A meta-analysis of blood and salivary cortisol levels in first-episode psychosis and high-risk individuals.

Dysregulated cortisol responses and glucose metabolism have been reported in psychosis. We performed a random-effects meta-analysis of cortisol responses in first-episode psychosis (FEP) and psychosis risk states, taking into consideration glucose metabolism. A total of 47 studies were included. Unstimulated blood cortisol levels were significantly higher (g = 0.48, 95 %CI: 0.25-0.70, p < 0.001) in FEP, but not in psychosis risk states (g = 0.39, 95 %CI: -0.42-1.21, p = 0.342), compared to controls. Cortisol awakening response (CAR) was attenuated in FEP (g = -0.40, 95 %CI: -0.68 - -0.12, p = 0.006), but not in psychosis risk states (p = 0.433). Glucose and insulin levels were positively correlated with unstimulated blood cortisol levels in FEP. Our meta-analysis supports previous findings of elevated blood cortisol levels and attenuated CAR in FEP. Future research should focus on identifying the common denominators for alterations in stress hormones and glucose metabolism.

Analysis of the causes of false negative and false positive results of preoperative axillary ultrasound in patients with early breast cancer - a single-centre study.

INTRODUCTION: Properly planned and performed diagnostic tests allow the optimal treatment option to be chosen for the patient. They also allow qualification for the correct surgical procedure. AIM OF THE STUDY: In this study we evaluated the clinical value of preoperative ultrasound scan (USS) testing performed during primary disease staging in patients with early breast cancer qualified to sentinel lymph node biopsy (SLNB). MATERIAL AND METHODS: The group of breast cancer patients who underwent SLNB from March 2012 to May 2013. As well as the standard procedure of the preoperative diagnostics model, in each patient the USS of axillary lymph nodes was performed additionally. The results were compared with the data from postoperative pathological reports. We attempted to define the factors influencing the possibility of obtaining false positive and false negative USS results. RESULTS: The analysis comprised 172 patients. In 14.4% of cases with normal USS result the pathological result was different from the expected one (pN1). In 42.3% of patients with suspicious axillary lymph nodes the result of the pathological report was positive. The sensitivity of the USS testing was 89.3%, and the specificity was 34.4%, PPV - 85.6%, NPV - 42.3%. CONCLUSIONS: Ultrasonographic assessment of axillary lymph nodes in breast cancer patients qualified for SLNB is a test with high sensitivity and high predictive value of the positive test result. The possibility of a result contrary to the actual nodal status may result primarily from the technical limitations of USS testing.

Overall survival and disease-free survival in breast cancer patients treated at the Oncology Centre in Bydgoszcz - analysis of more than six years of follow-up.

AIM OF THE STUDY: Malignant breast tumours are the largest oncological problem in the developed world. In the recent years the number of new diagnoses has exceeded 16,500 per year. Published data regarding far-distant results of breast cancer treatment that take under consideration the provincial division of the country may not be representative of the therapeutic effects achieved in specific oncological centres. The goal of this article is to analyse far-distant therapeutic results in breast cancer patients treated at the Oncology Centre in Bydgoszcz in 2006. They were compared with data available for Kujawsko-Pomorskie Voivodeship and with all-Poland results. MATERIAL AND METHODS: A cohort of 667 breast cancer patients at Bydgoszcz Oncology Centre between Jan 1 and Dec 31, 2006 was studied. The majority of the studied group were patients in stage I (26.2%) and II (48.3%) according to the TNM staging system, 17.5% were in stage III, and 6.4% in stage IV. The 5-year survival and 5-year disease-free survival rates were calculated. Median observation time was 79 months. RESULTS: A total of 148 patients (22.2%) suffered a relapse. There were 168 (25.2%) deaths caused by primary disease. The 5-year survival probability was 0.761 ±0.017 and the five-year disease-free survival probability was 0.807 ±0.016. Median survival time was 76.4 months, and median disease-free survival was 19.4 months. CONCLUSIONS: The five-year survival probability for breast cancer patients undergoing treatment at Bydgoszcz Oncology Centre was higher than all-Poland median five-year survival probability. The observation needs to be continued and should include the assessment of treatment in subsequent time periods.

