Comparative protective effects of N-acetylcysteine and melatonin against obesity-induced testicular dysfunction in rats.

N-acetylcysteine (NAC) and melatonin were reported to exert protective effects on testicular tissues. Thus, this study aimed to determine which of these is more efficient against obesity-induced testicular dysfunction in albino rats. A total of 32 adult male rats (195 ± 10 g) were divided into four groups: control, obese rats fed a high-fat diet (HFD), HFD+NAC (150 mg/kg per day, i.p.) and HFD+melatonin (10 mg/kg per day, i.p.), for 5 weeks. Testes and epididymis were weighed. Lipid profile, pituitary-testicular hormones, tumor necrosis factor α (TNFα), epididymal sperm parameters, testicular oxidant-antioxidant system, testicular and the epididymal histopathology and immunohistochemical localization for androgen receptors (AR) and Bax reaction were analyzed. Administration of NAC or melatonin significantly improved the lipid parameters, gonadal hormones, TNFα level, sperm count and abnormal morphology, oxidant-antioxidant system and the absolute testicular and epididymal mass with an enhancement of testicular architecture, AR expression and apoptosis as compared with that in the obese group. Additionally, as compared with the NAC group, the melatonin group had significantly reduced body mass index, total cholesterol, triglyceride, and TNFα and increased testosterone, sperm count, motility, superoxide dismutase activity, mitigated histomorphometrical changes, Bax expression, and increased testicular AR expression. Therefore, melatonin was more efficient than NAC in affording fortification against HFD-induced testicular dysfunction.

Impact of Exercise Training on Hematological Outcomes Following Hematopoietic Cell Transplantation: A Scoping Review.

PURPOSE: Hematopoietic cell transplantation (HCT) is associated with significant risk prior to hematopoietic engraftment. Endurance exercise can modify the bone marrow microenvironment, alter hematopoiesis and accelerate hematopoietic regeneration in mouse models of transplantation. METHODS: A systematic review was conducted to clarify the impact of exercise on clinically relevant hemato-logical outcomes in patients following HCT. RESULTS: A systematic search of the literature identified 13 studies (total of 615 participants; 313 in study arms). Studies included exercise regimens that were primarily low-to-moderate intensity. A total of five studies re-ported on engraftment and length of stay, which were largely unchanged with intervention. Rates of graft-ver-sus host disease were reported in six studies whereas red cell and platelet transfusion needs were reported in four studies, neither of which was different with exercise. Survival was reported in four studies and was significantly improved by exercise in one study. CONCLUSIONS: Exercise in patients receiving HCT appears feasible and safe. Heterogeneity in type and intensity of exercise was observed and few studies examined high intensity exercise. Outcome reporting was inconsis-tent regarding transplant-related outcomes. Standardized hematological outcome measures are needed to clarify the impact of higher intensity exercise on HCT.

Systematic review of controlled clinical studies using umbilical cord blood for regenerative therapy: Identifying barriers to assessing efficacy.

Clinical use of umbilical cord blood (UCB) for novel indications in regenerative therapy continues to rise, however, whether new indications are proven is less clear. An updated systematic search of the literature, focusing only on controlled clinical studies, is needed to properly assess potential efficacy. After updating our systematic search to April 1, 2018 (PROSPERO protocol CRD42016040157), a total of 16 studies were identified that addressed the treatment of cerebral palsy (four studies), type 1 diabetes (three studies), and nine other novel potential indications where only a single controlled study was identified. In the four controlled studies of patients with cerebral palsy, three used allogeneic cells and reported greater improvement in motor-related scores at 1, 3 and 6 months compared with controls. The results were mixed for other scores at other time points, including additional measures of mental and motor function. One study of autologous UCB treatment reported an improvement in motor function scores at 12 months compared with controls. In the three controlled studies of type 1 diabetes, two studies used autologous cells whereas one used allogeneic cord blood cells to "educate" autologous lymphocytes. Taken together, there was no clear difference in HbA1c levels or daily insulin requirements between treated patients and controls. For the nine published reports with a single controlled study, eight used allogeneic UCB cells and seven infused mesenchymal stromal cells derived from UCB. All but one study reported benefit. Many other published reports that lack a control group were not included in our analysis. More controlled studies are needed that use similar approaches regarding cell source and outcome measures at similar time points. Pooled estimates of results from multiple studies will be essential as published studies remain modest in size. Patients should continue to be enrolled in clinical trials because there are no novel potential indications remain unproven.

