Pulsed electric field induces exocytosis and overexpression of MAGE antigens in melanoma.

Nanosecond pulsed electric field (nsPEF) has emerged as a promising approach for inducing cell death in melanoma, either as a standalone treatment or in combination with chemotherapeutics. However, to date, there has been a shortage of studies exploring the impact of nsPEF on the expression of cancer-specific molecules. In this investigation, we sought to assess the effects of nsPEF on melanoma-specific MAGE (Melanoma Antigen Gene Protein Family) expression. To achieve this, melanoma cells were exposed to nsPEF with parameters set at 8 kV/cm, 200 ns duration, 100 pulses, and a frequency of 10 kHz. We also aimed to comprehensively describe the consequences of this electric field on melanoma cells' invasion and proliferation potential. Our findings reveal that following exposure to nsPEF, melanoma cells release microvesicles containing MAGE antigens, leading to a simultaneous increase in the expression and mRNA content of membrane-associated antigens such as MAGE-A1. Notably, we observed an unexpected increase in the expression of PD-1 as well. While we did not observe significant differences in the cells' proliferation or invasion potential, a remarkable alteration in the cells' metabolomic and lipidomic profiles towards a less aggressive phenotype was evident. Furthermore, we validated these results using ex vivo tissue cultures and 3D melanoma culture models. Our study demonstrates that nsPEF can elevate the expression of membrane-associated proteins, including melanoma-specific antigens. The mechanism underlying the overexpression of MAGE antigens involves the initial release of microvesicles containing MAGE antigens, followed by a gradual increase in mRNA levels, ultimately resulting in elevated expression of MAGE antigens post-experiment. These findings shed light on a novel method for modulating cancer cells to overexpress cancer-specific molecules, thereby potentially enhancing their sensitivity to targeted anticancer therapy.

Methods for Clinical Monitoring of Neuromuscular Transmission in Anesthesiology - A Review.

The administration of general anesthesia is a crucial aspect of surgery. However, it can pose significant risks to patients, such as respiratory depression and prolonged neuromuscular blockade. To avoid such complications, it is essential to monitor neuromuscular transmission during anesthesia. While clinical tests have been used for decades to evaluate muscle function, they are now known to be unreliable, and relying on them increases the risk of postoperative complications. Thankfully, there are now six methods available for neuromuscular monitoring during anesthesia: mechanomyography, acceleromyography, electromyography, kinemyography, phonomyography, and compressomyography. Each of these methods differs in terms of their approach and methodology, and their importance in clinical practice varies accordingly. Mechanomyography involves measuring the mechanical response of a muscle to nerve stimulation, while acceleromyography measures the acceleration of muscle contraction. Electromyography records the electrical activity of muscles, while kinemyography tracks muscle movement. Phonomyography records the sound waves produced by contracting muscles, and compressomyography involves monitoring the pressure changes in a muscle during contraction. Overall, understanding the differences between these methods and their clinical significance is crucial for anesthesiologists. This review aims to provide an updated understanding of the current methods available for neuromuscular monitoring during anesthesia, so that anesthesiologists can make informed decisions about patient care and reduce the risk of postoperative complications.

Hospitalizations of patients with sarcoidosis before and during the COVID-19 pandemic in Poland.

INTRODUCTION: Sarcoidosis is a multisystemic granulomatous disease that mostly affects the lungs and lymphatic system. Due to its rarity and variable clinical course, analyses of factors related to sarcoidosis should be based on large databases and long observation periods. OBJECTIVES: The aim of this study was to determine the characteristics of patients with sarcoidosis hospitalized in Poland over a long period (2016-2021). PATIENTS AND METHODS: We conducted a retrospective study using hospital discharge records compiled by the National Institute of Public Health NIH - National Research Institute. We analyzed the records of patients with sarcoidosis from the entire Polish population at their first hospitalization. RESULTS: We identified a total of 15 548 first-time hospitalizations for sarcoidosis. The mean annual disease incidence was 6.8 cases per 100 000. The mean (SD) age of the patients was 45.8 (13.6) years, and it was lower in men than in women (42.9 [12.5] vs 49.8 [14.2] years; P <0.001). There were significantly more hospitalizations among city dwellers (62.3% vs 37.3% for rural residents; P <0.001). At the beginning of the COVID­19 pandemic in Poland there was a decrease in the number of hospitalizations for sarcoidosis, followed by an increase in the subsequent year. The all­cause in­hospital death rate was significantly higher during the COVID­19 pandemic, as compared with the period before the pandemic (7.2 vs 2.3 per 1000; P <0.001). CONCLUSIONS: Health care changes related to the outbreak of the COVID­19 pandemic may have increased the health debt for inpatient sarcoidosis treatment. The occurrence of sarcoidosis in Poland may be related to demographic and territorial factors.

