Rapid Resolution of Graft-versus-Host-Disease-Related Central Serous Chorioretinopathy

Abstract

We present a 23-year-old female patient who developed bilateral, multifocal CSCR three months after BMT and two months after developing GvHD. At the time of diagnosis, her medications included cyclosporine and high-dose oral steroid for GvHD. CSCR resolved quickly after the resolution of GvHD, along with rapid tapering of steroids and restoration of emotional wellbeing. Rapid tapering of systemic steroids under close monitoring of a hematologist in the setting of resolved mild GvHD may facilitate prompt resolution of CSCR.     

免疫毒素去除T细胞在异基因造血干细胞移植中的应用

观察应用免疫毒素部分去除T细胞(TCD)的方法进行人类白细胞抗原／混合淋巴细胞培养(HLA/MLC)不相合异基因造血干细胞移植的临床疗效。采用蓖麻免疫毒素部分去T细胞对13例恶性血液病患者行HLA-MLC配型不相合的造血干细胞移植，其中慢性髓性白血病(CP1)6例；急性淋巴细胞白血病CR1 1例，CR2 1例，复发1例；急性髓性白血病CR1 2例，CR2 1例；骨髓增生异常综合征转化成急性髓性白血病M4型(CR1)1例。结果表明：13例患者中8例成功植入，其中2例发生Ⅱ度急性移植物抗宿主病(aGVHD)，2例发生Ⅲ-Ⅳ度aGVHD。随访8-90个月，2例发生Ⅲ-Ⅳ度aGvHD患者早期死亡，另有1例患者死于迟发感染，其余5例均无病存活至今。5例未植活的患者中4例回输同一供者外周血造血干细胞后3例未植入，1例植活，但死于移植相关合并症；1例再次行同基因造血干细胞移植成功并无病存活至今。结论：采用蓖麻免疫毒素部分去T细胞的方法行HLA/MLC配型不相合的异基因造血干细胞移植可减少重度aGVHD的发生，但移植早期排斥率(HVG)较高，临床应用效果有待进一步评估。     

Patient positioning and the accuracy of pulmonary artery pressure measurements (180f)

The measurement of pulmonary artery pressure (PAP) is a common nursing practice in hemodynamic monitoring of patients in the emergency room and intensive care unit. Several researchers have proposed that PAP should be measured with the patient in a supine position with legs horizontal in order to promote a relaxed state. The most widely used reference point is the phlebostatic axis, which is located at the intersection of the fourth intercostal space and the midchest level. However, this positioning requirement is in conflict with one of the goals of nursing care, which is to achieve comfortable positioning of the patient without compromising respiratory or cardiovascular function. In addition, since frequent readings are necessary, critically ill patients can lose valuable sleep time. The existing literature still fails to justify the validity of the phlebostatic axis as an external reference point for leveling the pressure transducer. In addition, findings on the accuracy of readings obtained in the supine, Fowler's and lateral recumbent positions are also in conflict. This paper reviewed research related to measurement of PAP in the supine, various Fowler's, and lateral positions in order to clarify the major factors which might have resulted in the conflicts in data on PAP measurements. Suggestions are also provided for nurse clinicians to obtain more accurate PAP measurements.     

Effects of lifestyle changes on adults with prediabetes: A systematic review and meta-analysis

Aims

To assess the efficacy, safety, and cost-effectiveness of lifestyle intervention, compared with treatment as usual in people with prediabetes as defined by the American Diabetes Association. For older studies, we used the 1985 World Health Organization definition.

A longitudinal assessment of change in marijuana use with other substance use problems

