BACKGROUND: Albumin administration is suggested in patients with sepsis and septic shock who have received large volumes of crystalloids. Given lack of firm evidence, clinical practice variation may exist. To address this, we investigated if patient characteristics or trial site were associated with albumin use in septic shock. METHODS: We conducted a post-hoc study of the CLASSIC international, randomised clinical trial of fluid volumes in septic shock. Associations between selected baseline variables and trial site with albumin use during ICU stay were assessed in Cox models considering death, ICU discharge, and loss-to-follow-up as competing events. Baseline variables were first assessed individually, adjusted for treatment allocation (restrictive vs. standard IV fluid), and then adjusted for allocation and the other baseline variables. Site was assessed in a model adjusted for allocation and baseline variables. RESULTS: We analysed 1541 of 1554 patients randomised in CLASSIC (99.2%). During ICU stay, 36.3% of patients in the restrictive-fluid group and 52.6% in the standard-fluid group received albumin. Gastrointestinal focus of infection and higher doses of norepinephrine were most strongly associated with albumin use (subgroup with highest quartile of norepinephrine doses, hazard ratio (HR) 2.58, 95% CI 1.89 to 3.53). HRs for associations between site and albumin use ranged from 0.11 (95% CI 0.05 to 0.26) to 1.70 (95% CI 1.06 to 2.74); test for overall effect of site: p < .001. CONCLUSIONS: In adults with septic shock, gastrointestinal focus of infection and higher doses of norepinephrine at baseline were associated with albumin use, which also varied substantially between sites.
- MeSH
- albuminy terapeutické užití MeSH
- dospělí MeSH
- lidé MeSH
- noradrenalin terapeutické užití MeSH
- sepse * farmakoterapie etiologie MeSH
- septický šok * farmakoterapie komplikace MeSH
- tekutinová terapie škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Large femoral defects after trauma, femoral non-unions, fractures complicated by osteomyelitis or defects after bone tumour resection present high burden and increased morbidity for patient and are challenging for reconstructive surgeons. Defects larger than 6 cm and smaller defects after failed spongioplasty are suitable for reconstruction using a free, eventually a pedicled vascularised bone flap. The free fibular flap is preferred but an iliac crest free flap or a pedicled medial femoral condyle flap can be also used. These vascularised flaps are ideal for bridging defects of long bones and can be also used as osteocutaneous or osteomuscular flaps for coverage of soft tissue defect if present. The patients and their families were informed that data will be submitted for publication and they gave their written informed consent prior to the submission. The study was approved by the institutional ethic committee. METHODS: We analysed a group of eight patients with large diaphyseal or distal metaphyseal femoral defects. A free fibular flap was used in six patients, a pedicled medial ipsilateral femoral condyle flap was used in two patients and a defect in one patient was reconstructed using an iliac crest free flap. RESULTS: All flaps healed completely in all patients and no fracture of the flap was detected during the study period. In one patient, a locking plate broke and was replaced by a compression plate. At the last check-up all patients were able to step on the reconstructed limb with full weight. DISCUSSION: Although our study comprises a heterogeneous group of cases, they all have been successfully treated by a similar technique, adapted in each case specifically to the needs of the patient. A major limitation parameter of reconstruction by a free vascularised flap is the size of bone defect needed to be reconstructed. In case of a bone defect longer than 6 cm and a concomitant soft tissue disruption, a vascularised double-barrel fibula is the preferred. CONCLUSION: Large femoral defects can be successfully reconstructed with good long-term results using suitable free or pedicled vascularised bone flaps, especially preferring the free fibular flap.
