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OBJECTIVE Schwann cells (SCs) have been shown to play an essential role in axon regeneration in both peripheral nerve injuries (PNIs) and spinal cord injuries (SCIs). The transplantation of SCs as an adjunctive therapy is currently under investigation in human clinical trials due to their regenerative capacity. Therefore, a reliable method for procuring large quantities of SCs from peripheral nerves is necessary. This paper presents a well-developed, validated, and optimized manufacturing protocol for clinical-grade SCs that are compliant with Current Good Manufacturing Practices (CGMPs). METHODS The authors evaluated the SC culture manufacturing data from 18 clinical trial participants who were recruited for autologous SC transplantation due to subacute SCI (n = 7), chronic SCI (n = 8), or PNIs (n = 3). To initiate autologous SC cultures, a mean nerve length of 11.8 ± 3.7 cm was harvested either from the sural nerve alone (n = 17) or with the sciatic nerve (n = 1). The nerves were digested with enzymes and SCs were isolated and further expanded in multiple passages to meet the dose requirements for transplantation. RESULTS An average yield of 87.2 ± 89.2 million cells at P2 and 150.9 ± 129.9 million cells at P3 with high viability and purity was produced. Cell counts and rates of expansion increased with each subsequent passage from P0 to P3, with the largest rate of expansion between P2 and P3. Larger harvest nerve lengths correlated significantly with greater yields at P0 and P1 (p < 0.05). In addition, a viability and purity above 90% was sustained throughout all passages in nearly all cell products. CONCLUSIONS This study presents reliable CGMP-compliant manufacturing methods for autologous SC products that are suitable for regenerative treatment of patients with SCI, PNI, or other conditions.

Background aims Extracellular vesicles (EVs) are being tested for their use as novel therapeutics. However, the optimal source of EVs is currently under investigation. Amniotic fluid (AF) is a natural source of EVs that can be easily obtained for use in regenerative medicine, yet AF-EV characterization has not been fully explored. Methods Here the authors demonstrate AF as a rich source of EVs and identify the microRNA and proteomic cargo. Bioinformatics analysis of this cargo revealed multiple pathway targets, including immunomodulatory, anti-inflammatory and free radical scavenging networks. The authors further demonstrated the therapeutic potential of this EV product as a novel preventative agent for bronchopulmonary dysplasia (BPD). Results Intra-tracheal administration of AF-EVs preserved alveolar development, attenuated vascular remodeling and pulmonary hypertension, decreased lung pro-inflammatory cytokine expression and reduced macrophage infiltration in an experimental BPD model. Conclusions The authors’ results suggest that AF is a viable biological fluid for EV harvest and that AF-EVs have strong therapeutic potential for pulmonary diseases, such as BPD, warranting further development to transition this novel EV product into the clinic.

Plasma-derived extracellular vesicles (EV) can serve as markers of cell damage/disease but can also have therapeutic utility depending on the nature of their cargo, such as miRNA. Currently, there are challenges and lack of innovations regarding early diagnosis and therapeutic options within different aspects of management of patients suffering from chronic pancreatitis (CP). Use of EV as biomarkers for pancreatic health and/or as adjuvant therapy would make a difference in management of these patients. The aim of this study was to characterize the miRNA cargo of EV purified from the plasma of CP patients and compared to those of healthy participants. EVs were isolated from plasma of 15 CP patients and 10 healthy controls. Nanoparticle tracking analysis was used to determine frequency and size, while NanoString technology was used to characterize the miRNA cargo. Relevant clinical parameters were correlated with EV miRNA cargo. ~ 30 miRNA species were identified to have significantly (p

The Production Assistance for Cellular Therapies (PACT) Program, is funded and supported by the US Department of Health and Human Services’ National Institutes of Health (NIH) National Heart Lung and Blood Institute (NHLBI) to advance development of somatic cell and genetically modified cell therapeutics in the areas of heart, lung, and blood diseases. The program began in 2003, continued under two competitive renewals, and ended June 2021. PACT has supported cell therapy product manufacturing, investigational new drug enabling preclinical studies, and translational services, and has provided regulatory assistance for candidate cell therapy products that may aid in the repair and regeneration of damaged/diseased cells, tissues, and organs. PACT currently supports the development of novel cell therapies through five cell processing facilities. These facilities offer manufacturing processes, analytical development, technology transfer, process scale‐up, and preclinical development expertise necessary to produce cell therapy products that are compliant with Good Laboratory Practices, current Good Manufacturing Practices, and current Good Tissue Practices regulations. The Emmes Company, LLC, serves as the Coordinating Center and assists with the management and coordination of PACT and its application submission and review process. This paper discusses the impact and accomplishments of the PACT program on the cell therapy field and its evolution over the duration of the program. It highlights the work that has been accomplished and provides a foundation to build future programs with similar goals to advance cellular therapeutics in a coordinated and centralized programmatic manner to support unmet medical needs within NHLBI purview.

Breastfeeding, use of pasteurised donor human milk when mother's own milk is unavailable and kangaroo mother care have independently proven benefits in improving survival of vulnerable sick babies. A triangulated approach called the Mother Baby Friendly Initiative Plus (MBFI+) model, bringing together the combined benefits of these proven interventions, was used to improve exclusive human milk feeding at health facilities through quality improvement and system strengthening approach. This quality improvement before-and-after uncontrolled study enrolled 5343 term and 278 very low birth weight (VLBW) mother-infant dyads. Pre- and post-intervention data were compared to evaluate effect on feeding-related healthcare processes and outcomes. Primary outcome which was incidence of exclusive human milk feeding during hospital stay, improved from 44 to 64.8% (RR 1.47, 95% CI: 1.40-1.55) among term and from 60.5 to 80.7% (RR: 1.33; 95% CI: 1.12-1.59) among VLBW neonates. Neonates receiving extended KMC improved from 43 to 71.1% (RR: 1.65; 95% CI: 1.30-2.10).Conclusion: MBFI+ approach improved exclusive human milk feeding among term and preterm VLBW neonates. What is Known: • Breastfeeding has immense health benefits to sick preterm neonates admitted in NICU. What is New: • Quality improvement approach can lead to system strengthening and can help overcome hindrances to achieve increased breastfeeding rates.