Background: Despite increasing marijuana use rates over the past decade, the longitudinal association between marijuana use and other substance use problems among adults is unclear. Objectives: To examine associations of self-reported changes in marijuana use and marijuana use frequency with self-reported other substance use problems over a 12-month period. Methods: Two waves (W1 and W2) of the Population Assessment of Tobacco and Health Study provided data. The study sample (N = 26,204, female = 13,261; male = 12,943, aged 18+) included W1-W2 never marijuana users, W1-W2 ex-users (used prior to 12 months of W1), and those who either quit, initiated, resumed, or continued marijuana use between W1 and W2. We used multinomial and binary logistic regression analyses. Results: The past-year marijuana use rate was 12.4% at W2. A quarter of W1 users quit using marijuana in the 12 months preceding their W2 interview, and one-third of all the W2 users were new/resumed users since W1. Compared to W1-W2 ex-users, W2 quitters were more likely to report alcohol use problems and tobacco addiction at W2. Compared to quitters, continued users were more likely to report alcohol use problems (RRR = 1.62, 95% CI = 1.27–2.07) and tobacco addiction (RRR = 1.37, 95% CI = 1.11–1.69). New users (RRR = 2.05, 95% CI = 1.12–3.74), resumed users (RRR = 2.69, 95% CI = 1.55–4.70), and continued users (RRR = 3.40, 95% CI = 2.08–5.55) reported more drug use problems. Compared to less frequent marijuana users, frequent users had greater odds of reporting alcohol use problems (RRR = 1.44, 95% CI = 1.21–1.72) and drug use problems (OR = 1.63, 95% CI = 1.19–2.23). Conclusions: Given increased prevalence of marijuana use, polysubstance use problems among marijuana users should be assessed.     

Effect of mTORC1/mTORC2 inhibition on T cell function: potential role in graft‐versus‐host disease control

The mechanistic target of rapamycin (mTOR) pathway is crucial for the activation and function of T cells, which play an essential role in the development of graft‐versus‐host disease (GvHD). Despite its partial ability to block mTOR pathway, the mTORC1 inhibitor rapamycin has shown encouraging results in the control of GvHD. Therefore, we considered that simultaneous targeting of both mTORC1 and mTORC2 complexes could exert a more potent inhibition of T cell activation and, thus, could have utility in GvHD control. To assess this assumption, we have used the dual mTORC1/mTORC2 inhibitors CC214‐1 and CC214‐2. In vitro studies confirmed the superior ability of CC214‐1 versus rapamycin to block mTORC1 and mTORC2 activity and to reduce T cell proliferation. Both drugs induced a similar decrease in Th1/Th2 cytokine secretion, but CC214‐1 was more efficient in inhibiting naïve T cell activation and the expression of T‐cell activation markers. In addition, CC214‐1 induced specific tolerance against alloantigens, while preserving anti‐cytomegalovirus response. Finally, in a mouse model of GvHD, the administration of CC214‐2 significantly improved mice survival and decreased GvHD‐induced damages. In conclusion, the current study shows, for the first time, the immunosuppressive ability of CC214‐1 on T lymphocytes and illustrates the role of CC214‐2 in the allogeneic transplantation setting as a possible GvHD prophylaxis agent.     

Ointments and transdermal nitroglycerin patches for stable angina pectoris

Summary Nitroglycerin (NTG) ointment is used for the prophylaxis against angina pectoris, but there are no data to support its effectiveness during long-term therapy. Continuous, once-daily application of isosorbide dinitrate cream produces tolerance with complete loss of efficacy within 1 week. Nitroglycerin patches are very popular and continuous once-daily application is still claimed by some investigators to provide 24 hour antiischemic and antianginal efficacy. This claim is based on data from postmarketing studies in a very large number of patients and placebo-controlled studies in smaller groups of patients from Italy, Yugoslavia, Greece, and Germany. In contrast, studies from the United States, Canada, England, and some centers in Germany have failed to show superiority of patches over placebo during continuous therapy. This controversy was addressed by the NTG cooperative study group, in which a total of 562 patients who were responders to sublingual nitroglycerin were studied. Patients received either placebo or NTG patches delivering low (15–30 mg/24 hr), moderate (45–60 mg/ 24 hr), or large (75 and 105 mg/24 hr) amounts of NTG. Four hours after the initial application, NTG patches increased exercise duration compared to placebo, but this beneficial effect had disappeared by 24 hours. Furthermore, after 8 weeks of continuous therapy, none of the NTG patches were superior to placebo, whether patients were or were not taking concomitant beta-blockers. Therefore, current opinion is that continous therapy with NTG patches produces pharmacologic tolerance and is ineffective. Pharmacologic tolerance can be minimized when patches are applied every morning and removed after 10–12 hours at night. However, patches delivering >15 mg NTG/24 hr are required to maintain an increased exercise duration for up to hour 8 after the patch application. Intermittent therapy with patches, however, may lead to rebound nocturnal angina in some patients. Also, intermittent therapy with patches has been associated with worsening of exercise performance in the morning prior to the patch renewal, compared to therapy with placebo patches. This has been referred to as the zero-hour effect and probably represents a rebound phenomenon following nitrate withdrawal. Patients experiencing either nocturnal or early morning angina during intermittent therapy with patches should either be switched to oral long-acting nitrates or should in addition be treated with a beta-blocker, provided there are no contraindications to beta-blocker treatment.The opinions expressed here are those of the authors and should not be taken as those of FDA.     

