Autologous regulatory T cells in clinical intraportal allogenic pancreatic islet transplantation

Allogeneic islet transplantation in type 1 diabetes requires lifelong immunosuppression to prevent graft rejection. This medication can cause adverse effects and increases the susceptibility for infections and malignancies. Adoptive therapies with regulatory T cells (Tregs) have shown promise in reducing the need for immunosuppression in human transplantation settings but have previously not been evaluated in islet transplantation. In this study, five patients with type 1 diabetes undergoing intraportal allogeneic islet transplantation were co-infused with polyclonal autologous Tregs under a standard immunosuppressive regimen. Patients underwent leaukapheresis from which Tregs were purified by magnetic-activated cell sorting (MACS) and cryopreserved until transplantation. Dose ranges of 0.14–1.27 × 10⁶ T cells per kilo bodyweight were transplanted. No negative effects were seen related to the Treg infusion, regardless of cell dose. Only minor complications related to the immunosuppressive drugs were reported. This first-in-man study of autologous Treg infusion in allogenic pancreatic islet transplantation shows that the treatment is safe and feasible. Based on these results, future efficacy studies will be developed under the label of advanced therapeutic medical products (ATMP), using modified or expanded Tregs with the aim of minimizing the need for chronic immunosuppressive medication in islet transplantation.     

Characteristics and outcomes of hip fractures in lower limb amputees

IntroductionLower limb amputees, regardless of age are at an increased risk of developing fragility fractures of the neck of femur. The characteristics and outcomes of the fractures of the neck of femur in lower limb amputees have not been studied in detail.MethodsWe undertook a retrospective review of a prospectively collected single centre and single surgeon database between March 1996 and January 2017, using a standard proforma to identify patients who required surgical intervention for fracture neck of femur and had sustained a previous lower limb amputation and compared them with a cohort of standard hip fracture patients.ResultsTwenty-seven patients, sustaining 28 fractures of the neck of femurs were identified of which 16 were females with mean age of 78 years (50-89). Nineteen fractures were sustained on the ipsilateral side of the amputation. Results showed that seventy percent of amputees returned to their previous level of mobility and prior residence. Mortality in this group is higher as compared to a standard hip fracture patient but pain and mobility were comparable in both groups.DiscussionThe incidence of both hip fractures and amputations in increasing worldwide but no study has compared outcomes of hip fractures in amputees and compared them to a standard hip fracture patient. Amputees exhibit reduced bone density both at the hip and stump end which increases risk for osteoporosis and fragility fractures in the hip. The management of our patients followed orthopaedic principles, well established surgical interventions and rehabilitation.ConclusionThis study reveals that hip fractures in amputees can have comparable results to a standard hip fracture cohort if preoperative optimisation, planning and postoperative rehabilitation is carried out.     

Patella fracture fixation with a non-locked anterior plating technique: A biomechanical study

ObjectivesThe purpose of this study was to compare the biomechanical attributes of patella fracture fixation with either anterior plating utilizing two parallel, longitudinal 2.0 mm plates technique versus a cannulated screw tension band technique.MethodsFive matched pairs (ten specimens) of fresh frozen cadavers were utilized. A transverse patella fracture (OTA 34C1.1) was fixed using either two 4.0 mm cannulated screw anterior tension band (CATB) or with two 2.0 mm stainless steel non-locking plates along the anterior cortex secured with 2.4 mm cortical screws traversing the fracture site. Specimens underwent 1000 cycles of simulated active knee range of motion before load to failure destructive testing.ResultsDuring cyclic loading there were no failures in the plate fixation group, and 2 out of 5 specimens catastrophically failed in the CATB group (p = 0.22). Average fracture displacement at the end of fatigue testing was 0.96 mm in the plate fixation group and 2.72 mm in the CATB group (p = 0.18). The specimens that withstood cyclic testing underwent a destructive load. Mean load to failure for the plate fixation specimens was 1286 N, which was not significantly different from the CATB group mean of 1175 N (p = 0.48). The mechanism of failure in the plate fixation cohort was uniformly via a secondary vertical patella fracture around the plates in all five specimens. In the CATB group, the mechanism of failure was via wire elongation and backing out of the screws.ConclusionsPatella fixation with anterior plating technique statistically performed equivalent to cannulated screw anterior tension band in ultimate load to failure strength and fatigue endurance under cyclical loading. No failures were observed cyclic simulated active range of motion in the anterior plate group. There was a trend towards improved fatigue endurance in the plate fixation group, however this did not reach statistical significance. We believe plate fixation technique represents a low-profile implant option for treatment of transverse patella fractures, which may allow for early active range of motion, and these data support biomechanical equivalency to standard of care.     