Effect of Donor Age and Donor Relatedness on Time to Allogeneic Hematopoietic Cell Transplantation in Acute Leukemia.

Relapse after allogeneic hematopoietic cell transplantation (HCT) for acute leukemia can be reduced when pursued early after first complete remission. The impact of donor age and donor relatedness on the time from diagnosis to transplant in patients with acute leukemia was examined to clarify the design of future prospective studies that can address optimal donor choice. Files of 100 consecutive patients undergoing transplantation for leukemia were reviewed. Recipients of related donors (RDs) and unrelated donors (UDs) were not significantly different in terms of recipient gender, age, underlying diagnosis, disease risk index, graft source, or donor HLA match. UDs were significantly younger than RDs (median age, 29 versus 51, P < .001). Multivariate linear regression revealed that when controlling for age of donor and recipient, the time from diagnosis to transplant was 35% longer with UDs compared with RDs (P = .018). No significant correlation was observed between donor and recipient age on length of time to transplant (P = .134 and P = .850, respectively), when controlling for other variables. The steps in UD procurement that contribute most to the longer time to transplant relate to activating the donor workup and scheduling the donor workup before cell collection. Understanding sources of delay in the transplant process will help transplant centers and UD registries reduce the time to transplant for patients with acute leukemia and will provide necessary insight for the design of prospective controlled studies that can address optimal donor choice.

Cell-Based Therapy Using Umbilical Cord Blood for Novel Indications in Regenerative Therapy and Immune Modulation: An Updated Systematic Scoping Review of the Literature.

Cell-based therapy using umbilical cord blood (UCB) is being used increasingly in novel applications. To balance heightened public expectations and ensure appropriateness of emerging cell-based treatment choices, regular evidence-based assessment of novel UCB-derived therapies is needed. We performed a systematic search of the literature and identified 57 studies (814 patients) for analysis. Sixteen of these studies (353 patients) included a control group for comparison. The most commonly reported novel indication for therapy was neurologic diseases (25 studies, 476 patients), including studies of cerebral palsy (12 studies, 276 patients). Other indications included diabetes mellitus (9 studies, 149 patients), cardiac and vascular diseases (7 studies, 24 patients), and hepatic diseases (4 studies, 106 patients). Most studies administered total nucleated cells, mononuclear cells, or CD34-selected cells (31 studies, 513 patients), whereas 20 studies described the use of UCB-derived mesenchymal stromal cells. The majority of reports (46 studies, 627 patients) described cellular products obtained from allogeneic sources, whereas 11 studies (187 patients) used autologous products. We identified 3 indications where multiple prospective controlled studies have been published: 4 of 4 studies reported clinical benefit in cerebral palsy, 1 of 3 studies reported benefit for cirrhosis, and 1 of 3 studies reported biochemical response in type 1 diabetes), although heterogeneity among the studies precluded meaningful pooled analysis of results. We anticipate a more clear understanding of the clinical benefit for specific indications once more controlled studies are reported. Patients should continue to be enrolled on registered clinical trials for novel therapies. Blood establishments, transplantation centers, and regulatory bodies need to prepare for greater clinical demand.

Cryopreservation of adult unrelated donor products in hematopoietic cell transplantation: the OneMatch experience and systematic review of the literature.

