Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 59
Filter
1.
Mod Pathol ; : 100558, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38969270

ABSTRACT

Adjuvant immunotherapy has been recently recommended for patients with metastatic ccRCC, but there are no tissue biomarkers to predict treatment response in ccRCC. Potential predictive biomarkers are mainly assessed in primary tumor tissue, whereas metastases remain understudied. To explore potential differences between genomic alterations and immune phenotypes in primary tumors and their matched metastases, we analyzed primary tumors (PTs) of 47 ccRCC patients and their matched distant metastases (METs) by comprehensive targeted parallel sequencing, whole-genome copy number variation (CNV) analysis, determination of microsatellite instability (MSI) and tumor mutational burden (TMB). We quantified the spatial distribution of tumor-infiltrating CD8+ T cells, and co-expression of the T-cell-exhaustion marker TOX by digital immunoprofiling and quantified tertiary lymphoid structures (TLS). Most METs were pathologically "cold". Inflamed, pathologically "hot" PTs were associated with a decreased disease-free survival (DFS), worst for patients with high levels of CD8+TOX+ T cells. Interestingly, inflamed METs showed a relative increase of exhausted CD8+TOX+ T cells and increased accumulative size of TLS compared to PTs. Integrative analysis of molecular and immune phenotypes revealed BAP1 and CDKN2A/B deficiency to be associated with an inflamed immune phenotype. Our results highlight the distinct spatial distribution and differentiation of CD8+ T cells at metastatic sites, and the association of an inflamed microenvironment with specific genomic alterations.

3.
J Clin Oncol ; 42(18): 2207-2218, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38484206

ABSTRACT

PURPOSE: Immunoscore (IS) is prognostic in stage III colorectal cancer (CRC) and may predict benefit of duration (6 v 3 months) of adjuvant infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. We sought to determine IS prognostic and predictive value in stage-III CRC treated with adjuvant FOLFOX or oral capecitabine and infusional oxaliplatin (CAPOX) in the SCOT and IDEA-HORG trials. METHODS: Three thousand sixty-one cases had tumor samples, of which 2,643 (1,792 CAPOX) were eligible for IS testing. Predefined cutoffs (IS-Low and IS-High) were used to classify cases into two groups for analysis of disease-free survival (3-year DFS) and multivariable-adjusted hazard ratios (mvHRs) by Cox regression. RESULTS: IS was determined in 2,608 (99.5%) eligible cases, with 877 (33.7%) samples classified as IS-Low. IS-Low tumors were more commonly high-risk (T4 and/or N2; 52.9% IS-Low v 42.2% IS-High; P < .001) and in younger patients (P = .024). Patients with IS-Low tumors had significantly shorter DFS in the CAPOX, FOLFOX, and combined cohorts (mvHR, 1.52 [95% CI, 1.28 to 1.82]; mvHR, 1.58 [95% CI, 1.22 to 2.04]; and mvHR, 1.55 [95% CI, 1.34 to 1.79], respectively; P < .001 all comparisons), regardless of sex, BMI, clinical risk group, tumor location, treatment duration, or chemotherapy regimen. IS prognostic value was greater in younger (≤65 years) than older (>65 years) patients in the CAPOX cohort (mvHR, 1.92 [95% CI, 1.50 to 2.46] v 1.28 [95% CI, 1.01 to 1.63], PINTERACTION = .026), and in DNA mismatch repair proficient than deficient mismatch repair disease (mvHR, 1.68 [95% CI, 1.41 to 2.00] v 0.67 [95% CI, 0.30 to 1.49], PINTERACTION = .03), although these exploratory analyses were uncorrected for multiple testing. Adding IS to a model containing all clinical variables significantly improved prediction of DFS (likelihood ratio test, P < .001) regardless of MMR status. CONCLUSION: IS is prognostic in stage III CRC treated with FOLFOX or CAPOX, including within clinically relevant tumor subgroups. Possible variation in IS prognostic value by age and MMR status, and prediction of benefit from extended adjuvant therapy merit validation.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Colorectal Neoplasms , Fluorouracil , Leucovorin , Neoplasm Staging , Organoplatinum Compounds , Humans , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/mortality , Colorectal Neoplasms/immunology , Female , Male , Middle Aged , Leucovorin/therapeutic use , Leucovorin/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Aged , Fluorouracil/administration & dosage , Fluorouracil/therapeutic use , Organoplatinum Compounds/therapeutic use , Organoplatinum Compounds/administration & dosage , Prognosis , Capecitabine/administration & dosage , Capecitabine/therapeutic use , Predictive Value of Tests , Disease-Free Survival , Oxaliplatin/therapeutic use , Oxaliplatin/administration & dosage , Adult , Chemotherapy, Adjuvant , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Deoxycytidine/administration & dosage
4.
Int Marit Health ; 74(4): 253-258, 2023.
Article in English | MEDLINE | ID: mdl-38111245

