237 research outputs found
Pulmonary diffusing capacity disturbances are related to nailfold capillary changes in patients with Raynaud's phenomenon with and without an underlying connective tissue disease
PURPOSE: The aim of this study was to evaluate whether pulmonary microvascular damage is part of a more generalized involvement of the microvasculature in the spectrum of scleroderma (Scl)-like syndromes. PATIENTS AND METHODS: We studied four groups of patients, all with Raynaud's phenomenon (RP), distinguished by the extent and nature of their underlying connective tissue disease. Twenty-two patients had primary RP (pRP), another 22 patients had RP and an undifferentiated connective tissue disease (uCTD), 15 patients had Scl, and eight patients had the CREST syndrome (CREST). Pulmonary vascular damage in these groups was assessed by measuring the pulmonary diffusing capacity (T1,CO) and its components: the diffusing capacity of the alveolocapillary membrane (Dm) and the pulmonary capillary blood volume (Vc). Results were compared with morphologic abnormalities of the nailfold capillaries, as determined by nailfold capillary microscopy, and related to the presence of antinuclear antibodies. RESULTS: Vc was below normal in 38% and 43% of patients with pRP and uCTD, respectively (versus 52% in patients with Scl or CREST combined). In contrast, Dm was below normal in only 5% and 26% of patients with pRP and uCTD, respectively (versus 61% in patients with Scl or CREST combined). In patients with Scl and CREST, Dm was significantly decreased as compared with the former groups (p less than 0.01). Dm was also the pulmonary function parameter that correlated most strongly with both nailfold capillary abnormalities and the presence of antinuclear antibodies, whereas Vc did not. CONCLUSION: Early pulmonary involvement in Scl syndromes is functionally characterized by a lowered Dm, correlating with morphologic changes of the nailfold capillaries. Decreased Vc is probably a reflection of RP of the pulmonary vasculature
Wnt3a Protein Reduces Growth Factor-Driven Expansion of Human Hematopoietic Stem and Progenitor Cells in Serum-Free Cultures
Definition of large bowel obstruction by primary colorectal cancer:A systematic review
Aim: Controversies on therapeutic strategy for large bowel obstruction by primary colorectal cancer mainly concern acute conditions, being essentially different from subacute obstruction. Clearly defining acute obstruction is important for design and interpretation of studies as well as for guidelines and daily practice. This systematic review aimed to evaluate definitions of obstruction by colorectal cancer in prospective studies. Method: A systematic search was performed in PubMed, Embase and the Cochrane Library. Eligibility criteria included randomized or prospective observational design, publication between 2000 and 2019, and the inclusion of patients with an obstruction caused by colorectal cancer. Provided definitions of obstruction were extracted with assessment of common elements. Results: A total of 16 randomized controlled trials (RCTs) and 99 prospective observational studies were included. Obstruction was specified as acute in 28 studies, complete/emergency in five, (sub)acute or similar terms in four and unspecified in 78. Five of 16 RCTs (31%) and 37 of 99 cohort studies (37%) provided a definition. The definitions included any combination of clinical symptoms, physical signs, endoscopic features and radiological imaging findings in 25 studies. The definition was only based on clinical symptoms in 11 and radiological imaging in six studies. Definitions included a radiological component in 100% of evaluable RCTs (5/5) vs. 54% of prospective observational studies (20/37, P = 0.07). Conclusion: In this systematic review, the majority of prospective studies did not define obstruction by colorectal cancer and its urgency, whereas provided definitions varied hugely. Radiological confirmation seems to be an essential component in defining acute obstruction
Wnt3a protein reduces growth factor-driven expansion of human hematopoietic stem and progenitor cells in serum-free cultures
Abstract
Ex vivo expansion of hematopoietic stem and progenitor cells (HSPC) is a promising approach
to improve insufficient engraftment after umbilical cord blood stem cell transplantation
(UCB-SCT). Although culturing HSPC with hematopoietic cytokines results in robust
proliferation, it is accompanied with extensive differentiation and loss of self-renewal capacity.
Wnt signaling has been implicated in regulating HSPC fate decisions in vivo and in promoting
HSPC self-renewal by inhibition of differentiation, but the effects of Wnt on the ex
vivo expansion of HSPC are controversial. Here, we demonstrate that exogenous Wnt3a
protein suppresses rather than promotes the expansion of UCB-derived CD34+ cells in
serum free expansion cultures. The reduced expansion was also observed in cultures initiated
with LinCD34+
CD38lowCD45RACD90+
cells which are highly enriched in HSC and
was also observed in response to activation of beta-catenin signaling by GSK3 inhibition.
