The utility of whole-exome sequencing in accurate diagnosis of neuromuscular disorders in consanguineous families in Jordan.

BACKGROUND: Neuromuscular disorders (NMDs) encompass a large group of genetic and acquired diseases affecting muscles, leading to progressive muscular weakness. These disorders are frequently inherited in an autosomal-recessive (AR) pattern with extreme heterogeneity and various clinical presentations. Consanguinity increases the likelihood of AR disorders, with high rates of cousin inbreeding in Jordan and other Arab countries. In Jordan, the implementation of genetic diagnosis is limited, with delayed or misdiagnosis of genetic disorders. Thus, the lack of genetic counselling and specialized treatment options is frequently encountered in the country. METHODS: Whole-exome sequencing (WES) was conducted for eleven probands from ten Jordanian families who have been formerly diagnosed with limb-girdle dystrophy (LGMD) and Charcot-Marie-Tooth disease (CMT). The previous diagnoses were established principally on clinical examination in the absence of genetic testing. Additionally, Sanger sequencing and segregation analysis were used to validate the resulted pathogenic variants. RESULTS: Multiple variants were identified using WES: For DYSF gene, a missense variant (c. 4076 T > C, p.Leu1359Pro) in exon 38; a nonsense variant (c. 4321C > T, p.Gln1441Ter) in exon 39; a single-nucleotide deletion (c. 5711delG, p.Gly1904AlafsTer101) in exon 51. Other variants included a missense variant (c. 122G > A, p.Arg41Gln) in exon 3 of MPV17 gene, a single-nucleotide deletion (c. 859 delC, p.Lue287Ser fs14*) in exon 6 of SGCB gene, a missense variant (c. 311G > A, p.Gly104Asp) in exon 2 of SLC25A46 gene, a nonsense variant (c. 496C > T, p.Arg166Ter) in exon 5 of SGCG gene, and a nonsense variant (c.3202C > T, p.Gln1068Ter) in exon 13 of SH3TC2 gene. CONCLUSION: Utilization of WES is helpful to facilitate rapid and accurate NMDs diagnosis, complementing a thorough clinical evaluation. This approach can be invaluable to aid in the identification of genetic risks among consanguineous couples. Subsequently, well-informed genetic counselling and potential individualized treatment can be provided.

The combinatorial use of propofol-fentanyl-ketamine for sedoanalgesia in patients undergoing urological procedures.

OBJECTIVES: To compare sedoanalgesia achieved using propofol-fentanyl-ketamine (PFK) combination with general anesthesia (GA) in terms of safety, hemodynamic stability, and perioperative complications. METHODS: Patients in the GA group were anesthetized using fentanyl (2 µg kg-1) and propofol (2 mg kg-1). The PFK group was anesthetized using a mixture of which each one ml contains 0.005 mg of fentanyl, 5 mg of propofol, 5 mg of ketamine, and 2 mg of lidocaine. Patients received an initial dose of 0.05 ml kg-1, followed by 0.05 mg kg-1 60 seconds later. Maintenance boluses of 0.025 ml kg-1 were administered every 3-5 minutes. Respiration occurred spontaneously through a simple face mask with 3 L min-1 O2. RESULTS: The GA group had 37 (37%) patients develop hypotensive episodes, compared to one (1%) episode in the PFK group (p<0.001). Five (5%) patients in the PFK group had an episode of transient O2 desaturation, compared to one (1%) patient in the GA group (p=0.212). The duration of induction and termination of anesthesia were significantly shorter in the PFK group (p<0.001). CONCLUSION: The PFK combination herein described is safe, effective, and provides intraoperative hemodynamic stability in patients with multiple comorbidities undergoing urological procedures.

A Co-Induction Technique Utilizing 4% Sevoflurane Followed by 0.75 mg/kg Propofol in Elderly Patients Undergoing Minimally Invasive Procedures: A Prospective Randomized Control Study.