AIMS CONCERT-HF is an NHLBI-sponsored, double-blind, placebo-controlled, Phase II trial designed to determine whether treatment with autologous bone marrow-derived mesenchymal stromal cells (MSCs) and c-kit positive cardiac cells (CPCs), given alone or in combination, is feasible, safe, and beneficial in patients with heart failure (HF) caused by ischaemic cardiomyopathy. METHODS AND RESULTS Patients were randomized (1:1:1:1) to transendocardial injection of MSCs combined with CPCs, MSCs alone, CPCs alone, or placebo, and followed for 12 months. Seven centres enrolled 125 participants with left ventricular ejection fraction of 28.6 ± 6.1% and scar size 19.4 ± 5.8%, in New York Heart Association class II or III. The proportion of major adverse cardiac events (MACE) was significantly decreased by CPCs alone (-22% vs. placebo, P = 0.043). Quality of life (Minnesota Living with Heart Failure Questionnaire score) was significantly improved by MSCs alone (P = 0.050) and MSCs + CPCs (P = 0.023) vs. placebo. Left ventricular ejection fraction, left ventricular volumes, scar size, 6-min walking distance, and peak oxygen consumption did not differ significantly among groups. CONCLUSIONS This is the first multicentre trial assessing CPCs and a combination of two cell types from different tissues in HF patients. The results show that treatment is safe and feasible. Even with maximal guideline-directed therapy, both CPCs and MSCs were associated with improved clinical outcomes (MACE and quality of life, respectively) in ischaemic HF without affecting left ventricular function or structure, suggesting possible systemic or paracrine cellular mechanisms. Combining MSCs with CPCs was associated with improvement in both these outcomes. These results suggest potential important beneficial effects of CPCs and MSCs and support further investigation in HF patients.

Objective To evaluate the sensitivity of the modified Brief Form of Bruininks Oseretsky Test in identifying motor differences secondary to malnutrition and poverty. Methods This longitudinal cohort study was conducted at Nowshero Feroze, Sindh from 2013 to 2014 and comprised data drawn from children who participated in a randomised controlled trial, that assessed responsive stimulation and nutrition interventions in the first two years of life. Outcome measures included motor development assessed using Brief Form of Bruininks Oseretsky Test, child anthropometry and household economic and demographic information. Data was analysed using SPSS 15 and STATA 12. Results Of the 1058 children, 570(53%) were boys. Moderate-severe stunting was reported in 171(16.12%) subjects, while moderate-severe underweight was reported in 117(11.1%). Also, 591(56%) subjects belonged to poor families, 343(32%) had illiterate mothers, and 392(37%) were food-insecure. Malnutrition, socio-economic status and maternal literacy were significantly associated with a 6-item motor composite of the Brief Form of Bruininks Oseretsky Test (p Conclusions The 6-item motor composite of the Brief Form of Bruininks Oseretsky Test was found to be a reliable tool to measure motor performance in Pakistani pre-school children.

The article's abstract is not available.

The current research was centered on the scholarly issues and social barriers faced by female students to get affirmation in higher education. The study expected to discover the difficulties, which the respondents needed to face to conquer the social impediments in getting advanced education. The review concentrated on huge number of social obstructions and difficulties, budgetary issues and scholastic issues that female needed to confront. Quantitative research approach was utilized to uncover the experience of respondents which they encountered while getting affirmation in college. The research was being conducted in District Zhob, Baluchistan Province, since it was encompassed by for the most part country Areas. Population of the present review comprised of the female understudies contemplating in different instructive organizations. The discoveries demonstrate that different variables in charge of social prohibition of young ladies from education area in Pakistan incorporate preservationist state of mind of family and inclination to kid's training. Not with standing this, female understudies likewise tended to face impression of their families about co-education as social and religious variables to advanced education in Pakistan. The focus acknowledged with this class was "saw fears and dangers to family respect". As the individuals from conservative society, families had for the most part negative demeanor for females towards advanced education.

BACKGROUND: Biochemical recurrence (BCR) is considered a decisive risk factor for clinical recurrence and the metastasis of prostate cancer (PCa). Therefore, we developed and validated a signature which could be used to accurately predict BCR risk and aid in the selection of PCa treatments. METHODS: A comprehensive genome-wide analysis of data concerning PCa from previous datasets of the Cancer Genome Atlas (TCGA) and the gene expression omnibus (GEO) was performed. Lasso and Cox regression analyses were performed to develop and validate a novel signature to help predict BCR risk. Moreover, a nomogram was constructed by combining the signature and clinical variables. RESULTS: A total of 977 patients were involved in the study. This consisted of patients from the TCGA (n=405), GSE21034 (n=131), GSE70770 (n=193) and GSE116918 (n=248) datasets. A 9-mRNA signature was identified in the TCGA dataset (composed of C9orf152, EPHX2, ASPM, MMP11, CENPF, KIF4A, COL1A1, ASPN, and FANCI) which was significantly associated with BCR (HR =3.72, 95% CI: 2.30–6.00, P

Background: Postpartum Depression is a serious issue that can lead to irreversible disasters if not timely recognized and diagnosed. There are various modes of delivery; which may contribute towards physical and mental trauma. Methods: It was a prospective descriptive cross- sectional study carried out to evaluate the alliance of postnatal depression with different modes of delivery i.e. vaginal or lower segment caesarean section. The study was conducted at Ziauddin University Hospital. A sample size of 200 was taken. It was carried out from June 2019 to December 2019. A Performa was designed that questioned about different socio-demographic characteristics and risk factors for post-natal depression (PND). Edinburg Post-Natal Depression Scale (EPNDS) was used for authenticated identification of women with depression in purpeurium. Results: Out of the total sample of 200 women, 100 were taken from the spontaneous vaginal delivery group and 100 from cesarean section group. Mean age was 21-34 years. It was noticed that 60% women who underwent cesarean section became a victim of depression and 40% women who had a normal vaginal delivery were identified to have post natal depression. Conclusion: The study identifies cesarean section to be one of the culprits of postnatal depression as compared to woman undergoing spontaneous vaginal delivery. There is an exponential rise in the frequency of performing unexplained cesarean sections that would also boost up the graphs of postnatal depression; hence there is a dire need to instruct women to follow up postnatal so that they can be evaluated for post partum depression.

In this study, we report 2 cases of abnormal systemic artery to left lower lobe (ASALLL) with hemoptysis. In case 1, a 15-year-old boy experienced intermittent hemoptysis for over a year. After diagnosis of ASALLL by chest-enhanced computerized tomography (CT), interventional embolization was performed to treat the abnormal arteries, and the patient was cured and discharged. Case 2 is a 36-year-old man with chest pain and hemoptysis recurring for many years and aggravating for 5 days. ASALLL was diagnosed by chest-enhancement CT examination. After thoracoscopic resection of the left lower lobe, the patient was discharged. These cases show that the clinical manifestations of ASALLL are mainly recurrent hemoptysis symptoms. For patients with hemoptysis, the disease should be found and not limited to symptomatic treatment. Chest-enhanced CT scanning can diagnose ASALLL, and interventional embolization or surgical treatment can be selected for treatment.

