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1.
BMC Pediatr ; 24(1): 452, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39010049

ABSTRACT

INTRODUCTION: Ethiopia implemented measures to reduce preterm mortality, and much is currently being done to avoid preterm death, yet preterm death remains the top cause of infant death. As a result, evaluating median time of recovery and determinants will provide information to planners and policymakers to design strategies to improve preterm survival. METHODS: Hospital-based retrospective follow-up study was conducted in four selected public hospitals of Addis Ababa from September 2018 to August 2021. Data were collected using a pretested structured questionnaire. Epi-data 4.6 and STATA Version 16 were used for data entry and analysis. Kaplan-Meier survival curve, log-rank test, and median time were computed. To find predictors of time to recovery, a multivariable Cox proportional hazards regression model was fitted, and variables with a p-value less than 0.05 were considered statistically significant. RESULTS: A total of 466 preterm babies were included in the study of which 261 (56.1%) preterm neonates survived and were discharged from NICUs. The median time to recovery was 10 days (95% CI: 9-12). Low birth weight (Adjusted hazard-ratio [AHR]: 1.91, 95% CI: 1.2-3.06), normal birth weight (AHR: 2.09, 95% CI: 1.16-3.76), late preterm (AHR: 1.91, 95% CI: 1.02-3.55), no hospital-acquired infection (AHR: 2.19, 95% CI: 1.36-3.5), no thrombocytopenia (AHR: 1.96, 95% CI: 1.27-3.02), continuous positive airway pressure (AHR: 0.66, 95% CI: 0.48-0.91), and kangaroo mother care (AHR: 2.04, 95% CI: 1.48-2.81) were found to be independent predictors of time to recovery of preterm babies. DISCUSSION/CONCLUSION: The recovery rate was found relatively low. Several predictors of preterm recovery time were discovered in the study. The majority of predictors were preventable or treatable. Therefore, emphasis should be given towards prevention and early anticipation, and management of these predictors. Studies to assess the quality of care and cause of low survival rate of preterm infants are recommended.


Subject(s)
Hospitals, Public , Infant, Premature , Intensive Care Units, Neonatal , Humans , Ethiopia/epidemiology , Infant, Newborn , Retrospective Studies , Female , Hospitals, Public/statistics & numerical data , Male , Follow-Up Studies , Time Factors
2.
World J Surg Oncol ; 22(1): 184, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39010072

ABSTRACT

BACKGROUND: The prognosis of advanced gastric cancer (AGC) is relatively poor, and long-term survival depends on timely intervention. Currently, predicting survival rates remains a hot topic. The application of radiomics and immunohistochemistry-related techniques in cancer research is increasingly widespread. However, their integration for predicting long-term survival in AGC patients has not been fully explored. METHODS: We Collected 150 patients diagnosed with AGC at the Affiliated Zhongshan Hospital of Dalian University who underwent radical surgery between 2015 and 2019. Following strict inclusion and exclusion criteria, 90 patients were included in the analysis. We Collected postoperative pathological specimens from enrolled patients, analyzed the expression levels of MAOA using immunohistochemical techniques, and quantified these levels as the MAOAHScore. Obtained plain abdominal CT images from patients, delineated the region of interest at the L3 vertebral body level, and extracted radiomics features. Lasso Cox regression was used to select significant features to establish a radionics risk score, convert it into a categorical variable named risk, and use Cox regression to identify independent predictive factors for constructing a clinical prediction model. ROC, DCA, and calibration curves validated the model's performance. RESULTS: The enrolled patients had an average age of 65.71 years, including 70 males and 20 females. Multivariate Cox regression analysis revealed that risk (P = 0.001, HR = 3.303), MAOAHScore (P = 0.043, HR = 2.055), and TNM stage (P = 0.047, HR = 2.273) emerged as independent prognostic risk factors for 3-year overall survival (OS) and The Similar results were found in the analysis of 3-year disease-specific survival (DSS). The nomogram developed could predict 3-year OS and DSS rates, with areas under the ROC curve (AUCs) of 0.81 and 0.797, respectively. Joint calibration and decision curve analyses (DCA) confirmed the nomogram's good predictive performance and clinical utility. CONCLUSION: Integrating immunohistochemistry and muscle fat features provides a more accurate prediction of long-term survival in gastric cancer patients. This study offers new perspectives and methods for a deeper understanding of survival prediction in AGC.


