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Expression of PD-1 in Tumor Cells is Associated with Shorter Survival in Non-metastatic Intestinal-type Gastric Adenocarcinoma

Iran J Allergy Asthma Immunol. 2022 Dec 24;21(6):600-615. doi: 10.18502/ijaai.v21i6.11519.

ABSTRACT

There is an urgent need to discover novel prognostic biomarkers and treatment strategies for gastric cancer (GC) patients. Several immune-related markers have been proposed as prognostic tools and immunotherapeutic targets to manage diseases. In this regard, we evaluated the expression pattern and prognostic significance of programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), CD45RO+ tumor-infiltrating lymphocytes (TILs), and DNA mismatch repair (MMR) proteins (MLH1, MSH2, PMS2, and MSH6) in non-metastatic intestinal-type gastric adenocarcinoma. Samples and data from 70 GC patients were collected. Immunohistochemistry staining was used to detect the markers. We then evaluated the prognosis significance of each marker and their intercorrelation. Cytoplasmic PD-1 expressed by tumor cells was significantly associated with poorer survival. However, multivariate analysis indicated stronger prognostic values for TNM stage, tumor location, and extracellular mucin. A significant positive association was found between CD45ROhigh TILs and PD-1 expression on tumor-infiltrating cells (TICs). All GC patients with deficient MMR (d‑MMR) had a higher number of CD45RO+ TILs and were associated with PD-1+ TICs and PD‑L1+ tumor cells (TCs). However, the difference was not statistically significant. Despite the association of PD‑1 overexpression on TCs with shorter overall survival, histopathological factors, including tumor location, TNM stage, and extracellular mucin, remain the most decisive prognostic factors in non-metastatic intestinal-type gastric adenocarcinoma. Additionally, our data support a prognostic role for d-MMR and CD45RO, but not PD-1 and PD-L1 expression on TICs.

PMID:36640052 | DOI:10.18502/ijaai.v21i6.11519

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Cytomorphology and immunocytochemical features of ovarian granulosa cell tumors in ascites or peritoneal washings: A retrospective review

J Obstet Gynaecol Res. 2023 Jan 14. doi: 10.1111/jog.15552. Online ahead of print.

ABSTRACT

AIM: To summarize the cytomorphology and immunocytochemistry features of OGCT in ascites or peritoneal washings.

METHODS: All cases of histology sections, cytology smears, cell block slides and immunohistochemical staining were reviewed. A panel of immunohistochemistry antibodies consisting of Inhibin, Calretinin, BerEP4 and MC was performed for diagnosis and differential diagnosis.

RESULTS: Seven positive cases (21.2%) in ascites and peritoneal washings were identified in 33 patients with OGCT, which is higher than early studies with positive rate of 7.4%. Clinicopathologic features including tumor size and the incidence of endometrial atypical hyperplasia or carcinoma (EAH/EC) displayed no statistical difference between groups with positive and negative cytology. Immunocytochemical results usually showed typical staining pattern with α-inhibin, calretinin positive and BerEP4, MC negative. Features of granulosa cells, including nuclear hyperplasia and overlapping, can be observed in all seven positive cases. Nuclear grooves or small conspicuous nucleoli were occasionally observed in the smear. However, features of cell clusters mimicking Call-Exner bodies, cytoplasmic vacuoles or single cell necrosis were not found on smear. Call-Exner bodies and mitosis can only be found on cell blocks. All cases of follow-up information were available and three cases displayed progression and there was a statistical difference between groups with positive and negative cytology.

CONCLUSION: OGCT with positive cytology in ascites and peritoneal washings tend to have a larger tumor size and higher rates of disease progression. A panel of complementary biomarkers can greatly increase the detection rate and help in differential diagnosis in ascites or peritoneal washings of OGCT.

PMID:36640051 | DOI:10.1111/jog.15552

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Difference analysis of Doppler ultrasound blood flow of Cunkou (radial artery) pulse, Renying (carotid artery) pulse, and Fuyang (anterior tibial artery) pulse

J Tradit Chin Med. 2023 Feb;43(1):168-174. doi: 10.19852/j.cnki.jtcm.2023.01.014.

ABSTRACT

OBJECTIVE: To analyze the Doppler ultrasound blood flow of Renying (carotid artery) pulse, Cunkou (radial artery) pulse, and Fuyang (anterior tibial artery) pulse in the normal group and the functional constipation with gastrointestinal heat (FCGH) group, and to compare and explore the differences of Renying, Cunkou and Fuyang pulses.