Background and objective IPF is a fatal and debilitating lung disorder increasing in incidence worldwide. To date, two approved treatments only slow disease progression, have multiple side effects and do not provide a cure. MSC have promising therapeutic potential as a cell-based therapy for many lung disorders based on the anti-fibrotic properties of the MSC. Methods Critical questions remain surrounding the optimal source, timing and efficacy of cell-based therapies. The present study examines the most effective sources of MSC. Human MSC were derived from adipose, WJ, chorionic membrane (CSC) and chorionic villi (CVC). MSC were injected into the ageing mouse model of BLM-induced lung fibrosis. Results All sources decreased Aschroft and hydroxyproline levels when injected into BLM-treated mice at day 10 with the exception of CSC cells that did not change hydroxyproline levels. There were also decreases in mRNA expression of αv -integrin and TNFα in all sources except CSC. Only ASC- and WJ-derived cells reduced AKT and MMP-2 activation, while Cav-1 was increased by ASC treatment as previously reported. BLM-induced miR dysregulation of miR-29 and miR-199 was restored only by ASC treatment. Conclusion Our data suggest that sources of MSC may differ in the pathway(s) involved in repair.

Objective: To assess the relevance of urine test (UT), urine culture (UC) and stone culture (SC) for postoperative infections and to investigate the optimal perioperative antibiotic treatment strategy in association with percutaneous nephrolithotomy (PCNL) in patients with renal calculi. Materials and methods: Between September 2016 and September 2018 1,060 patients treated with PCNL were included in the study. The results of UT, UC and SC were reviewed. The details of perioperatively administered antibiotics and postoperative infections were recorded. Results: A positive UT was associated with an increased incidence of infection; this was also the case in patients with negative UC (p < 0.05). There was no significant difference in incidence of infection between patients who were given a single dose of antibiotics compared with those given multiple doses when UC was negative, whether UT was positive or negative (all p > 0.05). The incidence of infection was decreased when pre-operative antibiotics were administered according to the sensitivity pattern based on UC (p < 0.05). This outcome was particularly evident when the treatment duration exceeded 7 days (p < 0.05). A positive SC was associated with increased incidence of infection, even if the patient had a negative UC and UT (p < 0.05). The incidence of infection was significantly decreased when antibiotic treatment was administered based on the results of SC (p < 0.05). Conclusion: Pre-operative prophylaxis with a single-dose antibiotic was sufficient in patients with negative UC, whether UT was positive or negative. Pre-operative treatment with antibiotics according to the bacterial sensitivity pattern should be administered for ≥7 days in patients with positive UC. The postoperative antibiotic treatment strategy should be tailored according to the SC results.

The emergence of biologics has revolutionized the way physicians treat many autoimmune inflammatory conditions. Although biologics have become a vital component of the treatment approach to many inflammatory diseases, these agents may potentially disrupt the natural immune response against pathogens, thereby increasing the risk for infections. Some infections may be preventable or have a lessened risk through appropriate vaccinations; thus, vaccination history should be taken carefully in preparation for biologics and updated annually to maximize benefits while minimizing adverse effects. The objective of this review is to summarize recent articles, including guidelines, published that address vaccinations among patients on biologics.

Objective Urinary incontinence is highly prevalent among women, with a substantial effect on health-related quality of life. This article aimed to investigate the independent factors for urinary incontinence (UI) and the relative importance of each factor. Methods This study was a cross-sectional survey of Chinese women in Guangzhou. Female 20 years and older were invited to participate. The International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form was used to determine whether respondents are experiencing UI. Univariate and multivariate unconditional logistic regression analyses were performed to determine the significant risk factors associated with UI. Results A total of 2626 women were invited to participate in the survey. The response rate was 80.5% (2114/2626). The prevalence of UI among the study population was 31.2%. Old age, increased body mass index, childbirth, family history of any female pelvic floor disorders, symptoms of chronic cough or rhinitis, wearing a corset, and often drinking were independent risk factors for UI. Conclusions Urinary incontinence is common among Chinese women in Guangzhou. Among the factors that we are concerned with, old age and vaginal delivery are the two with greatest impact. Moreover, wearing a corset and drinking are the 2 lifestyle factors associated with UI.

A phase 1 open-label, non-randomized clinical trial was conducted to determine feasibility and safety of autologous human Schwann cell (ahSC) transplantation accompanied by rehabilitation in participants with chronic spinal cord injury (SCI). Magnetic resonance imaging (MRI) was used to screen eligible participants to estimate an individualized volume of cell suspension to be implanted. The trial incorporated standardized multi-modal rehabilitation before and after cell delivery. Participants underwent sural nerve harvest, and ahSCs were isolated and propagated in culture. The dose of culture-expanded ahSCs injected into the chronic spinal cord lesion of each individual followed a cavity-filling volume approach. Primary outcome measures for safety and trend-toward efficacy were assessed. Two participants with American Spinal Injury Association Impairment Scale (AIS) A and two participants with incomplete chronic SCI (AIS B, C) were each enrolled in cervical and thoracic SCI cohorts (n = 8 total). All participants completed the study per protocol, and no serious adverse events related to sural nerve harvest or ahSC transplantation were reported. Urinary tract infections and skin abrasions were the most common adverse events reported. One participant experienced a 4-point improvement in motor function, a 6-point improvement in sensory function, and a 1-level improvement in neurological level of injury. Follow-up MRI in the cervical (6 months) and thoracic (24 months) cohorts revealed a reduction in cyst volume after transplantation with reduced effect over time. This phase 1 trial demonstrated the feasibility and safety of ahSC transplantation combined with a multi-modal rehabilitation protocol for participants with chronic SCI.

Background: Col4a3 -/- Alport mice present a model of heart failure with preserved ejection fraction (HFpEF) secondary to chronic kidney disease (CKD) wherein etiological relationships have been established between hypertension, pulmonary edema, inflammation, cardiac hypertrophy and fibrosis, diastolic dysfunction and underlying abnormalities of elevated low-density lipoprotein receptor (LDLR) expression, excess LDL-cholesterol (LDL-C) accumulation, and mitochondrial dysfunction in renal tubules. HFpEF is characteristically unresponsive to pharmacological intervention. Here, we tested the hypothesis that selective β 2 -Adrenoceptor (β 2 AR) modulation with salbutamol, a short-acting β 2 AR agonist, could alleviate symptoms of CKD and simultaneously augment cardiac function. Secondarily, we investigated the mechanism of actions of such β 2 AR-mediated therapeutics on cardiac and renal functions. Methods: Alport mice were injected intraperitoneally with salbutamol or DMSO vehicle as a single bolus of 200μg/dose in short-term studies or daily with 100 μg/dose for 2 weeks long-term. Cardiac and renal functions, cAMP levels, in vivo renal tubular LDL-C uptake and renal histology were evaluated post-injection. In vitro mechanistic studies were performed in HK-2, Alport dog smooth muscle and tubular epithelial cells differentiated from Alport patient-derived iPSCs. Protein-protein interactions were studied using co-immunoprecipitation experiments and LDL-C uptake was measured by live-cell imaging. Results: Short-term, salbutamol improved renal function in parallel with decreased LDLR levels and reduced uptake of LDL-C into renal tubules. Long-term, cardiac diastolic function assessed by isovolumetric relaxation time (IVRT), filling pressures (E/E’), and myocardial performance index, and systolic function reflected by ejection fraction, stroke volume and cardiac output improved significantly in parallel with increased cardiac cAMP. Mechanistically, in the kidney, salbutamol activated IDOL and hence lysosomal ubiquitination and degradation of LDLR via a novel β 2 AR-mediated, cAMP-independent pathway involving the Rac1/Cdc42 β 1 PixGEF. β 1 Pix reversibly sequesters IDOL into a complex with LDLR, thereby blocking the degradation pathway. β 2 AR stimulation dissipates the complex reactivating IDOL-mediated LDLR degradation thereby re-establishing LDL-C homeostasis and renal function. Using flow cytometry in HEK293T cells, ectopic expression of bPix stabilized membrane LDLR, sensitive to IDOL- but not PCSK-mediated degradation. Conclusions: β 2 AR agonism represents a potential treatment strategy to alleviate progression of CKD and heart failure associated with HFpEF phenogroup 3.

