Predictive Factors for Critical Weight Loss in Saudi Head and Neck Cancer Patients Undergoing (Chemo)Radiotherapy.

Weight loss is a significant health problem among patients with head and neck cancer (HNC) that is attributable primarily to the tumor or tumor therapy. Critical weight loss (CWL) is defined as the unintentional loss of ≥5% of weight. Therefore, this study's goal was to investigate and determine the possible factors influencing CWL among patients with HNC who have received radiotherapy or concurrent chemoradiotherapy (CCRT). We conducted a retrospective analysis of 175 patients who received radiotherapy or CCRT as either their primary, adjuvant, or combined treatment at the Oncology Center in King Abdullah Medical City. All patients were ≥18 years of age and diagnosed with HNC with no metastasis. The study results showed that 107 patients (61%) had CWL, while 68 (39%) did not. The following factors were significantly predictive of CWL with a multivariate regression analysis: pretreatment BMI (AOR = 1.1, 95% CI = 1.02-1.17), oral cavity cancer (AOR = 10.36, 95% CI = 1.13-94.55), and male sex (AOR = 3.15, 95% CI = 1.39-7.11). In conclusion, weight loss is highly prevalent among HNC patients during treatment. Accordingly, pretreatment BMI, cancer in the oral cavity, and being male can be considered predictive factors for CWL.

Vitamin C and/or garlic can antagonize the toxic effects of cadmium on growth performance, hematological, and immunological parameters of growing Japanese quail.

This study used 300 1-day-old, sexless, developing chicks of Japanese quail to estimate the ability of vitamin C and/or garlic to antagonize the venomous influence of cadmium (Cd) on the hematological, immunological, and performance characteristics of developing Japanese quail. The quail was separated into 5 similar groups of 60 chicks apiece, and 6 duplicates (10 each) were given to each sub-group. The control group received a basal diet without any supplements. The Cd group was nourished with a basal diet of + 80 mg cadmium chloride (CdCl2)/kg diet. The 3rd group was fed a basal diet + 80 mg CdCl2/kg diet and complemented with a 200 mg Vitamin C (Cd + C)/kg diet. The 4th group was nourished with a basal diet + 80 mg CdCl2/kg diet and complemented by a 500 mg dried garlic powder (Cd + G)/kg diet. The 5th group was fed a basal diet + 80 mg CdCl2/kg diet, complemented by a 200 mg vitamin C/kg diet + 500 mg dried garlic powder (Cd + CG)/kg diet. Results showed that in the 5th group in which cadmium was added together with Vit C + garlic, there was an improvement in both live weight gain (1-42 d) and feed consumption (1-21 and 1-42 d ) compared to the group in which Cd was added alone. The addition of Vit C alone and together with garlic seems to completely improve the cadmium-related increase in alkaline phosphatase (ALP), and Aspartate aminotransferase (AST), and Malondialdehyde (MDA) levels when compared to the control. Compared to cadmium-polluted diets, quail that got cadmium and feed additives significantly reduced cadmium residue. In addition, the cadmium group's serum immunoglobulin M (IgM) level decreased significantly. These data imply that dietary supplementation with (C) or (G) may be beneficial in retrogressing the drop in immunoglobulin G (IgG) and IgM caused by Cd and minimizing Cd's deleterious influence on immunity.

Exploring the Therapeutic Potential of Apigenin in Obesity-Associated Fibrinolytic Dysfunction: Insights From an Animal Study.

INTRODUCTION: Obesity (Obe) is a chronic metabolic disorder usually complicated by impaired fibrinolytic activity. Apigenin (Api) is one of the flavonoids that have anti-adiposity effects. This study aimed to explore the therapeutic potential of Api in high-fat diet (HFD)-induced obese rats. METHODS: Twenty-four Wistar adult male rats were randomly allocated into control group, supplemented with a normal pellet diet (NPD); Api group, supplemented with Api (10 mg/kg) for eight weeks; Obe group, obesity was induced by feeding HFD for eight weeks; and Obe/Api group, obese rats supplemented with Api for eight weeks. Body mass index (BMI), homeostatic model assessment of insulin resistance (HOMA-IR), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), total superoxide dismutase (t-SOD) activity, and plasminogen activator inhibitor-1 (PAI-1) were measured. RESULTS: Compared to the control group, Obe group exhibited a significant increase in BMI, HOMA-IR, TNF-α, MDA, and PAI-1. These results were also associated with a significant decrease in serum t-SOD activity. Supplementation of Api alleviated the measured deteriorated parameters and ameliorated visceral adiposity in obese rats. CONCLUSION: This study provides compelling evidence regarding a promising role for Api in ameliorating the impairment of fibrinolytic activity in an Obe animal model. The observed effects are likely mediated through Api's anti-obesity properties, as well as its indirect modulation of PAI-1, oxidative stress, and inflammation. Future clinical studies are recommended that may make benefit of the preclinical therapeutic use of apigenin in obesity-associated fibrinolytic dysfunctions.

Dysregulated Bradykinin: Mystery in the Pathogenesis of COVID-19.

The COVID-19 pandemic is rapidly spreading, and health care systems are being overwhelmed with the huge number of cases, with a good number of cases requiring intensive care. It has become imperative to develop safe and effective treatment strategies to improve survival. In this regard, understanding the pathogenesis of COVID-19 is highly important. Many hypotheses have been proposed, including the ACE/angiotensin-II/angiotensin receptor 1 pathway, the complement pathway, and the angiotensin-converting enzyme 2/mitochondrial assembly receptor (ACE2/MasR) pathway. SARS-CoV-2 binds to the ACE2 on the cell surface, downregulating the ACE2, and thus impairs the inactivation of bradykinin and des-Arg9-bradykinin. Bradykinin, a linear nonapeptide, is extensively distributed in plasma and different tissues. Kininogens in plasma and tissue are the main sources of the two vasoactive peptides called bradykinin and kallidin. However, the role of the dysregulated bradykinin pathway is less explored in the pathogenesis of COVID-19. Understanding the pathogenesis of COVID-19 is crucial for the development of new effective treatment approaches which interfere with these pathways. In this review, we have tried to explore the interaction between SARS-CoV-2, ACE2, bradykinin, and its metabolite des-Arg9-bradykinin in the pathogenesis of COVID-19.