Oral Contraceptive Use and Assessment of Breast Cancer Risk among Premenopausal Women via Molecular Characteristics: Systematic Review with Meta-Analysis.

Breast cancer is divided into four molecular subtypes. Each one has distinct clinical features. The aim of this study was to assess individual breast cancer subtype risk in premenopausal women taking oral contraceptives (OCs). Databases (MEDLINE; PubMed, EMBASE, and the Cochrane Library) were searched to January 2022 to identify case-control studies meeting the inclusion criteria. The influence of OCs intake on the risk of ER-positive breast cancer (ER+BC) was revealed to be non-significant with regard to reduction: OR = 0.9134, 95% CI: 0.8128 to 1.0265, p = 0.128. Assessment of ER-negative subtype breast cancer (ER-BC) risk indicated that OCs use significantly increased the risk: OR = 1.3079, 95% CI: 1.0003 to 1.7100, p = 0.050. Analysis for HER2-positive breast cancer (HER2+BC) risk showed that OCs use statistically non-significantly lowered the risk: OR = 0.8810, 95% CI: 0.5977 to 1.2984, p = 0.522. Meta-analysis with regard to Triplet-negative breast cancer (TNBC) risk showed non-statistically significant increased risk: OR = 1.553, 95% CI: 0.99 to 2.43, p = 0.055. The findings of the meta-analysis suggest that breast cancer risk in premenopausal women may vary with respect to molecular subtypes. Extensive scientific work is still necessary in order to understand the impact of OCs use on breast cancer risk in young women.

Oral Contraceptive Use and Breast Cancer Risk for BRCA1 and BRCA2 Mutation Carriers: Systematic Review and Meta-Analysis of Case-Control Studies.

Oral contraceptive use is one of the major modifiable risk factors for breast cancer. To investigate the effect of oral contraceptive taking on breast cancer risk by BRCA 1 and BRCA 2 mutation status, we conducted a systematic review and meta-analysis of case-controlled studies. Therefore, English language articles were retrieved by searching MEDLINE (PubMed), EMBASE and the Cochrane Library up to August 2021. Data were pooled from none case-control studies, comprising a total of 33,162 subjects, including 23,453 who had never used oral contraceptives. Overall meta-analysis indicated a statistically insignificant risk reduction: OR = 0.86, 95% CI: 0.70 to 1.06, p = 0.1594. However, increased breast cancer risk was associated with age at first use of OCs ≥20 years: OR = 1.21, 95% CI:1.07 to 1.36, p = 0.002. Multivariable meta-regression with covariates of age of first OC use (ß = 0.21, 95% CI: -0.25 to 0.67, p = 0.3767), duration of OC use (ß = -0.08, 95% CI; -0.51 to 0.34, p = 0.7093), and time since last OC use (ß = 0.32, 95% CI: -0.22 to 0.85, p = 0.2461) did not have a significant effect on the breast cancer risk. This meta-analysis suggests a diverse effect of oral contraceptive use against breast cancer in BRCA carrier mutation. The association between OC use and breast and ovarian cancers needs more investigation.

Nutritional Treatment of Patients with Colorectal Cancer.

Colorectal cancer is one of the most common cancers in Europe and the world. Cancer treatments have side effects and cause significant deterioration of the patient's nutritional status. Patient malnutrition may worsen the health condition and prevent the deliberate effects of the therapy. The aim of this review was to describe the available data about clinical nutrition in colorectal cancer patients. A large proportion of colorectal cancer patients suffer from malnutrition, which negatively affects the survival prognosis, quality of life, and oncological therapy. Therefore, monitoring nutritional status during the treatment is essential and can be used to arrange proper nutritional therapy to enhance patient responses, prevent side effects, and shorten recovery time. The principles of nutrition during anticancer therapy should mainly consider light and low-fat foods, the exclusion of lactose and gluten-containing foods in certain cases, or the introduction of special dietary products such as oral nutrition supplements and it should be tailored to patients' individual needs.

Oral Contraceptive Use and Breast Cancer Risk According to Molecular Subtypes Status: A Systematic Review and Meta-Analysis of Case-Control Studies.

