Πέμπτη 7 Ιανουαρίου 2021

Closure of Gastrointestinal Fistulas and Leaks with the Over-the-Scope Clip: Case-Series Analysis

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Abstract

Over-the-scope clip (OTSC) is widely used in clinics for the treatment of iatrogenic perforations and fistulas and for hemostasis. The aim of this study was to retrospectively evaluate cases applied with the over-the-scope clip for gastrointestinal fistula or leakage. The study included patients on whom over-the-scope clip was performed because of leakage or fistula in the gastroenterology surgery endoscopy unit between June 2016 and January 2020. The cases were evaluated in terms of age, gender, diagnosis, localization of the defect, additional disease, size of the defect, procedure success, clinical success, number of clips, time of over-the-scope-clip application after the first procedure and duration of follow-up. In 9 patients, 11 over-the-scope clips were used. The procedure was performed in the upper gastrointestinal tract in 5 (55.56%) cases and in the lower gastrointestinal tract in 4 (44.44%) cases. Technical success was achieved in all 11 procedures pe rformed in 9 cases. Long-term clinical success was achieved in 8 of 9 cases. The over-the-scope clip is an endoscopic method that can be used safely in the treatment of gastrointestinal fistulas and leakage of < 1 cm with a low possibility of morbidity and a high success rate.

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Trans-pulmonary closure of an aorto-pulmonary window in a patient of tetralogy of Fallot: a case report

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Abstract

We present a case of tetralogy of Fallot (TOF) accompanied by a type II aorto-pulmonary window with severe pulmonary arterial hypertension in a pediatric patient. A successful repair of tetralogy of Fallot with trans-pulmonary patch closure of aorto-pulmonary window was done.

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Increasing role of cardiac surgeons in managing cardiac perforations during ever-expanding percutaneous interventions: a mini-review

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Abstract

Iatrogenic cardiac injury is a catastrophic event and its management should be emergent. Cardiac surgeons need to be aware of basics related to the catheter-based intervention techniques and their outcomes. This mini-review discusses cardiac perforations and role of surgical team during catheter-based interventions.

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Modulation of TNFR 1-triggered two opposing signals for inflammation and apoptosis via RIPK 1 disruption by geldanamycin in rheumatoid arthritis

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Abstract

Objectives

To evaluate the ability of geldanamycin to modulate two opposing TNFα/TNFR1-triggered signals for inflammation and cell death.

Methods

The effects of geldanamycin on TNFα-induced proinflammatory cytokine production, apoptosis, NF-κB activation, caspase activation, and necroptosis in a human rheumatoid synovial cell line (MH7A) were evaluated via ELISA/qPCR, flow cytometry, dual-luciferase reporter assay, and western blotting assay, respectively. In addition, therapeutic effects on murine collagen-induced arthritis (CIA) were also evaluated.

Results

Geldanamycin disrupted RIPK1 in MH7A, thereby inhibiting TNFα-induced proinflammatory cytokine production and enhancing apoptosis. TNFα-induced NF-κB and MLKL activation was inhibited, whereas caspase 8 activation was enhanced. Recombinant RIPK1 restored the geldanamycin-mediated inhibition of TNFα-induced NF-κB activation. In addition, GM showed more clinical effectiveness than a conventional biologic TNF inhibitor, etanercept, in murine CIA and significantly attenuated synovial hyperplasia, a histopathological hallmark of RA.

Conclusions

GM disrupts RIPK1 and selectively inhibits the TNFR1-triggered NF-κB activation signaling pathway, while enhancing the apoptosis signaling pathway upon TNFα stimulation, thereby redressing the balance between these two opposing signals in a human rheumatoid synovial cell line. Therapeutic targeting RIPK1 may be a novel concept which involves TNF inhibitor acting as a TNFR1-signal modulator and have great potential for a more fundamental, effective, and safer TNF inhibitor.

Key Points
• Geldanamycin (GM) disrupts RIPK1 and selectively inhibits the TNFR1-triggered NF-κB activation signaling pathway while enhancing the apoptosis signaling pathway upon TNFα stimulation, thereby redressing the balance between these two opposing signals in a human rheumatoid synovial cell line, MH7A.
• GM showed more clinical effectiveness than a conventional biologic TNF-inhibitor, etanercept, in murine collagen-induced arthritis (CIA), and significantly attenuated synovial hyperplasia, a histopathological hallmark of RA.
• Therapeutic targeting RIPK1 may be a novel concept which involves TNF inhibitor acting as a TNFR1-signal modulator and have great potential for a more fundamental, effective, and safer TNF-inhibitor.
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Relationship between clinicopathologic factors and FDG avidity in radioiodine-negative recurrent or metastatic differentiated thyroid carcinoma

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Abstract

Background

In this study, we investigated the relationship between clinicopathologic factors, BRAFV600E mutation status and [18F] F-fluoro-2-deoxyglucose (FDG) avidity in patients with radioiodine (RAI)-negative recurrent or metastatic differentiated thyroid cancer (DTC).