Mental health of patients suffering from connective tissue diseases. Negative and positive concept and selected correlates. / Zdrowie psychiczne osób z chorobami tkanki lacznej. Ujecie negatywne i pozytywne oraz wybrane korelaty.

OBJECTIVES: The purpose of the research was to assess mental health of people suffering from connective tissue diseases, both in negative terms, i.e., the presence of disorders, and in positive terms - patients'well-being. Due to the specificity of connective tissue diseases, among others their unpredictable course and the pain that often accompanies patients, selected clinical and sociodemographic variables were included in the analyses. METHODS: 101 people participated in the study, 81 women and 20 men aged 18 to 57 years, suffering from various connective tissue diseases. Some people completed questionnaires during support group meetings (38.6%), others via the internet. The HADS-M scale was used to examine indicators of mental health in negative terms, the PERMA-Profiler questionnaire was used to assess well-being (an indicator of mental health in positive terms), and the authors' own survey was used to obtain clinical and sociodemographic data. RESULTS: Subjects suffering from connective tissue diseases are characterized by high severity of anxiety and depressive symptoms. Relationships between mental health and selected clinical and sociodemographic variables were observed, e.g., greater pain is associated with higher rates of anxiety and depression, and lower well-being; the level of well-being increases with age. CONCLUSIONS: It is important to monitor the mental health of people with chronic somatic diseases, including connective tissue diseases, especially in young people at the initial period of the disease, suffering from severe pain, residents of villages and small towns where access to support is limited.

Sexual and mental health of woman suffering from selected connective tissue diseases: an original paper.

OBJECTIVES: The aim of the study was to assess the sexual and mental health of women suffering from connective tissue diseases and to determine the potential interrelationships between the studied clinical variables and sexual and mental health. METHODS: The study was conducted in a group of women with connective tissue diseases. To assess somatic health, we used The Health Assessment Questionnaire (HAQ-DI), and to assess sexual health, we used the Female Sexual Function Index (FSFI) and Sexual Satisfaction Questionnaire (KSS). The mental health was assessed by using the Hospital Anxiety and Depression Scale (HADS-M) and the PERMA-Profiler (PL). RESULTS: The study involved 81 women suffering from connective tissue diseases, especially rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS) and juvenile idiopathic arthritis (JIA). Clinical symptoms of sexual dysfunction were observed in 54% women. The biggest difficulties occur in sexual desire, orgasm and arousal. Patients had symptoms of anxiety and depressive disorders. Higher levels of anxiety and depression are associated with poorer overall sexual functioning and better overall sexual functioning, and all its dimensions are associated with a higher level of mental well-being. There was also an observed relationship with the functional limitation due to pain and duration of the disease. CONCLUSION: The study confirms the existence of difficulties in the sexual functioning of women suffering from connective tissue diseases and shows the relationship between sexual and mental health and basic disease. The observed relationships are important information in the treatment and medical care of people with this group of rheumatic diseases. Key Points • The article presents one of the few studies about sexual functioning of Polish population women with connective tissue diseases. • The aim was to assess the sexual and mental health of women with various connective tissue diseases and determine the potential interrelationships between the clinical variables and sexual and mental health. • The study confirms difficulties in the sexual functioning of women with connective tissue diseases. The biggest difficulties occur in sexual desire, orgasm and arousal. Patients also had mental disorders symptoms. • The study presents conclusions and indications which may be important and help specialists approach the treatment process in an interdisciplinary way.

Thyroid hormones in persons with schizophrenia: A systematic review and meta-analysis.

