The Application of Umbilical Cord Blood-derived Platelet Gel for Skin Ulcers Associated With Chronic Graft-Versus-Host Disease in Pediatrics: A Randomized Trial.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative strategy against a variety of malignant and nonmalignant disorders. However, acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively) commonly complicate this approach, culminating in substantial morbidities and mortalities. The integumentary system is the preponderant organ involved in cGVHD, and its response to existing treatments, including well-versed immunosuppressants and novel targeted therapies, is not desirable. Despite the rarity, ulcers of sclerotic skin cGVHD are treatment-refractory and associated with significant morbidities and an exaggerated risk of infectious complications. Platelet-rich plasma (PRP) and its derivatives are endowed with growth factors and proangiogenic molecules and hold regenerative potential. This study aimed to assess the safety and efficacy of the application of platelet gel-containing dressing against ulcerative skin cGVHD in pediatric patients. This randomized trial is conducted at the hematopoietic stem cell transplantation unit of the Children's Medical Center Hospital in Tehran, Iran. Twenty-one pediatric patients (aged between 5 and 15 years) were initially enrolled, and 16 met the inclusion criteria. All cases (4 females) were recipients of allo-HSCT who had been complicated with symmetrically or near-symmetrically ulcerative sclerotic skin cGVHD. Fresh umbilical cord blood (UCB) was obtained from healthy donors and underwent centrifugation using a novel PRP preparation kit in a single-step process. Platelet gel was produced by adding thrombin to the isolated buffy coat layer. Two similar ulcers of each patient were randomized to receive either conventional dressing or platelet gels up to 6 times. At each time point evaluation, ulcer size and its relative reduction compared to the basal size were recorded. Included patients received a total of 80 platelet gel-containing dressings. While the mean sizes of randomized ulcers at the beginning of the study were similar, their differences became significant 15 days after the initiation of intervention (P = .019). In addition, the mean reduction in the ulcers' surface area (in comparison to their baseline values) was significantly higher for the intervention arm at all evaluation points (P = .001 for day 5 and P < .001 for subsequent time points). At the end of the trial, the number of ulcers with a more than 50% reduction in size was 14 (87.5%) in the intervention arm (including 6 completely healed ulcers) versus 1 (6.25%, which was not completely healed) in the control arm (P < .001). None of the patients exhibited any localized or systemic treatment-related adverse events. In this study, using a relatively large number of cases, we showed that UCB-derived platelet gel is a safe, feasible, and effective curative approach for skin ulcers of sclerotic skin cGVHD in pediatric patients. Designing upcoming trials on the efficacy of this therapeutic approach for ocular, mucosal, and acute skin GVHD is prudent. Retrospectively registered at the Iranian Registry of Clinical Trials (registration number IRCT20190101042197N1) on August 24, 2020.

Evaluation of safety and efficacy of allogeneic adipose tissue-derived mesenchymal stem cells in pediatric bronchiolitis obliterans syndrome (BoS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

BACKGROUND: Allo-HSCT is a definite approach for the management of a wide variety of lethal and debilitating malignant and non-malignant disorders. However, its two main complications, acute and chronic graft-versus-host disease (GVHD), exert significant morbidities and mortalities. BoS, as a manifestation of chronic lung GVHD, is a gruesome complication of allo-HSCT, and for those with steroid-refractory disease, no approved second-line therapies exist. Mesenchymal stem cells (MSCs) exert anti-inflammatory and growth-promoting effects, and their administration against a wide range of inflammatory and neurologic disorders, as well as GVHD, has been associated with promising outcomes. However, literature on the safety and effectiveness of MSC therapy for BoS and pediatric cGVHD is scarce. METHODS: We designed a single-arm trial to administer adipose tissue (AT)-derived MSCs to pediatric patients with refractory BoS after allo-HSCT. AT-MSCs from obese, otherwise healthy donors were cultured in an ISO class 1 clean room and injected into the antecubital vein of eligible patients with a dose of 1 × 106/kg. The primary endpoints included a complete or partial response to therapy [in terms of increased forced expiratory volume in one second (FEV1) values and steroid dose reduction] and its safety profile. RESULTS: Four eligible patients with a median age of 6.5 years were enrolled in the study. Steroid-induced osteoporosis and myopathy were present in three cases. A partial response was evident in three cases after a single injection of AT-MSCs. The treatment was safe and tolerable, and no treatment-related adverse events were noted. Two patients developed manageable COVID-19 infections one and 4 months after AT-MSC injection. After a median follow-up duration of 19 months, all cases are still alive and have had no indications for lung transplantation. CONCLUSIONS: AT-MSCs could be safely administered to our pediatric cases with BoS post-allo-HSCT. Considering their advanced stage of disease, their sub-optimal functional capacity due to steroid-induced complications, and COVID-19 infection post-treatment, we believe that AT-MSC therapy can have possible efficacy in the management of pediatric BoS. The conduction of further studies with larger sample sizes and more frequent injections is prudent for further optimization of AT-MSC therapy against BoS. Trial registration Iranian Registry of Clinical Trials (IRCT), IRCT20201202049568N2. Registered 22 February 2021, https://en.irct.ir/trial/53143 .

