142 research outputs found
Determinants of Pain-Induced Disability in German Women with Endometriosis during the COVID-19 Pandemic
(1) Background: The main aim of this research was to examine the factors leading to pain induced disability by assessing the impact of demographic, endometriosis-specific, pandemic-specific,
and mental health factors. (2) Methods: Women with endometriosis who attended online support
groups were invited to respond to an online survey during the first wave of the COVID-19 pandemic in
Germany. The Pain Disability Index (PDI) was employed to assess disability-related daily functioning.
Independent predictors of pain-induced disability were determined using univariate and multivariate
logistic regression analyses. (3) Results: The mean PDI score of the study population was 31.61
(SD = 15.82), which was significantly higher (p < 0.001) than that reported in a previously published
normative study of the German population. In the present study, a high level of pain-induced
disability, as defined by scores equal to or higher than the median of the study population, older age
(OR 1.063, 95% CI 1.010–1.120, p = 0.020), dysmenorrhea (OR 1.015, 95% CI 1.005–1.026, p = 0.005),
dysuria (OR 1.014; 95% CI 1.001–1.027, p = 0.029), lower back pain (OR 1.018, 95% CI 1.007–1.029,
p = 0.001), and impaired mental health (OR 1.271, 95% CI 1.134–1.425, p < 0.001) were found to be
independent risk factors. Pandemic-specific factors did not significantly influence the pain-induced
disability of the participants in this study. (4) Conclusions: The level of pain-induced disability was
significantly higher among the women with endometriosis than among women in the normative
German validation study. Our findings identified risk factors for experiencing a high level of pain induced disability, such as demographic and specific pain characteristics. Pandemic-specific factors
did not significantly and independently influence the pain-induced disability during the first wave
of the COVID-19 pandemic in Germany. Impaired mental health negatively influenced functioning
during daily activities. Thus, women with endometriosis should be managed by a multidisciplinary
team of healthcare professionals to prevent negative effects of pain-induced disability on their
quality of life
Factors Associated with Increased Analgesic Use in German Women with Endometriosis during the COVID-19 Pandemic
(1) Background: Endometriosis is a frequent chronic pain condition in women of fertile
age. Pain management with analgesics is frequently used by women with endometriosis. During the
COVID-19 pandemic, access to health services was temporarily restricted in various countries for
persons without serious conditions, resulting in increased physical and mental health issues. The
present study was conducted in order to assess the risk factors predicting increased analgesic intake
by women with endometriosis during the COVID-19 pandemic. (2) Methods: The increased intake
of over-the-counter (OTC) and prescription-only (PO) analgesics was assessed with an anonymous
online questionnaire, along with demographic, pandemic-specific, disease-specific, and mental health
characteristics. Anxiety and depression were assessed with the Generalized Anxiety Disorder Scale
(GAD-2) and the Patient Health Questionnaire for Depression (PHQ-2), respectively. Pain-induced
disability was assessed with the pain-induced disability index (PDI). (3) Results: A high educational
level (OR 2.719; 95% CI 1.137–6.501; p = 0.025) and being at higher risk for depressive disorders, as
measured by PHQ-2 ≥ 3 (OR 2.398; 95% CI 1.055–5.450; p = 0.037), were independent risk factors
for an increased intake of OTC analgesics. Current global pain-induced disability (OR 1.030; 95% CI
1.007–1.054; p = 0.010) was identified as a risk factor for an increased intake of PO pain medication.
The degree of reduction in social support and in social networks were independent predictors of an
increased intake of PO analgesics in a univariate logistic regression analysis, but lost significance
when adjusted for additional possible influencing factors. (4) Conclusions: In this population, an
increased intake of OTC analgesics was related to a higher educational level and having a depressive
disorder, while a higher pain-induced disability was an independent risk factor for an increased
intake of PO analgesics. Pandemic-specific factors did not significantly and independently influence
an increased intake of analgesics in women with endometriosis during the first wave of the COVID19 pandemic in Germany. Healthcare providers should be aware of the possible factors related to
increased analgesic use in women with endometriosis in order to identify persons at risk for the
misuse of pain medication and to prevent potential adverse effects
In renal cell carcinoma the PTEN splice variant PTEN-Δ shows similar function as the tumor suppressor PTEN itself
BACKGROUND:
Loss of PTEN is involved in tumor progression of several tumor entities including renal cell carcinoma (RCC). During the translation process PTEN generates a number of splice variants, including PTEN-Δ. We analyzed the impact of PTEN-Δ in RCC progression.