ABSTRACT

BACKGROUND: The number of international travels has grown substantially over the last decade, both globally and in Poland. Thousands of Poles travel to tropical or subtropical countries in Asia, Africa or South America each year. The aim of this paper was to discuss the characteristics of Polish travellers seeking pre-travel consultation at the largest diagnostic and treatment travel medicine clinic in Poland. MATERIALS AND METHODS: This retrospective study was based on the analysis of medical records of 1291 patients seeking pre-travel advice at the University Centre of Maritime and Tropical Medicine in Gdynia, Poland, between 1 July and 31 December 2022. The study comprised the analysis of the following patient variables: age, sex, travel details (purpose and length of travel, continents and countries to be visited, activities planned). The study also aimed to evaluate the range of prevention measures which were recommended/ administered (preventive vaccinations, chemoprophylaxis). In addition, it assessed the health status of the patients presenting at the travel medicine clinic. RESULTS: Patients who sought pre-travel advice were mostly people aged 18-35 years old (50.1%), travelling for tourism (72.2%), for a maximum period of 4 weeks (85.0%), travelling in December (24.3%) or in November (22.2%). Most of the Polish travellers consulted at the clinic travelled to Asia (56.2%), mainly to Thailand (27.3%), Vietnam (10.8%) or India (8.7%). Most travellers were planning a beach holiday (56.4%). As regards extreme activities, scuba diving was the most popular among the patients involved in the study (22.5%). The most frequently administered immunoprophylaxis were vaccines against typhoid fever (76.3%) and hepatitis A (56.2%). Other commonly recommended/prescribed prevention measures included: probiotics (75.9%), repellents (73.6%), antimalarial drugs (60.9%), and antidiarrheal antibiotics (51.9%). The analysis of patient interviews demonstrated that 42.4% of Polish travellers consulted at the clinic complained of no medical problems while 36.0% were taking chronic medications, mainly for allergies (17.1%) or thyroid disorders (12.2%). CONCLUSIONS: A growing number of people from Poland travel to destinations where the risk of infectious disease exposure or transmission is high. Providing a patient with appropriate advice during a pre-travel consultation will help protect the traveller against travel-associated risks at their intended destinations.


Subject(s)
Travel , Tropical Medicine , Humans , Adolescent , Young Adult , Adult , Poland , Retrospective Studies , Universities , Thailand
5.
Cancer Cell ; 41(9): 1650-1661.e4, 2023 09 11.
Article in English | MEDLINE | ID: mdl-37652006

ABSTRACT

Deep learning (DL) can accelerate the prediction of prognostic biomarkers from routine pathology slides in colorectal cancer (CRC). However, current approaches rely on convolutional neural networks (CNNs) and have mostly been validated on small patient cohorts. Here, we develop a new transformer-based pipeline for end-to-end biomarker prediction from pathology slides by combining a pre-trained transformer encoder with a transformer network for patch aggregation. Our transformer-based approach substantially improves the performance, generalizability, data efficiency, and interpretability as compared with current state-of-the-art algorithms. After training and evaluating on a large multicenter cohort of over 13,000 patients from 16 colorectal cancer cohorts, we achieve a sensitivity of 0.99 with a negative predictive value of over 0.99 for prediction of microsatellite instability (MSI) on surgical resection specimens. We demonstrate that resection specimen-only training reaches clinical-grade performance on endoscopic biopsy tissue, solving a long-standing diagnostic problem.


