Breakdown of Phosphatidylserine Asymmetry Following Treatment of Erythrocytes with Lumefantrine

Background: Lumefantrine, a commonly used antimalarial drug, inhibits hemozoin formation in parasites. Several other antimalarial substances counteract parasitemia by triggering suicidal death or eryptosis of infected erythrocytes. Eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine-exposure at the erythrocyte surface. Signaling involved in eryptosis include increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i), formation of ceramide, oxidative stress and/or activation of p38 kinase, protein kinase C (PKC), or caspases. The present study explored, whether lumefantrine stimulates eryptosis. Methods: Cell volume has been estimated from forward scatter, phosphatidylserine-exposure from annexin V binding, [Ca²⁺]_i from Fluo3-fluorescence, reactive oxygen species from 2'',7''-dichlorodihydrofluorescein-diacetate fluorescence, content of reduced glutathione (GSH) from mercury orange fluorescence, and ceramide abundance from binding of fluorescent antibodies in flow cytometry. Results: A 48 h exposure to lumefantrine (3 µg/mL) was followed by a significant increase of annexin-V-binding without significantly altering forward scatter, [Ca²⁺]_i, ROS formation, reduced GSH, or ceramide abundance. The annexin-V-binding following lumefantrine treatment was not significantly modified by p38 kinase inhibitors SB203580 (2 μM) and p38 Inh III (1 μM), PKC inhibitor staurosporine (1 µM) or pancaspase inhibitor zVAD (1 or 10 µM). Conclusions: Lumefantrine triggers cell membrane scrambling, an effect independent from entry of extracellular Ca²⁺, ceramide formation, ROS formation, glutathione content, p38 kinase, PKC or caspases.     

Successful treatment of relapsing autoimmune thrombotic thrombocytopenic purpura with rituximab

Thrombotic thrombocytopenic purpura (TTP) is a rare but life‐threatening condition characterized by thrombotic microangiopathy. The standard treatment for TTP is plasmapheresis. For refractory or relapsing cases, various immunosuppressive agents have been tried, and among them rituximab has shown promising results. TTP is rarer in the pediatric age group and the use of rituximab in children with TTP is limited. Reported herein is the successful treatment of relapsing autoimmune TTP with rituximab in a 12‐year‐old girl.     

Preparation and optimization of aloe ferox gel loaded with Finasteride-Oregano oil nanocubosomes for treatment of alopecia

Alopecia areata is a skin disorder characterized by scarless, localized hair loss that is usually managed by topical treatments that might further worsen the condition. Therefore, the current study aimed to develop nano-cubosomes loaded with finasteride (FI) and oregano oil (Or) to improve drug solubility and permeation through skin and then incorporate it into an aloe ferox gel base. An l-optimal coordinate exchange design was adopted to optimize nano-cubosomes. Phytantriol and Alkyl Acrylate were employed as the lipid material, and surfactant respectively for cubosomes manufacture. The produced formulations were assessed for their particle size, entrapment efficiency (EE%), FI steady-state flux (Jss) and minimum inhibitory concentration (MIC) against Pro-pionibacterium acnes. Optimal FI-Or-NCu had a particle size of 135 nm, EE% equals 70%, Jss of 1.85 μg/cm2.h, and MIC of 0.44 μg/ml. The optimum formulation loaded gel gained the highest drug release percent and ex vivo skin permeation compared to FI aqueous suspension, and pure FI loaded gel. Aloe ferox and oregano oil in the optimized gel formulation had a synergistic activity on the FI permeation across the skin and against the growth of p. acne bacteria which could favor their use in treating alopecia. Thus, this investigation affirms the ability of FI-Or-NCu loaded aloe ferox gel could be an effective strategy that would enhance FI release and permeation through skin and maximize its favorable effects in treating alopecia.     

Early infection in post-autologous hematopoietic stem cell transplant patients: Princess Noorah Oncology Center experience

Objectives:To assess local epidemiology and risk factors for bacterial, fungal, and viral infections among the autologous bone marrow transplant population.Methods:This study is a retrospective correlational cohort design comprising 150 adult patients who underwent autologous transplants at Princess Noorah Oncology Center, Jeddah, Saudi Arabia between 2014 and 2020.Results:The study findings indicate that bacterial infection prevalence differed significantly across the different disease status pre-salvage as patients with the relapsed disease were more likely to have bacterial infections. The median of engraftment days differed significantly between those who had a bacterial infection and those who did not. Interestingly, previous pneumonia infection had a positive relationship with the number of hospital stays.Conclusions:Bacterial infections are the dominant type of infection among the autologous patient population. The research reflects authentic practice and reports unique characteristics of autologous transplant patients in terms of the prevalence and types of infection these patients experience.     