BACKGROUND: The frequency of cryopreserving blood stem or progenitor products from unrelated donors is not known and the underlying reasons are poorly documented. Greater insight is needed to develop policies on cryopreservation that balance donor safety with patient needs. STUDY DESIGN AND METHODS: Cryopreservation requests between January 1, 2014, and May 31, 2016, at the OneMatch Stem Cell and Marrow Network at Canadian Blood Services were reviewed and a systematic review of the literature was performed. RESULTS: Thirty products of 719 (4.2%) unrelated donor collections facilitated by OneMatch were cryopreserved. Patient-related reasons were most common and included the need to delay transplant for continued antimicrobial treatment (six patients), patient too deconditioned to proceed with scheduled transplant (five patients), and/or need for more treatment for relapsed disease (three patients). Donor-related issues leading to cryopreservation requests were less common (five cases), mainly due to lack of donor availability after attempting to reschedule. Cryopreservation of a product that was never infused occurred infrequently (two cases, 7%). In our systematic review of the literature, 993 cases were identified in 32 published reports. Both patient-related and donor-related reasons were cited but not specifically reported, precluding quantitative insight regarding the relative frequency of causes. The impact of cryopreservation on hematopoietic engraftment appears negligible when compared to controls in a subset of studies; however, reporting of outcomes was inconsistent. CONCLUSION: Future studies with standard outcome measures are needed to clarify the impact of cryopreservation on engraftment and other transplant outcomes. International guidelines that consider the ethical framework surrounding requests for donor product cryopreservation are needed.

Thrombotic and bleeding outcomes following the perioperative interruption of anticoagulation among patients with nonvalvular atrial fibrillation and active cancer.

BACKGROUND: Patients with cancer are at an increased risk of developing atrial fibrillation (AF) and often need to undergo procedures or surgery that requires periprocedural interruption of anticoagulation. Anticoagulated patients with cancer might be at increased risk of postprocedural thromboembolic and bleeding complications. Data on postprocedural outcomes among patients with concurrent active cancer and AF are sparse. OBJECTIVE: To assess the 30-day risk of postoperative thromboembolic and major bleeding complications after the periprocedural interruption of anticoagulation among patients with AF and active cancer. METHODS: We conducted a single-center retrospective cohort study in patients with active cancer and AF who required periprocedural interruption of anticoagulation for invasive procedures between August 2015 and May 2019. The primary endpoints were the 30-day postoperative risks of arterial thromboembolism (ATE) and major bleeding. The secondary endpoints included the 30-day risks of venous thromboembolism, clinically relevant nonmajor bleeding, and overall mortality. RESULTS: Two hundred sixty-four patients undergoing 302 periprocedural interruptions were included in our study. The 30-day risk of ATE was 0.7% (95% CI, 0.1%-2.4%), and the 30-day risk of major bleeding was 1.7% (95% CI, 0.6%-3.9%). The 30-day risks of venous thromboembolism and clinically relevant nonmajor bleeding were 0.7% (95% CI, 0.1%-2.4%) and 4.3% (95% CI, 2.5%-7.3%), respectively. The overall risk of mortality at 30 days was 1.3% (95% CI, 0.4%-3.4%). There was one fatal postoperative stroke. CONCLUSIONS: Patients with AF and active cancer in this study were at relatively low risk for ATE and postoperative bleeding complications when patients were managed according to commonly applied perioperative management recommendations.

Intravitreal methotrexate infusion for prophylaxis of proliferative vitreoretinopathy after pars plana vitrectomy for rhegmatogenous retinal detachment.