A pandemic brought on by COVID-19 has created a scalable health crisis. The search to help alleviate COVID-19-related complications through therapeutics has become a necessity. Zofin is an investigational, acellular biologic derived from full-term perinatal amniotic fluid that contains extracellular vesicles. Extracellular nanoparticles as such have been studied for their immunomodulatory benefits via cellular therapeutics and, if applied to COVID-19-related inflammation, could benefit patient outcome. Subjects (n=8) experiencing mild-to-moderate COVID-19 symptoms were treated with the experimental intervention. Complete blood count, complete metabolic panel, inflammatory biomarkers, and absolute lymphocyte counts were recorded prior to and on days 4, 8, 14, 21, and 30 as markers of disease progression. Additionally, chest x-rays were taken of the patients prior to and on days 8 and 30. Patients experienced no serious adverse events. All COVID-19-associated symptoms resolved or became stable with no indication of disease worsening as found by patient and chest x-ray reports. Inflammatory biomarkers (CRP, IL-6, TNF- α ) and absolute lymphocyte counts improved throughout the study period. Findings from a proof-of-concept, expanded access trial for COVID-19 patients prove the acellular biologic is safe and potentially effective to prevent disease progression in a high-risk COVID-19 population with mild-to-moderate symptoms.

During the development of the female genital tract, any insult to the normal development process results in a set of intriguing abnormalities known as Müllerian duct abnormalities. The uterine didelphys is the second least common type of anomaly among these, which may commonly be associated with a longitudinal vaginal septum (lateral fusion defect). However uterine didelphys along with a transverse vaginal septum (lateral fusion plus resorption defect) is a very rare finding and to the best of our knowledge, thecase that we hereby report is the second one in literature.A 16-year-old unmarried girl presented with primary amenorrhoea and cyclical pain for 18months.On clinical examination and imaging, a case of uterine didelphys and transverse vaginal septum was found. Her urinary tract was normalon USG and MRI evaluation. Excision of the septum was done by abdomino-vaginal approach. The patient was discharged well.We conclude that a patient presenting with primary amenorrhea especially with cyclical dysmenorrhea with a transverse vaginal septum on examination should be thoroughly investigated for associated upper genital tract abnormalities as the treatment strategy and prognosis is largely dependent on the correct classification of the anomaly.

Background: Various factors lead to hypovitaminosis (decreased vitamin D levels in serum/blood), in general population, sunlight being one of the major factors. Doctors and staff nurses are particularly at risk due to long working hours indoors, which deprives them of adequate Ultraviolet light exposure.Methods: It was a prospective descriptive cross sectional study conducted at Ziauddin University Hospital, Keamari campus, from August 2018 to July 2019. The objective of this study was to determine the status of vitamin D deficiency among doctors and staff nurses working at Ziauddin University Hospital. All those doctors and staff nurses were included in the study, who were already advised by physicians to get serum vitamin D levels done for their symptoms. Results: A total sample of 118 was collected. 56 doctors and 62 staff nurses participated in the survey. 85 out of 118 (72%) subjects were either deficient or insufficient of vitamin D. Conclusion: Even though doctors and nurses are considered to have better understanding of vitamin D deficiency symptoms and morbidity it causes; still this study found out that majority of the healthcare providers working at Ziauddin hospital were deficient of this vitamin.

Event-Related Potential (ERP) analyses have revealed several language-related components in sentence processing literature. More recently, researchers attempted to apply machine-learning techniques to classify the language-structure dependent ERP signals in a more reliable and efficient way. The purpose of the current paper is to propose a classification technique based on data-driven approach to detect syntactic anomaly from language-related ERP components. We specifically examined whether sentences with syntactic violations elicited differential patterns of ERP signals and the abnormal patterns can be reliably classified by machine-learning techniques. The specific aim of the study is to develop a multi-channel fusion convolutional neural network (MCF-CNN) including two branches of CNNs and a trunk merged by an intermediate fusion layer to obtain trained linguistic features from the raw data and perform the classification. We extracted different linguistic ERP components from syntactic violations and put them in the fusion. As a next procedure we combined the features in the fusion layer of the proposed neural network architecture. Experimental results demonstrate that the proposed method provides more than 92% classification accuracy.

Introduction The electrophysiologic impact of cell-based therapy on the injured myocardium remains highly controversial. We aimed to perform a meta-analysis of studies comparing arrhythmia burden following transendocardial stem cell therapy vs placebo in patients with chronic ischemic heart disease (CIHD). Methods and results PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched. No restriction of stem cell type was specified. The outcomes included sustained supraventricular or ventricular arrhythmias (VAs), sudden cardiac death (SCD), and resuscitated sudden cardiac arrest (SCA). Effect sizes were reported as odds ratio (OR) and 95% CI. Poisson regression was used to account for zero-events data. Twelve randomized trials that included 736 patients (384 in the cell therapy group and 352 in the placebo group) were analyzed. Six different cell types were used. Follow-up ranged from 6 to 12 months. There was a significant decrease in risk of SCD in the cell therapy group, (FE OR, 0.19 [0.04, 0.93]; P = .04). In subgroup analysis, there was a significantly lower risk of SCD or resuscitated SCA in the cell therapy group limited to studies that did not use skeletal myoblasts, (FE OR, 0.23 [0.06, 0.83]; P = .03). There was no significant difference in the incidence of sustained VA between groups (FE OR, 0.91 [0.47, 1.77]; P = .8), even after stratifying by cell type. There was no difference in supraventricular arrhythmias between groups. Conclusion Nonskeletal myoblast transendocardial cell therapy was associated with a significantly lower risk of SCD or resuscitated SCA compared to control, with no proarrhythmic effects.