Methods

From 2015 to 2018 all patients with suspected recurrent or metastatic radioiodine-negative DTC patients who underwent FDG positron emission tomography/computed tomography (PET/CT) were retrospectively reviewed. Suspected lesions on FDG PET/CT were biopsied and underwent BRAFV600E mutation testing by immunohistochemistry and real-time PCR. Tumor size, recurrent versus metastatic disease, histopathologic features including classical type versus aggressive subtypes (poorly differentiated, tall cell, columnar cell, hobnail variants) and BRAFV600E mutation status were correlated with the SUVmax of highest hypermetabolic lesions on FDG PET/CT by the univariate analysis using logistic regression.

Results

Sixty-three consecutive patients, 55 (87.3%) female, with median age of 48 (range 17–81) were included. The majority of patients had BRAFV600E mutation and classical subtype, 55/63 (87.3%) and 45/63(71.4%), respectively. Thyroglobulin at the time of suspected recurrence was 262.7 ng/ml (range 16.3–1000) and patients received a median 3 prior RAI treatments. Fifty-four patients (85.7%) had local recurrence. The majority of patients 58/63 (92.1%) had FDG-avid disease on PET/CT. On univariate analysis, tumor size aggressive histopathologic types and distant metastasis are the significant factors for predicting FDG uptake, p = 0.04, p = 0.001 and p = 0.004 respectively. Although FDG uptake of BRAFV600E bearing recurrent/metastatic RAIR DTC lesions was higher than those without the mutation, the difference did not reach statistical significance, SUVmax of 7.11 versus 4.91, respectively, p� ��= 0.2.

Conclusion

The majority of recurrent or metastatic RAI-negative DTC have BRAFV600E mutation and detectable disease on FDG PET/CT. FDG avidity of the recurrent or metastatic RAI-negative DTC is independently associated with the aggressive histopathologic features.

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SH2 domain-containing protein tyrosine phosphatase-2 (SHP-2) prevents cardiac remodeling after myocardial infarction through ERK/SMAD signaling pathway

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Abstract

In this study, we aimed to investigate the role of SH2 domain-containing protein tyrosine phosphatase-2 (SHP-2) in cardiac remodeling after myocardial infarction (MI) and explore the underlying molecular mechanism. MI model was established by ligation of the left anterior descending coronary artery. C57/BL6J mice were randomly administered with 3.0 mg/kg/day PHPS1 (PHPS1-treated group) or normal saline (model group) by intraperitoneal injection. After 4 weeks of infusion, the effects of PHPS1 on cardiac remodeling were evaluated. Echocardiography results showed that PHPS1 treatment aggravated the MI-induced deterioration of cardiac function, with worse cardiac function parameters. PHPS1 treatment significantly increased the infarcted area, as well as the fibrotic area and the expression of collagen I and collagen III. Western blots and immunofluorescence staining showed that PHPS1 treatment up-regulated the expression of p-GRK2, p-SMAD2/3 and p-ERK1/2, while U0126 reversed the effect of PHPS1. The present study indicated that PHPS1 treatment contributed to myocardial fibrosis and infarction by activating ERK/SMAD signaling pathway, suggesting that SHP-2 may be a promising treatment target for cardiac remodeling after MI.

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Effective clearance of uremic toxins using functionalised silicon Nanoporous membranes

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Abstract

In-house fabricated silicon nanoporous membranes (SNMs), functionalized for efficient clearance of uremic toxins, can lead to compact and portable dialysis systems. Efficacy of 15 nm thick SNMs, with average pore diameter of 8 nm, was tested for dialysis of two uremic toxins - urea and creatinine using custom made teflon apparatus of 2, 10 and 30 ml. The apparatus consisted of two reservoirs, with the cis containing the uremic fluid, and the trans containing the dialysate. Peristalsis was found to enhance the clearance rate by a factor of four as compared to unstirred condition. Functionalisation of the SNMs reduced protein binding, and surface binding of urea from 23% to negligible values. A lateral array of nine SNMs and a new design for the dialysis apparatus, increased the clearance rate by a factor of twelve from that of the single SNM. The arrays cleared about 42% of urea and 48% of creatinine from 30 ml of diluted se rum samples, in 15 min. Periodic replacement of the trans fluid cleared about 81% of high concentration uremic toxins from the cis reservoir in 45 mins. The SNM arrays are stable, reproducible, and with the superior clearance rates for urea and creatinine, they have the potential to be used as membranes for portable hemodialysers.