Subject(s)
Algorithms , Colorectal Neoplasms , Humans , Biomarkers , Biopsy , Microsatellite Instability , Colorectal Neoplasms/genetics
6.
Int Marit Health ; 74(2): 81-82, 2023.
Article in English | MEDLINE | ID: mdl-37417839
7.
Int Marit Health ; 74(2): 122-128, 2023.
Article in English | MEDLINE | ID: mdl-37417846

ABSTRACT

BACKGROUND: The seafarers' professional group is one of the most numerous in the world. According to the statistics of the European Maritime Safety Agency (2020), there are approximately 280,000 people employed at sea in the European Union. The specific work environment on the ship (climatic, physical, chemical, psychological factors, etc.) is related to experiencing long-term stress. The World Health Organization considers work-related stressors to be very important determinants of health and disease. One of the basic psychological resources related to adaptation to demanding working conditions are strategies for coping with stress. The aim of the study is to assess the occurrence of harmful psychosocial factors in the work of seafarers and the stress coping strategies and their relationship with somatic diseases. MATERIALS AND METHODS: One hundred and fifteen seafarers who received a maritime health certificate participated in the study at the Occupational Medicine Clinic. The study was part of a larger project looking at the prevalence of cardiovascular risk factors among seafarers. The study used the Coping Questionnaire in Stressful Situations (CISS) (Endler and Parker) and a general questionnaire created for the purposes of the study. RESULTS: Thirty six per cent respondents were exposed to traumatic event and to having nightmares, 13% had been discriminated at least once in the workplace. A positive correlation was found between discrimination and depression, nightmares and trauma. In addition, people who admitted having experienced trauma slept shorter (also while at home) and experienced nightmares more often. The most common style of coping was task oriented (29; 28.5%), and avoidance oriented (15%). The study also found a positive correlation between depression and the style of emotion-oriented coping and avoidance-oriented coping. CONCLUSIONS: The specific working conditions and exposure to traumatic events have a negative impact on the health of seafarers by increasing the risk of depression and cardiovascular diseases. The coping styles with stress depend on the position in the ship hierarchy.


Subject(s)
Adaptation, Psychological , Ships , Humans , Surveys and Questionnaires , Stress, Psychological/epidemiology , Stress, Psychological/psychology
8.
Curr Psychol ; : 1-11, 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-37359650

ABSTRACT

Opinions on abortion are more polarized than opinions on most other moral issues. Why are some people pro-choice and some pro-life? Religious and political preferences play a role here, but pro-choice and pro-life people may also differ in other aspects. In the current preregistered study (N = 479), we investigated how pro-choice women differ in their moral foundations from pro-life women. When the Moral Foundations Questionnaire (MFQ) was applied (i.e., when declared moral principles were measured), pro-life women scored higher than pro-choice women in loyalty, authority, and purity. However, when women were asked about moral judgments indirectly via more real-life problems from the Moral Foundations Vignettes (MFV), pro-choice women scored higher than pro-life women in emotional and physical care and liberty but lower in loyalty. When we additionally controlled for religious practice and political views, we found no differences between groups in declaring moral foundations (MFQ). However, in the case of real-life moral judgments (MFV), we observed higher care, fairness, and liberty among pro-choice and higher authority and purity among pro-life. Our results show intriguing nuances between women pro-choice and pro-life as we found a different pattern of moral foundations in those groups depending on whether we measured their declared abstract moral principles or moral judgment about real-life situations. We also showed how religious practice and political views might play a role in such differences. We conclude that attitudes to abortion "go beyond" abstract moral principles, and the real-life context matters in moral judgments. Supplementary information: The online version contains supplementary material available at 10.1007/s12144-023-04800-0.

9.
Front Psychiatry ; 13: 1025414, 2022.
Article in English | MEDLINE | ID: mdl-36387009

ABSTRACT

Schizophrenia is a chronic, highly individualized disease with many symptoms that can occur with varying severity in different patients. Schizophrenia affects 1% of the population, but occurs in almost 20% of patients after 40 years of age. It should be noted that the next peak in the incidence of schizophrenia occurs at the age of 60 years, affects mostly females, and is closely associated with a high risk of developing memory disorders. Therefore, postadolescent schizophrenia includes two distinct groups of patients: those whose symptoms onset at the age of 45 or 60. The purposes of this literature review were as follows: (1) synthetically characterize the clinical manifestations of schizophrenia; (2) discuss difficulties in the diagnosis of schizophrenia, especially in patients over 40 years of age; (3) discuss the clinical utility of different classes of marker in diagnostic and differentiating schizophrenia from neurodegenerative diseases in elderly people; (4) discuss therapeutic options for schizophrenia, pharmacotherapy, and psychotherapy, emphasizing the role of caregivers of people with psychosis in therapy, in preadolescence and postadolescence schizophrenia. We have tried to primarily discuss the findings of original articles from the last 10 years with an indication of their clinical implications with the issues discussed in the various subsections. Moreover, despite many years of research, no specific, precise algorithm has been developed that can be used in clinical practice during the diagnosis of schizophrenia. For this reason, the diagnosis of schizophrenia is primarily based on an interview with the patient and his family, as well as on the experience of a psychiatrist. It also seems that schizophrenia treatment should be carried out holistically, including pharmacotherapy, psychotherapy, and the support of caregivers of patients who have this psychosis, which increases the achievement of therapeutic success. Finally, we must be aware of the difficulties in diagnosing schizophrenia in the elderly and the need to modify pharmacological treatment. Currently, no guidelines have been developed for the differentiation of negative symptoms in elderly patients with schizophrenia from amotivation/avolition/apathy symptoms in elderly patients with neurodegenerative disorders.