- MeSH
- chirurgické laloky * MeSH
- dospělí MeSH
- femur * chirurgie transplantace MeSH
- fibula transplantace chirurgie zranění MeSH
- fraktury femuru chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- retrospektivní studie MeSH
- senioři MeSH
- transplantace kostí * metody MeSH
- volné tkáňové laloky transplantace MeSH
- výsledek terapie MeSH
- zákroky plastické chirurgie * metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Breast cancer is the most frequently diagnosed cancer in women worldwide. Although dramatically increased survival rates of early diagnosed cases have been observed, late diagnosed patients and metastatic cancer may still be considered fatal. The present study's main focus was on cancer‐associated fibroblasts (CAFs) which is an active component of the tumor microenvironment (TME) regulating the breast cancer ecosystem. Transcriptomic profiling and analysis of CAFs isolated from breast cancer skin metastasis, cutaneous basal cell carcinoma, and squamous cell carcinoma unravelled major gene candidates such as IL6, VEGFA and MFGE8 that induced co‐expression of keratins‐8/‐14 in the EM‐G3 cell line derived from infiltrating ductal breast carcinoma. Western blot analysis of selected keratins (keratin‐8, ‐14, ‐18, ‐19) and epithelial‐mesenchymal transition‐associated markers (SLUG, SNAIL, ZEB1, E‐/N‐cadherin, vimentin) revealed specific responses pointing to certain heterogeneity of the studied CAF populations. Experimental in vitro treatment using neutralizing antibodies against IL-6, VEGF‐A and MFGE8 attenuated the modulatory effect of CAFs on EM‐G3 cells. The present study provided novel data in characterizing and understanding the interactions between CAFs and EM‐G3 cells in vitro. CAFs of different origins support the pro‐inflammatory microenvironment and influence the biology of breast cancer cells. This observation potentially holds significant interest for the development of novel, clinically relevant approaches targeting the TME in breast cancer. Furthermore, its implications extend beyond breast cancer and have the potential to impact a wide range of other cancer types.
- MeSH
- antigeny povrchové MeSH
- fibroblasty asociované s nádorem * metabolismus MeSH
- fibroblasty metabolismus MeSH
- keratiny genetika metabolismus MeSH
- lidé MeSH
- maligní melanom kůže MeSH
- MFC-7 buňky MeSH
- mléčné bílkoviny genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- nádorové mikroprostředí genetika MeSH
- nádory prsu * farmakoterapie genetika metabolismus MeSH
- prognóza MeSH
- transkriptom MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Ulcerative colitis (UC) with concomitant primary sclerosing cholangitis (PSC) represents a distinct disease entity (PSC-UC). Mayo endoscopic subscore (MES) is a standard tool for assessing disease activity in UC but its relevance in PSC-UC remains unclear. AIM: To assess the accuracy of MES in UC and PSC-UC patients, we performed histological scoring using Nancy histological index (NHI). METHODS: MES was assessed in 30 PSC-UC and 29 UC adult patients during endoscopy. NHI and inflammation were evaluated in biopsies from the cecum, rectum, and terminal ileum. In addition, perinuclear anti-neutrophil cytoplasmic antibodies, fecal calprotectin, body mass index, and other relevant clinical characteristics were collected. RESULTS: The median MES and NHI were similar for UC patients (MES grade 2 and NHI grade 2 in the rectum) but were different for PSC-UC patients (MES grade 0 and NHI grade 2 in the cecum). There was a correlation between MES and NHI for UC patients (Spearman's r = 0.40, P = 0.029) but not for PSC-UC patients. Histopathological examination revealed persistent microscopic inflammation in 88% of PSC-UC patients with MES grade 0 (46% of all PSC-UC patients). Moreover, MES overestimated the severity of active inflammation in an additional 11% of PSC-UC patients. CONCLUSION: MES insufficiently identifies microscopic inflammation in PSC-UC. This indicates that histological evaluation should become a routine procedure of the diagnostic and grading system in both PSC-UC and PSC.
- Publikační typ
- časopisecké články MeSH
Atmospheric new particle formation (NPF) is a naturally occurring phenomenon, during which high concentrations of sub-10 nm particles are created through gas to particle conversion. The NPF is observed in multiple environments around the world. Although it has observable influence onto annual total and ultrafine particle number concentrations (PNC and UFP, respectively), only limited epidemiological studies have investigated whether these particles are associated with adverse health effects. One plausible reason for this limitation may be related to the absence of NPF identifiers available in UFP and PNC data sets. Until recently, the regional NPF events were usually identified manually from particle number size distribution contour plots. Identification of NPF across multi-annual and multiple station data sets remained a tedious task. In this work, we introduce a regional NPF identifier, created using an automated, machine learning based algorithm. The regional NPF event tag was created for 65 measurement sites globally, covering the period from 1996 to 2023. The discussed data set can be used in future studies related to regional NPF.
- Publikační typ
- časopisecké články MeSH
