Establishing delivery route-dependent safety and efficacy of living biodrug mesenchymal stem cells in heart failure patients.

BACKGROUND: Mesenchymal stem cells (MSCs) as living biopharmaceuticals with unique properties, i.e., stemness, viability, phenotypes, paracrine activity, etc., need to be administered such that they reach the target site, maintaining these properties unchanged and are retained at the injury site to participate in the repair process. Route of delivery (RoD) remains one of the critical determinants of safety and efficacy. This study elucidates the safety and effectiveness of different RoDs of MSC treatment in heart failure (HF) based on phase II randomized clinical trials (RCTs). We hypothesize that the RoD modulates the safety and efficacy of MSC-based therapy and determines the outcome of the intervention. AIM: To investigate the effect of RoD of MSCs on safety and efficacy in HF patients. METHODS: RCTs were retrieved from six databases. Safety endpoints included mortality and serious adverse events (SAEs), while efficacy outcomes encompassed changes in left ventricular ejection fraction (LVEF), 6-minute walk distance (6MWD), and pro-B-type natriuretic peptide (pro-BNP). Subgroup analyses on RoD were performed for all study endpoints. RESULTS: Twelve RCTs were included. Overall, MSC therapy demonstrated a significant decrease in mortality [relative risk (RR): 0.55, 95% confidence interval (95%CI): 0.33-0.92, P = 0.02] compared to control, while SAE outcomes showed no significant difference (RR: 0.84, 95%CI: 0.66-1.05, P = 0.11). RoD subgroup analysis revealed a significant difference in SAE among the transendocardial (TESI) injection subgroup (RR = 0.71, 95%CI: 0.54-0.95, P = 0.04). The pooled weighted mean difference (WMD) demonstrated an overall significant improvement of LVEF by 2.44% (WMD: 2.44%, 95%CI: 0.80-4.29, P value ≤ 0.001), with only intracoronary (IC) subgroup showing significant improvement (WMD: 7.26%, 95%CI: 5.61-8.92, P ≤ 0.001). Furthermore, the IC delivery route significantly improved 6MWD by 115 m (WMD = 114.99 m, 95%CI: 91.48-138.50), respectively. In biochemical efficacy outcomes, only the IC subgroup showed a significant reduction in pro-BNP by -860.64 pg/mL (WMD: -860.64 pg/Ml, 95%CI: -944.02 to -777.26, P = 0.001). CONCLUSION: Our study concluded that all delivery methods of MSC-based therapy are safe. Despite the overall benefits in efficacy, the TESI and IC routes provided better outcomes than other methods. Larger-scale trials are warranted before implementing MSC-based therapy in routine clinical practice.

Serendipitous Discovery: A Case of Twin Congenital Pseudarthrosis of the Clavicle in Saudi Arabia and Literature Review.

Congenital pseudarthrosis of the clavicle (CPC) is a rare disorder with an unknown etiology, which is caused by a failure of the clavicle ossification nuclei union process. This is the first CPC twin instance documented in Saudi Arabia, and the fourth overall. In the 33rd week, a set of twins was born prematurely with respiratory distress syndrome. They were both admitted to the neonatal intensive care unit. X-rays of the chest were taken, and the clavicular deformity was discovered. Because the twins were born via a cesarean section, a traumatic clavicular fracture was ruled out. The family members were evaluated, and the same defect was discovered in the father as well, highlighting a genetic predisposition.

Nervous System Response to Neurotrauma: A Narrative Review of Cerebrovascular and Cellular Changes After Neurotrauma.

Neurotrauma is a significant cause of morbidity and mortality worldwide. For instance, traumatic brain injury (TBI) causes more than 30% of all injury-related deaths in the USA annually. The underlying cause and clinical sequela vary among cases. Patients are liable to both acute and chronic changes in the nervous system after such a type of injury. Cerebrovascular disruption has the most common and serious effect in such cases because cerebrovascular autoregulation, which is one of the main determinants of cerebral perfusion pressure, can be effaced in brain injuries even in the absence of evident vascular injury. Disruption of the blood-brain barrier regulatory function may also ensue whether due to direct injury to its structure or metabolic changes. Furthermore, the autonomic nervous system (ANS) can be affected leading to sympathetic hyperactivity in many patients. On a cellular scale, the neuroinflammatory cascade medicated by the glial cells gets triggered in response to TBI. Nevertheless, cellular and molecular reactions involved in cerebrovascular repair are not fully understood yet. Most studies were done on animals with many drawbacks in interpreting results. Therefore, future studies including human subjects are necessarily needed. This review will be of relevance to clinicians and researchers interested in understanding the underlying mechanisms in neurotrauma cases and the development of proper therapies as well as those with a general interest in the neurotrauma field.