We conducted a systematic review and meta-analysis to investigate the effect of oral contraceptives (OCs) on risk of breast cancer (BrCa) by status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). We searched the MEDLINE (PubMed), Embase and the Cochrane Library database and bibliographies of pertinent articles published up to 2020. Therein, we identified nineteen eligible case-control studies which provided data by breast cancer subtypes: ER-positive (ER+), ER-negative (ER-), HER2-positive (HER2+) and Triplet-negative (TN). Summary risk estimates (pooled OR [pOR]) and 95% confidence intervals (CIs) were calculated using fixed/random effects models. The summary meta-analysis showed that over-use of OCs led to significant increased risk of TNBrCa (OR = 1.37, 95% CI; 1.13 to 1.67, p = 0.002), as well as of ER-BrCa (OR = 1.20, 95% CI: 1.03 to 1.40, p = 0.019). There was also a significant reduction in the risk of ER+BrCa (OR = O.92, 95% CI: 0.86 to 0.99, p = 0.026,) and a slight reduction in the risk of HER2+BrCa (OR = 0.95, 95% CI; 0.79 to 1.14, p = 0.561) after taking OCs. Meta-analysis indicated that OC use has different impacts on risk of breast cancer subtypes defined by receptor status. The identified differences between individual subtypes of breast cancer may reflect different mechanisms of carcinogenesis.

Pain Control: Normalization of the BPCQ Questionnaire on a Group of Patients Diagnosed with Malignant Cancer.

The purpose of this article is to examine the applicability of the Beliefs about Pain Control Questionnaire (BPCQ) among cancer patients and develop norms that allow differentiation of patients with diagnosed cancer in terms of beliefs about pain control. Normalization aims to establish the value of test results in the study population. The study involved 1187 patients diagnosed with cancer in outpatient care Maria Sklodowska-Curie Cancer Center and Institute of Oncology, in Warsaw. The applied tool was the Beliefs about Pain Control Questionnaire developed by S. Skevington. The results are most strongly differentiated in each dimension of pain control by education, income, and professional status. Sten norms were developed to determine the level of beliefs about pain control in low, average, and high categories. The BPCQ assessment applies to cancer patients, and the assessment of the location of pain control in patients will allow for the identification of patients whose standard therapy should be supplemented with psychotherapeutic support.

Oral Contraceptive Use and Breast Cancer Risk Assessment: A Systematic Review and Meta-Analysis of Case-Control Studies, 2009-2020.

To perform a meta-analysis of case-control studies that addressed the association between oral contraceptive pills (OC) use and breast cancer (BrCa), PubMED (MEDLINE), Embase, and the Cochrane Library were searched to identify case-control studies of OC and BrCa published between 2009 and 2020. We used the DerSimonian-Laird method to compute pooled odds ratios (ORs) and confidence intervals (CIs), and the Mantel-Haenszel test to assess the association between OC use and cancer. Forty-two studies were identified that met the inclusion criteria and we included a total of 110,580 women (30,778 into the BrCa group and 79,802 into the control group, of which 15,722 and 38,334 were using OC, respectively). The conducted meta-analysis showed that the use of OC was associated with a significantly increased risk of BrCa in general, OR = 1.15, 95% CI: 1.01 to 1.31, p = 0.0358. Regarding other risk factors for BrCa, we found that increased risk was associated significantly with early menarche, nulliparous, non-breastfeeding, older age at first parity, postmenopause, obesity, smoking, and family history of BrCa. Despite our conclusion that birth control pills increase the cancer risk being supported by extensive previous studies and meta-analyzes, further confirmation is required.

Use of Oral Contraceptives as a Potential Risk Factor for Breast Cancer: A Systematic Review and Meta-Analysis of Case-Control Studies Up to 2010.

Despite numerous studies evaluating the risk of breast cancer among oral contraception users, the effect of oral contraceptive on developing breast cancer remains inconclusive. Therefore, we conducted a systematic review of literature with meta-analysis in order to quantitative estimate this association. The bibliographic database MEDLINE and EMBASE, and reference lists of identified articles were searched, with no language restrictions, from the start of publication to August 2010. We performed a reanalysis and overall estimate of 79 case-control studies conducted between 1960-2010, including a total of 72,030 incidents, histologically confirmed cases of breast cancer and 123,650 population/hospital controls. A decrease was observed in cancer risk in OC users before age 25 years (0.91, 0.83-1.00). However, the use of OCs before the first full-term pregnancy had a significant increased risk of breast cancer (OR, 1.14, 1.01-1.28, p = 0.04), as did OC use longer than 5 years (1.09, 1.01-1.18, p = 0.02). Pooled crude odds ratios of breast cancer in ever-users of oral contraceptives was 1.01 [95% confidence interval (CI), 0.95-1.07], compared with never-users. There was no significant increase in risk among premenopausal women (1.06, 0.92-1.22), postmenopausal women (0.99, 0.89-1.10), or nulliparous women (1.02, 0.82-1.26). Oral contraceptives do not appear to increase the risk of breast cancer among users. However, OC use before a first full-term pregnancy or using them longer than 5 years can modify the development of the breast cancer.