Background and Objectives: Elderly patients constitute a large segment of healthcare receivers. Considering the functional deterioration of multiple organ systems with aging, achieving a safe perioperative approach is challenging. Our aim is to study the safety and effectiveness of a genuinely regimented co-induction technique in order to minimize anesthesia-related complications. Materials and Methods: One hundred and five patients were assigned to three groups according to the induction technique: propofol, sevoflurane and co-induction group. Inclusion criteria: patients with age ≥65 and American Society of Anesthesiologists physical status classification (ASA) II-III who underwent endoscopic urological procedures. The propofol group received a dose of 1.5 mg kg-1 of propofol over two minutes for induction. The sevoflurane group received 8% of sevoflurane and 100% oxygen through a plastic facemask with the fresh gas flow set at 8 L min-1. The co-induction group received 4% sevoflurane through plastic facemask for two minutes, followed by a 0.75 mg kg-1 dose of propofol. After ensuring full range jaw relaxation, the laryngeal mask airway (LMA) was inserted. Results: Overall, the co-induction technique had a favorable profile in terms of respiratory adverse events, while the sevoflurane group had a favorable profile in terms of hemodynamic stability. Furthermore, 24 (68.6%) patients receiving inhalational sevoflurane had episodes of transient apnea, which constitutes 77.4% of the 31 episodes of transient apnea in the studied sample (p < 0.001). Moreover, six (17.1%) patients in the sevoflurane group had an episode of partial laryngospasm (p = 0.034). Compared with the co-induction group, we found that the propofol group had significantly less systolic and diastolic blood pressures in the second minute, with p values of (0.018) and (0.015), respectively. Conclusions: The co-induction technique utilizing 4% sevoflurane at 8 L min-1 flow of oxygen inhaled over two minutes followed by 0.75 mg kg-1 of propofol achieved less respiratory adverse events compared with the sevoflurane group, and less hemodynamic instability compared with the propofol group.

The effect of ondansetron administration 20 minutes prior to spinal anaesthesia on haemodynamic status in patients undergoing elective caesarean section: A comparison between two different doses.

BACKGROUND AND AIMS: Spinal anaesthesia is currently the most common method used for managing patients undergoing elective caesarean sections. Recent meta-analyses have been supporting the use of 5-HT3 antagonists, like ondansetron, to attenuate hypotension induced by spinal block. Various doses of ondansetron were given intravenously five minutes before spinal block. However, a consensus on definitive dose and timing for maximal benefit is yet to be agreed upon. METHODS: Our prospective randomised clinical trial investigated a new approach by administrating intravenous ondansetron 20 minutes before spinal anaesthesia. This work investigated ondansetron effect on both haemodynamic changes and vasopressors use by dividing patients into three groups. The first group O4 (n = 51) received 4 mg ondansetron, the second group O6 (n = 51) received 6 mg ondansetron, and the control group C (n = 50) received normal saline. We recorded systolic blood pressure (SBP), diastolic blood pressure (DBP) and the mean blood pressure (MBP) at different time intervals. RESULTS: There was no significant difference in blood pressure measurements among the study groups (P > 0.05). The consumption of ephedrine in the control group is higher than both of the ondansetron groups (P > 0.001), with a mean dose of 27.2 ± 20.5 mg of ephedrine for group C, compared to 17.8 ± 14.9 and 14.7 ± 11.3 in O4 and O6 groups, respectively. Episodes of hypotension and number of patients with hypotension were not significantly different among the studied groups (P = 0.07; P = 0.96, respectively). CONCLUSIONS: Prophylactic 4 and 6 mg ondansetron given 20 minutes before spinal anaesthesia in caesarean section does not reduce the incidence of hypotension.

Bifocal Tibial Kaposiform Hemangioendothelioma Responsive to Vincristine Therapy: A Case Report.

BACKGROUND Kaposiform hemangioendothelioma is a rare locally aggressive vascular endothelial-derived spindle cells neoplasm. Herein, we report a rare case of bifocal tibial kaposiform hemangioendothelioma. CASE REPORT A 9-year-old female presented with a 2-year history of pain and swelling in the left leg. The patient had a high plasma level of the D-dimer and fibrinogen. Radiography revealed a centric lytic lesion on the left proximal tibial metaphysis and an eccentric lateral distal tibial metaphyseal. Histopathologic examination of the sample taken from the distal tibia revealed a dense spindle cell tumor with lobular architecture composed of compact spindle cells compressing small slit-like vascular spaces, forming glomeruloid nests. No necrosis was identified. Based on these findings and the positive immunohistochemical staining for CD31, CD34, and D2-40, the patient was diagnosed with kaposiform hemangioendothelioma. Treatment was started by using vincristine chemotherapy, after which the patient developed temporary peroneal neuropathy, which improved over the next 3 months. CONCLUSIONS Bifocal tibial kaposiform hemangioendothelioma lesions are unique in pediatric patients and can be successfully treated with vincristine chemotherapy. In these cases, the treating physician should be aware of peroneal neuropathy as a potential complication of vincristine administration.