Subject(s)
Gastrectomy , Monoamine Oxidase , Stomach Neoplasms , Subcutaneous Fat , Humans , Male , Female , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Stomach Neoplasms/metabolism , Aged , Survival Rate , Prognosis , Subcutaneous Fat/diagnostic imaging , Subcutaneous Fat/pathology , Subcutaneous Fat/metabolism , Middle Aged , Follow-Up Studies , Monoamine Oxidase/metabolism , Monoamine Oxidase/analysis , Retrospective Studies , Nomograms , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/analysis , Tomography, X-Ray Computed/methods
3.
Am J Cardiol ; 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38972536

ABSTRACT

The United Network for Organ Sharing (UNOS) adopted new criteria for the heart allocation score on October 18, 2018 to reflect the changing trends of candidates' mortality while awaiting transplant. We examined the impact of these policy changes on rates of left ventricular assist device (LVAD) implantation and outcomes after transplant from a relatively newer UNOS database. The UNOS registry was used to identify first-time adult heart recipients with LVAD at listing or transplant who underwent transplantation between January 1, 2016 and March 10, 2020. Survival data were collected through March 30, 2023. Those listed before October 18, 2018 but transplanted after were excluded. Patients were divided into before or after change groups. Demographics and clinical parameters were compared. Survival was analyzed with Kaplan-Meier curves and log-rank tests. A p <0.05 was considered significant. We identified 4,387 heart recipients with LVAD in the before (n = 3,606) and after (n = 781) score change eras. The after group had a lower rate of LVAD implantation while listed than the before group (20.4% vs 34.9%, p <0.0001), and were more likely to be female (25.1% vs 20.2%, p = 0.002); in both groups, most recipients (62.8%) were white. There was significantly farther distance from the donor hospital to transplant center in the after group (264.4 NM vs 144.2 NM, p <0.0001) and decreased waitlist days (84.9 ± 105.1 vs 369.2 ± 459.5, p <0.0001). Recipients in the after group were more likely to use extracorporeal membrane oxygenation (3.7% vs 0.5%, p <0.0001) and intravenous inotropes (19.1% vs 7.5%, p <0.0001) and receive a Centers for Disease Control and Prevention increased risk donor organ (37.9% vs 30.5%, p <0.0001). Survival at 3 years was comparable between the 2 groups. The allocation score change in 2018 yielded considerable changes in mechanical circulatory support device implantation strategy and outcomes. The rate of LVAD implantation decreased with increased utilization of temporary mechanical circulatory support devices.

4.
Virchows Arch ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977466

ABSTRACT

Tumor budding, a biomarker traditionally evaluated using hematoxylin and eosin (H&E) staining, has gained recognition as a prognostic biomarker for stage II colon cancer. Nevertheless, while H&E staining offers valuable insights, its limitations prompt the utilization of pan-cytokeratin immunohistochemistry (IHC). Consequently, this study seeks to evaluate the prognostic significance of tumor budding using IHC in a contemporary cohort of stage II colon cancer patients, aiming to deepen our understanding of this critical facet in cancer prognosis. We conducted a retrospective, population-based cohort study including 493 patients with stage II colon cancer and evaluated tumor budding using IHC, following the H&E-based guidelines proposed by the International Tumor Budding Consensus Conference Group. Correlation between H&E-based and IHC-based tumor budding was assessed using a four-tiered scoring system that included a zero budding (Bd0) category. Survival analyses explored the prognostic significance of tumor budding assessed by IHC and H&E. As expected, IHC-based tumor budding evaluation yielded significantly higher bud counts compared to H&E (p < 0.01). Interestingly, 21 patients were identified with no tumor budding using IHC. This was associated with significantly improved recurrence-free survival (HR = 5.19, p = 0.02) and overall survival (HR = 4.47, p = 0.04) in a multivariate analysis when compared to tumors with budding. The Bd0 category demonstrated a 100% predictive value for the absence of recurrence. In conclusion, IHC-based tumor budding evaluation in stage II colon cancer provides additional prognostic information. The absence of tumor budding is associated with a favorable prognosis and may serve as a potential marker for identifying patients with no risk of recurrence.

