Donor lymphocyte infusion leads to diversity of specific T cell responses and reduces regulatory T cell frequency in clinical responders

T cell responses against malignant cells play a major role in maintaining remission and prolonging overall survival in patients after allogeneic stem cell transplantation and donor lymphocyte infusion (DLI) due to graft-versus-leukemia effect. For better characterization of the T cell responses, we assessed frequency and diversity of leukemia-associated antigen (LAA)-specific cytotoxic T cells using ELISpot and pMHC multimer assays and analyzed the frequency of regulatory T cells (Treg) as well as cytokine profiles before/after DLI. The data were correlated to the clinical course of patients. Significantly more LAA-derived T cell epitopes (p = 0.02) were recognized in clinical responders (R) when compared to nonresponders (NR). In addition, pMHC multimer-based flow cytometry showed a significantly higher frequency of LAA-specific T cells in R versus NR. The frequency of Treg in R decreased significantly (p = 0.008) while keeping stable in NR. No differences in T cell subset analysis before/after DLI were revealed. Clinical responders were correlated to specific immune responses and all clinical responders showed an increase of specific immune responses after DLI. Cytokine assays using enzyme-linked immunosorbent assay showed a significant increase of IL-4 after DLI. Taken together, an increase of specific CTL responses against several LAA after DLI was detected. Moreover, this study suggests that enhanced LAA diversity in T cell responses as well as decreasing numbers of Treg contribute to clinical outcome of patients treated with DLI.     

A multidisciplinary evidence-based guideline for minimally invasive surgery: part 2—laparoscopic port instruments, trocar site closure, and electrosurgical techniques

Minimally invasive surgery (MIS) is practiced by different surgical disciplines applying similar basic techniques. In 2007, the Dutch Health Care inspectorate indicated the need for a guideline including multidisciplinary agreements for MIS aiming towards better patient care and safety. A multidisciplinary guideline development group was founded consisting of general surgeons, gynecologists, an anesthesiologist, and an urologist. All members were authorized by their scientific professional associations. Clinically important aspects were identified and discussed. The best available evidence on these aspects was gathered by systematic review. Recommendations for clinical practice were formulated based on the evidence and a consensus of expert opinion. The guideline was externally reviewed by members of the participating scientific associations and their feedback was integrated. Identified important topics were: laparoscopic entry techniques, intra-abdominal pressure, laparoscopic port instruments, electrosurgical techniques, prevention of trocar site herniation, patient positioning, anesthesiology, perioperative care, patient information, multidisciplinary user consultation, and complication registration. The text of each topic contains an introduction with an explanation of the problem and a summary of the current literature. The current available evidence on safety aspects in minimally invasive surgery is limited. Few conclusions could be deduced from evidence-based data. This underscores the need for larger studies with adequate design and methodology to define conclusions of importance. Above all, the development of this multidisciplinary guideline facilitated a rich discussion, which resulted in a very complete and implementable guideline. This is the second of three papers on the multidisciplinary guideline for minimally invasive surgery, in which we present our literature reviews, conclusions, and practical recommendations for the use of specific port instruments, port site closure, and electrosurgical and ultrasonic techniques.     

The effect of sleep positional therapy on nocturnal gastroesophageal reflux measured by esophageal pH-impedance monitoring

Background & Aims

The aim of the study was to evaluate the effect of an electronic positional therapy wearable device on nocturnal gastroesophageal reflux measured by pH-impedance reflux monitoring.

Methods

We performed a single-center, prospective, interventional study in 30 patients with nocturnal reflux symptoms and a nocturnal esophageal acid exposure time (AET) ≥1.5% measured off acid-suppressive medication by ambulatory pH-impedance reflux monitoring. Patients were treated with an electronic positional therapy wearable device for 2 weeks. The device vibrates in the right lateral decubitus position so it conditions patients to avoid that sleep position. After 2 weeks treatment, the pH-impedance study was repeated. Primary outcome was the change in nocturnal AET. Secondary outcomes include change in number of reflux episodes and reflux symptoms.

Results

Complete data were available for 27 patients (13 females, mean age 49.8 years). The median nocturnal AET decreased from 6.0% (IQR, 2.3–15.3) to 3.1% (0.1–10.8) after 2 weeks of treatment (p = 0.079). The number of reflux episodes was significantly reduced after 2 weeks of treatment (baseline: 8.0 (3.0–12.3) vs. end: 3.0 (1.0–8.0); p = 0.041). Treatment led to a statistically significant decrease in time spent in right lateral decubitus position (baseline: mean 36.9% ± 15.2% vs. end: 2.7% ± 8.2%; p = <0.001) and an increase in the left lateral decubitus position (baseline 29.2% ± 14.8% vs. end: 63.3% ± 21.9%; p = <0.001). Symptom improvement was reported by 70.4% of the patients.

Conclusions

Sleep positional therapy using an electronic wearable device promotes sleeping in the left lateral decubitus position and improves reflux parameters measured by pH-impedance reflux monitoring.     

