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constructs) may provide clarity for 'non-experts', enabling mainstream use of theory-driven approaches in intervention development.

Powered transvenous lead extraction (TLE) tools are commonly required to remove the leads with long implant duration due to fibrotic adhesions. However, comparative data are lacking among different types of TLE tools.

To compare the efficacy and safety of two different rotational mechanical dilator sheaths in retrospectively analyzed patients who underwent TLE.

A total of 566 lead extractions from 302 patients using TightRail™(333 lead extractions from 169 patients) and Evolution

(233 lead extractions from 133 patients) mechanical dilator sheaths were performed between July 2009 and June 2018. Acute and long-term outcomes of study groups were compared. There is no statistically significant difference between Evolution

and TightRail™ groups in procedural success (93.9% vs. 94%), clinical success (99.2% vs. 98%), and major complications (3.8% vs. 1.2%), respectively (p > .05). In multivariate regression analysis, lead dwell time, the number of extracted leads, and baseline leukocyte count were found as independent predictors of procedural success (p < .05). During the median follow-up of 36.6 (0.2-118) months, all-cause mortality was observed in 73 patients (25.6% in the Evolution

vs. 23.1 in the TightRail™group, p > .05). Chronic renal disease, heart failure, and coagulopathy were shown as independent predictors of all-cause mortality in multivariate regression analysis (p < .05).

TLE using TightRail™or Evoluation

mechanical dilator sheaths was a safe and effective therapeutic option. Both mechanical dilator sheaths showed similar efficacy, safety, and all-cause mortality at acute and long-term follow-up of patients who underwent TLE.

TLE using TightRail™ or Evoluation® mechanical dilator sheaths was a safe and effective therapeutic option. Both mechanical dilator sheaths showed similar efficacy, safety, and all-cause mortality at acute and long-term follow-up of patients who underwent TLE.Coronavirus disease-2019 (COVID-19), which emerged in late 2019 and caused a pandemic, has significantly affected outpatient admissions to dermatology outpatient clinics. There have been changes in the number and composition of the patients who applied to the outpatient clinics. The dermatology outpatient clinic applications have dramatically decreased due to restrictions and prohibitions, and active participation of dermatologists in the field immediately after the pandemic. The composition of the diagnoses has also altered for reasons such as excessive use of hygiene products and types of protective equipment usage related to COVID-19. Intensive precautions have been taken in the first 3 months of the pandemic (March, April, and May). As of 12 May, controlled socialization started with new regulations. This period has been called "the normalization process." This study aims to evaluate the changes of the patients admitted to dermatology outpatient clinics within the normalization process. Despite the increasing number of COVID-19 patients and related deaths in the whole country with the new normal, the admissions to dermatology outpatient clinics have increased. During this period, acne and related diseases, pigmentation disorders, and viral skin infections had increased; dermatoses, xerosis cutis, and superficial fungal infections had reduced. It seems that nonurgent dermatological complaints affect the quality of life of patients and cause the need for an application. Although restrictions reduce these numbers, measures should be taken to protect patients and society during the ongoing pandemic.

Radiofrequency ablation (RFA) is an effective treatment modality for atrial fibrillation (AF); however, serious complications can occur. We present the case of a highly morbid consequence, the esophagopericardial fistula (EPF).

A hemodynamically unstable patient with a history of AF and recent RFA presented with chest pain and was found to have pneumopericardium and pericardial effusion. The patient went to the operating room emergently for combined management with surgical pericardial window and endoscopic stent placement.

EPF must be on the differential diagnosis while evaluating patients who develop constitutional symptoms or sudden onset chest pain days or weeks after catheter ablation for AF. Early detection followed by aggressive management with a combined surgical and endoscopic approach may be considered for successful treatment of this type of postablation esophageal perforation if an atrioesophageal fistula is effectively ruled out.