5.
Cell Rep Methods ; 4(7): 100817, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38981473

ABSTRACT

Deep-learning tools that extract prognostic factors derived from multi-omics data have recently contributed to individualized predictions of survival outcomes. However, the limited size of integrated omics-imaging-clinical datasets poses challenges. Here, we propose two biologically interpretable and robust deep-learning architectures for survival prediction of non-small cell lung cancer (NSCLC) patients, learning simultaneously from computed tomography (CT) scan images, gene expression data, and clinical information. The proposed models integrate patient-specific clinical, transcriptomic, and imaging data and incorporate Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome pathway information, adding biological knowledge within the learning process to extract prognostic gene biomarkers and molecular pathways. While both models accurately stratify patients in high- and low-risk groups when trained on a dataset of only 130 patients, introducing a cross-attention mechanism in a sparse autoencoder significantly improves the performance, highlighting tumor regions and NSCLC-related genes as potential biomarkers and thus offering a significant methodological advancement when learning from small imaging-omics-clinical samples.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Deep Learning , Lung Neoplasms , Humans , Lung Neoplasms/genetics , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/pathology , Tomography, X-Ray Computed/methods , Biomarkers, Tumor/genetics , Prognosis , Male , Female , Gene Expression Regulation, Neoplastic , Transcriptome
6.
Sci Rep ; 14(1): 16230, 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39004629

ABSTRACT

Our objective was to examine the impact of elective neck dissection (END) on the prognosis of patients with cT2N0 maxillary sinus squamous cell carcinoma (MS-SCC) and to determine factors that predict the occurrence of occult metastasis in this patient population. A retrospective analysis was conducted using data from the SEER database. Patients with cT2N0 MS-SCC were included in the study and divided into two groups: those who received END and those who did not. The impact of END on disease-specific survival (DSS) and overall survival (OS) was assessed using propensity score matching. Multivariate logistic regression analysis was performed to determine predictors for occult metastasis. A total of 180 patients were included in the study, with 40 cases receiving END. Following propensity score matching, patients treated with END and those without showed similar DSS and OS rates. Occult metastasis was observed in 9 patients, corresponding to a rate of 22.5%. High-grade tumors were independently associated with a higher risk of occult metastasis compared to low-grade tumors (hazard ratio 1.52, 95% confidence interval 1.17-2.00). cT2 MS-SCC carries an occult metastasis rate of 22.5%, with histologic grade being the primary determinant of occult metastasis. END does not confer a significant survival benefit in this patient population.


Subject(s)
Carcinoma, Squamous Cell , Neck Dissection , Humans , Male , Female , Middle Aged , Aged , Retrospective Studies , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/mortality , Neoplasm Staging , Elective Surgical Procedures , Prognosis , Maxillary Sinus Neoplasms/pathology , Maxillary Sinus Neoplasms/surgery , Maxillary Sinus Neoplasms/mortality , Adult , SEER Program , Propensity Score
7.
Front Nutr ; 11: 1421560, 2024.
Article in English | MEDLINE | ID: mdl-39010859