Sarcoidosis among hospitalized patients in Poland: a study based on a national hospital registry.

INTRODUCTION: Sarcoidosis is a systemic granulomatous disease mainly affecting the lungs, although granulomas can also involve any other organ. OBJECTIVES: We sought to describe patients during their first hospitalization for sarcoidosis in Poland from 2008 to 2015. To our knowledge, this is the first evaluation of the disease in Poland based on a hospital morbidity database. PATIENTS AND METHODS: We conducted a retrospective, population­based study, using hospital discharge records compiled by the National Institute of Public Health in the years 2008 to 2015. RESULTS: Among the 23 097 patients included in the study, men were predominant (54.7%). The mean and median ages at hospitalization were 44.7 years (95% CI, 44.5-44.9) and 42 years, respectively. Most patients (65%) resided in urban areas. The average annual incidence rate of sarcoidosis was 7.5 per 100 000 (95% CI, 7.1-7.9). The lungs were the most commonly affected organ (57.9%), while the remaining cases included sarcoidosis of lymph nodes and no lung involvement (18%), the skin (1.4%), and other or unspecified sites (22.7%). Skin sarcoidosis occurred significantly more frequently in women, while sarcoidosis of the lungs with coexisting sarcoidosis of lymph nodes was significantly more prevalent in men. Seasonal variability in sarcoidosis incidence was observed. CONCLUSIONS: Sex and age may have a significant impact on the occurrence of sarcoidosis in Poland. Changes in seasonality may suggest the role of environmental factors. These data on sarcoidosis in Poland may be helpful in comparative analyses with other European countries.

A novel biomarker panel for irritable bowel syndrome and the application in the general population.

Biological markers that measure gut health and diagnose functional gastro-intestinal (GI) disorders, such as irritable bowel syndrome (IBS), are lacking. The objective was to identify and validate a biomarker panel associated with the pathophysiology of IBS that discriminates IBS from healthy controls (HC), and correlates with GI symptom severity. In a case-control design, various plasma and fecal markers were measured in a cohort of 196 clinical IBS patients and 160 HC without GI symptoms. A combination of biomarkers, which best discriminates between IBS and HC was identified and validated in an independent internal validation set and by permutation testing. The correlation between the biomarker panel and GI symptom severity was tested in IBS patients and in a general population cohort of 958 subjects. A set of 8 biomarker panel was identified to discriminate IBS from HC with high sensitivity (88.1%) and specificity (86.5%). The results for the IBS subtypes were comparable. Moreover, a moderate correlation was found between the biomarker panel and GI symptom scores in the IBS (r = 0.59, p < 0.001) and the general population cohorts (r = 0.51, p = 0.003). A novel multi-domain biomarker panel has been identified and validated, which correlated moderately to GI symptom severity in IBS and general population subjects.

Volatile Organic Compounds in Exhaled Air as Novel Marker for Disease Activity in Crohn's Disease: A Metabolomic Approach.

BACKGROUND: Disappearance of macroscopic mucosal inflammation predicts long-term outcome in Crohn's disease (CD). It can be assessed by ileocolonoscopy, which is, however, an invasive and expensive procedure. Disease activity indices do not correlate well with endoscopic activity and noninvasive markers have a low sensitivity in subgroups of patients. Volatile organic compounds (VOCs) in breath are of increasing interest as noninvasive markers. The aim of this study was to investigate whether VOCs can accurately differentiate between active CD and remission. METHODS: Patients participated in a 1-year follow-up study and Harvey-Bradshaw index, blood, fecal, and breath samples were collected at regular intervals. Patients were stratified into 2 groups: active (fecal calprotectin >250 µg/g) or inactive (Harvey-Bradshaw index <4, C-reactive protein <5 mg/L, and fecal calprotectin <100 µg/g) disease. Breath samples were analyzed by gas chromatography-time-of-flight mass spectrometry. Random forest analyses were used to find the most discriminatory VOCs. RESULTS: Eight hundred thirty-five breath-o-grams were measured, 140 samples were assigned as active, 135 as inactive disease, and 110 samples of healthy controls. A set of 10 discriminatory VOCs correctly predicted active CD in 81.5% and remission in 86.4% (sensitivity 0.81, specificity 0.80, AUC 0.80). These VOCs were combined into a single disease activity score that classified disease activity in more than 60% of the previously undetermined individuals. CONCLUSIONS: We showed that VOCs can separate healthy controls and patients with active CD and CD in remission in a real-life cohort. Analysis of exhaled air is an interesting new noninvasive application for monitoring mucosal inflammation in inflammatory bowel disease.