10.
Article in English | MEDLINE | ID: mdl-36294125

ABSTRACT

(1) The aim of this study was to estimate the scale of mobile phone addiction among young adults as well as to establish whether the low level of perceived social support is related to problematic smartphone use, and whether an addictive pattern of mobile phone use is related to the prevalence of depressiveness and excessive daytime sleepiness. (2) The study was carried out using the diagnostic poll method via the questionnaire technique. Both the author's own questionnaire and the following standardized research tools were used: the Mobile Phone Problem Use Scale for Adolescents (MPPUSA), the Beck Depression Inventory (BDI), the Epworth Sleepiness Scale (ESS), and the Multidimensional Scale of Perceived Social Support (MSPSS). (3) Perceived social support was significantly lower in the group of respondents who problematically used their mobile phones in comparison with the ones who used them in a proper way. Severity of depressive symptoms and daytime sleepiness was significantly higher in respondents addicted to their mobiles compared to nonaddicted ones. (4) Conclusions: An important correlation between phone addiction and the prevalence of depressive symptoms and excessive daytime sleepiness exists. Problematic mobile phone use concerns individuals with low levels of perceived social support.


Subject(s)
Behavior, Addictive , Cell Phone Use , Cell Phone , Disorders of Excessive Somnolence , Young Adult , Adolescent , Humans , Disorders of Excessive Somnolence/epidemiology , Behavior, Addictive/epidemiology , Behavior, Addictive/diagnosis , Surveys and Questionnaires , Social Support
11.
Article in English | MEDLINE | ID: mdl-36293697

ABSTRACT

(1) The aim of the study was to analyze nurses' attitudes toward a patient's death, taking into account the emotions they experience and the general perception of death. (2) The study involved 516 nurses from the West Pomeranian Voivodeship in Poland. The research was carried out using the diagnostic survey method using The Death Attitudes Profile Revisited (DAP-R-PL), the Scale of Fear and Fascination with Death, and a demographic questionnaire. (3) Research has shown that nurses accept the phenomenon of death as a natural process of human life; however, they adopt the attitude of fear of death. Most of the respondents experienced: sadness (73.4%), helplessness (58.5%), and regret (43.6%) due to the patient's death. (4) Both age, sex, marital status, and place of residence significantly influenced the attitudes of nurses toward the patient's death. Therefore, it is important to provide psychological support or special education in the case of dealing with the fear of death.


Subject(s)
Nurses , Terminal Care , Humans , Attitude to Death , Terminal Care/psychology , Attitude of Health Personnel , Surveys and Questionnaires
12.
JCO Clin Cancer Inform ; 6: e2200032, 2022 08.
Article in English | MEDLINE | ID: mdl-36007219

ABSTRACT

PURPOSE: Comprehensive targeted next-generation sequencing (NGS) panels are routinely used in modern molecular cancer diagnostics. In molecular tumor boards, the detected genomic alterations are often discussed to decide the next treatment options for patients with cancer. With the increasing size and complexity of NGS panels, the discussion of these results becomes increasingly complex, especially if they are reported in a text-based form, as it is the standard in current molecular pathology. METHODS: We have developed the Molecular Tumor Profiling pilot (MTPpilot) webservice using HTML, PHP, JavaScript, and MySQL to support the clinical discussion of NGS results at molecular tumor boards. RESULTS: MTPpilot integrates various public genome, network, and cancer mutation databases with interactive visualization tools to assess the functional impact of mutations and support clinical decision making at tumor boards. CONCLUSION: MTPpilot is tailored for discussion of NGS gene panel results at molecular tumor boards. It is freely available as a webservice at MTPpilot.