EPF must be on the differential diagnosis while evaluating patients who develop constitutional symptoms or sudden onset chest pain days or weeks after catheter ablation for AF. Early detection followed by aggressive management with a combined surgical and endoscopic approach may be considered for successful treatment of this type of postablation esophageal perforation if an atrioesophageal fistula is effectively ruled out.Multiple sclerosis (MS) is a common degenerative disorder of the central nervous system. The decreased frequency and dysfunction of Treg cells cause inflammation and disease progression. Ozone autohemotherapy can be used as a potential therapeutic approach to regulate the immune system responses and inflammation in MS. For this purpose, 20 relapsing-remitting multiple sclerosis patients were under treatment with ozone twice weekly for 6 months. The frequency of Treg cell, the expression levels of the Treg cell-related factors (FoxP3, IL-10, TGF-β, miR-17, miR-27, and miR-146A), and the secretion levels of IL-10 and TGF-β were assessed. We found a significant increase in the number of Treg cells, expression levels of FoxP3, miRNAs (miR-17 and miR-27), IL-10, and TGF-β factors in patients after oxygen-ozone (O2 -O3 ) therapy compared to before treatment. In contrast, oxygen-ozone therapy notably decreased the expression level of miR-146a in treated patients. Interestingly, the secretion levels of both IL-10 and TGF-β cytokines were considerably increased in both serum and supernatant of cultured peripheral blood mononuclear cells in posttreatment condition compared to pretreatment condition. According to results, oxygen-ozone therapy raised the frequency of Treg cell and its relevant factors in treated MS patients. Oxygen-ozone therapy would contribute to improving the MS patients by elevating the Treg cell responses.Radiotherapy is a leading treatment for various types of cancer. However, exposure to high-dose ionizing radiation causes acute gastrointestinal injury and gastrointestinal syndrome. This has significant implications for human health, and therefore, radioprotection is a major area of research. Radiation induces the loss of intestinal stem cells; hence, the protection of stem cells expressing LGR5 (a marker of intestinal epithelial stem cells) is a key strategy for the prevention of radiation-induced injury. In this study, we identified valproic acid (VPA) as a potent radioprotector using an intestinal organoid culture system. VPA treatment increased the number of LGR5+ stem cells and organoid regeneration after irradiation. N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT, an inhibitor of NOTCH signaling) blocked the radioprotective effects of VPA, indicating that NOTCH signaling is a likely mechanism underlying the observed effects of VPA. In addition, VPA acted as a radiosensitizer via the inhibition of histone deacetylase (HDAC) in a colorectal cancer organoid. These results demonstrate that VPA exerts strong protective effects on LGR5+ stem cells via NOTCH signaling and that the inhibition of NOTCH signaling reduces these protective effects, providing a basis for the improved management of radiation injury.

Treatment of early rectal cancer (ERC) is undergoing a revolution towards rectum preservation. Adjuvant and neoadjuvant therapy alongside local excision (LE) means that organ preservation is a real possibility for most patients and a viable alternative for frailer patients. This study presents our 12-year experience as a specialist regional ERC unit, evolving towards organ preservation.

Data were collected prospectively between 2006 and 2018 for all patients referred to the regional ERC multidisciplinary team with suspected or confirmed ERC. Patients considered suitable for LE, or those declining radical surgery, were offered LE or neoadjuvant short-course radiotherapy (SCRT), delay and LE with subsequent rescue surgery or contact brachytherapy for unfavourable histopathology.

In all, 102 patients underwent LE. Ten patients were excluded (N=92). 45 patients underwent LE directly and 47 patients received SCRT and LE. After SCRT and LE, a pathological complete response was achieved in 44.7%. This approach also resulted in a lower rate of lymphovascular invasion (22.2% vs. 6.4%), fewer distant recurrences (4.4% vs. Pyrrolidinedithiocarbamate ammonium concentration 0%) and a better disease-specific mortality (11.1% vs. 0%) (P<0.05). Although statistically insignificant, fewer patients required rescue surgery after SCRT (15.6% vs. 4.3%).

Organ preservation with a good oncological outcome is better achieved by neoadjuvant radiotherapy, delay and LE. To achieve this, careful patient selection, thorough preoperative investigation, experienced surgical technique and a deep appreciation of tumour biology managed via a dedicated ERC network is paramount.

Organ preservation with a good oncological outcome is better achieved by neoadjuvant radiotherapy, delay and LE. To achieve this, careful patient selection, thorough preoperative investigation, experienced surgical technique and a deep appreciation of tumour biology managed via a dedicated ERC network is paramount.Endometriosis is an inflammation-dependent disease that shares similarities with malignant tumors including attachment and infiltration. Tripartite motif-containing 24 (TRIM24) has been illustrated in inflammatory responses and gynecological tumors, and Nod-like receptor protein 3 (NLRP3) inflammasome has been implicated in endometriosis. However, the involvement of TRIM24 and the role of NLRP3/caspase-1/interleukin-1β (IL-1β)-mediated pyroptosis in endometriosis remain obscure. In this study, we originally detected the decreased expression of TRIM24 in the ectopic endometrium of endometriosis compared with the normal endometrium. Then we measured the promoted protein expression of pyroptotic biomarkers (NLRP3, procaspase-1, caspase-1, pro-IL-1β, and IL-1β) using Western blot analysis and the stimulated secretion of IL-1β and IL-18 by enzyme-linked immunosorbent assay in ectopic human endometrial stromal cells (hESC) compared with normal hESC. TRIM24-small-interfering RNA (siTRIM24) was used to silence TRIM24, whereas TRIM24-pcDNA3.1 was used for overexpressing TRIM24. The migration of hESC was determined by a Transwell migration assay. Coimmunoprecipitation and ubiquitination analyses were conducted to explore the interaction between TRIM24 and NLRP3. Subsequently, we found that TRIM24 negatively regulated NLRP3/caspase-1/IL-1β-mediated pyroptosis and cell migration of hESC, and CY-09, the specific inhibitor of NLRP3, could reverse the promoted pyroptosis and cell migration induced by siTRIM24. Furthermore, TRIM24 interacted with NLRP3 and the upregulation of TRIM24 facilitated the ubiquitination of NLRP3 in ectopic hESC. Our findings suggest that TRIM24 may participate in the progression of endometriosis through the NLRP3/caspase-1/IL-1β-mediated pyroptotic pathway via ubiquitination of NLRP3, which reveals the significant molecular mechanism underlying endometriosis.

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