There is accumulating evidence that individuals with schizophrenia show altered levels of thyroid hormones. However, a qualitative and quantitative synthesis of findings in this field has not been performed so far. Therefore, we aimed to perform a systematic review and meta-analysis of studies investigating the levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), total thyroxine (tT4), free triiodothyronine (fT3) and total triiodothyronine (tT3) in multiple-episode schizophrenia (MES) and first-episode psychosis (FEP). Electronic databases were searched from their inception until 30th May 2020 by two independent reviewers. Random-effects meta-analyses and meta-regression analyses were performed. Altogether, 19 studies were included. Persons with FEP had significantly lower TSH levels (5 studies, g = -0.26, 95%CI: -0.47 to -0.06, p = 0.013, I2 = 21.3%), higher fT4 levels (3 studies, g = 0.58, 95%CI: 0.15-1.01, p = 0.008, I2 = 64.6%) and lower tT3 levels (2 studies, g = -0.60, 95%CI: -0.82 to -0.37, p < 0.001, I2 = 0%) compared to controls. Elevated TSH levels were found in persons with MES (13 studies, g = 0.20, 95%CI: 0.02-0.39, p = 0.031, I2 = 50.0%). Our findings imply that the levels of TSH might be decreased in persons with FEP and increased in those with MES. Other alterations need to be confirmed by additional studies. These findings imply the need to monitor the levels of TSH and thyroid hormones from the onset of psychosis.

Glucose homeostasis in unaffected first-degree relatives of schizophrenia patients: A systematic review and meta-analysis.

It has been proposed that type 2 diabetes and schizophrenia-spectrum disorders share overlapping genetic backgrounds. Therefore, we aimed to perform a systematic review and meta-analysis of studies comparing fasting levels of glucose and insulin, the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), glucose levels during the oral glucose tolerance test (OGTT) and the levels of glycated hemoglobin (HbA1c) in unaffected first-degree relatives of patients with schizophrenia and controls. Online searches covered the publication period from database inception until May 8th 2020. Meta-analyses were performed using random-effects models with Hedges' g as the effect size estimate. Out of 2556 records identified, 12 studies representing 672 relatives of schizophrenia patients and 6446 controls were found to be eligible. There were no significant differences in fasting levels of glucose (g = 0.54, 95%CI = -0.26 to 1.35, p = 0.188) and insulin (g = 0.07, 95%CI = -0.14 to 0.29, p = 0.491), HOMA-IR (g = 0.12, 95%CI = -0.19 to 0.43, p = 0.433), and the levels of HbA1c (g = 0.38, 95%CI = -0.02 to 0.77, p = 0.061) between relatives of schizophrenia patients and controls. Two studies demonstrated significantly higher 2-hour glucose levels during OGTT in relatives of patients with schizophrenia (g = 0.90, 95%CI = 0.49 to 1.31, p < 0.001). Our findings do not support the hypothesis that familial liability to psychosis is related to altered fasting parameters of glucose homeostasis. However, this population might show impaired glucose tolerance. More studies are needed to confirm these observations.

Analysis of the treg cell population in the peripheral blood of ovarian cancer patients in relation to the long-term outcomes.

OBJECTIVES: There is growing evidence that Treg cell infiltration into the cancer nest is associated with poor prognosis. How- ever, the Treg cell population in the peripheral blood may change when a different type of anticancer therapy is applied. Since Treg cells may support tumor growth by enhancing the suppressive profile of the cancer microenvironment, the assessment of Treg cells can bring to light important information regarding prognosis. Thus we decided to analyze the Treg cell population in the peripheral blood in relation to long-term outcomes in the group of patients with ovarian cancer. MATERIAL AND METHODS: The 80 patients included in the study were treated surgically followed by chemiotherapy for ovar- ian cancer between October 2010 through May 2011.The peripheral blood samples from the patients were collected directly prior to chemotherapy. Information on any patients who died was retrieved from the database of the Cuiavia-Pomerania Regional Office of the National Health System of Poland. CD4+CD25+FOXP3+ lymphocytes T were assed by flow cytometry. We have analyzed the long term outcomes of treatment regarding to the level of Treg cells in peripheral blood. RESULTS: We found that patients with serous adenocarcinomas had significantly higher Treg levels compared to those patients with non-serous types. Patients who had a higher percentage of Treg cells within the CD4+ cell population prior to the beginning of the treatment had worse long-term outcomes from the applied therapy. CONCLUSIONS: The assessment of Treg levels prior to the start of chemotherapy is clinically useful and may predict overall survival in ovarian cancer patients.