METHODS: Sixty normal subjects and 60 patients with gastrointestinal heat constipation were collected in the department of ultrasound, Beijing Anzhen Hospital, Capital Medical University. Doppler ultrasound was used to observe the blood flow indexes including maximum systolic velocity (Vp), maximum diastolic velocity (Vd), mean velocity (Vm), pulse index (PI), resistance index (RI), vascular diameter (D), and circulation blood flow cycle (ET) of Renying pulse, Cunkou pulse and Fuyang pulse in the normal group and patients with gastrointestinal heat constipation. The differences of these three pulses were compared between the normal group and the FCGH group.

RESULTS: The PI, Vp, Vm, RI, and D of the three pulses in the normal group were statistically significant different ( < 0.01). In the comparison of Doppler flow diagram of three pulses in the FCGH group, there were significant differences in PI, Vd, Vp, Vm, RI, and D ( < 0.01).

CONCLUSION: Under normal conditions, the indexes of Renying pulse Doppler flow diagram, Cunkou pulse Doppler flow diagram, and Fuyang pulse Doppler flow diagram are significantly different. In the FCGH group, most of the indexes of Renying pulse Doppler flow diagram, Cunkou pulse Doppler flow diagram, and Fuyang pulse Doppler flow diagram are different. This result verified the necessity of simultaneous examinations of all Renying, Cunkou, and Fuyang pulses in modern Chinese medicine.

PMID:36640009 | DOI:10.19852/j.cnki.jtcm.2023.01.014

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Subinhibitory concentrations of florfenicol increase the biofilm formation of Piscirickettsia salmonis

J Fish Dis. 2023 Jan 14. doi: 10.1111/jfd.13757. Online ahead of print.

ABSTRACT

Public health is facing a new challenge due to the increased bacterial resistance to most of the conventional antibacterial agents. Inadequate use of antibiotics in the Chilean aquaculture industry leads to the generation of multidrug resistance bacteria. Many fish pathogenic bacteria produce biofilm upon various sources of stress such as antibiotics, which provides several survival advantages for the bacterial life in community and can constitute a reservoir of pathogens in the marine environment. Being florfenicol a broad-spectrum antibiotic commonly used to treat infections in aquaculture, the aim of this study was to assess whether this antibiotic modulates in vitro the biofilm formation in several isolates of Piscirickettsia salmonis. Standard antibiotic-micro broth 96-flat well plates were used to determinate the minimal inhibitory concentration of florfenicol in eight different P. salmonis isolates. In vitro findings, with P. salmonis growing in the presence and absence of the antibiotic, exhibited a statistically significantly increase (p < .05) in biofilm formation in all the bacterial isolates cultivated with sub-MIC (defined as the half of the minimal inhibitory concentration in the presence of antibiotic) of florfenicol compared with controls (antibiotic-free broth). In conclusion, sub-MIC of florfenicol induced an increased biofilm formation in all P. salmonis isolates tested.

PMID:36639965 | DOI:10.1111/jfd.13757

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Short-term evaluation of renal markers in overweight adult cats

Vet Med Sci. 2023 Jan 14. doi: 10.1002/vms3.1021. Online ahead of print.

ABSTRACT

BACKGROUND: Obesity has been proposed as an independently risk factor for chronic kidney disease (CKD) in people, but its role in feline kidney function is unknown.

OBJECTIVE: Obesity has been proposed as an independent risk factor for chronic kidney disease (CKD) in people, but its role in feline kidney function is unknown. This study prospectively evaluated the effect of overweight on the concentration of symmetric dimethylarginine (SDMA) and creatinine in a cohort of healthy cats.

METHODS: Forty healthy adult cats were included, 14 with a body condition score (BCS) = 5 and 26 with a BCS > 5. Cats were examined every 6 months, for up to 12 months. SDMA and creatinine were measured at baseline and follow-up.

RESULTS: No effect was found for time of follow-up (p = 0.072), overweight (p = 0.9442) or their interaction (p = 0.902) on SDMA, though a significant effect was found for age (p < 0.001) [older cats showing higher SDMA] and sex (p = 0.007) [male cats showing higher SDMA]. Regarding creatinine, no effect for time (p = 0.671), age (p = 0.061), overweight (p = 0.319) or the latter’s interaction (p = 0.386) were found.

CONCLUSIONS: In the short term, markers of renal function did not show an association with overweight. The role of obesity in feline kidney function still warrants further evaluation.

PMID:36639961 | DOI:10.1002/vms3.1021

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Cross-sectional study evaluating the association of haemophilia-related distress and clinically relevant outcomes

Haemophilia. 2023 Jan 14. doi: 10.1111/hae.14741. Online ahead of print.