Perceived awareness of sleep paralysis phenomenon (old hag syndrome) and its most common risk factors among people from Al-Ahsa,Saudi Arabia

Objectives:To assess prevalence and perception of sleep paralysis and its relationship with socioeconomic determinants, and risk factors in a cross-sectional sample of Saudi general population from Al-Ahsa city.Methods:A cross-sectional sampling survey was conducted during 2020 to 2021. The targets were aged above 18 and belonged to Al-Ahsa. Patients were sent self-reported anonymous questionnaires to complete.Results:A total of 524 participants, whose ages ranged from 18 to 60 years, were analyzed. Among 85.7% of participants aged 55 years and over, compared to 65.8% of those who were aged under 35, 379 (72.3%) respondents were females. Moreover, 438 (83.6%) participants were university graduates, 271 (51.7%) were students and 40.8% had psychological disorders including anxiety (25.2%) and depression (5.7%). Family history of sleep paralysis was reported by 369 (70.4%) participants. A total of 97.5% study participants were aware of sleep paralysis.Conclusion:Sleep paralysis is a common occurrence in people residing in Al-Ahsa, Saudi Arabia. A considerable number of the society held wrong beliefs regarding sleep paralysis. Therefore, raising public of identity of sleep paralysis is crucial. We recommend applying the study in other cities within Saudi Arabia to identify common risk factors and perceptions among the society.     

Pamidronate treatment in rheumatology practice: a comprehensive review

Pamidronate, along with other bisphosphonates, has been used for treatment of bone pain secondary to malignant involvement or metastatic disease for years. Some data, however, have also accumulated on the utility of pamidronate in a variety of benign conditions frequently handled by rheumatologists. This study aims to review the available published data regarding the potential use of pamidronate in rheumatology practice. Methods include the review of relevant articles retrieved by a PUBMED search utilizing the index term “pamidronate”. All available randomized control trials, open trials, and case series, as well as properly reported case studies evaluating usage of pamidronate in rheumatic disorders, have been included in the literature review. The efficacy of pamidronate in patients with spondyloarthropathies; synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome; hypertrophic osteoarthropathy; osteoporotic vertebral fractures; chronic back pain due to disk disease or spinal stenosis; Charcot arthropathy; transient osteoporosis; and complex regional pain syndrome-I, has been demonstrated in more than 40 reports, the majority of which, however, were not controlled studies. In some of reviewed conditions, aside from providing analgesic relief, pamidronate may also have disease-modifying properties. While used in different doses in a variety of rheumatic disorders, pamidronate was generally reported to be well tolerated with an overall good safety profile. Pamidronate may represent an effective and safe choice for a spectrum of rheumatic patients, suffering from intractable musculoskeletal pain, unresponsive to traditionally recommended therapies. Large randomized, controlled studies examining the efficacy of pamidronate in the rheumatic conditions are urgently needed.     

Effectiveness of an early mobility protocol for stroke patients in Intensive Care Unit

Objectives:To evaluate the effectiveness of an early mobility protocol for stroke patients in the intensive care unit.Methods:Participants were patients with first or recurrent stroke (n=60, age=49.02±6.36 years, body mass index=32.95±5.67 kg/m²) admitted to the intensive care stroke unit in general hospitals, Riyadh during October and December 2016. Single group pretest-posttest design involving an early mobility protocol was started within first 24 hours admission. Pre and post measurements of muscle strength, pulmonary function and quality of life were carried out.Results:There were significant improvements in muscle strength of upper and lower extremities´ muscles after treatment (p<0.05), pulmonary functions including Forced Vital Capacity, Forced Expiratory Volume 1 (p<0.05) and quality of life, namely, Barthel Index and modified Rankin Scale (p<0.01).Conclusion:This study demonstrates that initiating an early mobility protocol is safe and effective for intensive care unit stroke patients and supports introducing the current protocol as a standard protocol in neurogenic Intensive Care Units.