Clinical significance of Van Nuys Prognostic Index as a qualification criterion to sentinel lymph node biopsy in patients diagnosed with ductal carcinoma in situ.

UNLABELLED: Diagnose of ductal carcinoma in situ (DCIS) requires, at least in a part of cases, assessment of auxiliary lymph nodes. The aim of the study was to analyze clinical value of Van Nuys Prognostic Index (VNPI) as the important criterion for qualification of DCIS patients to sentinel lymph node biopsy (SLNB). MATERIAL AND METHODS: Analysis included patients diagnosed with DCIS and qualified to SLNB, operated in years 2004-2013. We performed a statistical analysis to assess correlation between VNPI value and positive pathological verification of excised sentinel lymph node (SLN). The influence of other clinical factors on presence of metastases in SLN was also determined. RESULTS: 3,6% of DCIS patients were diagnosed with metastases in SLN. Metastases were diagnosed in 6.7% patients with VNPI > 10 points vs 3.4% in patients with VNPI < 10 points. In 75% of patients with metastatic SLN the value of VNPI was at least 10 points. In premenopausal patients metastases in SLN were diagnosed in 8.1% of cases vs 1.4% in postmenopausal patients. In patients diagnosed with cancer of the other breast metastases in SLN were found in 6.3% of cases vs 3.2% in one-sided cancer. Patients with multifocal cancer were over twice as often diagnosed with metastases in SLN (5% vs 2%). There was no correlation found between VNPI value and positive pathological verification of SLN. No differences between prevalence of SLN metastases depending on selected clinical features were found. CONCLUSIONS: Recommendation of VNPI as the criterion of qualification to SLNB starting with 10 points could be more favourable in patients with DCIS. Deciding on SLNB in DCIS patients, we should also take into consideration other clinical features.

Diagnostic value of preoperative axillary lymph node ultrasound assessment in patients with breast cancer qualified for sentinel lymph node biopsy.

INTRODUCTION: Sentinel lymph node biopsy (SLNB) is a standard procedure in the therapeutic management of patients with non-advanced breast cancer. AIM: To analyse the utility of ultrasound scan (USS) examination in the process of patient qualification for SLNB and to estimate the optimal time to perform USS in the clinical preoperational assessment of axillary lymph nodes. MATERIAL AND METHODS: A prospective analysis of 702 patients with invasive breast cancer treated with SLNB between 7.03.2012 and 27.05.2013 was performed. The patients were divided into three groups: I (USS < 8 weeks before SLNB), II (USS > 8 weeks before SLNB and another one on the day before SLNB) and III (USS > 8 weeks before SLNB without perioperative USS). In these patients the percentage of metastases in the sentinel lymph node and the clinical factors influencing the diagnostic value of preoperative ultrasound scan were assessed. RESULTS: Metastatic lesions in sentinel lymph nodes were found in 154 (21.9%) patients. The highest percentage of metastases was noted in patients operated on in the second and third month from the beginning of preoperative diagnostics. None of the factors tested (size of the original tumour, histological malignancy grading, kind of preoperative diagnostics, Ki-67 value, biological type of the tumour, age) had a statistically significant influence on the diagnostic value of perioperative USS examination in the analysed time span. CONCLUSIONS: The lowest percentage of metastases in the sentinel lymph node was noted in the patients qualified for SLNB who had the ultrasound performed directly before the surgical procedure (not more than 4 weeks before the surgery).

The biological role of Treg cells in ectopic endometrium homeostasis.