The presence of Wnt3a protein during the culture reduced the frequency of multilineage
CFU-GEMM and the long-term repopulation ability of the expanded HSPC. These data suggest
that Wnt signaling reduces expansion of human HSPC in growth factor-driven expansion
cultures by promoting differentiation of HSPC
Determining sensitivity and specificity of HER2 testing in breast cancer using a tissue micro-array approach
INTRODUCTION: Overexpression of the human epidermal growth factor receptor 2 (HER2) as a result of HER2 gene amplification is associated with a relatively poor prognosis in breast cancer and is predictive of HER2-targeting therapy response. False-positive rates of up to 20% for HER2 testing have been described. HER2-testing laboratories are therefore encouraged to participate in external quality control schemes in order to improve HER2-testing standardization. METHODS: This study investigated the feasibility of retesting large numbers of invasive breast cancers for HER2 status on tissue micro-array (TMA) as part of a quality control scheme. For this assessment different HER2 testing methods were used including HER2 detecting antibodies SP3, 4B5, Herceptest and mono color silver in situ hybridization (SISH) and dual color SISH. Final HER2 status for each tumor on the TMA was compared to the local testing result for the same tumor. Discordances between these two results were investigated further by staining whole tumor sections. RESULTS: For this study, 1,210 invasive breast carcinomas of patients treated in six hospitals between 2006 and 2008 were evaluated. Results from the three immunohistochemistry (IHC) and two in situ hybridization (ISH) assays performed on the TMAs were compared. The final HER2 status on TMA was determined with SP3, 4B5 and mono color SISH. Concordance between local HER2 test results and TMA retesting was 98.0%. Discordant results between local and TMA retesting were found in 20 tumors (2.0%). False positive HER2 IHC results were identified in 13 (1.3%) tumors; false negative IHC results in seven (0.7%) tumors. CONCLUSIONS: Retesting large volumes of HER2 classified breast carcinomas was found to be feasible and can be reliably performed by staining TMAs with SP3, 4B5 and mono color SISH in combination with full-sized slides for discordant cases. The frequency of false-positive results was lower than previously reported in the literature. This method is now offered to other HER2-testing laboratories
Decompressing Stoma as Bridge to Elective Surgery is an Effective Strategy for Left-sided Obstructive Colon Cancer:A National, Propensity-score Matched Study
OBJECTIVE: The purpose of this population-based study was to compare decompressing stoma (DS) as bridge to surgery (BTS) with emergency resection (ER) for left-sided obstructive colon cancer (LSOCC) using propensity-score matching. SUMMARY BACKGROUND DATA: Recently, an increased use of DS as BTS for LSOCC has been observed in the Netherlands. Unfortunately, good quality comparative analyses with ER are scarce. METHODS: Patients diagnosed with nonlocally advanced LSOCC between 2009 and 2016 in 75 Dutch hospitals, who underwent DS or ER in the curative setting, were propensity-score matched in a 1:2 ratio. The primary outcome measure was 90-day mortality, and main secondary outcomes were 3-year overall survival and permanent stoma rate. RESULTS: Of 2048 eligible patients, 236 patients who underwent DS were matched with 472 patients undergoing ER. After DS, more laparoscopic resections were performed (56.8% vs 9.2%, P < 0.001) and more primary anastomoses were constructed (88.5% vs 40.7%, P < 0.001). DS resulted in significantly lower 90-day mortality compared to ER (1.7% vs 7.2%, P = 0.006), and this effect could be mainly attributed to the subgroup of patients over 70 years (3.5% vs 13.7%, P = 0.027). Patients treated with DS as BTS had better 3-year overall survival (79.4% vs 73.3%, hazard ratio 0.36, 95% confidence interval 0.20-0.65) and fewer permanent stomas (23.4% vs 42.4%, P < 0.001). CONCLUSIONS: In this nationwide propensity-score matched study, DS as a BTS for LSOCC was associated with lower 90-day mortality and better 3-year overall survival compared to ER, especially in patients over 70 years of age
Quality assessment of estrogen receptor and progesterone receptor testing in breast cancer using a tissue microarray-based approach
Assessing hormone receptor status is an essential part of the breast cancer diagnosis, as this biomarker greatly predicts response to hormonal treatment strategies. As such, hormone receptor testing laboratories are strongly encouraged to participate in external quality control schemes to achieve optimization of their immunohistochemical assays. Nine Dutch pathology departments provided tissue blocks containing invasive breast cancers which were all previously tested for estrogen receptor and/or progesterone receptor expression during routine practice. From these tissue blocks
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