Blocking “don't eat me” signal of CD47-SIRPα in hematological malignancies,an in-depth review

Hematological malignancies express high levels of CD47 as a mechanism of immune evasion. CD47-SIRPα triggers a cascade of events that inhibit phagocytosis. Preclinical research supports several models of antibody-mediated blockade of CD47-SIRPα resulting in cell death signaling, phagocytosis of cells bearing stress signals, and priming of tumor-specific T cell responses. Four different antibody molecules designed to target the CD47-SIRPα interaction in malignancy are currently being studied in clinical trials: Hu5F9-G4, CC-90002, TTI-621, and ALX-148. Hu5F9-G4, a humanized anti-CD47 blocking antibody is currently being studied in four different Phase I trials. These studies may lay the groundwork for therapeutic bispecific antibodies. Bispecific antibody (CD20-CD47SL) fusion of anti-CD20 (Rituximab) and anti-CD47 also demonstrated a synergistic effect against lymphoma in preclinical models. This review summarizes the large body of preclinical evidence and emerging clinical data supporting the use of antibodies designed to target the CD47-SIRPα interaction in leukemia, lymphoma and multiple myeloma.     

Initial misdiagnosis of Vogt-Koyanagi-Harada disease

Purpose

To report the initial misdiagnosis of patients with Vogt–Koyanagi–Harada (VKH) disease.

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.     

Ameliorated effects of green tea extract on lead induced liver toxicity in rats

In the present study, the effect of green tea extract (GTE) on lead induced toxicity was studied in Sprague–Dawley rats. Four groups of rats were used in the study. Lead and GTE was given orally to the rats with drinking water for 8 weeks. Lead concentration in the digested tissues of liver was detected using atomic absorption spectroscopy. The activities of glutathione-S-transferase (GST) and superoxide dismutase (SOD) were used as markers to evaluate the anti oxidant status of tissues. Lead exposure was found to attenuate the antioxidant potential of liver, which was however augmented when supplemented with green tea extract. Liver enzymes ALT, AST and ALP and serum protein determinations indicated the protective effects of green tea extract. Histopathological studies of liver revealed that supplementation of green tea extract resulted in mild degeneration and congestion of the blood vessels and an enhanced regenerative capacity.     

Comparison of efficacy and safety of intralesional triamcinolone and combination of triamcinolone with 5-fluorouracil in the treatment of keloids and hypertrophic scars: Randomised control trial

The treatment of keloid and hypertrophic scar is challenging with no universally accepted mode for permanent ablation. Conventional therapies yield unpredictable results, significant complications and require elaborate hardware.

C‐punch excision: a novel technique

A conventional skin punch biopsy instrument has a circular hollow blade, which can be used to make a full circular incision to evacuate subcutaneous abnormalities such as lipomas. Here, we present a modified punch instrument, in which the cutting element has a C‐shape to form a pivotal skin fragment (miniflap) to access subcutaneous tissues. The “C” part comprises almost half of a circle. The C‐punch incision gives access to subcutaneous abnormalities, while keeping a connecting neck to the surrounding skin, which allows for efficient resealing of the skin surface. Therefore, there is less potential for subsequent scarring.