METHODS:
In specimens of RCC patients the expression of PTEN-Δ and PTEN was quantified. The PTEN expressing RCC cell line A498 and the PTEN deficient 786-O cell line were stably transfected with the PTEN-Δ or PTEN transcript. In Caki-1 cells that highly express PTEN-Δ, this isoform was knocked down by siRNA. Cell migration, adhesion, apoptosis and signaling pathways activities were consequently analyzed in vitro.
RESULTS:
Patients with a higher PTEN-Δ expression had a longer lymph node metastasis free and overall survival. In RCC specimens, the PTEN-Δ expression correlated with the PTEN expression. PTEN-Δ as well as PTEN induced a reduced migration when using extracellular matrix (ECM) compounds as chemotaxins. This effect was confirmed by knockdown of PTEN-Δ, inducing an enhanced migration. Likewise a decreased adhesion on these ECM components could be shown in PTEN-Δ and PTEN transfected cells. The apoptosis rate was slightly increased by PTEN-Δ. In a phospho-kinase array and Western blot analyses a consequently reduced activity of AKT, p38 and JNK could be shown.
CONCLUSIONS:
We could show that the PTEN splice variant PTEN-Δ acts similar to PTEN in a tumor suppressive manner, suggesting synergistic effects of the two isoforms. The impact of PTEN-Δ in context of tumor progression should thus be taken into account when generating new therapeutic options targeting PTEN signaling in RCC
Prognostic Impact of Immunoglobulin Kappa C (IGKC) in Early Breast Cancer
We studied the prognostic impact of tumor immunoglobulin kappa C (IGKC) mRNA expression as a marker of the humoral immune system in the FinHer trial patient population, where 1010 patients with early breast cancer were randomly allocated to either docetaxel-containing or vinorelbine-containing adjuvant chemotherapy. HER2-positive patients were additionally allocated to either trastuzumab or no trastuzumab. Hormone receptor-positive patients received tamoxifen. IGKC was evaluated in 909 tumors using quantitative real-time polymerase chain reaction, and the influence on distant disease-free survival (DDFS) was examined using univariable and multivariable Cox regression and Kaplan–Meier estimates. Interactions were analyzed using Cox regression. IGKC expression, included as continuous variable, was independently associated with DDFS in a multivariable analysis also including age, molecular subtype, grade, and pT and pN stage (HR 0.930, 95% CI 0.870–0.995, p = 0.034). An independent association with DDFS was also found in a subset analysis of triple-negative breast cancers (TNBC) (HR 0.843, 95% CI 0.724–0.983, p = 0.029), but not in luminal (HR 0.957, 95% CI 0.867–1.056, p = 0.383) or HER2-positive (HR 0.933, 95% CI 0.826–1.055, p = 0.271) cancers. No significant interaction between IGKC and chemotherapy or trastuzumab administration was detected (Pinteraction = 0.855 and 0.684, respectively). These results show that humoral immunity beneficially influences the DDFS of patients with early TNBC
Prognostic impact of CD4-positive T cell subsets in early breast cancer : a study based on the FinHer trial patient population
Background: The clinical importance of tumor-infiltrating cluster of differentiation 4 (CD4) T cells is incompletely understood in early breast cancer. We investigated the clinical significance of CD4, forkhead box P3 (FOXP3), and B cell attracting chemokine leukocyte chemoattractant-ligand (C-X-C motif) 13 (CXCL13) in early breast cancer. Methods: The study is based on the patient population of the randomized FinHer trial, where 1010 patients with early breast cancer were randomly allocated to adjuvant chemotherapy containing either docetaxel or vinorelbine, and human epidermal growth factor receptor 2 (HER2)-positive patients were also allocated to trastuzumab or no trastuzumab. Breast cancer CD4, FOXP3, and CXCL13 contents were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR), and their influence on distant disease-free survival (DDFS) was examined using univariable and multivariable Cox regression and Kaplan-Meier estimates in the entire cohort and in selected molecular subgroups. Interactions between variables were analyzed using Cox regression. The triple-negative breast cancer (TNBC) subset of the HE10/97 randomized trial was used for confirmation. Results: High CXCL13 was associated with favorable DDFS in univariable analysis, and independently in multivariable analysis (HR 0.44, 95% CI 0.29-0.67, P Conclusions: The results provide a high level of evidence that humoral immunity influences the survival outcomes of patients with early breast cancer, in particular of those with TNBC.Peer reviewe