The impact of the COVID-19 pandemic on the mental health of young people: A comparison between China and the United Kingdom

Purpose: As COVID-19 spreads globally and affects people''s health, there are concerns that the pandemic and control policies may have psychological effects on young people (age from 17 to 35 years). This psychological impact might vary in different countries, and thus we compared the prevalence of selfreported psychological distress, loneliness and posttraumatic stress symptoms (PTSS) among young people in the United Kingdom (UK) and China at the beginning of the COVID-19 pandemic. Methods: Data of this study came from two sources. One source was the first wave of COVID-19 study in Understanding Society, a special wave of the UK household longitudinal study, which provided the highquality, national-wide representative panel data. The sample comprised 1054 young people. The other source was an online survey on the mental health of 1003 young people from Shanghai, a highly developed area in China. The questionnaire included questions on the prevalence of common mental disorders (cut-off score ≥ 4), loneliness and potential PTSS (cut-off ≥ 33). Univariable analyses were conducted to test the differences in the self-reported prevalence of psychological distress and loneliness between the two groups. Multivariable logistic regression analyses were run to explore the predictors of psychological distress and loneliness among all the young people from England and Shanghai. Results: Among the samples with self-reported psychological distress, the UK sample accounted for 34.4% (n = 1054) and the Chinese sample accounted for 14.1% (n = 1003). The difference between the two groups was statistically significant (p < 0.001). Additionally, 57.1% of people in the UK and 46.7% in China reported that they sometimes or often felt lonely, of which the difference is statistically significant (p < 0.001). Regression analysis of the entire samples showed that nationality, gender, psychotherapy and loneliness were significant predictors of 12-item General Health Questionnaire scores, while the variables of age and living alone were not. Significant predictors of self-reported loneliness were the nationality, gender, age, living alone and psychotherapy. In China, 123 (12.3%) young people, 49 men (11.3%) and 74 women (13.0%), met the criteria of PTSS symptoms (cut-off scores ≥ 33). These scores were only collected in China. Conclusion: This evidence suggests that mental health and loneliness reported by young people were lower in China than that in the UK during the studied period. More research is needed to understand these differences. If the differential negative psychological impacts are confirmed, country-specific measures of prevention and intervention should be adopted to improve the mental health of young people under the ongoing impact of the pandemic.     

介入治疗内脏动脉瘤的远期疗效

目的观察介入治疗内脏动脉瘤(VAA)的远期疗效。方法回顾性分析30例接受介入治疗VAA患者(41个瘤灶),术后随访时间均12个月,观察治疗效果及并发症。结果对12个肾动脉瘤、8个脾动脉瘤行动脉瘤填塞术,其中5个脾动脉瘤、5个肾动脉瘤采用裸支架辅助填塞;对13个脾动脉瘤、1个肝动脉瘤行动脉瘤栓塞术;对4个肾动脉瘤行载瘤动脉支架植入术,其中3个采用多层裸支架植入术、1个采用覆膜支架植入术;对2个肾动脉瘤、1个腹腔干动脉瘤行保守治疗;均获得成功。1个脾动脉瘤栓塞术后出现部分脾梗死,1个左肾多发动脉瘤植入支架后瘤腔小部分显影。术后随访12～55个月,平均(23.44±12.48)个月,期间脾梗死者梗死面积未增大、未见脓肿形成,瘤腔部分显影病变显影面积未增大。30例患者中,1例因心力衰竭死亡,余均存活,无VAA复发及其他并发症。结论介入治疗VAA远期疗效较好,且安全性较高。     

基于纳米材料的肿瘤消融联合免疫治疗研究进展

影像学引导消融治疗已逐渐成为治疗不可切除实体肿瘤的重要方式,但消融治疗后存在肿瘤局部复发及全身转移风险。免疫治疗可通过增强机体自身免疫细胞功能间接清除肿瘤细胞,但多数实体肿瘤对免疫治疗的反应率较低。近年来,基于纳米材料的肿瘤消融技术发展迅速,为增强局部消融效果及提高系统免疫应答提供了新的可能。本文对基于纳米材料的消融联合免疫治疗肿瘤研究进展进行综述。     

Sex-Positivity,Medical Mistrust,and PrEP Conspiracy Beliefs Among HIV-Negative Cisgender Black Sexual Minority Men in Atlanta,Georgia

