Bile acid sequestrants in poor healing after endoscopic therapy of Barrett's esophagus.

BACKGROUND/AIMS: Endoscopic therapy for neoplastic Barrett's esophagus (BE) has become the standard of care over the past two decades. In clinical practice, we regularly encounter patients who fail to achieve complete squamous epithelialization of the esophagus. Although the therapeutic strategies in the individual stages of BE, dysplasia, and esophageal adenocarcinoma are well studied and largely standardized, the problem of inadequate healing after endoscopic therapy is only marginally considered. This study aimed to shed light on the variables influencing inadequate wound healing after endoscopic therapy and the effect of bile acid sequestrants (BAS) on healing. METHODS: Retrospective analysis of endoscopically treated neoplastic BE in a single referral center. RESULTS: In 12.1% out of 627 patients, insufficient healing was present 8 to 12 weeks after previous endoscopic therapy. The average follow-up duration was 38.8±18.4 months. Complete healing was achieved in 13 patients already after intensifying proton pump inhibitor therapy. Out of 48 patients under BAS, 29 patients (60.4%) showed complete healing. An additional eight patients (16.7%) improved, but only partial healing was achieved. Eleven (22.9%) patients showed no response to BAS augmented therapy. CONCLUSION: In cases of insufficient healing even under exhaustion of proton pump inhibitors, treatment with BAS can be an option as an ultimate healing attempt.

Ultrahypofractionated Low-Dose Total Skin Electron Beam in Advanced-Stage Mycosis Fungoides and Sézary Syndrome.

PURPOSE: The aim of this study was to assess the safety and efficacy of an ultrahypofractionated low-dose total skin electron beam therapy (TSEBT) regimen in patients with advanced mycosis fungoides (MF) or Sézary syndrome (SS). METHODS AND MATERIALS: In this multicenter observational study from 5 German centers, 18 total patients with MF or SS underwent TSEBT with a total dose of 8 Gy in 2 fractions. The primary endpoint was the overall response rate. RESULTS: Fifteen of 18 patients with stage IIB-IV MF or SS were heavily pretreated with a median of 4 prior systemic therapies. The overall response rate was 88.9% (95% confidence interval [CI], 65.3-98.6), with 3 complete responses (16.9%; 95% CI, 3.6-41.4). At a median follow-up period of 13 months, the median time to next treatment (TTNT) was 12 months (95% CI, 8.2-15.8), and the median progression-free survival was 8 months (95% CI, 2-14). A significant reduction in the modified severity-weighted assessment tool, total Skindex-29 score (Bonferroni-corrected P < .005), and all subdomains (Bonferroni-corrected P < .05) was observed after TSEBT. Half of the irradiated patients (n = 9) developed grade 2 acute and subacute toxicities. One patient had confirmed grade 3 acute toxicity. Chronic grade 1 toxicity has been observed in 33% of patients. Patients with erythroderma/SS or prior radiation therapy appear at higher risk of skin toxicities. CONCLUSIONS: TSEBT with 8 Gy in 2 fractions achieves good disease control and symptom palliation with acceptable toxicity, greater convenience, and fewer hospital visits.

[Thyroid disease during pregnancy]. / Schilddrüsenerkrankungen in der Schwangerschaft.

Thyroid disease is the second most endocrinopathy during pregnancy 1. Thyroid dysfunction affects 2-3 % of pregnant women 2. Early diagnosis and initiation of therapy are important due to the potential complications in both mother and fetus. This article provides an overview of current recommendations regarding thyroid diagnostics and constellations during pregnancy that require therapy.

Reducing Surgical Site Infection by Prophylactic Negative Pressure Wound Therapy in a Cohort of General Surgery Patients.