Background: Non-ischemic dilated cardiomyopathy (NIDCM) responds variably to intramyocardial injection of mesenchymal stem cells (MSCs). We hypothesized that NIDCM genotype may influence responsiveness to MSC therapy and performed genotyping on all patients in the POSEIDON-DCM trial. Methods: POSEIDON-DCM patients (n = 34) underwent genetic sequence analysis and deletion/duplication testing. The results were classified as positive for pathological variants (PV+; n = 8), negative for any variants (V−; n = 6), or as variants of uncertain significance (VUS; n = 20). All outcomes of therapy were analysed for each category of genetic results. Findings: The 3 groups were indistinguishable at baseline with regard to ejection fraction (EF), demographics, medication use, or functional parameters. V− patients had an increase in EF at 12 months: +13.6% (IQR = +7.8%; +20.5%; p = 0.002), compared with VUS (+6.5%; IQR = +0.9%, +11.1%; p = 0.005) and PV+(−5.9%; IQR = −12.7%, +1.0; p = 0.2; p = 0.01 between groups). Six-minute walk distance improved in V- patients, but not in VUS and PV+. V− patients improved MLHFQ, compared to the other 2 groups, which did not improve over time. EPCCFUs increased by 9.7 ± 1.9 in V− (p = 0.009) compared to VUS and PV+ patients. V− patients had one-year survival (100%) compared with VUS (85%) and PV+ (40%; p = 0.015 log-rank). Similarly, MACE rates were lower in V− (0%) than PV+ (61.9%) or VUS (42.2%; p = 0.021 log-rank). Interpretation: Our findings support the concept that the genetic profile of NIDCM patients plays a role in responsiveness to MSC therapy, with V− patients more likely to benefit and the converse for PV+. This observation emphasizes the need for further genetic studies, because of important implications for the management of NIDCM syndromes. Keywords: Precision medicine, Variants of uncertain significance, Positive for pathologic/likely pathologic variant, Dilated cardiomyopathy

The 2019 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for Mood, Cognition and Fatigue following Stroke is a comprehensive set of evidence-based guidelines addressing three important issues that can negatively impact the lives of people who have had a stroke. These include post-stroke depression and anxiety, vascular cognitive impairment, and post-stroke fatigue. Following stroke, approximately 20% to 50% of all persons may be affected by at least one of these conditions. There may also be overlap between conditions, particularly fatigue and depression. If not recognized and treated in a timely matter, these conditions can lead to worse long-term outcomes. The theme of this edition of the CSBPR is Partnerships and Collaborations, which stresses the importance of integration and coordination across the healthcare system to ensure timely and seamless care to optimize recovery and outcomes. Accordingly, these recommendations place strong emphasis on the importance of timely screening and assessments, and timely and adequate initiation of treatment across care settings. Ideally, when screening is suggestive of a mood or cognition issue, patients and families should be referred for in-depth assessment by healthcare providers with expertise in these areas. As the complexity of patients treated for stroke increases, continuity of care and strong communication among healthcare professionals, and between members of the healthcare team and the patient and their family is an even bigger imperative, as stressed throughout the recommendations, as they are critical elements to ensure smooth transitions from acute care to active rehabilitation and reintegration into their community.

High-level quadriplegia is a devastating condition with limited treatment options. Bone marrow derived stem cells (BMSCs) are reported to have immunomodulatory and neurotrophic effects in spinal cord injury (SCI). We report a subject with complete C2 SCI who received three anatomically targeted intrathecal infusions of BMSCs under a single-patient expanded access investigational new drug (IND). She underwent intensive physical therapy and was followed for >2 years. At end-point, her American Spinal Injury Association Impairment Scale (AIS) grade improved from A to B, and she recovered focal pressure touch sensation over several body areas. We conducted serial neurophysiological testing to monitor changes in residual connectivity. Motor, sensory, and autonomic system testing included motor evoked potentials (MEPs), somatosensory evoked potentials (SSEPs), electromyography (EMG) recordings, F waves, galvanic skin responses, and tilt-table responses. The quality and magnitude of voluntary EMG activations increased over time, but remained below the threshold of clinically obvious movement. Unexpectedly, at 14 months post-injury, deep inspiratory maneuvers triggered respiratory-like EMG bursting in the biceps and several other muscles. This finding means that connections between respiratory neurons and motor neurons were newly established, or unmasked. We also report serial analysis of MRI, International Standards for Neurological Classification of SCI (ISNCSCI), pulmonary function, pain scores, cerebrospinal fluid (CSF) cytokines, and bladder assessment. As a single case, the linkage of the clinical and neurophysiological changes to either natural history or to the BMSC infusions cannot be resolved. Nevertheless, such detailed neurophysiological assessment of high cervical SCI patients is rarely performed. Our findings indicate that electrophysiology studies are sensitive to define both residual connectivity and new plasticity.

INTRODUCTION: Uterine inversion is the collapse of uterine fundus into the endometrial cavity resulting in turning the uterus partially or completely inside out. Uterine inversion during cesarean section is an extremely rare obstetric complication and the exact incidence is not known. CASE DESCRIPTION: We report complete inversion of uterus in 38-year-old female, Gravida 2 Para 1+0, 38+0 weeks gestational age, admitted for elective lower segment cesarean section due to previous 1 scar. Delivery of the baby was uneventful. Complete inversion of uterus through uterine incision was noticed immediately after detachment of placenta. Oxytocin infusion was discontinued immediately, and uterine inversion was reversed manually by exteriorizing uterus and then making a fist and applying force on the fundus. Uterus was closed back in two layers, but it remained relaxed despite, massaging, oxytocin and sublingual misoprostol; therefore, modified B-lynch sutures were applied. This helped the patient to be prevented from any further complications. She was discharged as planned and was stable on follow up visits. CONCLUSION: Uterine inversion was promptly identified and corrected without any major complications.

The U.S. Food and Drug Administration (FDA) provides guidance for expanded access to experimental therapies, which in turn plays an important role in the Twenty-first Century Cures Act mandate to advance cell-based therapy. In cases of incurable diseases where there is a lack of alternative treatment options, many patients seek access to cell-based therapies for the possibility of treatment responses demonstrated in clinical trials. Here, we describe the use of the FDA’s expanded access to investigational new drug (IND) to address rare and emergency conditions that include stiff-person syndrome, spinal cord injury, traumatic brain stem injury, complex congenital heart disease, ischemic stroke, and peripheral nerve injury. We have administered both allogeneic bone marrow-derived mesenchymal stem cell (MSC) and autologous Schwann cell (SC) therapy to patients upon emergency request using Single Patient Expanded Access (SPEA) INDs approved by the FDA. In this report, we present our experience with 10 completed SPEA protocols.