Because the public health response to the disproportionate HIV burden faced by Black sexual minority men (BSMMM) has focused on sexual risk reduction and disease prevention, other vital components of sexual health (e.g., intimacy, pleasure, benefits of sex) have been often overlooked. Sex-positive describes a more open, holistic approach toward sex and sexuality that prioritizes these other components, though such an approach is rarely applied to BSMM's sexual health. For sex-positive BSMM, risk/preventive discourse may foster or exacerbate medical mistrust as a reaction to the dissonance between how these men view sexual health and how the medical establishment views it, which may discourage sexual healthcare-seeking. We assessed sex-positivity and its association with medical mistrust and PrEP conspiracy beliefs among 206 HIV-negative cisgender BSMM in Atlanta, Georgia. We performed exploratory factor analytic procedures on responses to a sex-positivity scale, followed by multivariable linear regressions to determine sex-positivity’s associations with medical mistrust and PrEP conspiracy beliefs. We extracted two sex-positivity factors: sexual freedom (α?=?0.90), reflecting openness toward casual sex and rejection of sexual mores, and essence of sex (α?=?0.77), reflecting the intimate, relational, and pleasurable qualities of sex. Sexual freedom was independently associated with perceived provider deception (β?=?0.19, CI?=?0.04, 0.34). Essence of sex was independently associated with PrEP conspiracy beliefs (β?=?0.16, CI?=?0.02, 0.31) and marginally associated with perceived provider deception (β?=?0.14, CI?=???0.00, 0.29). Healthcare providers and public health practitioners may cultivate greater trust with BSMM by incorporating a sex-positive approach into patient/participant interactions, clinical decision-making, and interventions. Improving access to sexual pleasure acknowledges BSMM’s right to optimal, holistic sexual health.

     

Do larger reductions yield larger returns? patient-reported outcomes as a function of specimen weight in bilateral reduction mammoplasty

BackgroundPatients undergoing breast reduction mammoplasty for symptomatic macromastia have a significantly improved quality of life postoperatively. However, there are no data that examine the effect of reduction mammoplasty on quality of life as a function of the weight of tissue removed. Because the process by which insurance providers consider patients’ candidacy for this breast reduction mammoplasty is most often based on the proposed weight of tissue to be removed, this gap in our understanding is particularly glaring. We therefore designed a prospective trial with the intent of investigating the correlation between breast reduction specimen weight and postoperative pain and quality of life.MethodsAfter obtaining institutional review board (IRB) approval, patients presenting for breast reduction mammoplasty at a single academic medical center between January 2016 and September 2019 were prospectively enrolled in the study. Study participants completed the Numerical Pain Rating Scale (NPRS), the short-form McGill Pain Questionnaire (SF-MPQ), and the BREAST-Q at set time points (preoperatively, 1 week/1 month/3 months/6 months postoperatively). Patients were divided into three cohorts based on breast reduction specimen weights: small (<500 g reduction), intermediate (500–1000 g reduction), and large (>1000 g reduction). The surveys were then analyzed while controlling for demographic factors and complications.ResultsA total of 85 women were enrolled in the study and completed pre- and postoperative surveys (small reduction n = 21 (25%), intermediate n = 45 (53%), and large n = 19 (22%)). Regardless of reduction specimen weight, patients reported decreased overall pain and increased satisfaction with their breasts, as well as improved psychosocial, sexual, and physical well-being at each postoperative visit. Preoperative SF-MPQ pain scores were significantly lower in the small specimen weight group compared with either the intermediate or the large group (p = 0.001). Postoperatively, both the intermediate and large groups reported significant improvement in pain at each time point. The small specimen weight group did not report significant pain improvement until 3 months postoperatively.ConclusionsPatients undergoing breast reduction mammoplasty experience decreased pain and improved quality of life regardless of reduction specimen weight. Improvement in these parameters manifests as early as 1 week postoperatively and maintained at 3 months postoperatively. These data suggest that many patients who are denied coverage for reduction mammoplasty on the basis of low projected reduction specimen weight would derive significant benefit from the procedure.     

Anterior tibial artery injury is not the contraindication of medial plantar flap: digital subtraction angiography evidence and clinical application

The medial plantar artery (MPA) is often sacrificed as the vascular pedicle of the medial plantar flap (MPF). However, for patients with ankle soft tissue defect caused by traffic accident, the anterior tibial artery (ATA) could be damaged and the blood supply of the distal foot would only come from the MPA and the lateral plantar artery (LPA). In this case, sacrificing the MPA for the MPF means that the LPA will become the mainly source of blood supply of the distal foot. Whether the blood supply of the distal foot is adequately guaranteed remains to be discussed. A total of seven patients with ankle soft tissue defect and ATA injury were enrolled in the study. The digital subtraction angiography (DSA) was performed to observe the hemodynamics of the ipsilateral foot. The MPF was harvested only when the foot arterial network consisting of the MPA, the LPA, the deep plantar arch, and the deep plantar artery of DPA, and the blood redistribution existed. DSA results showed the blood from the posterior tibial artery was redistributed to the ipsilateral foot and the MPA is not the dominant artery in the foot. Seven MPFs were harvested, and all flaps survived completely. No complications, such as pain, ulcer, and necrosis, occurred in the ipsilateral toes. The DSA could accurately and intuitively evaluate the hemodynamics of foot in patients with ATA injury. The DSA data and clinical practice proved that the ATA injury is not the contraindication of the MPF.