Meckel-Gruber syndrome together with Dandy-Walker malformation: an atypical case report of a 2nd recurrence in a consanguine marriage.

Meckel-Gruber syndrome is a lethal disorder characterized by occipital encephalocele, polycystic kidneys, and polydactyly. In most cases, it is identified and terminated antenatally. In this report, the authors present a case of Meckel-Gruber syndrome together with Dandy-Walker malformation. A pregnant woman referred at the 28th week of gestation with an abnormal ultrasound scan showing posterior encephalocele and bilaterally enlarged kidneys. Further imaging also indicated communication between the 4th ventricle and posterior cerebellar cerebrospinal fluid space, after which the fetus was diagnosed with Meckel-Gruber syndrome and Dandy-Walker malformation. Pregnancy termination was refused by the parents and the offspring was prematurely born to be the 2nd recurrence of Meckel-Gruber syndrome in this consanguine family. Remarkably, at the 3 different pregnancies, ultrasound was inconclusive before the 7th month of gestation. Though up to date Meckel-Gruber syndrome is ultimately lethal, the lifespan of affected newborns varied greatly. We suggest developing a severity classification to estimate life expectancy in unterminated cases.

Urinary Tract Infections in the Kingdom of Saudi Arabia, a Review.

Urinary tract infections (UTIs) are among the most common infections and are associated with an increased rate of antimicrobial resistance in Saudi Arabia. Better knowledge of the most common pathogens and their antimicrobial resistance patterns will be useful for creating new treatment guidelines. PubMed, Web of Science, Scopus, and Google Scholar were searched using suitable keywords to identify UTI publications until November 2022. Eligible studies were selected and analyzed. A total of 110 records were found, but only 58 articles were analyzed. Most studies were retrospective, and just a few were cross-sectional or prospective. The majority of the studies were conducted in the central region followed by the Eastern region. Escherichia coli and Klebsiella spp. were the most common pathogens. There was a significant resistance rate against co-trimoxazole and ciprofloxacin. On the other hand, amikacin was one of the most effective antibiotics. Overall, only a few studies have been published on UTIs in Saudi Arabia. Moreover, not all regions have been represented, so the full scope of the issue is unknown. UTIs are still a major problem, and resistance has developed against commonly used antibiotics. Thus, large epidemiological studies are needed to battle the rapid emergence of antimicrobial resistance.

A Comparison of the Knowledge, Attitude, Practice and Motivation Towards Blood Donation Among Albanian, Saudi and Turkish Citizens.

Background and Objectives: Blood donation is a remarkably safe medical procedure. However, it is affected by attitudes, beliefs, and knowledge level. A knowledge, attitude, and practice survey was carried out in Albania, KSA (Kingdom of Saudi Arabia) and Turkey to understand and identify: (1) the factors that influence blood donation, and stop people from blood donation, (2) the behavior and approach of the people towards blood donation (3) the knowledge level among donors and non-donors, and (4) the blood donation-related misconceptions. Materials and Methods: This search was conducted through online surveys using Google Forms, which were shared through social media platforms, ie, Facebook, WhatsApp, Gmail, etc. A self-administered questionnaire form was shared to random people through social media platforms and 1281 responses were received. Results: A total of 1281 forms were filled and submitted through Google Forms. Among these answers, 858 were from Albania, 273 were from KSA, 90 were from Turkey, and the remaining was from other countries. According to the answers, only 32% people were blood donors in Albania compared to 46% in KSA and Turkey. The factors primarily encouraging the people in Albania, Turkey, and KSA to donate blood included intention to help others in need, save lives, and help their family members. The primary reasons preventing people from blood donation included that they were not asked and some medical reasons. In Albania 88.6% would donate if asked, compared to 86% in KSA and in 77.7% in Turkey 77.7%. Conclusion: Despite considerable differences in the culture and demographics of the three countries, several common factors emerged from the surveys. Some of these results reflected an encouraging attitude toward blood donation. Further future planning with emphasis on educational programs and more organizations of donor recruitment campaigns can increase blood donations to fulfill the patients' needs in these countries.