Introduction: Pre-clinical studies have shown great promise in the use of cell-based therapies for stroke. Intra-arterial (IA) delivery directs the cells to the injured brain, is minimally invasive and widely available, making it attractive for clinical translation. Our group and others have shown the safety and efficacy of IA Mesenchymal Stem Cell (MSC) treatment in a rodent stroke model at 24 hours post-reperfusion. The optimal timing of a single dose of IA MSC is unknown. Also, whether an additional dose will lead to greater benefit and the optimal timing of the second dose need to be determined for successful translation of IA MSC to clinic. The objective of this study is to determine if dual dose IA-MSC treatment is superior to single dose and find the optimal timing for the second dose. Methods: We used a reversible middle cerebral artery occlusion (rMCAO) model for stroke in rats. IA-MSCs were administered using a PE-10 catheter at 1, 2 and 4 day after stroke as single dose. Based on the results of the first experiment, dual doses were given at 1-4, 1-6 and 1-15 day. Behavioral analysis of rotarod, neurological deficit scoring and stroke volume were determined at 30 days after treatment. Results: Single dose IA-MSC at 1day was superior (p=0.02, 0.01, 0.04) to single dose given on day 2 and no benefit was seen when given on day 4. Among the dual dose groups, 1-6 day after stroke showed significant improvement in neurodeficit score and stroke volume (p=0.007, p=0.03). However, the percentage increase in improvement in 1-6day (dual) was much higher than that observed in 1day (single) group (Fig 1). Detailed results will be presented at the meeting. Conclusion: The results of our study indicate that 1day after stroke is optimal for single dose of IA-MSC. An additional dose at 6days after stroke enhances the effect of IA-MSC in aiding symptomatic recovery and stroke lesion reduction. In summary, our findings contribute to understanding of the benefit of dual dose of IA MSC for translation to the clinic.

Background: Previously, we demonstrated that early administration of Wharton’s Jelly Mesenchymal Stem Cell-derived (WJ-MSC) exosomes attenuates pulmonary hypertension (PH) and improves lung structure in experimental bronchopulmonary dysplasia (BPD). The optimal dose is however not known. The purpose of this study was to determine the optimal WJ-MSC exosome dose for lung regeneration in severe BPD complicated by PH. Objective: To elucidate the most effective and safe MSC exosome dose to prevent neonatal hyperoxia-induced lung injury and PH. Design/Methods: …

Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus sensu lato tapeworms, continues to be a public health problem in many endemic countries, including Pakistan. Patient level data, including age, sex, and cyst(s) location for surgically managed CE patients for the years 2013-2016 from hospitals located in Punjab and Khyber Pakhtunkhwa provinces were obtained from medical charts. Direct and indirect costs associated with surgically managed CE patients treated in private and public hospitals were then estimated and applied to country-level case numbers estimated through the Global Burden of Disease Study. A total cost of US$4,068,666 (95% CI: US$3,097,684 – US$5,295,702) was estimated for the year 2017, with US$3,951,853 (95% CI: US$2,981,400 – US$5,177,610) attributable to direct diagnosis and treatment-related costs and US$117,137 (95% CI: US$91,841 – US$146, 979) attributable to wage losses during the treatment period. Mean direct cost per patient (US$1,056) was approximately 72% of the country's per capita gross domestic product (GDP). Surgical management continues to be the treatment of choice for CE patients in Pakistan. If physicians were to adhere to World Health Organization Informal Working Group on Echinococcosis (WHO-IWGE) cyst stage-specific treatment guidelines, it is likely that the number of surgical interventions would decrease as would treatment costs.

Inclusion of women and minorities in clinical research is critical to fully assess the safety and efficacy of innovative therapies. With inadequate representation of demography, generalizability is impaired since pharmacokinetics and pharmacodynamics differ in these patient populations. This study was designed to analyze the voluntary participation rates of different demographic groups in cell-based therapy clinical trials conducted by the Interdisciplinary Stem Cell Institute (ISCI) at the University of Miami, Miller School of Medicine. ISCI conducted eight clinical trials between 2007 and 2017. The trials enrolled patients with ischemic and non-ischemic cardiomyopathy, idiopathic pulmonary fibrosis (IPF), aging-frailty, and Type-2 Diabetes. Participants received cell-based therapy (n = 218) or placebo (n = 33). Among the 251 participants, 29.5% were Hispanic and 20% were women. The proportion of individuals participating in each trial was compared to that of the respective disease populations attending University of Miami Health System clinics to calculate the participation to prevalence ratio (PPR). Distribution of women accurately reflected the population attending the University of Miami Health System in trials for dilated cardiomyopathy (DCM) and aging-frailty but was under-represented in others. Similarly, Hispanics and whites were accurately represented in three of the five disease fields, with Hispanics under-represented in frailty and diabetes, and whites over-represented in DCM and IPF. Black patients were accurately represented in the diabetes trial but were under-represented in all others. This study provides insight into challenges of achieving representative inclusion in research. Novel community engagement strategies are necessary to improve inclusion of women and under-represented minorities in clinical research of cell-based therapy.

Neurophysiological testing can provide quantitative information about motor, sensory, and autonomic system connectivity following spinal cord injury (SCI). The clinical examination may be insufficiently sensitive and specific to reveal evolving changes in neural circuits after severe injury. Neurophysiologic data may provide otherwise imperceptible circuit information that has rarely been acquired in biologics clinical trials in SCI. We reported a Phase 1 study of autologous purified Schwann cell suspension transplantation into the injury epicenter of participants with complete subacute thoracic SCI, observing no clinical improvements. Here, we report longitudinal electrophysiological assessments conducted during the trial. Six participants underwent neurophysiology screening pre-transplantation with three post-transplantation neurophysiological assessments, focused on the thoracoabdominal region and lower limbs, including MEPs, SSEPs, voluntarily triggered EMG, and changes in GSR. We found several notable signals not detectable by clinical exam. In all six participants, thoracoabdominal motor connectivity was detected below the clinically assigned neurological level defined by sensory preservation. Additionally, small voluntary activations of leg and foot muscles or positive lower extremity MEPs were detected in all participants. Voluntary EMG was most sensitive to detect leg motor function. The recorded MEP amplitudes and latencies indicated a more caudal thoracic level above which amplitude recovery over time was observed. In contrast, further below, amplitudes showed less improvement, and latencies were increased. Intercostal spasms observed with EMG may also indicate this thoracic “motor level.” Galvanic skin testing revealed autonomic dysfunction in the hands above the injury levels. As an open-label study, we can establish no clear link between these observations and cell transplantation. This neurophysiological characterization may be of value to detect therapeutic effects in future controlled studies.