Stroke is a life-threatening condition caused by interruption of the blood supply to any part of the brain. Stroke causes acute neurological disorders and long-term disabilities and imposes economic, social and health impacts on individuals and their families.1 Survivors of stroke are left with mental and physical disabilities that cause social and economic burdens and impair quality of life (QOL). In Saudi Arabia stroke is becoming a rapidly increasing problem and a primary cause of morbidity and mortality.2 Worldwide the incidence of first-time stroke was 17 million during 1990-2000.3 Cerebrovascular diseases including stroke is a leading cause of mortality,4 and stroke is the fifth leading cause of death, but it remains the first cause of disability in the USA.5 By 2030 there will be almost 12 million stroke deaths and 70 million stroke survivors globally.6 Stroke has an adverse influence on the QOL of patients. The onset of stroke is sudden, and unlike other disabling conditions, it leaves patients and their family’s ill prepared for its sequelae.7 Stroke may create unique conditions that affect the patients’ QOL, involving dysfunctions in physical, emotional, memory, thinking, and social interactions.8Stroke is an urgent health care issue. It is a common cause of the hospital admissions. Immediate admission to the neuro-intensive care unit can facilitate early stroke treatment strategies.9 Stroke patients in the intensive care unit (ICU) experience a decrease in physical activity that represents a significant stress on the body and leads to a considerable decrease in functional status, increases morbidity, mortality rate, and duration of hospital stay and cost of care.10 In addition to comorbid diseases, patients on mechanical ventilation have many barriers to mobility because they are surrounded by tubes, catheters, life support and monitoring equipment. Additionally, other factors besides weakness, such as sleep loss, lack of social communication, nutritional status, sedation, and an ICU culture that encourages bed rest further contribute to functional deterioration.11 There is considerable loss of the muscle mass during the initial weeks of immobility in the ICU, therefore its management is inherently related to QOL after discharge.12 Considerable published evidence indicates that patients in ICUs have high morbidity and mortality, high costs of care and a marked decline in functional status.13,14Early and progressive mobilization program has been described as a key component for patients in the ICU. It may decrease post stroke complications such as infections, deep venous thrombosis, pneumonia, pressure ulcers, falls and de-conditioning with bed rest.15 It has been recognized that mobilization of post stroke patients is essential to prevent hospital-associated complications, functional decline and facilitate recovery.16 Moreover, the benefits of early mobilization include decreased ICU-acquired weakness, improved functional recovery within hospital,17 Effective stroke intervention begins the day the patient has a stroke.18 It has a positive effect on patient functional ability, promotes positive psychological effects and improves walking at hospital discharge and reduces hospital length of stay.19 While on the other hand, long term inactivity may affect the patients’ physical, social, emotional, behavioral, and psychological pattern.20 In addition, secondary changes associated with stroke-related inactivity include muscle atrophy, a shift in muscle fiber type to a greater predominance of fast-fatigable, insulin-resistant fibers, loss of cardiovascular fitness, and increased intramuscular fat.21 Therefore, early mobilization program which is a complex intervention that needs crucial patient assessment and management, as well as interdisciplinary team collaboration and training.22,23 The early mobilization may improve patient outcomes and recovery.24 Few studies have investigated the role of increased mobility in ICU patients. Therefore, this prospective intervention trial evaluated the effectiveness of an early mobility program administered by physical therapists and nursing personnel for stroke patients admitted in ICU.     

Reference values for ultrasonograpy of peripheral nerves

Introduction: High‐resolution ultrasonography (HRU) is a novel method that provides morphological information about peripheral nerves. We aimed to determine reference values for nerve cross‐sectional area (CSA) on HRU. Methods: One hundred healthy volunteers had HRU of median, radial, ulnar, fibular, tibial, sural, and superficial fibular nerves at defined sites. The CSA was measured and the effects of age, gender, and body mass index (BMI) were evaluated. Results: CSA values in healthy subjects are described. CSA is larger in lower limb motor nerves than in sensory nerves at similar sites, and the CSA tends to be symmetrical. The strongest effect on CSA was for age, although gender and BMI had some effects. Conclusions: This study provides normative values for HRU, and it suggests that further research with age‐ and gender‐specific distributions must be a key priority in the development of HRU for use as a diagnostic test for peripheral nerve diseases. Muscle Nerve 53 : 538–544, 2016     

Venous thromboembolism prophylaxis in medically ill patients: a mixed treatment comparison meta-analysis

The American College of Chest Physicians guidelines recommend unfractionated heparin (UFH), low molecular weight heparins (LMWHs) or fondaparinux for prevention of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), in medically-ill patients. Direct oral anticoagulants (DOACs) have been evaluated relative to enoxaparin for VTE prophylaxis though head-to-head comparisons of these agents are lacking. Therefore, we conducted a mixed treatment comparisons meta-analysis to evaluate the safety and efficacy of established treatments and DOACs for VTE prophylaxis in medically-ill patients. A comprehensive literature search was conducted to identify randomized trials evaluating UFH, LMWHs or DOACS for the prevention of VTE in medically ill patients. Articles were retrieved and cross-referenced for additional trials, evaluated and entered into ADDIS (version 1.16.6) to generate direct and indirect treatment comparisons for VTE, DVT, PE, death from any cause, and bleeding. Ten articles were included and eight anticoagulants were evaluated in a treatment network representing data on 28,382 patients. We found each treatment had similar efficacy in preventing VTE, DVT, PE, death from any cause and each had similar risk of minor and major bleeding. Overall, placebo was associated with more VTE and DVT events compared to LMWHs and DOACs. We found that UFH, LMWHs and DOACs are comparable in preventing VTE, DVT, PE, and death from any cause and in association with minor and major bleeding. Anticoagulant selection for VTE prophylaxis in medically-ill patients should be individualized by patient characteristics, risks and preferences along with specific pharmacokinetic and pharmacodynamic considerations.