Pathogen reduction of whole blood: Supplementing fibrinogen partly corrects clot formation in a massive transfusion model.

BACKGROUND: The use of whole blood (WB) to treat trauma patients is becoming more common. Similar to the treatment of individual components, pathogen inactivation (PI) technologies are available to treat WB. The impact of PI on WB function is not well understood. This study investigated the impact of PI of WB with riboflavin/ultraviolet (UV) light on its hemostatic function by modeling transfusion scenarios for trauma patients and assessing transfusion efficacy by rotational thromboelastometry (ROTEM). As fibrinogen is affected by PI of WB, the effect of fibrinogen supplementation commonly used in trauma patients was also analyzed in this model. STUDY DESIGN AND METHODS: Trauma transfusion scenarios were simulated by mixing untreated WB or WB treated with the Mirasol PI technology (riboflavin/UV) in different ratios with hemodiluted blood, and the thromboelasticity was monitored by ROTEM. The impact of supplementation with the fibrinogen concentrate RiaSTAP was investigated in this model. RESULTS: Pathogen-inactivated WB (PI-WB) showed decreased activity in the hemostatic profile compared to the untreated control. Hemodiluted blood at a hematocrit (hct) of 20%, which was reconstituted with PI-WB or untreated WB, exhibited increased alpha values, maximum clot firmness, and clot formation time. Simulating transfusion scenarios by blood replacement with PI-WB resulted in a significant difference in ROTEM parameters between reconstituted PI-treated and -untreated WB (p ≥ .05). The effect of PI treatment waned when PI-WB was enriched with fibrinogen. CONCLUSION: ROTEM investigations suggest that PI treatment has a negative impact on WB clot formation unless fibrinogen supplementation is used.

Pathogen inactivation treatment of plasma and platelet concentrates and their predicted functionality in massive transfusion protocols.

BACKGROUND: Trauma transfusion packages for hemorrhage control consist of red blood cells, plasma, and platelets at a set ratio. Although pathogen reduction improves the transfusion safety of platelet and plasma units, there is an associated reduction in quality. This study aimed to investigate the impact of riboflavin/ultraviolet light-treated plasma or platelets in transfusion trauma packages composed of red blood cell, plasma, and platelet units in a ratio of 1:1:1 in vitro by modeling transfusion scenarios for trauma patients and assessing function by rotational thromboelastometry. STUDY DESIGN AND METHODS: Pathogen-reduced or untreated plasma and buffy coat platelet concentrate units produced in plasma were used in different combinations with red blood cells in trauma transfusion packages. After reconstitution of these packages with hemodiluted blood, the hemostatic functionality was analyzed by rotational thromboelastometry. RESULTS: Hemostatic profiles of pathogen-inactivated buffy coat platelet concentrate and plasma indicated decreased activity compared with their respective controls. Reconstitution of hemodiluted blood (hematocrit = 20%) with packages that contained treated or nontreated components resulted in increased alpha and maximum clot firmness and enhanced clot-formation time. Simulating transfusion scenarios based on 30% blood replacement with a transfusion trauma package resulted in a nonsignificant difference in rotational thromboelastometry parameters between packages containing treated and nontreated blood components (p ≥ 0.05). Effects of pathogen inactivation treatment were evident when the trauma package percentage was 50% or greater and contained both pathogen inactivation-treated plasma and buffy coat platelet concentrate. CONCLUSION: Rotational thromboelastometry investigations suggest that there is relatively little impact of pathogen inactivation treatment on whole blood clot formation unless large amounts of treated components are used.

Platelet concentrate functionality assessed by thromboelastography or rotational thromboelastometry.

BACKGROUND: There is poor correlation between in vivo platelet concentrate (PC) transfusion outcome and in vitro tests, which typically do not test the functional effectiveness of platelets (PLTs), but rather measure PLT characteristics. We hypothesize that the application of thromboelastography (TEG) or rotational thromboelastometry (ROTEM) to evaluate the procoagulant activity of stored PLTs can predict PLT quality and, ultimately, distinguish among hyper- and nonresponsive PCs. Additionally, we hypothesize that due to their procoagulant properties, PLT microvesicles (PMVs) contribute to the clot signature in these methods. STUDY DESIGN AND METHODS: After the TEG assays were validated, buffy coat PCs were evaluated during the storage time and reconstituted with frozen plasma to different PLT concentrations. Poor quality PCs were generated and assessed by TEG and other in vitro tests. The contribution of PMVs to the TEG clot signature was assessed. RESULTS: Hemostatic analysis showed no significant change in maximum amplitude (MA) during storage of PCs up to Day 10. On Day 8 of storage, PCs that had been manipulated to have poor quality showed a significant decrease in MA. PMV-rich samples contributed to a significant increase in MA, and PMV count showed a significant correlation with maximum clot formation (r = 0.51, p < 0.01). CONCLUSION: TEG was optimized for use with buffy coat PCs, although it was found to lack sensitivity to detect normal storage-related quality changes. Hemostatic measurement was sufficiently sensitive to dissect PLT and PMV contributions to clot formation and to detect PCs stored under poor conditions.