Introduction: Although preclinical studies of cell delivery in models of ischemic heart failure (HF) suggest a beneficial interaction between mesenchymal stromal cells (MSCs) and c-kit+ cardiac progenitor cells (CPCs) resulting in additive therapeutic effects, no clinical trial has examined a combination of different cell types in ischemic HF. Furthermore, comparative studies of different cell products in humans are rare. CONCERT-HF (NCT02501811) is an NHLBI-sponsored, randomized, double-blind, placebo-controlled, Phase II trial of the Cardiovascular Cell Therapy Research Network (CCTRN) investigating feasibility, safety, and efficacy of MSCs and CPCs, alone and in combination, in patients with chronic ischemic HF. Objectives: To address the following questions: Is combined treatment with MSCs and CPCs feasible and safe in patients with ischemic HF? Do MSCs and CPCs, given alone or in combination, alleviate LV dysfunction, reduce scar size, improve quality of life, and/or augment functional capacity? Is either cell type more effective than the other? Is the combination of MSCs and CPCs more efficacious than MSCs alone or CPCs alone? Methods: Patients were randomized (1:1:1:1) to receive i) the combination of autologous bone marrow-derived MSCs and autologous CPCs, ii) MSCs alone, iii) CPCs alone, or iv) placebo. Target doses were 150 x 10 6 MSCs and 5 x 10 6 CPCs. All patients underwent bone marrow aspiration and right heart catheterization. Endomyocardial biopsy was performed only in the MSC + CPC and CPC alone groups; a “sham biopsy” was performed in the MSC alone and placebo groups. All patients underwent study product injection using the NOGA ® XP Mapping System and were followed for 12 months. Results: A total of 125 patients (116 M, 9 F), 62.5 ± 8.9 years old, were enrolled at 7 CCTRN centers between Nov 2016 and Oct 2018. Baseline LVEF (cardiac MRI) was 28.6 ± 6.1% with a mean scar size of 31.8 ± 10.9 g and NYHA class II (80%) or class III (15.2%). Conclusions: CONCERT-HF is the first cell therapy trial to assess a combination of different cell types and to directly compare two different cell products in patients with HF. All patients will complete follow-up by the end of June and final primary (12-month) safety and outcomes data will be available in August 2020.

Introduction: Bronchopulmonary dysplasia (BPD) or chronic lung injury of newborn is a life-threatening condition in preterm infants with few effective therapies. Mesenchymal stem cells (MSC) are a promising therapeutic strategy for BPD. The ideal MSC source for BPD prevention is however unknown. Umbilical cord tissue (UCT) MSC may potentially have more anti-inflammatory and pro-angiogenic properties. Hypothesis: We hypothesized that the UCT-MSC will have superior lung regenerative effect in BPD owing to superior anti-inflammatory and pro-angiogenic properties as compared to BM-MSC. Methods: Newborn rats (n=10-12/group) were randomly assigned to normoxia or hyperoxia (85% O 2 ) from postnatal day (P) 1 to 21 were given intra-tracheal (IT) BM or UCT-MSC (1 x 10 6 cells/50 μl), or placebo (PL) on P3. Results: Hyperoxia PL-treated pups had marked alveolar simplification, vascular rarefaction, remodeling and lung inflammation. Administration of both BM-MSC and UCT-MSC significantly improved alveolar structure, vascular density, pulmonary hypertension, vascular remodeling and lung inflammation. However, the improvement in alveolar structure and lung inflammation was more marked in hyperoxic pups who received UCT-MSC. In vitro studies demonstrated greater TSG-6 and IL-10 expression in UCT-MSC as compared to BM-MSC. Moreover, lung epithelial cells incubated with UCT-MSC conditioned media had greater wound healing following scratch injury. Conclusion: These findings demonstrate that while both BM and UCT-MSC have lung regenerative effects, UCT-MSC have greater anti-inflammatory and alveolar protective effects in experimental BPD. These findings have significant implications for cellular therapy in BPD, as it suggests that UCT-MSC are a superior cellular source for preterm lung protection.

Gorniak et al. 2020 - PLoS One., Also funded by American Heart Association Grant (16BGIA27250047) and University of Houston HEALTH Research Institute Basic Biomedical Science Research Grant (2019).

In this clinical research project, we will conduct a highly rigorous clinical trial where we randomize the patients between umbilical cord (UC)-derived mesenchymal stem cell (MSC) and standard of care (SOC). This study will ask the question whether the allogenic MSCs are effective in reducing death and/or progression of COVID-19 disease when administered to patients with moderate to severe symptoms. MSCs are unique group of cells with minimal immune reactivity and produce multiple beneficial effects, which include reduction of severe inflammatory reaction. There is convincing evidence from human studies that intravenous (IV) delivery of MSCs can directly impact the hyper-inflammatory responses of COVID-19 induced injury of the heart and lungs. Our study will evaluate the safety and efficacy of allogenic UC-derived MSCs administered intravenously to COVID-19 patients with moderate to severe symptom in a randomized, controlled clinical trial. In addition, we will determine whether : (i) UC-derived MSCs are effective in reducing 30-day all-cause mortality (primary endpoint) and (ii) UC-derived MSCs are effective in preventing progression to mechanical ventilation, and/or reducing an inflammatory response, and/or improving overall patient condition (secondary endpoints).

Background Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), which accounts for majority of RCC-related deaths. It is clearly essential to further identify more novel prognostic signatures and therapeutic targets. Material and methods We identified differentially expressed genes (DEGs) between ccRCC and adjacent normal tissues in GEO database using a Robust Rank Aggregation (RRA) method. An mRNA signature (mRNASig) based on DEGs was developed using Cox and LASSO analysis in the TCGA database and validated in the ICGC database. Afterward, the influence of mRNASig mRNAs on the immune microenvironment in ccRCC was explored using comprehensive bioinformatics analysis. Results A total of 957 robust DEGs were identified using the RRA method. mRNASig comprised CEP55, IFI44, NCF4, and TCIRG1 and was developed and validated to identify high-risk patients who had poorer prognosis than low-risk patients. A nomogram was also constructed based on mRNASig, AJCC stage, and tumor grade. The mRNASig were closely related to a variety of tumor-infiltrating lymphocytes, especially including CD8+ T cells, activated CD4+ memory T cells, regulatory T cells, activated NK cells, and resting NK cells. The mRNASig were also correlated positively with the expression of CTLA4, LAG3, PDCD1, TIGIT, and HAVCR2. Conclusion We developed and validated mRNASig to assist clinicians in making personalized treatment decisions. Furthermore, CEP55, IFI44, NCF4, and TCIRG1 may be novel potential targets for future treatment of ccRCC.