Bowel ultrasonography as an aid for diagnosis of intestinal acute graft-versus-host-disease after allogeneic haematopoietic stem cell transplantation

Objective

Aim of our prospective study was to investigate accuracy of bowel ultrasonography in detecting gastrointestinal acute graft versus host disease (GVHD), when using clinical assessment as gold standard. In a subgroup of patients, bowel ultrasonography was compared with colonoscopy and histology in diagnosing of gastrointestinal acute GVHD.

Methods

Fifty-two patients underwent allogeneic hematopoietic stem cell transplantation and developed gastrointestinal symptoms.

Results

Clinical assessment lead to a diagnosis of gastrointestinal acute GVHD in 17/52 patients, no gastrointestinal acute GVHD was detected in 20/52 patients, while 15 patients were not able to complete the study. Bowel ultrasonography detected either bowel wall thickness of the ileum and the colon or dilation in 16/17 patients and showed 94% sensitivity (95% CI 0.69–0.99), 95% specificity (95% CI 0.73–0.99), and 94.5% accuracy. Colonoscopy was performed in 13/52 patients, showing gastrointestinal acute GVHD in 11/13. In these 11 patients, histology confirmed the diagnosis of gastrointestinal acute GVHD, and bowel ultrasonography detected findings compatible with gastrointestinal acute GVHD in all 11 patients, and was negative in the 2 patients with no gastrointestinal acute GVHD.

Conclusion

Bowel ultrasonography can be considered a valuable tool to add to clinical assessment for patients with suspected gastrointestinal acute GVHD for addressing a prompt and appropriate treatment.     

Human papillomavirus reactivation following treatment of genital graft‐versus‐host disease

Vaginal chronic graft‐versus‐host disease (cGVHD) is a common complication of stem cell transplantation. Human papillomavirus (HPV) disease can reactivate after transplantation, presumably because of immune factors affecting systemic immunity, such as waning antibody titers, impaired T‐ and B‐lymphocyte responses, and the use of immunosuppressive therapies. However, a relationship between the use of local immunosuppressive agents and HPV reactivation and spread has not been previously described, to our knowledge. A 30‐year‐old woman, 2 years post transplant receiving systemic cyclosporine for cGVHD, was treated with vaginal dilators, topical corticosteroids, and estrogen for vaginal cGVHD. Colposcopy and biopsy for abnormal cytology revealed condylomatous cervicitis. Over the next 4 months, while continuing dilator therapy, linear verrucous lesions developed in the vagina and vulva, and were successfully treated with laser therapy. Use of local immunosuppression and dilators for genital GVHD can enhance spread of HPV infection. Integration of HPV screening and treatment into the care of women with genital cGVHD and development of strategies to manage both conditions simultaneously are warranted.     

通过Fas-FasL途径体外清除小鼠同种异体反应性T细胞

目的　通过Fas Fas配体 (FasL)途径清除小鼠同种异体反应性T细胞 (ARTC) ,为减轻异基因骨髓移植 (allo BMT)后的移植物抗宿主病探索新的手段。方法　用磁性细胞分离系统分离BALB c小鼠 (H 2 d)Sca 1+早期造血细胞 (HC) ,然后借助逆转录病毒基因转移技术对其转染外源小鼠FasL(mFasL)cDNA基因 ;扩增 1周后与异基因BAC小鼠 (H 2 d ×b)脾细胞进行单向混合淋巴细胞培养(OWMLC) 6d ,观察处理后的BAC小鼠脾细胞对Na251 CrO4标记的BALB c小鼠脾细胞的杀伤作用。结果　成功分离出BALB c小鼠Sca 1+HC ,纯度为 (89.0± 6 .1) %。BAC小鼠脾细胞与转染外源mFasL的BALB cHC以 1∶5比例共培养 6d后 ,对BALB c源脾细胞杀伤率在不同效、靶比例时均呈显著降低 (P<0 .0 1)。结论　体外反应中 ,转染外源mFasLcDNA并高表达的早期HC可清除针对自身MHC抗原的ARTC。