Escalated Dose Donor Lymphocyte Infusion Treatment in Patients with Primary Immune Deficiencies After HSCT with Reduced-Intensity Conditioning Regimen.

OBJECTIVE/BACKGROUND: Mixed chimerism is a major concern after allogenic hematopoietic stem cell transplantation (HSCT) using a reduced-intensity conditioning (RIC) regimen in primary immunodeficiencies (PIDs). A donor lymphocyte infusion (DLI) escalating dose regimen has been developed with the aim of reducing toxicity while preserving efficacy. However, the graft-versus-host disease (GvHD) development remains the most common and adverse effect of DLI and continues to be a limiting factor in its application, especially nonmalignant diseases such as PIDs. We prospectively evaluated PID patients after HSCT using RIC in Childrens Medical Center, who were candidates for an escalating dose of DLI for MC from 2016 to 2018. METHODS: With the median follow-up of 16.4 months, 12 patients (nine males and three females) with a median age of 3.72 years received DLI. The median number of DLI was 3.2 (range, 1-5), the maximum and total dose of DLIs administered per patient were 3.6 × 107 (range, 1-5) cells/kg CD3+ and 9.3 × 107 (range, 1-15) cells/kg CD3+ cells, respectively. RESULTS: Median donor chimerism at baseline before the DLIs was 41% (range, 11-73%), patients received DLIs at a median of 105 (range, 37-230) days and 52 (range, 3-168) days after the HSCT and onset of the MC, respectively. At the final assessment, six (54.5%) patients improved after DLIs at a median of 47.3 days. CONCLUSION: PID patients may benefit from DLI with an escalating dose regimen, but the GvHD development remains a concern during the DLI, and the optimum dose and frequency must be standardized.

Spatial distribution of regional infrastructures in the northeast of Iran using GIS and Mic Mac observation (A case of Khorasan Razavi province).

Nowadays, recognizing the current situation and forecasting the desired status of spatial analysis of infrastructures regarding security and defense considerations is of great importance. Besides, the use of approaches such as futures studies and its simultaneous application with GIS has the most fundamental contribution to the field of decision-making and appropriate planning method in studies on the spatial defense planning. Accordingly, this paper aims to evaluate the spatial distribution of regional infrastructures in the northeast of Iran using a passive defense approach. In this regard, a descriptive-analytical research methodology, library-documentary studies, and statistical surveys were used in the model framework along with software (Mic Mac and Scenario Wizard) and system analysis (GIS) to achieve the research objective. The statistical population of the study was defined in two human and spatial scales. The entire geographical space of Khorasan Razavi province made the spatial scale. On the human scale, 40 experts (n = 15) and elites (n = 25) in the field of this study were selected as the statistical sample using a purposive non-random model. It is noteworthy that all of the subjects had the required scientific and executive knowledge. According to the total research indicators, the vulnerable zones of the study area could be distinguished into five categories of areas with very high (7.33%), high (16.52%), moderate (29.78%), low (16.94%), and very low (29.4%) vulnerability. Also, according to the results, the density and dispersion patterns of the study area infrastructures were concentrated, clustered, and randomly self-clustered, respectively. In the meantime, factors such as legal, policy, and institutional infrastructure criteria were identified as key drivers influencing the spatial distribution of the province infrastructures. Therefore, it is possible to realize the future models in three scenarios of high desirability (green status), acceptable (yellow status), and crisis (red status). Finally, the paper concludes with some suggestions to increase the desirability of infrastructures in Khorasan Razavi province.