A personalized app to improve quality of life of patients with a stoma: A protocol for a multicentre randomized controlled trial

Aim

Proper education, guidance and support is crucial before and following creation of a stoma. Patients with a stoma and their close relatives need to adapt to and cope with this new – and sometimes unforeseen – situation, which may result in insecurities and a variety of psychosocial problems. Self-efficacy is associated both with a reduction in psychosocial problems and with improved quality of life. The main objective of this study was to investigate whether self-reported quality of life of patients with a stoma can be enhanced by offering personalized and timed guidance, as well as peer contact, in a patient-centred mobile application.

Method

A multicentre, double-blind, randomized controlled trial will be conducted. Consented adults >18 years of age who will receive an ileostomy or colostomy and possess an eligible smartphone will be included. The intervention group will be given the full version of the application (containing personalized and timed guidance, such as operation-specific information and information on the associated care pathway) to install on their smartphone. In addition, the intervention group has access to a protected peer-support platform within the app. The control group will receive a restricted version of the application that contains only generic (non-personalized) stoma-related information. The primary outcome is quality of life, 3 months postoperatively. Secondary outcomes are Patient Reported Outcome Measures (PROMs), such as psychological adaption, as well as number of complications, re-admission and re-operation rates and the length of hospital stay.

Results

Patient enrolment began in March 2021. Data collection was not complete when this protocol was submitted.

Conclusion

We hypothesize that patients with a stoma who are supported by the intervention version of the app will report a significantly higher quality of life than patients with a stoma who are supported by the control version of the app (ie, are not offered personalized and timed guidance and information and do not have access to peer support in the app).     

Patient satisfaction with stoma care and their expectations on mobile apps for supportive care

Aim

Self-efficacy in stoma care is essential, as it reduces morbidity and psychosocial problems. Mobile applications (apps) may optimise patients' self-efficacy. This article investigates patients' satisfaction with stoma care, their attitudes towards a supporting app aiming to promote self-efficacy and evaluate which functionalities are desired.

Method

A survey was sent to members of the two stoma-related patient associations in the Netherlands. Associations between patient characteristics, satisfaction concerning received stoma care, and willingness to use an app were evaluated.

Results

The survey was completed by 1868 patients. Overall satisfaction was scored as 6.6, with shortfalls reported in the preoperative information provision, stoma site selection, and postoperative care. Patients of older age, who were unaware of getting a stoma, had an ileostomy, a low quality of life or psychosocial problems, were less satisfied. An app was expected to be of added value by 59.4% of the patients having a stoma for less than three years, compared to the significantly lower 43.8% expectation rate of the remaining study population (p < 0.001). Moreover, patients with a high frequency of physical or psychosocial problems expressed higher levels of interest.

Conclusion

Patients were only moderately satisfied with their received stoma care. A supportive app is most likely beneficial for patients who had a stoma for less than three years, were in an acute situation, and/or have stoma-related problems. Most patients prefer information via internet or on paper, although apps may offer additional benefits. It is important to acknowledge digital literacy and to council patients appropriately about the benefits and help them to use apps.     

Examining socioeconomic disparities in changes in adolescent mental health before and during different phases of the coronavirus disease 2019 pandemic

This study examined socioeconomic disparities in changes in adolescent mental health between fall 2019 (pre-COVID-19), spring 2020 (initial coronavirus disease 2019 (COVID-19) phase), and fall 2020 (prevailing COVID-19 phase). Using data from 1429 adolescents (M_age = 17.9) from tertiary vocational schools in the Netherlands with n = 386 participating in all three waves, linear and latent basis growth curve models were assessed and multigroup analyses conducted. Results showed a small but significant decrease in life satisfaction and small but significant increases in emotional problems, peer relationship problems, conduct problems, and hyperactivity-inattention problems. For emotional problems and peer relationship problems, increases between pre-COVID-19 and the initial COVID-19 phase were more pronounced than increases between the initial and prevailing COVID-19 phase. In contrast, linear decreases were found for life satisfaction and linear increases for conduct problems and hyperactivity-inattention problems over the course of the study. Mental health patterns were largely comparable for adolescents from families with varying socioeconomic status.     

The impact of resveratrol on skin wound healing,scarring, and aging

Resveratrol is a well-known antioxidant that harbours many health beneficial properties. Multiple studies associated the antioxidant, anti-inflammatory, and cell protective effects of resveratrol. These diverse effects of resveratrol are also potentially involved in cutaneous wound healing, scarring, and (photo-)aging of the skin. Hence, this review highlighted the most relevant studies involving resveratrol in wound healing, scarring, and photo-aging of the skin. A systematic review was performed and the database PubMed was searched for suitable publications. Only original articles in English that investigated the effects of resveratrol in wound healing, scarring, and (photo-)aging of the skin were analysed. The literature search yielded a total of 826 studies, but only 41 studies met the inclusion criteria. The included studies showed promising results that resveratrol might be a feasible treatment approach to support wound healing, counteract excessive scarring, and even prevent photo-aging of the skin. Resveratrol represents an interesting and promising novel therapy regime but to confirm resveratrol-associated effects, more evidence based in vitro and in vivo studies are needed.