Subject(s)
High-Throughput Nucleotide Sequencing , Neoplasms , Genomics , High-Throughput Nucleotide Sequencing/methods , Humans , Mutation , Neoplasms/diagnosis , Neoplasms/genetics , Software
13.
Int J Occup Med Environ Health ; 35(1): 53-62, 2022 Feb 15.
Article in English | MEDLINE | ID: mdl-34533137

ABSTRACT

OBJECTIVES: The aim of the presented study was to compare the health locus of control (HLC) between employed and unemployed patients after kidney transplantation (KT), and to investigate the relationship between HLC and the quality of life (QoL). MATERIAL AND METHODS: The study group consisted of 101 KT patients and the control group of 60 hemodialysis (HD) patients. The applied methods were: the Multidimensional Health Locus of Control Questionnaire (MHLC), the WHO Quality of Life Questionnaire (WHOQoL-BREF), and a survey collecting information on the socio-demographic status and work experience. RESULTS: Overall, 57.5% of KT patients were employed and 42.5% were unemployed. In the HD group, 25% were employed and 71% were unemployed, while 4% did not disclose their employment status. The unemployed KT patients, in comparison with the employed ones, presented a higher feeling of the impact of chance on their health (unemployed M±SD 23.68±6.59; employed M±SD 21.02±4.57) and a lower level of QoL on the Somatic Scale (unemployed Me = 14.00, IQR = 3.00; employed Me = 1450, IQR = 3.00) and the Environmental Scale (unemployed M±SD 15.39±2.83; employed M±SD 16.85±3.24). In the employed KT group, the Internal Control Scale (MHLC) correlated with all QoL scales (the Somatic Scale: r = 0.292, p = 0.036; the Psychological Scale: r = 0.455, p = 0.001; the Social Scale: r = 0.304, p = 0.029; and the Environmental Scale: r = 0.307, p = 0.027). In the unemployed KT group, the Internal Control Scale (MHLC) correlated significantly with the Somatic Scale (r = 0.396, p = 0.013) and the Psychological Scale (r = 0.374, p = 0.019). CONCLUSIONS: The employed KT patients have a higher level of independence, with results indicating a strong internal type. Additionally, the working patients assess their QoL better, both in terms of their health condition and the organization of satisfying environment. The obtained knowledge about the psychological characteristics of KT patients may be useful for the occupational activation programs and psycho-education for those with weaker predispositions. Int J Occup Med Environ Health. 2022;35(1):53-62.


Subject(s)
Kidney Transplantation , Quality of Life , Employment , Humans , Internal-External Control , Kidney Transplantation/psychology , Quality of Life/psychology , Surveys and Questionnaires
14.
J Immunother ; 45(1): 35-42, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34406159

ABSTRACT

Molecular or immunological differences between responders and nonresponders to immune checkpoint inhibitors (ICIs) of clear cell renal cell carcinomas (ccRCCs) remain incompletely understood. To address this question, we performed next-generation sequencing, methylation analysis, genome wide copy number analysis, targeted RNA sequencing and T-cell receptor sequencing, and we studied frequencies of tumor-infiltrating CD8+ T cells, presence of tertiary lymphoid structures (TLS) and PD-L1 expression in 8 treatment-naive ccRCC patients subsequently treated with ICI (3 responders, 5 nonresponders). Unexpectedly, we identified decreased frequencies of CD8+ tumor-infiltrating T cells and TLS, and a decreased expression of PD-L1 in ICI responders when compared with nonresponders. However, neither tumor-specific genetic alterations nor gene expression profiles correlated with response to ICI or the observed immune features. Our results underline the challenge to stratify ccRCC patients for immunotherapy based on routinely available pathologic primary tumor material, even with advanced technologies. Our findings emphasize the analysis of pretreated metastatic tissue in line with recent observations describing treatment effects on the tumor microenvironment. In addition, our data call for further investigation of additional parameters in a larger ccRCC cohort to understand the mechanistic implications of the observed differences in tumor-infiltrating CD8+ T cells, TLS, and PD-L1 expression.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , B7-H1 Antigen , CD8-Positive T-Lymphocytes , Carcinoma, Renal Cell/therapy , Humans , Immunotherapy , Kidney Neoplasms/therapy , Lymphocytes, Tumor-Infiltrating , Tumor Microenvironment
15.
J Clin Med ; 10(23)2021 Dec 03.
Article in English | MEDLINE | ID: mdl-34884399