Background: Surgical site infection (SSI) is one of the leading complications in health care. Negative pressure wound therapy (NPWT) is meanwhile widely prophylactically used for preventing SSIs. For evaluating the results of the implantation of this technique, we used the Simon single-arm study design and examine whether NPWT has a prophylactic effect on reducing SSIs in a cohort of general surgery patients. Methods: This single-arm, two-stage study includes 81 elective general surgery patients and corresponds to the Simon's design. The sample size calculation was based on a reduction in the superficial SSI rate from 12 to 4% (power 80%, significance level 5%) using a NPWT system. In compliance with Simon's two-Stage design, the study required the recruitment of 34 patients in stage I and 47 patients in stage II. The two-stage design method would be discarded in case of a wound infection in 3 or more patients in stage I or 6 or more patients in stage II. Using the NPWT system in the operating room, a negative pressure wound dressing was applied post-operatively and removed after 7 days. According to the criteria of the Centres for Disease Control and Prevention (CDC), post-operative wound documentation followed on day 7 and 30. Results: In stage I, no SSI was apparent. In stage II, 3 patients had SSIs (CDC grade I). Conclusion: A prophylactic NPWT can significantly reduce the wound infection rate in elective general surgery.

Artificial intelligence-assisted staging in Barrett's carcinoma.

BACKGROUND: Artificial intelligence (AI) is increasingly being used to detect neoplasia and interpret endoscopic images. The T stage of Barrett's carcinoma is a major criterion for subsequent treatment decisions. Although endoscopic ultrasound is still the standard for preoperative staging, its value is debatable. Novel tools are required to assist with staging, to optimize results. This study aimed to investigate the accuracy of T stage of Barrett's carcinoma by an AI system based on endoscopic images. METHODS: 1020 images (minimum one per patient, maximum three) from 577 patients with Barrett's adenocarcinoma were used for training and internal validation of a convolutional neural network. In all, 821 images were selected to train the model and 199 images were used for validation. RESULTS: AI recognized Barrett's mucosa without neoplasia with an accuracy of 85 % (95 %CI 82.7-87.1). Mucosal cancer was identified with a sensitivity of 72 % (95 %CI 67.5-76.4), specificity of 64 % (95 %CI 60.0-68.4), and accuracy of 68 % (95 %CI 64.6-70.7). The sensitivity, specificity, and accuracy for early Barrett's neoplasia < T1b sm2 were 57 % (95 %CI 51.8-61.0), 77 % (95 %CI 72.3-80.2), and 67 % (95 %CI 63.4-69.5), respectively. More advanced stages (T3/T4) were diagnosed correctly with a sensitivity of 71 % (95 %CI 65.1-76.7) and specificity of 73 % (95 %CI 69.7-76.5). The overall accuracy was 73 % (95 %CI 69.6-75.5). CONCLUSIONS: The AI system identified esophageal cancer with high accuracy, suggesting its potential to assist endoscopists in clinical decision making.

Low-dose total skin electron beam therapy plus oral bexarotene maintenance therapy for cutaneous T-cell lymphoma.

BACKGROUND: Total skin electron beam therapy (TSEBT) combined with systemic therapy or maintenance treatment is a reasonable approach to enhance the remission rate and duration in mycosis fungoides (MF) and Sézary syndrome (SS). This study assesses the efficacy of oral bexarotene therapy after low-dose TSEBT for patients with MF and SS. METHODS: In this prospective observational study, we recruited MF/SS patients for treatment with low-dose total skin electron beam therapy (TSEBT) with or without bexarotene therapy to describe outcomes and toxicities. RESULTS: Forty-six subjects with MF or SS underwent TSEBT between 2016 and 2021 at our institute. Following TSEBT, 27 patients (59 %) received oral bexarotene treatment. The median follow-up was 13 months. The overall response rate (ORR) for the cohort was 85 %. The response rate was significantly higher with combined modality (CM) than TSEBT alone (96 % vs. 68 %, p = 0.03). Median progression-free survival (PFS) for the CM was 17 months versus five months following TSEBT alone (p = 0.001). One patient (4 %) in the retinoid group discontinued the bexarotene therapy because of adverse events. The administration of bexarotene therapy did not increase radiation-related toxicities. CONCLUSIONS: Response rate and progression-free survival might be improved with TSEBT in combination with oral bexarotene compared to TSEBT alone.

Graduated compression stockings in the prevention of postoperative pulmonary embolism. A propensity-matched retrospective case-control study of 24 273 patients.