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Therapeutic approach for global myocardial injury using bone marrow-derived mesenchymal stem cells by cardiac support device in rats

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Abstract

Bone marrow-derived mesenchymal stem cells (BMSCs) have been considered a promising therapeutic approach to cardiovascular disease. This study intends to compare the effect of BMSCs through a standard active cardiac support device (ASD) and intravenous injection on global myocardial injury induced by isoproterenol. BMSCs were cultured in vitro, and the transplanted cells were labeled with a fluorescent dye CM-Dil. Isoproterenol (ISO) was injected into the rats; 2 weeks later, the labeled cells were transplanted into ISO-induced heart-jury rats through the tail vein or ASD device for 5 days. The rats were sacrificed on the first day, the third day, and the fifth day after transplantation to observe the distribution of cells in the myocardium by fluorescence microscopy. The hemodynamic indexes of the left ventricle were measured before sacrificing. H&E staining and Masson's trichrome staining were used to evaluate the cardiac histopatholo gy. In the ASD groups, after 3 days of transplantation, there were a large number of BMSCs on the epicardial surface, and after 5 days of transplantation, BMSCs were widely distributed in the ventricular muscle. But in the intravenous injection group, there were no labeled-BMSCs distributed. In the ASD + BMSCs-three days treated group and ASD + BMSCs -five days-treated group, left ventricular systolic pressure (LVSP), the maximum rate of left ventricular pressure rise (+dP/dt), the maximum rate of left ventricular pressure decline (-dP/dt) increased compared with model group and intravenous injection group (P < 0.05). By giving BMSCs through ASD device, cells can rapidly and widely distribute in the myocardium and significantly improve heart function.

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The clinical efficacy and safety of single-agent pembrolizumab in patients with recurrent granulosa cell tumors of the ovary: a case series from a phase II basket trial

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Summary

Background Treatment of recurrent, unresectable granulosa cell tumor (GCT) of the ovary can be challenging. Given the rarity of the tumor, alternative therapies have been difficult to evaluate in large prospective clinical trials. Currently, to our knowledge, there are no reports of the use of immune checkpoint inhibitors in GCT patients. Here, we present a case series of GCT patients treated with pembrolizumab who were enrolled in a phase II basket trial in advanced, rare solid tumors (ClinicalTrials.gov: NCT02721732). Cases We identified 5 patients with recurrent GCT (4 adult and 1 juvenile type); they had an extensive history of systemic therapy at study enrollment (range, 3–10), with most regimens resulting in less than 12 months of disease control. Pembrolizumab was administered in these patients, as per trial protocol. Although there were no objective responses according to the irRECIST guidelines, 2 patients with adult-type GCT exp erienced disease control for ≥ 12 months (565 and 453 days). In one, pembrolizumab represented the longest duration of disease control compared to prior lines of systemic therapy (565 days vs. 13 months). In the other, pembrolizumab was the second longest systemic therapy associated with disease control (453 days vs. 22 months) compared to prior lines of therapy. In this patient, pembrolizumab was discontinued following withdrawal of consent. PD-L1 expression was not observed in any baseline tumor samples. Pembrolizumab was well tolerated, with no grade 3 or 4 treatment-related adverse events. Conclusions Although our results do not support the routine use of pembrolizumab monotherapy in unselected GCT patients, some patients with adult-type GCT may derive a clinical benefit, with a low risk of toxicity. Future studies should investigate the role of immunotherapy and predictors of clinical benefit in this patient population.

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Mesenteric Venous Thrombosis Due to Coronavirus

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Lymphatic filariasis

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Abstract

Lymphatic filariasis (LF) is an important neglected parasitic disease according to the World Health Organization. In this study, we aimed to determine the prevalence of human LF in Asia using a systematic review and meta-analysis approach. Records from 1990 to 2018 in reputable databases including PubMed, Science Direct, Embase, and Cochrane Library were searched using a panel of related keywords. All 48 countries of Asia were searched one by one in combination with the keywords. In all, 41,742 cases identified in this study were included in the analysis. According to our findings, the pooled prevalence of LF in Asia was estimated at 3% (95% CI: [1.7, 5.2]). There was no major trend in the cumulative prevalence of LF over time. Some countries in Asia including China, Japan, Vietnam, and South Korea succeeded in eliminating LF as a public health problem, but others still need to monitor the disease. Based on the initiative of the WHO starting in 2000, some co untries in Asia succeeded in eliminating LF as a public health problem. Other countries have taken steps to eliminate the disease with variable degrees of success. These efforts might be affected by issues such as climate change.

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Regulation of human THP-1 macrophage polarization by Trichinella spiralis

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Abstract

Trichinella spiralis is a foodborne zoonotic nematode, which causes trichinellosis. During the infection, parasite evades the host immune responses by direct and indirect (through excretory-secretory products) contact with host immune cells. One of the main targets for immunomodulation induced by helminths are macrophages. In this study, we examined whether direct contact of different stages of T. spiralis can affect the polarization of human THP-1 macrophages. Co-culture of adult parasite stage and cells in direct contact without LPS addition had a significant impact on TNFα levels. Interestingly, in settings with the addition of LPS, the levels of IL-1β and TNFα significantly increased in adult parasite and newborn larvae (NBL) but not for muscle larvae (ML). While we tested muscle larvae ESP products to compare its effect with whole ML parasite, we detect an increase of pro-inflammatory cytokines like IL-1β and TNFα in no LPS conditions. Whereas, muscle larvae ESP significantly suppressed the inflammatory response measured by IL-1β, TNFα, and IL-6 levels and anti-inflammatory IL-10 compared to LPS control. Our findings indicate the anti-inflammatory potential of T. spiralis muscle larvae excretory-secretory products and propose signaling pathways which might be engaged in the mechanism of how muscle larvae ESP affect human macrophages.

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