Background & Aims Depression and anxiety can have negative effects on patients and are important to treat. There have been few studies of their prevalence among patients with cirrhosis. We aimed to characterize the prevalence and risk factors for depression and anxiety in a large multi-center cohort of patients with cirrhosis. Methods We conducted a telephone-based survey of patients with cirrhosis at 3 health systems in the United States (a tertiary-care referral center, a safety net system, and a Veterans hospital) from April through December 2018. Of 2871 patients approached, 1021 (35.6%) completed the survey. Depression and anxiety were assessed using the PHQ-9 (range 0–25) and STAI (range 20–80) instruments, with clinically significant values defined as PHQ-9 ≥15 and STAI ≥40. We performed multivariate logistic regression analysis to identify factors associated with significant depression and anxiety. Results The median PHQ-9 score was 7 (25th percentile–75th percentile, 3–12) and the median STAI score was 33 (25th percentile–75th percentile, 23–47); 15.6% of patients had moderately severe to severe depression and 42.6% of patients had high anxiety. In multivariable analyses, self-reported poor health (odds ratio [OR], 4.08; 95% CI, 1.79–9.28), being widowed (OR, 2.08; 95% CI, 1.07–4.05), fear of hepatocellular carcinoma (OR, 1.89; 95% CI, 1.04–3.42), higher household income (OR, 0.30; 95% CI, 0.10–0.95), and Hispanic ethnicity (OR, 0.57; 95% CI, 0.33–0.97) were associated with moderately severe to severe depression. Male sex (OR, 0.71; 95% CI, 0.51–0.98), self-reported poor health (OR, 2.73; 95% CI, 1.73–4.32), and fear of hepatocellular carcinoma (OR, 2.24; 95% CI, 1.33–3.78) were associated with high anxiety. Conclusions Nearly 1 in 6 patients with cirrhosis have moderately severe to severe depression and nearly half have moderate–severe anxiety. Patients with cirrhosis should be evaluated for both of these disorders.

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous condition involving multiple comorbidities. Phenotypic classification of HFpEF associated with chronic kidney disease (CKD) manifests worse outcomes, compared to other HFpEF phenotypes. Few treatments improve morbidity and mortality in HFpEF. Stem cell therapy promotes cardiac repair in ischemic and non-ischemic cardiomyopathies. We hypothesized that allogeneic stem cell treatment ameliorates HFpEF in a large animal model of CKD. Methods: Yorkshire pigs (n=26) underwent 5/6 embolization-mediated nephrectomy and 4-weeks later received either: allogeneic mesenchymal stem cells (MSCs) (10х10 6 ), Kidney stem cells (KSC; 10х10 6 ), combination (ACCT; MSC+KSC; 1:1 ratio [5х10 6 each]), or placebo (n=6-7/ group). Cell therapy was delivered via the patent renal artery of the remnant kidney. RNAsec analysis compared placebo and ACCT groups. Results: Mean arterial pressure increased significantly in the placebo- (21.89±6.05 mmHg, p-6 , NES = -2.32) in ACCT. Consistent with these results, there was a downregulation of canonical drivers of tubular damage and regeneration, including SOX9 (-2.39 fold, p=0.0004) and apoptosis of kidney cell types (-24.89 fold, p=0.004), including podocytes (-2.065 fold, p=0.04) with ACCT. ACCT administration also downregulated genes related to oxidative stress (-4.6 fold, p Conclusion: Intra-renal artery allogeneic cell therapy was safe. Beneficial effects were observed in the ACCT and MSC groups in the kidney and heart. These findings have important implications on the use of cell therapy for HFpEF and cardiorenal syndrome.

Objective To analyze the CT imaging results of patients with COVID-19 who previously received several follow-up visits and to explain the changes in pulmonary inflammation. Methods Cases of 15 patients with COVID-19 were retrospectively analyzed: their epidemiology, clinical history, laboratory tests, and multiple CT chest scans obtained during the disease period were studied. Results The CT scans of the 15 patients showed different results. Four patients had no abnormal findings in their chest CT scans. The first scan of 1 patient revealed right lower lobe inflammation, while the lesion had been completely absorbed in follow-up. Two patients showed bilateral pulmonary inflammation in the first scan which had been absorbed by follow-up but the last examination showed extensive fibrosis. Two patients had no abnormalities in their first CT scans, while pulmonary inflammation was found in the second scan and this had not been completely absorbed by the last follow-up. One patient had pulmonary interstitial lesions with no evidence of National Cochlear Implant Programme (NCIP) on the first and second CT scans. NCIP was found at the third scan, and pulmonary inflammation was not completely absorbed at the last follow-up. Three patients were in the early stage of inflammation at the first scan, and the lesions were absorbed and repaired at the last follow-up. However, the lesions were not completely absorbed. One patient was in the advanced stage at the first scan, and the last follow-up pulmonary lesions were not completely absorbed. The first CT scan of 1 patient revealed large ground-glass opacity in the lungs involving the inner and middle bands. After follow-up, the disease progressed, and this condition was consistent with severe manifestations. Conclusion The follow-up of chest CT can reflect the change process of NCIP and the treatment effect. The first CT scan of lung lesions has a certain predictive effect on the outcome and prognosis of patients.

Hydrocephalus and Posterior Reversible Encephalopathy Syndrome (PRES) are under-diagnosed conditions in peri-partum period. As eclampsia mimics these conditions and it can mislead the clinician to an incorrect diagnosis causing potential morbidity and mortality. A case of a 35 year old pregnant woman with seizures presented that was initially diagnosed as eclampsia but failure to regain consciousness post-delivery led to a multidisciplinary team formation and further investigation through Magnetic Resonance Imaging (MRI) that finally revealed communicating hydrocephalous and PRES. Prompt management was initiated by placing a Ventriculo-Peritoneal (VP) shunt resulting in full neurological recovery afterwards. As per author’s knowledge there has not been a similar case reported as yet.

Cat scratch disease is an infectious disease resulting from inoculation of Bartonella species through a cat scratch or bite, often presenting as an erythematous papule at the site of inoculation with nearby painful lymphadenopathy. The diagnosis of this disease is complicated by a wide variety of clinical presentations, as the primary lesion may not be initially noticed. Furthermore, cervical and axillary lymph nodes are the most commonly involved regions of tender lymphadenopathy, but there have been reported cases that do not fit the typical clinical picture – such the case discussed in this report of a pediatric Bartonella henselae infection that initially presented as left inguinal lymphadenopathy with underlying necrosis and abscess formation. In this case, a 9-year-old boy presented to the ED with a 4-day history of increasing mass in the left groin, as well as a subjective fever for the previous 2 days. An ultrasound revealed a necrotic abscess in the left inguinal lymph node which necessitated empiric antibiotic therapy and surgical excision; titers revealed a recent infection with Bartonella henselae. Atypical presentations of cat scratch disease, such as inguinal lymphadenopathy, have historically confounded the diagnosis. However, positive serology studies ultimately yielded the correct diagnoses in these children. Given that cat scratch disease can present in an atypical fashion in approximately 5 - 25% of cases, physicians should keep the disease on the differential even when presented with rare presentations such as inguinal lymphadenopathy; serological testing for B. henselae can be utilized once more likely etiologies have been ruled out.

Trisomy 9 Mosaic syndrome is one of many rare syndromes. Less than 100 cases is known to date. Our case is the only one we’re aware of in the Panhandle region. We present this case to bring awareness of this rare syndrome to providers in how to facilitate management.