ABSTRACT

Objective: Handgrip strength (HGS) and the high-sensitivity modified Glasgow prognostic score (HS-mGPS) are associated with the survival of patients with cancer. However, no studies have investigated the combined effect of HGS and HS-mGPS on the overall survival (OS) of patients with colon cancer. Methods: Prospective follow-up data of colon cancer patients undergoing radical resection from April, 2016 to September, 2019 were retrospectively collected. We combined the HGS and HS-mGPS to create a new composite index, HGS-HS-mGPS. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using Cox regression models to assess the association between variables and OS. Risk factors on OS rates were investigated by Cox analyses and the nomogram was constructed using significant predictors and HGS-HS-mGPS. The predictive performance of the nomogram was evaluated by receiver operating characteristic curve and calibration curve. Results: This study included a total of 811 patients, of which 446 (55.0%) were male. The HGS optimal cut-off values of male and female patients were 28.8 and 19.72 kg, respectively. Multivariate analysis revealed that low HGS and high HS-mGPS were independent risk factors of colon cancer after adjusting confounders (adjusted HR = 3.20; 95% CI: 2.27-4.50; p < 0.001 and adjusted HR = 1.55; 95% CI: 1.12-2.14; p = 0.008 respectively). Patients with low HGS and high HS-mGPS had a 10.76-fold higher mortality risk than those with neither (adjusted HR = 10.76; 95% CI: 5.38-21.54; p < 0.001). A nomogram predicting 1-, 3-, and 5 year OS was constructed based on three clinicopathologic prognostic factors. Importantly, incorporating HGS-HS-mGPS into the nomogram model meaningfully improved the predictive performance. The decision curve analyses demonstrated the application value of the HGS-HS-mGPS nomogram for predicting OS of patients with colon cancer. Conclusion: HGS-HS-mGPS is associated with the survival of patients with colon cancer. These findings indicate the usefulness of HGS and HS-mGPS measurements in clinical practice for improving patient assessment, cancer prognosis, and precise intervention.

8.
J Hepatocell Carcinoma ; 11: 1389-1402, 2024.
Article in English | MEDLINE | ID: mdl-39011125

ABSTRACT

Background: The dominant artery blood supply is a characteristic of hepatocellular carcinoma (HCC). However, it is not known whether the blood supply can predict the post-hepatectomy prognosis of patients with HCC. This retrospective study investigated the prognostic value of the portal venous and arterial blood supply estimated on triphasic liver CT (as a portal venous coefficient, PVC, and hepatic arterial coefficient, HAC, respectively) in patients with HCC following hepatectomy. Methods: HCC patients who were tested by triphasic liver CT 2 weeks before hepatectomy and received R0 hepatectomy at the Second Affiliated Hospital, Kunming Medical University between January 1, 2016 and December 31, 2020, were retrospectively screened. Their PVC and HAC, and other variables were analyzed for the prediction of overall survival (OS) and recurrence-free survival (RFS) using the least absolute shrinkage and selection operator and Cox proportional hazard regression models. Results: Four hundred and nineteen patients (53.2 ± 10.6 years of age and 370 men) were evaluated. A shorter OS was independently associated with higher blood albumin and total bilirubin grade [hazard ratio (HR) 2.020, 95% confidence interval (CI) 1.534-2.660], higher Barcelona Clinic Liver Cancer (BCLC) stage (HR 1.514, 95% CI 1.290-1.777), PVC ≤ 0.386 (HR 1.628, 95% CI 1.149-2.305), and HAC > 0.029 (HR 1.969, 95% CI 1.380-2.809). A shorter RFS was independently associated with male (HR 1.652, 95% CI 1.005-2.716), higher serum α-fetoprotein ≥ 400 ng/mL (HR 1.672, 95% CI 1.236-2.263), higher BCLC stage (HR 1.516, 95% CI 1.300-1.768), tumor PVC ≤ 0.386 (HR 1.641, 95% CI 1.198-2.249), and tumor HAC > 0.029 (HR 1.455, 95% CI 1.060-1.997). Conclusion: Tumor PVC or HAC before hepatectomy is valuable for independently predicting postoperative survival of HCC patients.

9.
Indian J Hematol Blood Transfus ; 40(3): 375-384, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39011253

ABSTRACT

Haplo-identical stem cell transplant using post-transplant cyclophosphamide is increasingly being used in children without a matched sibling donor. Between 2010 and June 2021, 127 children underwent 138 transplants with a median age of 7.1 years for malignant and non-malignant disorders. Conditioning regimens included both myeloablative and reduced intensity regimens with peripheral blood stem cells as the main graft source. Engraftment occurred in 113 [81.9%] at a median of 16 days [range: 10-32] with primary graft failure in 10.2%. Cumulative incidence of grade II-IV acute graft versus host disease (GVHD) was 49.5% and chronic GVHD in 40.7%. Majority [92.7%] had at least one infection with 31% incidence of bacterial infection, 76% incidence of viral and 16% incidence of fungal infection. The 2-year overall survival (OS) is 54.9 ± 4.6% with a lower survival among young children aged 0-5 years [28.2 ± 6.4%] compared to 5-10 years [71.3 ± 6.8%] and 11-15 years [55.7 ± 8.8%] [p = 0.032]. 2-year OS has gradually improved from 25.0 ± 2.1% for 2010-2013 to 47.5 ± 6.2% for 2014-2017 and 67.1 ± 6.6% for 2018-2021 [p = 0.049]. On multivariate analysis, bacterial infection [p = 0.017], invasive fungal disease [p = 0.002] and graft failure [p = 0.029] negatively impacted overall survival. Haplo-identical SCT with post-transplant cyclophosphamide is a reasonable option for children who do not have a matched sibling donor. Strategies to reduce graft failure, infection related mortality and GVHD needs to be explored.

