Methodological Issues with Head and Neck Cancer Prognostic Risk Prediction Models.

OBJECTIVE: Prognostic risk prediction models estimate the probability of developing head and neck cancer (HNC), providing valuable information for managing the disease. While different prognostic HNC risk prediction models have been developed worldwide, a comprehensive evaluation of their methods is lacking. We conducted a scoping review with a critical assessment aiming to identify the methodological strengths and limitations of HNC risk prediction models. METHOD: We searched Medline, Embase, Scopus, Web of Science, and CAB Abstracts databases and included full-text-available peer-reviewed published papers on developing or validating a prognostic HNC risk prediction model. Study quality was appraised using the PROBAST tool. RESULTS: Nine papers were included. Although all had a high risk of bias, mainly in the analysis domain, only two studies had high concerns about clinical applicability. CONCLUSION: Currently published studies provide insufficient information on methods, making it difficult to judge the models' quality and applicability. Future investigations should follow the guidelines in reporting the prediction modelling studies.

Functional Outcomes and Urological Complications after Genital Gender Affirming Surgery with Urethral Lengthening in Transgender Men.

PURPOSE: We determined the urological complications and lower urinary tract function after genital gender affirming surgery with urethral lengthening in transgender men. MATERIALS AND METHODS: A single center, retrospective cohort study was performed from January 2013 to January 2018. Patient demographics, medical history, perioperative data, surgical and urological complications, and preoperative and postoperative urological outcomes were obtained. RESULTS: Of the 63 patients included in the study 8 (13%) underwent metoidioplasty and 55 (87%) phalloplasty, comprised of 27 (43%) free radial forearm flap, 19 (30%) anterolateral thigh flap and 9 (14%) superficial circumflex iliac artery perforator flap surgeries. In phalloplasty the types of urethral lengthening were tube-in-tube free radial forearm flap in 27 (49%), free radial forearm flap (second fasciocutaneous flap) in 18 (33%), superficial circumflex iliac artery perforator flap in 5 (9%) or labial in 5 (9%). Mean followup was 23 months (range 12 to 71). Stricture formation occurred in 35 (63%) phalloplasty and 5 (63%) metoidioplasty cases. Urethral fistula formation occurred in 15 (27%) phalloplasty and 4 (50%) metoidioplasty cases. Mean time to strictures and fistulas was approximately 3 months. Overall 46 (73%) patients needed revision surgery because of fistulas/strictures. After treatment 44 (70%) patients were able to void from the tip of the phallus. No clinically relevant differences in International Prostate Symptom Scores, frequency volume charts and uroflowmetry were found preoperatively vs postoperatively. CONCLUSIONS: Genital gender affirming surgery with urethral lengthening is a complex procedure with a high complication rate. After treating complications no clinically relevant differences in urological functioning were recorded. The majority of transgender men could void from the tip of the penis and showed favorable urological outcomes.

Research priorities for specialized nursing practice in the United Arab Emirates.

BACKGROUND: Globally, nurses are undertaking expanded and more specialized roles in healthcare planning and service delivery in response to changing patterns and levels of health service demand. This means the nursing profession is increasingly considered as leaders in health service policy, research and practice. The United Arab Emirates has strengthened nursing governance and practice by establishing a Nursing and Midwifery Council and increasing the activity of nursing specialization, service leadership and research. This study aimed to identify clinically relevant research priorities to facilitate nursing contributions to evidence-based care and strengthening health services in the country. METHODS: A two-stage Delphi study design was used. RESULTS: The first round involved 783 participants. The second round involved 1116 participants, as more clinical settings were accessed. In total, 58 research priorities across a variety of nursing specialties (paediatrics, emergency care, intensive care, labour and maternity care, operating theatre and long-term care) were identified as highly important. CONCLUSION: These identified priorities will guide a more informed programme of research in each nursing specialty, with the aim of strengthening the evidence base to improving outcomes for patients and their families in the United Arab Emirates. IMPLICATIONS FOR NURSING PRACTICE, RESEARCH AND POLICY: The findings provide guidance on key areas for nurses to focus research contributions to enhance evidence-based care and strengthen health systems. The identified priorities may also guide researchers in academic institutions to conduct research informed by current, clinically relevant issues. The findings may help inform funders and policymakers to support allocation of funding to research that has potential to contribute to enhancing nursing care in specialist areas.