ABSTRACT

Gut microbiome and colonic inflammation can be associated with the predisposition and progression of Parkinson's disease (PD). The presented study aimed to compare gastrointestinal microbiota composition between patients diagnosed with PD and treated only with Levodopa to healthy controls. In this prospective study, patients were recruited in 1 academic hospital from July 2019 to July 2020. The detailed demographic data and medical history were collected using a set of questionnaires. Fecal samples were obtained from all participants. Next-Generation Sequencing was used to assess the microbiota composition. The endpoint was the difference in composition of the gut microbiota. In this study, we enrolled 27 hospitalized PD patients with well-controlled symptoms. The control group included 44 healthy subjects matched for age. Among PD patients, our results presented a higher abundance of Bacteroides phylum, class Corynebacteria among phylum Actinobacteria, class Deltaproteobacteria among phylum Proteobacteria, and genera such as Butyricimonas, Robinsoniella, and Flavonifractor. The species Akkermansia muciniphila, Eubacterium biforme, and Parabacteroides merdae were identified as more common in the gut microbiota of PD patients. In conclusion, the patients diagnosed with PD have significantly different gut microbiota profiles in comparison with healthy controls.

17.
Rev Med Suisse ; 17(752): 1665-1669, 2021 Sep 29.
Article in French | MEDLINE | ID: mdl-34585865

ABSTRACT

Caring for victims of harassment can be difficult. Different forms exist, some of which are difficult to detect. Every general practitioner must pay attention to the various warning signs that the victim may present. Careful, empathetic listening on the part of the general practitioner is necessary to take care of these victims. An important place in the consultation is the medical report, which can be used later in a legal process. The general practitioner does not work alone, can count on other medical and non-medical partners. Victims of harassment are also supported by various associations.


La prise en charge des victimes de harcèlement peut s'avérer difficile. Différentes formes, dont certaines difficiles à détecter, existent. Chaque médecin de premier recours doit prêter attention aux différents signaux d'alerte et facteurs de risque que peut présenter la victime. Une écoute attentive, empathique de la part du médecin généraliste est nécessaire pour prendre en charge ces victimes. Le constat médical tient une place importante, qui peut servir plus tard dans une démarche judiciaire. Le médecin ne travaillant pas seul peut compter sur d'autres partenaires médicaux et non médicaux. Les victimes de harcèlement sont par ailleurs soutenues par différentes associations.


Subject(s)
Physicians, Primary Care , Sexual Harassment , Humans
18.
Lab Invest ; 101(12): 1561-1570, 2021 12.
Article in English | MEDLINE | ID: mdl-34446805

ABSTRACT

CD8+ tumor-infiltrating T cells can be regarded as one of the most relevant predictive biomarkers in immune-oncology. Highly infiltrated tumors, referred to as inflamed (clinically "hot"), show the most favorable response to immune checkpoint inhibitors in contrast to tumors with a scarce immune infiltrate called immune desert or excluded (clinically "cold"). Nevertheless, quantitative and reproducible methods examining their prevalence within tumors are lacking. We therefore established a computational diagnostic algorithm to quantitatively measure spatial densities of tumor-infiltrating CD8+ T cells by digital pathology within the three known tumor compartments as recommended by the International Immuno-Oncology Biomarker Working Group in 116 prospective metastatic melanomas of the Swiss Tumor Profiler cohort. Workflow robustness was confirmed in 33 samples of an independent retrospective validation cohort. The introduction of the intratumoral tumor center compartment proved to be most relevant for establishing an immune diagnosis in metastatic disease, independent of metastatic site. Cut-off values for reproducible classification were defined and successfully assigned densities into the respective immune diagnostic category in the validation cohort with high sensitivity, specificity, and precision. We provide a robust diagnostic algorithm based on intratumoral and stromal CD8+ T-cell densities in the tumor center compartment that translates spatial densities of tumor-infiltrating CD8+ T cells into the clinically relevant immune diagnostic categories "inflamed", "excluded", and "desert". The consideration of the intratumoral tumor center compartment allows immune phenotyping in the clinically highly relevant setting of metastatic lesions, even if the invasive margin compartment is not captured in biopsy material.