10.
Indian J Hematol Blood Transfus ; 40(3): 392-399, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39011262

ABSTRACT

Hodgkin's lymphoma treatment outcomes have been the true success story of modern medicine. Various data from western as well as Indian studies are available for classical Hodgkin's lymphoma (cHL). Here we report treatment outcomes from a tertiary cancer care centre in Karnataka over a 5 year period. This was a retrospective review of cHL cases aged 15 years and above diagnosed between January 2015 and December 2019 at Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India. The case files of the patients were retrieved and relevant data was collected. Two hundred patients of cHL were included in this study. Median age was 28 years with male to female ratio of 1.56:1. B symptoms were present in 58% cases. Mixed cellularity (46.5%) was the most common histological subtype. Majority patients had advanced stage at presentation (stage III/IV) (62.5%). Extranodal disease was present in 19.5% cases. GHSG early-favourable cases were 15.5%, early-unfavourable cases were 22.0%, while 62.5% were advanced cases. The most common chemotherapy regimen used was ABVD. Eighty-three (41.5%) patients received radiation therapy. Median follow-up was 34.2 months (range 4.1-67.8). The rates for complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) were 84.5%, 8.5%, 5.0% and 2.0% respectively. PFS and OS rate at 6 years were 69.5% and 84.1% respectively. HL is one of the malignancies with high cure rate. The treatment outcome at our centre is comparable to western data and data from other tertiary centres from India.

12.
World Neurosurg ; 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39013497

ABSTRACT

BACKGROUND: Brain metastases (BMs) from colorectal cancer (CRC) are a small percentage of metastatic patients and surgery is considered the best choice to improve survival. While most research has focused on the risk of CRC spreading to the brain, no studies have examined the characteristics of BMs in relation to surgery and outcome. In this study, we evaluate the clinical and radiological features of BMs from CRC patients who underwent surgery and analyze their outcomes. METHODS: The study is a retrospective observational analysis that included a cohort of 31 patients affected by CRC surgically-treated for their related BMs. For all patients clinical and surgical data (number, site, side, tumor and edema volume and morphology) were recorded. RESULTS: Analysis found that synchronous diagnosis and lesion morphology, particularly cystic versus solid, had the most significant impact on survival (6 versus 22 months, p=0.04). To compare BMs with cystic morphology to those with solid morphology, a multivariate analysis was conducted. No significant differences were observed between the two groups in terms of age, sex, clinical onset, or performance status. The analysis revealed no significant differences in localization with regard to site, tumor and edema volume, biology, or complications rate. CONCLUSION: BMs derived from CRC have a significantly different prognosis depending on whether they present as a solid or cystic pattern. Although solid pattern is more common, cystic BMs in this tumor type are less frequent and are associated with a poorer prognosis, regardless of molecular expression, location, size and adjuvant treatment.