ABSTRACT

INTRODUCTION: In chronic diseases, disease-related distress can impact disease outcomes. Distress and haemophilia-related distress has been demonstrated in people with haemophilia (PwH). The association of haemophilia-related distress on disease outcomes among PwH is unknown.

AIM: To study the association of haemophilia-related distress with haemophilia specific outcomes, including adherence to prophylactic therapy, the presence of a target joint, healthcare utilization and work-impairment.

METHODS: In a cross-sectional study, adults with haemophilia A or B were enrolled in a study to validate the haemophilia-related distress questionnaire (HRDq). In this planned analysis, univariate and multivariate associations between the HRDq total score and disease outcomes were explored.

RESULTS: The 114 participants in this analysis were male, mostly with haemophilia A (92%) and severe disease (52%) with a median age of 31.9 years. On univariate analysis, HRDq total score (5-point change) was associated with the presence of a target joint (P = .002), high healthcare utilization (P = .011), poor adherence (P = .033) and work-impairment (P ≤ .001). After adjustment for age, race, severity and other potential confounders, adherence (aβ 0.33, 95% CI .17, .49) and work-impairment (aβ 4.69, 95% CI 3.27-6.1) remained statistically significantly associated with HRDq total score.

CONCLUSION: Haemophilia-related distress is associated with poor adherence to factor prophylaxis and work-impairment. The direction of the association (causation) is yet to be determined and requires future study.

PMID:36639952 | DOI:10.1111/hae.14741

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Sensory impairment and cognitive function among older adults in China: The mediating roles of anxiety and depressive symptoms

Int J Geriatr Psychiatry. 2023 Jan;38(1):e5866. doi: 10.1002/gps.5866.

ABSTRACT

OBJECTIVES: Through a cross-sectional study, we explored the association between sensory impairment and cognitive function in Chinese older adults, and tested the mediating roles of anxiety and depressive symptoms between this relationship.

METHODS: Based on the 2018 Chinese Longitudinal Healthy Longevity Survey, a total of 10,895 older adults aged 65 and above were selected as samples for research. Anxiety, depressive symptoms and cognitive function were evaluated by the Generalized Anxiety Disorder, the Center for Epidemiologic Studies Depression (CES-D10) and the Chinese version of modified Mini-Mental State Examination scales, respectively. Sensory impairment was assessed from self-reported vision and hearing functions. Multiple linear regression and SPSS Macro PROCESS were used for statistical analysis.

RESULTS: Compared with no sensory impairment, vision impairment (B = -1.012, 95%CI: -1.206, -0.818), hearing impairment (B = -2.683, 95%CI: -2.980, -2.386) and dual sensory impairment (B = -6.302, 95%CI: -6.585, -6.020) have a significant association with cognitive function in older adults, respectively. Anxiety and depressive symptoms not only acted as independent mediators, but also played sequential mediating effects on the relationship between sensory impairment and cognitive function.

CONCLUSIONS: Greater attention should be paid to anxiety and depressive symptoms of older adults with sensory impairment, which might be beneficial to maintain cognitive function.

PMID:36639927 | DOI:10.1002/gps.5866

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Depression and anxiety in patients with uveal melanoma undergoing curative proton treatment-A prospective study

Cancer Rep (Hoboken). 2023 Jan 13:e1780. doi: 10.1002/cnr2.1780. Online ahead of print.

ABSTRACT

OBJECTIVE: We prospectively addressed whether patient characteristics, oncological outcomes, or metastatic risk impacted depression and anxiety in patients undergoing curative proton treatment for uveal melanoma (UM).

METHODS: We assessed patient-reported outcomes regarding anxiety (GAD-7) before and 2 years after proton therapy and depression (PHQ-9) before, 1, and 2 years after proton therapy. We performed descriptive statistics and used linear mixed effect modeling to analyze how the oncological outcome and baseline characteristics impacted anxiety and depression scores.