INTRODUCTION: Recommendations for venous thromboembolism and deep venous thrombosis (DVT) prophylaxis using graduated compression stockings (GCS) is historically based and has been critically examined in current publications. Existing guidelines are inconclusive as to recommend the general use of GCS.Patients/Methods: 24 273 in-patients (general surgery and orthopedic patients) undergoing surgery between 2006 and 2016 were included in a retrospectively analysis from a single center. From January 2006 to January 2011 perioperative GCS was employed additionally to drug prophylaxis and from February 2011 to March 2016 patients received drug prophylaxis alone. According to german guidelines all patients received venous thromboembolism prophylaxis with weight-adapted LMWH. Risk stratification (low risk, moderate risk, high risk) was based on the guideline of the American College of Chest Physicians. Data analysis was performed before and after propensity matching (PM). The defined primary endpoint was the incidence of symptomatic or fatal pulmonary embolism (PE). A secondary endpoint was the incidence of deep venous thromboembolism (DVT). RESULTS: After risk stratification (low risk n = 16 483; moderate risk n = 4464; high risk n = 3326) a total of 24 273 patient were analyzed. Before to PM the relative risk for the occurrence of a PE or DVT was not increased by abstaining from GCS. After PM two groups of 11 312 patients each, one with and one without GCS application, were formed. When comparing the two groups, the relative risk (RR) for the occurrence of a pulmonary embolism was: Low Risk 0.99 [CI95% 0.998-1.000]; Moderate Risk 0.999 [CI95% 0.95-1.003]; High Risk 0.996 [CI95% 0.992-1.000] (p > 0.05). The incidence of PE in the total group LMWH alone was 0.1% (n = 16). In the total group using LMWH + GCS, the incidence was 0.3% (n = 29). RR after PM was 0.999 [CI95% 0.998-1.00]. CONCLUSION: In comparison to prior studies with only small numbers of patients our trial shows in a large group of patients with moderate and high risk developing VTE we can support the view that abstaining from GCS-use does not increase the incidence of symptomatic or fatal PE and symptomatic DVT.

Report of a Quality Improvement Program for Reducing Postoperative Complications by Using a Surgical Risk Calculator in a Cohort of General Surgery Patients.

PURPOSE: The study investigates whether postoperative complications in elective surgery can be reduced by using a risk calculator via raising the awareness of the surgeon in a preoperative briefing. Postoperative complications like wound infections or pneumonia result in a high burden for healthcare systems. Multiple quality improvement programs address this problem like the ACS NSQIP Surgical Risk Calculator® (SRC). METHODS: To determine whether the preoperative usage of the SRC could reduce inpatient postoperative complications, two groups of 832 patients each were compared using propensity score matching. The SRC was employed retrospectively in the period 2012/2013 in one group ("Retro") and prospectively in the other group ("Prosp") in the period 2014/2015. Actual inpatient postoperative complications were classified by SRC complication categories and compared with the Clavien-Dindo complication classification system (Dindo et al. in Ann Surg 240:205-213, 2004). RESULTS: Comparing SRC "serious complication" and SRC "any complication," a nonsignificant increase in the "Prosp"-group was apparent (serious complication: 6.6% vs. 8.5%, p = 0.164; any complication: 8.5% vs. 9.7%, p = 0.444). CONCLUSION: Use of the SRC neither reduces inpatient postoperative complications nor the severity of complications. The calculations of the SRC rely on a 30-day postoperative follow-up. Poor sensitivity and medium specificity of the SRC showed that the SRC could not make accurate predictions in a short follow-up time averaging 6 days. Alternatively, since the observed complication rate was low in our study, in an environment of already highly implemented risk management tools, reductions in complications are not easily achieved.

Comparison of PELDOR and RIDME for Distance Measurements between Nitroxides and Low-Spin Fe(III) Ions.

EPR-based nanometre distance measurements are becoming ever more important in structural biology. Usually the distance constraints are measured between two nitroxide spin labels. Yet, distance measurements between a metal center and spin labels enable, e.g., the localization of metal ions within the tertiary fold of biomolecules. Therefore, it is important to find methods that provide such distance information quickly, with high precision and reliability. In the present study, two methods, pulsed electron-electron double resonance (PELDOR) and relaxation-induced dipolar modulation enhancement (RIDME), are compared on the heme-containing and spin-labeled cytochrome P450cam. Special emphasis is put on the optimization of the dead-time free RIDME experiment and several ways of data analysis. It turned out that RIDME appears to be better suited for distance measurements involving metal ions like low-spin Fe(3+) than PELDOR.