13.
J Wildl Dis ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39013547

ABSTRACT

Chronic phalaris toxicity (CPT) is a neurological disease caused by animals ingesting toxins produced by early growth stages of Phalaris aquatica, a pasture plant introduced to the southeastern regions of Australia postcolonization. Little is known about the clinical progression of CPT in wildlife, as incidents are sporadic and predominantly reported when animals are in the end stages of disease and in a poor welfare state. We studied a cohort of 35 eastern gray kangaroos (Macropus giganteus) affected by CPT to clarify clinical prognosis and survival rates. Kangaroos were captured in May, June, and July of 2022 at Plenty Gorge Parklands, Victoria, Australia. Each animal was radiotracked for 180 d, clinical progression and disease outcomes monitored twice a week. By the conclusion of the study, 24 animals had died (19 by euthanasia due to deterioration, five found dead). Ten animals survived, with two demonstrating a reduction in clinical signs and eight showing full resolution of clinical signs. One animal was disqualified from the study. The overall survival rate was 29.4% (95% confidence interval 17.5-49.5%). The survival duration of animals that died ranged from 5 to 133 d. There was no difference in survival rate based on sex (P=0.2), age class (P=0.49) or the month of capture (P=0.49). These results suggest that CPT is an important health and welfare concern for at-risk macropod populations, with high case-fatality rates and prolonged clinical durations. Further research to manage the disease via methods such as reducing Phalaris aquatica plant coverage and preventative treatments for animals is warranted to reduce disease incidences and improve disease outcomes in wildlife populations.

14.
Cancer Biol Med ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-39015009

ABSTRACT

OBJECTIVE: Australia has relatively high multiple myeloma (MM) incidence and mortality rates. Advancements in MM treatment over recent decades have driven improvements in MM survival in high-income countries; however, reporting in Australia is limited. We investigated temporal trends in population-wide MM survival across 3 periods of treatment advancements in New South Wales (NSW), Australia. METHODS: Individuals with an MM diagnosis in the NSW Cancer Registry between 1985 and 2015 with vital follow-up to 2020, were categorized into 3 previously defined treatment eras according to their diagnosis date (1985-1995, chemotherapy only; 1996-2007, autologous stem cell transplantation; and 2008-2015, novel agents including proteasome inhibitors and immunomodulatory drugs). Both relative survival and cause-specific survival according to Fine and Gray's competing risks cumulative incidence function were calculated by treatment era and age at diagnosis. RESULTS: Overall, 11,591 individuals were included in the study, with a median age of 70 years at diagnosis. Five-year relative survival improved over the 36-year (1985-2020) study period (31.0% in 1985-1995; 41.9% in 1996-2007; and 56.1% in 2008-2015). For individuals diagnosed before 70 years of age, the 5-year relative survival nearly doubled, from 36.5% in 1985-1995 to 68.5% in 2008-2015. Improvements for those > 70 years of age were less pronounced between 1985-1995 and 1996-2007; however, significant improvements were observed for those diagnosed in 2008-2015. Similar overall and age-specific patterns were observed for cause-specific survival. After adjustment for gender and age at diagnosis, treatment era was strongly associated with both relative and cause-specific survival (P < 0.0001). CONCLUSIONS: Survival of individuals with MM is improving in Australia with treatment advances. However, older age groups continue to experience poor survival outcomes with only modest improvements over time. Given the increasing prevalence of MM in Australia, the effects of MM treatment on quality of life, particularly in older age, warrant further attention.

15.
ANZ J Surg ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39016342

ABSTRACT

BACKGROUND: Nutritional risk index (NRI) and carcinoembryonic antigen (CEA) are useful prognostic markers in colorectal cancer (CRC); however, the prognostic value of a combination of the NRI and CEA, namely, the NRI and CEA score (NCS), needs further investigation. METHODS: Stage I-III CRC patients were collected and then divided into three subgroups by counting the NCS: NCS 1: high NRI with normal CEA; NCS 2: high NRI with elevated CEA or low NRI with normal CEA; and NCS 3: low NRI with elevated CEA. The differences in outcome, counted as disease-free survival (DFS) and overall survival (OS), were tested among the subgroups. RESULTS: A total of 285 patients were enrolled, with 108 in NCS 1, 118 in NCS 2 and 59 in NCS 3. Patient features, including age, tumour deposit, T stage, N stage and TNM stage, were significantly different in the NCS subgroups. Both the DFS (log-rank = 26.06, P<0.001) and OS (log-rank = 39.10, P<0.001) were significant in different NCS subgroups, even in maximum tumour diameter ≤4 cm cases (DFS: log-rank = 21.42, P<0.001; OS: log-rank = 30.95, P<0.001), and NCS 1 patients displayed the best outcome compared with the rest of the subgroups. NCS was also found to be an independent risk factor for both DFS and OS. CONCLUSIONS: NCS was a useful prognostic indicator in stages I-III CRC patients.