Subject(s)
CD8-Positive T-Lymphocytes , Image Processing, Computer-Assisted , Immunophenotyping/methods , Melanoma/pathology , Adult , Aged , Aged, 80 and over , Deep Learning , Female , Humans , Male , Melanoma/immunology , Middle Aged
19.
Ann Agric Environ Med ; 28(2): 271-276, 2021 Jun 14.
Article in English | MEDLINE | ID: mdl-34184510

ABSTRACT

INTRODUCTION: The article discusses the antimicrobial resistance of poultry-isolated bacteria in the Wielkopolska region of Poland. MATERIAL AND METHODS: From August 2014 - June 2016, antibiotic resistance screening tests were performed involving 4,496 samples of Escherichia coli and 84 samples of Klebsiella spp., and the following antibiotics: amoxicillin, amoxicillin with clavulanic acid, colistin, doxycycline, enrofloxacin, florfenicol, neomycin, norfloxacin, spectinomycin, and trimethoprim with sulfamethoxazole. The research used broth the microdilution method and CLSI standards. RESULTS: During the investigation period of 22 months a growing percentage of E. coli isolates showed antibiotic resistance to amoxicillin, amoxicillin with clavulanic acid, colistin, enrofloxacin, neomycin, norfloxacin, spectinomycin, and trimethoprim with sulfamethoxazole. Resistance to doxycycline and florfenicol decreased. The most efficient antibiotics against E. coli were colistin (84.64 %), neomycin (80.62 %), and amoxicillin with clavulanic acid (73.05 %). Klebsiella samples were the most susceptible to neomycin (85.71 %), colistin (84.52 %), and trimethoprim with sulfamethoxazole (73.81 %). CONCLUSIONS: Antibiotic resistance of pathogenic micro-organisms, such as Escherichia coli and Klebsiella spp., is a serious problem both for poultry producers and for public health protection. Low efficiency of numerous antibiotic groups forces reflection on limiting the use of medicines in food-producing animals.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial , Enterobacteriaceae Infections/veterinary , Escherichia coli Infections/veterinary , Escherichia coli/drug effects , Klebsiella/drug effects , Poultry Diseases/microbiology , Animals , Chickens/microbiology , Enterobacteriaceae Infections/microbiology , Escherichia coli/genetics , Escherichia coli/isolation & purification , Escherichia coli Infections/microbiology , Klebsiella/genetics , Klebsiella/isolation & purification , Microbial Sensitivity Tests , Poland
20.
Int J Mol Sci ; 22(11)2021 May 29.
Article in English | MEDLINE | ID: mdl-34072512

ABSTRACT

Synthetic materials commonly used in the packaging industry generate a considerable amount of waste each year. Chitosan is a promising feedstock for the production of functional biomaterials. From a biological point of view, chitosan is very attractive for food packaging. The purposes of this study were to evaluate the antibacterial activity of a set of chitosan-metal oxide films and different chitosan-modified graphene (oxide) films against two foodborne pathogens: Campylobacter jejuni ATCC 33560 and Listeria monocytogenes 19115. Moreover, we wanted to check whether the incorporation of antimicrobial constituents such as TiO2, ZnO, Fe2O3, Ag, and graphene oxide (GO) into the polymer matrices can improve the antibacterial properties of these nanocomposite films. Finally, this research helps elucidate the interactions of these materials with eukaryotic cells. All chitosan-metal oxide films and chitosan-modified graphene (oxide) films displayed improved antibacterial (C. jejuni ATCC 33560 and L. monocytogenes 19115) properties compared to native chitosan films. The CS-ZnO films had excellent antibacterial activity towards L. monocytogenes (90% growth inhibition). Moreover, graphene-based chitosan films caused high inhibition of both tested strains. Chitosan films with graphene (GO, GOP, GOP-HMDS, rGO, GO-HMDS, rGOP), titanium dioxide (CS-TiO2 20:1a, CS-TiO2 20:1b, CS-TiO2 2:1, CS-TiO2 1:1a, CS-TiO2 1:1b) and zinc oxide (CS-ZnO 20:1a, CS-ZnO 20:1b) may be considered as a safe, non-cytotoxic packaging materials in the future.


Subject(s)
Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Biocompatible Materials , Chitosan , Food Microbiology , Food Packaging , Membranes, Artificial , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Bacterial Outer Membrane/drug effects , Cell Membrane Permeability/drug effects , Chitosan/chemistry , Metals/chemistry , Polymers
SELECTION OF CITATIONS
SEARCH DETAIL
...