Although retrograde menstruation is observed in up to 90% of women, endometriosis actually develops in only 15% of women. There is considerable evidence in the literature that ectopic endometrial cells are able to evade immune surveillance and that the immune response in the microenvironment of ectopic lesions is limited. Endometriosis develops when a deficiency in the local immune response has been generated, and progression of the disease is related to the intensity of this process. Over the last couple of decades it has been well known that T regulatory lymphocytes (Tregs) play a crucial role in controlling a variety of physiological and pathological immune responses. In this review we have focused on the physiological alteration of Treg cell infiltration into the endometrium during the reproductive processes of women. We discuss how a disturbance in Treg cell expansion is involved in generating such pathological processes as miscarriage and ectopic pregnancy development. We hypothesize about the role Treg cells might play in the survival of endometriosis foci in ectopic localization and in the evasion of such lesions from host immune surveillance.

Quantitative measurements of tumoral p95HER2 protein expression in metastatic breast cancer patients treated with trastuzumab: independent validation of the p95HER2 clinical cutoff.

PURPOSE: P95HER2 (p95) is a truncated form of the HER2, which lacks the trastuzumab-binding site and contains a hyperactive kinase domain. Previously, an optimal clinical cutoff of p95 expression for progression-free survival (PFS) and overall survival (OS) was defined using a quantitative VeraTag assay (Monogram Biosciences) in a training set of trastuzumab-treated metastatic breast cancer (MBC) patients. EXPERIMENTAL DESIGN: In the current study, the predictive value of the p95 VeraTag assay cutoff established in the training set was retrospectively validated for PFS and OS in an independent series of 240 trastuzumab-treated MBC patients from multiple institutions. RESULTS: In the subset of 190 tumors assessed as HER2-total (H2T)-positive using the quantitative HERmark assay (Monogram Biosciences), p95 VeraTag values above the predefined cutoff correlated with shorter PFS (HR = 1.43; P = 0.039) and shorter OS (HR = 1.94; P = 0.0055) where both outcomes were stratified by hormone receptor status and tumor grade. High p95 expression correlated with shorter PFS (HR = 2.41; P = 0.0003) and OS (HR = 2.57; P = 0.0025) in the hormone receptor-positive subgroup of patients (N = 78), but not in the hormone receptor-negative group. In contrast with the quantitative p95 VeraTag measurements, p95 immunohistochemical expression using the same antibody was not significantly correlated with outcomes. CONCLUSIONS: The consistency in the p95 VeraTag cutoff across different cohorts of patients with MBC treated with trastuzumab justifies additional studies using blinded analyses in larger series of patients.

Analysis of Treg cell population alterations in the peripheral blood of patients treated surgically for ovarian cancer - a preliminary report.

PROBLEM: Treg cells constitute the main cell population that enables cancer cells to evade immune surveillance. An alteration in the Treg cell population might correspond to the diminishment of the tumour mass in patients with cancer and could therefore be a useful marker of the intensity of the selective suppression of the host immune system and also of the degree of radicalism of a procedure. Certainly, it is well known that in order for anti-cancer therapy to succeed the proper immune response against cancer cells must be restored. Furthermore, monitoring the level of selective immune system suppression during cancer therapy might yield information that would support a decision to supplement standard therapy by immunotherapy or to increase the degree of radicalism of the applied therapy. METHOD OF STUDY: We examined the Treg cell populations in the peripheral blood of a group of patients treated surgically for ovarian cancer. In each patient, the peripheral blood samples were collected both prior to and 1 day after the surgical procedure, and then again 5 days after the procedure. The presence of regulatory T cells in the samples was analyzed by means of flow cytometry. RESULTS: In our study, the percentages of FOXP3(+) cells in the subpopulation of CD4(+) T lymphocytes found in the peripheral blood of the patients before the surgical intervention were statistically significantly higher than those observed in the peripheral blood of these same patients after the surgical procedure. CONCLUSION: It would seem that the alteration in the Treg cell subpopulation could be a key factor in determining the status of the tumour microenvironment. Most likely, it could provide information about whether the proper level of anti-cancer immune response could be restored. The possibility of restoring the immune response may directly correspond to the degree of radicalism of the surgical intervention.