16.
J Anim Sci ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39017626

ABSTRACT

Mortality is an economically important trait usually handled as a discrete outcome from hatch time until selection in most broiler breeder programs. However, in other species, it has been shown that not only does the genetic component change over time, but there are maternal genetic effects to be considered when mortality is recorded early in life. This study aimed to investigate alternative trait definitions of mortality with varying models and effects. Three years' worth of data were provided by Cobb-Vantress, Inc. and included two mortality traits. The first trait was binary, whether the bird died or not (OM), and the second trait was a categorical weekly mortality trait (WM). After data cleaning, six weeks of data for the two given mortality traits were used to develop five additional trait definitions. The definitions were broiler mortality (BM), early and late mortality (EM & LM), and two traits with repeated records as cumulative or binary (CM and RM, respectively). Variance components were estimated using linear and threshold models to investigate whether either model had a benefit. Genomic breeding values were predicted using the BLUP90 software suite, and linear regression validation (LR) was used to compare trait definitions and models. Heritability estimates ranged from 0.01 (0.00) to 0.16 (0.01) under linear and 0.04 (0.01) to 0.21 (0.01) under threshold models, indicating genetic variability within the population across these trait definitions. The genetic correlation between EM and LM ranged from 0.48 to 0.81 across the different lines, indicating they have divergent genetic backgrounds and should be considered different traits. The LR accuracies showed that EM and LM used together in a two-trait model have comparable accuracies to that of OM while giving a more precise picture of mortality. When including the maternal effect, the direct heritability considerably decreased for EM, indicating that the maternal effect plays an important role in early mortality. Therefore, a suitable approach would be a model with EM and LM while considering the maternal effect for EM. Single nucleotide polymorphism effects were estimated, and no individual SNP explained more than 1% of the additive genetic variance. Additionally, the SNP with the largest effect size and variance were inconsistent across trait definitions. Chicken mortality can be defined in different ways, and reviewing these definitions and models may benefit poultry breeding programs.

17.
Methods Mol Biol ; 2826: 219-230, 2024.
Article in English | MEDLINE | ID: mdl-39017896

ABSTRACT

One way memory B cells provide protection is by rapidly differentiating into plasma cells. Plasma cells are vital in providing long-term protection against pathogens; however, they can also be detrimental to health in the case of antibody-mediated autoimmunity. Therefore, compounds which modulate the survival of plasma cells have been of interest for therapeutic intervention. Investigation of ex vivo plasma cell survival has previously been limited by the low frequency of plasma cells in the blood. Here we describe a novel ex vivo culture system that only requires 3000-5000 cells per condition. This method permits the assessment of human plasma cell survival derived from blood and can assess the impact of small molecule inhibitors on plasma cell viability.


Subject(s)
Cell Survival , Plasma Cells , Humans , Plasma Cells/immunology , Plasma Cells/cytology , Plasma Cells/drug effects , Cell Survival/drug effects , Cell Culture Techniques/methods , Cells, Cultured , Flow Cytometry/methods
18.
Article in English | MEDLINE | ID: mdl-39017913

ABSTRACT

A Mycobacterium smegmatis transcriptional regulator, MSMEG_5850, and its ortholog in M. tuberculosis, rv0775 were annotated as putative TetR Family Transcriptional Regulators. Our previous study revealed MSMEG_5850 is involved in global transcriptional regulation in M. smegmatis and the presence of gene product supported the survival of bacteria during nutritional starvation. Phylogenetic analysis showed that MSMEG_5850 diverged early in comparison to its counterparts in virulent strains. Therefore, the expression pattern of MSMEG_5850 and its counterpart, rv0775, was compared during various in-vitro growth and stress conditions. Expression of MSMEG_5850 was induced under different environmental stresses while no change in expression was observed under mid-exponential and stationary phases. No expression of rv0775 was observed under any stress condition tested, while the gene was expressed during the mid-exponential phase that declined in the stationary phase. The effect of MSMEG_5850 on the survival of M. smegmatis under stress conditions and growth pattern was studied using wild type, knockout, and supplemented strain. Deletion of MSMEG_5850 resulted in altered colony morphology, biofilm/pellicle formation, and growth pattern of M. smegmatis. The survival rate of wild-type MSMEG_5850 was higher in comparison to knockout under different environmental stresses. Overall, this study suggested the role of MSMEG_5850 in the growth and adaptation/survival of M. smegmatis under stress conditions.