Decreased levels of platelet-derived soluble glycoprotein VI detected prior to the first diagnosis of coronary artery disease in HIV-positive individuals.

HIV-positive patients are at increased risk for coronary artery disease (CAD); changes in platelet activation may play a role. This study was performed to determine if levels of soluble glycoprotein VI (sGPVI), a platelet-specific marker of activation, were different in HIV-positive patients compared with HIV-negative controls and further if levels were predictive of CAD in HIV. Twenty-four HIV-positive individuals (HIV cases) with CAD were compared with 46 age- and sex-matched HIV-positive controls without CAD and 41 HIV-negative controls (healthy controls). Platelet activation (represented by sGPVI level) was compared 12 months and 1 month prior to CAD diagnosis. sGPVI was quantified by ELISA. sGPVI levels were higher in HIV-positive subjects (combined) than healthy controls (122.5 ng/mL [interquartile ranges (IQR) 90.3-160.5] versus 84.7 ng/mL [IQR 48.6-119.5], p <0.001). Twelve months before the event, there was no difference in sGPVI between HIV cases and HIV controls (113.4 ng/mL [IQR 85.6-141.65] versus 128.0 ng/mL [IQR 96.6-179.4], p = 0.369). One month prior to the event, sGPVI was significantly lower in HIV cases compared with HIV controls (109.0 ng/mL [IQR 79.4-123.4] versus 133.9 ng/mL [IQR 112.7-171.9], p = 0.010). These results remained significant following adjustment for possible confounders. This work demonstrates that HIV infection is associated with higher sGPVI levels. A fall in sGPVI immediately prior to first coronary artery event may reflect a loss of negative-feedback mechanism and be an important pathological step in the development of symptomatic CAD, but further work is needed to confirm these findings and determine their clinical impact.

Circulating levels of soluble EMMPRIN (CD147) correlate with levels of soluble glycoprotein VI in human plasma.

Extracellular matrix metalloproteinase inducer (EMMPRIN; CD147), which binds to the platelet-specific collagen receptor glycoprotein (GP) VI, is expressed in a range of cell types including platelets and leukocytes, and has been implicated in neoplastic disease and atherosclerotic coronary disease. Both CD147 and GPVI can be shed from cell membranes and detected in plasma. However, while the relationship between soluble CD147 (sCD147), soluble GPVI (sGPVI) and standard markers of platelet activation has received little attention, such analysis may help reveal pathways mediating release of sCD147. We investigated the relationship between sCD147 and platelet markers including sGPVI, soluble and platelet-bound CD62P (P-selectin), active αIIbß3 (assessed by PAC-1 binding) and platelet CD147 in 25 patients with stable angina pectoris (SAP), 13 patients with no coronary artery disease (CAD) and 10 healthy donors. Plasma levels of sCD147 significantly correlated with sGPVI (r = 0.46, p = .004), but did not correlate with any other platelet markers examined. Linear regression analysis identified that sCD147 levels could be predicted by sGPVI levels (ß = .445, p = 0.003) and age (ß = 0.304, p = 0.038), but were independent of potential clinical confounders such as CAD, diabetes and medication usage. As sCD147 strongly correlates with platelet-specific sGPVI, a common platelet source and/or mechanism of release may contribute to sCD147 levels in vivo.

Focusing on plasma glycoprotein VI.

New methods for analysing both platelet and plasma forms of the platelet-specific collagen receptor, glycoprotein VI (GPVI) in experimental models or human clinical samples, and the development of the first therapeutic compounds based on dimeric soluble GPVI-Fc or anti-GPVI antibody-based constructs, coincide with increased understanding of the potential pathophysiological role of GPVI ligand binding and shedding. Platelet GPVI not only mediates platelet activation at the site of vascular injury where collagen is exposed, but is also implicated in the pathogenesis of other diseases, such as atherosclerosis and coagulopathy, rheumatoid arthritis and tumour metastasis. Here, we describe some of the critical mechanisms for generating soluble GPVI from platelets, and future avenues for exploiting this unique platelet-specific receptor for diagnosis and/or disease prevention.