Background: Proliferative vitreoretinopathy (PVR) is the leading cause of recurrent retinal detachment after surgical repair of rhegmatogenous retinal detachment (RRD). Our study aimed to assess the efficacy and safety of intravitreal methotrexate infusion (IMI) for the prevention of PVR after pars plana vitrectomy (PPV) in eyes with RRD. Methods: This prospective comparative interventional study was conducted from September 2020 to November 2021 at Ain Shams University Hospitals, Egypt. We recruited a consecutive, non-randomized sample of 47 eyes of 47 patients with RRD undergoing PPV. Participants were allocated to a control group or an intervention group that received IMI during surgery. Each group was subdivided into subgroups of eyes at high-risk of developing PVR and eyes with established preoperative PVR grade C. Outcome measures at the 3-month postoperative follow-up were the rate of retinal attachment, incidence of PVR, reoperation rate to flatten the retina, and changes in the retina and/or optic nerve function as assessed by full-field electroretinogram and flash visual evoked potential. Results: Data from 47 eyes (23 and 24 eyes in the intervention and control groups, respectively) were evaluated. Subgroups IA, IB, and IIB each included 12 eyes, subgroup IIA included 11 eyes, and all subgroups had comparable sex ratios and age distributions. Postoperative PVR at 1 month and between 1 and 3 months was present in 13% and 4% of eyes in the intervention group, respectively. Reoperation to flatten the retina was required in 2 (9%) eyes in the intervention group, while 22 eyes (96%) had complete flattening of the retina at 3 months. No significant differences were found between the study groups and the corresponding subgroups regarding the outcome measures (all P > 0.05). No adverse events attributable to IMI were detected up to 3 months postoperatively. Conclusions: Although IMI was safe for intraocular use in eyes with RRD and PVR grade C or a high risk of developing PVR, it did not affect the anatomical success rate or development of PVR up to 3 months after PPV. Further multicenter randomized clinical trials with longer follow-up periods and larger sample sizes are needed to verify these preliminary outcomes.

Aggressive angiomayxoma in men: Case report and systematic review.

Introduction: Aggressive angiomyxoma is a rare benign mesenchymal tumor and occurs rarely in males. This study aimed to review all the cases of AAM in men in the English literature up to September 2020 and investigate the clinical, histochemical, and radiological characteristics of AAM and discuss the best treatment choices according to available data. Methods: A comprehensive search of the PubMed, Google Scholar, and Embase databases up to September 2020 was performed looking for reported cases of male patients with AAM. The search excluded articles in languages other than English, reported female cases, and superficial angiomyxoma cases. Results: Among the 97 patients, the mean age was 48.2 years with an incidence peak between 40 and 60 years. The sites commonly involved were the scrotum (42.3%). On ultrasound, the tumor was hypoechoic (85.7%) with a well-defined margin (100%), whereas on MRI, most cases were isointense on T1-weighted images (53.8%), and hyperintense on T2-weighted images (85.7%). Immunohistochemistry revealed that the tumor tended to be positive for vimentin (100%), CD34 (63.4%), ER (50%), and PR (53.3%) while S-100 showed 91% negativity. Wide and complete surgical excision was conducted in most cases (72%), and follow-up duration ranged from 1 month to 144 months with a recurrence rate of 11.8%. Conclusion: Although the occurrence of AAM is rare in men, consideration should be taken in the differential diagnosis of a mass in the genitourinary region. According to our review, the most decisive immunohistochemistry profile is the positivity of Vimentin and CD34 with the negativity of S-100. Although hormonal treatment is controversial, we suggest a novel algorithm for the management of aggressive angiomyxoma.

Comparison complications rate between double-J ureteral stent and percutaneous nephrostomy in obstructive uropathy due to stone disease:A randomized controlled trial.

Background: Obstructive uropathy due to stone disease is seen every day in urological practice. Percutaneous nephrostomy and double j ureteral stent procedures are used. Methodology: A randomized controlled trial was conducted in one center from January 2021 to January 2022. A total of 104 patients of age ≥18 years who had unilateral or bilateral obstructive uropathy due to stone disease were divided into two groups. In Group A, 50 patients underwent to double j stent while in Group B, 54 patients who underwent percutaneous nephrostomy insertion tube. Under local anesthesia, the stent was inserted by cystoscopy. While the percutaneous nephrostomy was done under ultrasound guidance by using local anesthetic agent. Complications were noted in immediate postoperative period and on follow up. Results: Mean age of Group A was 35 ± 12.7 years whereas mean age in Group B was 36.7 ± 12.5 years and 49 out of patients were male. The most common complication in double j group and nephrostomy group was hematuria (16% and 5.5% respectively). Post DJ stent, complications like septicemia, painful trigon irritation, and stent encrustation were seen in 8.0%, 10.0%, 10.0% and 4.0% patients respectively. On the other hand, post-PCN septicemia, tube dislodgment or blockage, and injury to adjacent organs were seen in 3.7%, 5.5% and 1.8% respectively. In our trial, overall success rate for double j stenting was up to 84.0% and for percutaneous nephrostomy (PCN) was 96.29% (p < 0.0001). Conclusion: We found percutaneous nephrostomy is better and had overall higher success rate with less complications post procedure.