19.
Arch Microbiol ; 206(8): 355, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39017938

ABSTRACT

Cryptococcus neoformans is an opportunistic pathogenic fungus that produces melanin during infection, an important virulence factor in Cryptococcal infections that enhances the ability of the fungus to resist immune defense. This fungus can synthesize melanin from a variety of substrates, including L-DOPA (L-3,4-dihydroxyphenylalanine). Since melanin protects the fungus from various stress factors such as oxidative, nitrosative, extreme heat and cold stress; we investigated the effects of environmental conditions on melanin production and survival. In this study, we investigated the effects of different pH values (5.6, 7.0 and 8.5) and temperatures (30 °C and 37 °C) on melanization and cell survival using a microtiter plate-based melanin production assay and an oxidative stress assay, respectively. In addition, the efficacy of compounds known to inhibit laccase involved in melanin synthesis, i.e., tunicamycin, ß-mercaptoethanol, dithiothreitol, sodium azide and caspofungin on melanization was evaluated and their sensitivity to temperature and pH changes was measured. The results showed that melanin content correlated with pH and temperature changes and that pH 8.5 and 30 °C, were best for melanin production. Besides that, melanin production protects the fungal cells from oxidative stress induced by hydrogen peroxide. Thus, changes in pH and temperature drastically alter melanin production in C. neoformans and it correlates with the fungal survival. Due to the limited antifungal repertoire and the development of resistance in cryptococcal infections, the investigation of environmental conditions in the regulation of melanization and survival of C. neoformans could be useful for future research and clinical phasing.


Subject(s)
Cryptococcus neoformans , Melanins , Oxidative Stress , Temperature , Cryptococcus neoformans/metabolism , Cryptococcus neoformans/drug effects , Melanins/metabolism , Hydrogen-Ion Concentration , Hydrogen Peroxide/metabolism , Laccase/metabolism , Tunicamycin/pharmacology , Caspofungin/pharmacology , Sodium Azide/pharmacology , Mercaptoethanol/pharmacology , Dithiothreitol/pharmacology , Cryptococcosis/microbiology , Microbial Viability/drug effects , Lipopeptides/pharmacology , Lipopeptides/metabolism
20.
Ann Surg Oncol ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39017972

ABSTRACT

BACKGROUND: The significance of lymphovascular invasion (LVI) in esophageal adenocarcinoma (EAC) has not yet been described. Potential utility as an adjunct to current staging guidelines remains unknown. METHODS: The National Cancer Database was queried from 2006 to 2020. Univariate and multivariable models, Kaplan Meier method, and log-rank test were used. Subgroup analyses by pN stage were conducted. RESULTS: Of 9,689 patients, 23.2% had LVI. LVI was an independent prognostic factor (hazard ratio [HR] 1.401, 95% confidence interval [CI] 1.307-1.502, p < 0.0001) with reduction in median survival to 20.0 months (95% CI 18.9-21.4) from 39.7 months (95% CI 37.8-42.3, p < 0.0001). Multivariable survival analysis adjusted on pN and pT stage found that patients with LVI had decreased survival in a given pN stage (p < 0.001). pN0/LVI+ patients had a similar prognosis to the higher staged pN1/LVI- (28.6 months), although pN1/LVI- patients did slightly worse (p = 0.0135). Additionally, patients with pN1/LVI+ had equivalent survival compared with pN2/LVI- (p = 0.178) as did pN2/LVI+ patients compared with pN3/LVI- (p = 0.995). CONCLUSIONS: In these data, LVI is an independent negative prognostic factor in EAC. LVI was associated with a survival reduction similar to an upstaged nodal status irrespective of T stage. Patients with LVI may be better classified at a higher pN stage.

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