RESULTS: Of 130 (65 female) patients included, six developed metastatic disease and three died during the 2-year follow-up. The mean anxiety declined from 5.86 (SE = 0.56) at baseline to 3.74 (SE = 0.46) at 2 years (β = 2.11; SE = 0.6; p < .001). Depressive symptoms decreased moderately from 4.36 (SE = 0.37) at baseline to 3.67 (SE = 0.38) 2 years later. Patients with unfavorable metastatic risk or disease progression had elevated anxiety and depression scores. Although female patients reported overall higher anxiety scores, both sexes recovered substantially and to a similar extent during the 2-year follow-up (β = 2.35; SE 0.87; p = .007 vs. β = 1.88; SE = 0.60; p = .002). A trend for prolonged depressive symptoms was observed in patients living alone compared to patients living with family members 1 year after the treatment (M = 5.04 [SE = 0.85] vs. M = 3.73 [SE = 0.31], β = 1.32; SE = 0.92; p = .152). Patients with high baseline anxiety levels showed initially more severe depressive symptoms, which improved significantly during follow-up (β = 1.65; SE = 0.68; p = .017).

CONCLUSION: Most patients undergoing proton therapy for UM experienced mild, transient depressive symptoms and anxiety. Patients with high pre-treatment anxiety, unfavorable prognoses, and patients living alone may be more vulnerable to prolonged depressive symptoms. To these patients a more tailored support could be offered at an early stage of the disease.

PMID:36639921 | DOI:10.1002/cnr2.1780

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Genome-wide re-sequencing data reveals the genetic diversity and population structure of Wenchang chicken in China

Anim Genet. 2023 Jan 13. doi: 10.1111/age.13293. Online ahead of print.

ABSTRACT

Wenchang (WC) chicken, the only indigenous chicken breed listed in Chinese genetic resources in Hainan province, is well known for its excellent meat quality and is sold all over southeast Asia. In recent years, the number of WC has decreased sharply with considerable variability in the quality at market. To explore the genetic diversity and population structure of WC chickens, the whole-genome data of 235 WC individuals from three conservation farms were obtained using the Illumina 150 bp paired-end platform and used in conjunction with the sequencing data from 123 individuals from other chicken breeds (including eight Chinese indigenous chicken breeds and three foreign or commercial breeds) downloaded from a public database. A total of 12 111 532 SNPs were identified, of which 11 541 878 SNPs were identified in WC. The results of gene enrichment analyses revealed that the SNPs harbored in WC genomes are mainly related to environmental adaptation, disease resistance and meat quality traits. Genetic diversity statistics, quantified by expected heterozygosity, observed heterozygosity, linkage disequilibrium, nucleotide diversity and fixation statistics, indicated that WC displays high genetic diversity compared with other Chinese indigenous chicken breeds. Genetic structure analyses showed that each population displayed great differentiation between WC and the other breeds, indicating the uniqueness of WC. In conclusion, the results of our study provide the first genomic overview of genetic variants, genetic diversity and population structure of WC from three conservation farms. This information will be valuable for the future breeding and conservation of WC and other surveyed populations.

PMID:36639920 | DOI:10.1111/age.13293

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Baricitinib or imatinib in hospitalized COVID-19 patients: results from COVINIB, an exploratory randomized clinical trial

J Med Virol. 2023 Jan 13. doi: 10.1002/jmv.28495. Online ahead of print.

ABSTRACT

BACKGROUND: Baricitinib and imatinib are considered therapies for COVID-19, but their ultimate clinical impact remains to be elucidated, so our objective is to determine whether these kinase inhibitors provide benefit when added to standard care in hospitalized COVID-19 patients.

METHODS: Phase-2, open-label, randomized trial with a pick-the-winner design conducted from September 2020 to June 2021 in a single Spanish center. Hospitalized adults with COVID-19 pneumonia and a symptom duration ≤ 10 days were assigned to 3 arms: imatinib (400 mg qd, 7 days) plus standard-care, baricitinib (4 mg qd, 7 days) plus standard-care, or standard-care alone. Primary outcome was time to clinical improvement (discharge alive or a reduction of 2 points in an ordinal scale of clinical status) compared on a day-by-day basis in order to identify differences ≥ 15% between the most and least favorable groups. Secondary outcomes included oxygenation and ventilatory support requirements, additional therapies administered all-cause mortality and safety.

RESULTS: 165 patients analyzed. Predefined criteria for selection of the most advantageous arm were met for baricitinib, but not for imatinib. However, no statistically significant differences were observed in formal analysis, but a trend towards better results in patients receiving baricitinib was found compared to standard care alone (HR for clinical improvement 1.41, 95%CI 0.96-2.06; HR for discontinuing oxygen 1.46, 95%CI 0.94-2.28). No differences were found regarding additional therapies administered or safety.

CONCLUSIONS: Baricitinib plus standard care showed better results for hospitalized COVID-19 patients, being the most advantageous therapeutic strategy among those proposed in this exploratory clinical trial. This article is protected by copyright. All rights reserved.

PMID:36639911 | DOI:10.1002/jmv.28495