Validation of the prognostic performance of Breast Cancer Index (BCI) in hormone receptor-positive (HR+) postmenopausal breast cancer patients in the TEAM trial
Purpose: Early-stage HR+ breast cancer patients face a prolonged risk of recurrence even after adjuvant endocrine therapy. The Breast Cancer Index (BCI) is significantly prognostic for overall (0-10 years) and late (5-10 years) distant recurrence risk (DR) in N0 and N1 patients. Here, BCI prognostic performance was evaluated in HR+ postmenopausal women from the TEAM trial.Experimental Design: 3544 patients were included in the analysis (N=1519 N0, N=2025 N+). BCI risk groups were calculated using pre-specified cut-points. Kaplan-Meier analyses and logranktests were used to assess the prognostic significance of BCI risk groups based on DR. Hazard ratios (HR) and confidence intervals (CI) were calculated using Cox models with and without clinical covariates.Results: For overall 10-year DR, BCI was significantly prognostic in N0 (N=1196) and N1 (N=1234) patients who did not receive prior chemotherapy (p<0.001). In patients who were DRfree for 5 years, 10-year late DR rates for low- and high-risk groups were 5.4% and 9.3% (N0 cohort, N=1285) and 4.8% and 12.2% (N1 cohort, N=1625) with multivariate HRs of 2.25 (95% CI: 1.30-3.88; p=0.004) and 2.67 (95% CI: 1.53-4.63; p=<0.001), respectively. Late DR performance was substantially improved using previously optimized cut-points, identifying BCIlow-risk groups with even lower 10-year late DR rates of 3.8% and 2.7% in N0 and N1 patients, respectively.Conclusions: The TEAM trial represents the largest prognostic validation study for BCI to date and provides a more representative assessment of late DR risk to guide individualized treatment decision-making for HR+ early-stage breast cancer patients
Adjuvant tamoxifen and exemestane in postmenopausal early breast cancer:ten-year analysis of the randomised phase III TEAM trial
Surgical oncolog
Current Approaches to the Management of Sentinel Node Procedures in Early Vulvar Cancer in Germany : A Web-Based Nationwide Analysis of Practices
Background: Lymph node involvement is the most important prognostic factor for recurrence and survival in vulvar cancer. Sentinel node (SN) procedure can be offered in well-selected
patients with early vulvar cancer. This study aimed to assess current management practices with
respect to the sentinel node procedure in women with early vulvar cancer in Germany. Methods: A
Web-based survey was conducted. Questionnaires were e-mailed to 612 gynecology departments.
Data were summarized as frequencies and analyzed using the chi-square test. Results: A total of
222 hospitals (36.27%) responded to the invitation to participate. Among the responders, 9.5% did
not offer the SN procedure. However, 79.5% evaluated SNs by ultrastaging. In vulvar cancer of the
midline with unilateral localized positive SN, 49.1% and 48.6% of respondents, respectively, would
perform ipsilateral or bilateral inguinal lymph node dissection. Repeat SN procedure was performed
by 16.2% of respondents. For isolated tumor cells (ITCs) or micrometastases, 28.1% and 60.5% of
respondents, respectively, would perform inguinal lymph node dissection, whereas 19.3% and 23.8%,
respectively, would opt for radiation without further surgical intervention. Notably, 50.9% of respondents would not initiate any further therapy and 15.1% would opt for expectant management.
Conclusions: The majority of German hospitals implement the SN procedure. However, only 79.5%
of respondents performed ultrastaging and only 28.1% were aware that ITC may affect survival in
vulvar cancer. There is a need to ensure that the management of vulvar cancer follows the latest
recommendations and clinical evidence. Deviations from state-of-the-art management should only
be after a detailed discussion with the concerned patient
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