The effect of a lifestyle management educational program on blood pressure, heart rate, and body mass index in patients with hypertension.

BACKGROUND: Hypertension (HTN) is one of the most prevalent risk factors for arteriosclerosis and coronary artery disease (CAD). Its side effects can be decreased through the use of some methods and interventions. The present study was conducted with the aim to evaluate the effects of a lifestyle management on blood pressure, heart rate, and body mass index (BMI) of patients with HTN who have undergone angioplasty. METHODS: This clinical trial was conducted on 2 groups in 3 stages in an educational hospital in Isfahan, Iran, in 2014. The study participants consisted of 60 patients with HTN who had undergone angioplasty. The participants were randomly allocated to the study and control groups. The intervention was implemented in 6 educational sessions during 3 weeks, and then, follow-up was conducted through phone calls in the study group. The collected data were analyzed using independent t-test, chi-square, Mann-Whitney U test, and ANOVA in SPSS software. RESULTS: Repeated measures ANOVA results indicated that the effect of time (P < 0.001) and group (P = 0.027) on systolic blood pressure (SBP) was significant. The effect of time (P = 0.015) and group (P = 0.040) on diastolic blood pressure (DBP) was also significant. In terms of BMI, both effects of time (P = 0.010) and group (P = 0.034) were significant. However, the effect of time (P = 0.899) and group (P = 0.900) on heart rate was not significant. CONCLUSION: The lifestyle management program implemented in the present study was effective on decreased DBP, SBP, and BMI in patients with HTN who had undergone angioplasty. Thus, nurses could implement this program as a part of their care provision program for patients.

Effects of a Lifestyle Modification Program on Knowledge, Attitude and Practice of Hypertensive Patients with Angioplasty: A Randomized Controlled Clinical Trial.

BACKGROUND: Lack of knowledge, attitude and practice are some of the barriers of having a healthy lifestyle and controlling high blood pressure. This study aimed to determine the effectiveness of a lifestyle modification program on knowledge, attitude and practice of hypertensive patients with angioplasty. METHODS: This study was a randomized controlled clinical trial conducted from November to April 2014 on 60 hypertensive patients with angioplasty in Shahid Chamran hospital of Isfahan, Iran. The samples were randomly assigned to two equal groups. Data collection was performed in three stages by a researcher-made questionnaire. The intervention plan was 6 education sessions and then follow up were done by phone call. The gathered data were analyzed via SPSS (V.20), using t-test, Chi-square, repeated measurement, and post hoc LSD test and ANOVA statistics. RESULTS: The mean score of knowledge, attitude and practice in the experimental group immediately after the intervention was 77.8±7.2, 88.3±6.4 and 86.2±6.5, respectively and one month after the intervention was 80.8±7.4, 91.1±3.5 and 92.5±2.2, respectively. But in the control group, the mean score of knowledge, attitude and practice immediately after the intervention (34.90±11.23, 61.11±6.28, and 38.64±7.15) and one month after the intervention was (38.64±7.15, 59.56±6.31 and 37.27±7.26. CONCLUSION: Lifestyle modification program can be effective in promoting the knowledge, attitude and practice of hypertensive patients with angioplasty. Nurses can use this program in their care provision programs for these patients. Trial Registration Number:IRCT2015062420912N3.

Rigid contact lens fitting based on keratometry readings in keratoconus patients: predicting formula.

AIM: To find a simple mathematical correlation between the lens base curve (BC) and keratometry findings (krf). METHODS: This retrospective study included 400 keratoconic eyes (350 patients) previously fit with rigid contact lenses at an academic eye center over a five year period. The patients were classified into five groups based on the keratometry findings (krf<7, krf:7-8, krf>8, krf-krs (difference between two keratometry; flat and steep)= 0.3-0.6, krf-krs >0.6mm as groups 1 to 5, respectively. Multivariate linear regression and Munro's correlation coefficient were employed to defer the formulas. RESULTS: A linear correlation could be found in all groups except for patients in group 3. For group 1, BC=0.211×krf+ 5.904. For group 2, BC=0.456×krf+4.160. For group 4, BC= 0.321×krf+5.219. For group 5, BC=0.337×krf+ 5.090. CONCLUSION: The development of new formulas for RGP fitting enables ophthalmologists to work with confidence and prevents unnecessary and frequent lens trials. The customary lens fitting methods are needed to be replaced by new formulas, which help to save time and costs.