Effect of fluoxetine on the testes of adult albino rats and the possible protective role of curcumin.

Fluoxetine (FLX) is extensively used for the treatment of a diversity of psychiatric disorders, mainly depression. However, it can adversely affect male fertility. This study was done to clarify the changes which take place in the testes after the oral administration of FLX and to evaluate the possible preventative role of curcumin. Seventy-six adult male albino rats were randomly divided into four equal groups. Control group: kept without any treatment. Curcumin group: received daily dose of curcumin (150 mg/kg body weight) through oral gavage for 8 weeks. FLX group. They were given daily dose of FLX (10 mg/kg body weight) given through oral gavage for 8 weeks. FLX and curcumin group. They were given FLX together with curcumin with the same previous doses through oral gavage daily for 8 weeks. By the end of the experiment, blood samples were collected for the biochemical study of testosterone. All the animals were anaesthetized by ether inhalation, and the testis specimens were dissected out and weighed. The specimens were subjected to histopathological, immunohistochemical, and morphometrical evaluation. FLX decreased serum testosterone, diminished both epithelial height and diameter of seminiferous tubules, increased collagen fiber deposition in testicular tissue and induced positive immune reaction to B-cell lymphoma-2-associated X protein. In the FLX and curcumin group, the FLX-induced changes were less remarkable. Exposure to FLX led to pronounced testicular alterations. Co-administration of curcumin with FLX ameliorated these changes.

Comparing Assessments of Physical Functional Independence in Older Adults With Mobility Limitations.

OBJECTIVES: The aims of the study were (1) to assess the agreement and correlation between self-reported functional independence and observations of family caregivers in a heterogeneous population of community-dwelling older adults with disabilities and (2) to determine how self-reports and caregiver reports correlate with evaluator rated functional independence over time. DESIGN: Data were drawn from a larger, randomized controlled trial examining the effects of a caregiver-inclusive intervention on outcomes of care recipients and their family caregivers. Functional independence measures were obtained using a self-report version of the Functional Independence Measure (care recipient self-reported Functional Independence Measure, caregiver self-reported Functional Independence Measure) and the Functional Autonomy Measurement System (evaluator perspective). They were administered at baseline (preintervention) and after the intervention at 6, 22, and 58 wks. RESULTS: Bivariate correlation analyses of 90 dyads consisting of older care recipients and their family caregivers reported moderate to very strong correlations between the three functional independence measures across all time points (rS = 0.45-0.91, P < 0.01). Bland-Altman analyses revealed a small systematic bias between care recipient and caregiver assessments of functional independence, with participants reporting higher scores across all time points (mean difference = 2.00-2.97). CONCLUSIONS: There is substantial consistency among the self-assessed, caregiver-assessed, and evaluator assessed functional independence of older adults. Caregivers may be used as proxies for community-dwelling older adults without severe cognitive impairments with functional limitations. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: After reviewing this article, readers will be able to: (1) Describe the strength of association between self-reported functional independence and observations of family caregivers in a heterogeneous population of community-dwelling older adults with disabilities over time; (2) Describe the level of agreement between self-reported functional independence and observations of family caregivers over time; and (3) Describe the associations among self-reported, caregiver reported and evaluator rated functional independence over time. LEVEL: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Towards real-time in-implant epileptic seizure prediction.

We present an architecture of an epileptic seizure prediction system suitable for an implantable implementation. The microsystem comprises a neural interface, a spectral analysis processor and an artificial neural network (ANN). The neural interface and the spectral analysis processor have been prototyped in a 0.35 microm CMOS technology with experimental results are presented. The wavelet-based artificial neural network predicts the onsets of seizure up to two minutes before their occurrence in an in-vitro epilepsy model using a mouse hippocampal brain slice with recurrent spontaneous seizures.