality and AFHCU.

CONCLUSION: The DEFINE AFib study will provide valuable insights into the association between dynamic measures of AF and AFHCU in a patient population with known AF. The results may demonstrate the impact of ICM-detected AF on patient outcomes and help isolate novel AF patterns predictive of clinical risk.

PMID:39803627 | PMC:PMC11721724 | DOI:10.1016/j.hroo.2024.09.018