Compromised ITAM-based platelet receptor function in a patient with immune thrombocytopenic purpura.

BACKGROUND: Receptors on platelets that contain immunoreceptor tyrosine-based activation motifs (ITAMs) include collagen receptor glycoprotein (GP) VI, and FcgammaRIIa, a low affinity receptor for immunoglobulin (Ig) G. OBJECTIVES: We examined the function of GPVI and FcgammaRIIa in a patient diagnosed with immune thrombocytopenic purpura (ITP) who had unexplained pathological bruising despite normalization of the platelet count with treatment. METHODS AND RESULTS: Patient platelets aggregated normally in response to ADP, arachadonic acid and epinephrine, but not to GPVI agonists, collagen or collagen-related peptide, or to FcgammaRII-activating monoclonal antibody (mAb) 8.26, suggesting ITAM receptor dysfunction. Plasma contained an anti-GPVI antibody by MAIPA and aggregated normal platelets. Aggregating activity was partially (approximately 60%) blocked by FcgammaRIIa-blocking antibody, IV.3, and completely blocked by soluble GPVI ectodomain. Full-length GPVI on the patient platelet surface was reduced to approximately 10% of normal levels, and a approximately 10-kDa GPVI cytoplasmic tail remnant and cleaved FcgammaRIIa were detectable by western blot, indicating platelet receptor proteolysis. Plasma from the patient contained approximately 150 ng mL(-1) soluble GPVI by ELISA (normal plasma, approximately 15 ng mL(-1)) and IgG purified from patient plasma caused FcgammaRIIa-mediated, EDTA-sensitive cleavage of both GPVI and FcgammaRIIa on normal platelets. CONCLUSIONS: In ITP patients, platelet autoantibodies can curtail platelet receptor function. Platelet ITAM receptor dysfunction may contribute to the increased bleeding phenotype observed in some patients with ITP.

In vitro fermentation of sugar beet arabinan and arabino-oligosaccharides by the human gut microflora.

AIMS: To determine the fermentation profiles by human gut bacteria of arabino-oligosaccharides of varying degree of polymerization. MATERIALS AND METHODS: Sugar beet arabinan was hydrolyzed with a commercial pectinase and eight fractions, of varying molecular weight, were isolated by gel-filtration chromatography. Hydrolysis fractions, arabinose, arabinan and fructo-oligosaccharides were fermented anaerobically by gut bacteria. Total bacteria, bifidobacteria, bacteroides, lactobacilli and the Clostridium perfringens/histolyticum sub. grp. were enumerated using fluorescent in situ hybridization. RESULTS: Bifidobacteria were stimulated to different extents depending on molecular weight, i.e. maximum increase in bifidobacteria after 48 h was seen on the lower molecular weight fractions. Lactobacilli fluctuated depending on the initial inoculum levels. Bacteroides numbers varied according to fraction; arabinan, arabinose and higher oligosaccharides (degree of polymerization, dp > 8) resulted in significant increases at 24 h. Only carbohydrate mixtures with dp of 1-2 resulted in significant increases at 48 h (log 8.77 +/- 0.23). Clostridia decreased on all substrates. CONCLUSIONS: Arabino-oligosaccharides can be considered as potential prebiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: Arabinan is widely available as it is a component of sugar beet pulp, a co-product from the sugar beet industry. Generation of prebiotic functionality from arabinan would represent significant added value to a renewable resource.

Effect on the cholesterol content of fresh lamb of supplementing the feed of Awassi ewes and lambs with Lactobacillus acidophilus.

Lactating ewes and their lambs were provided daily with two enteric capsules of a freeze-dried culture of selected strains of Lactobacillus acidophilus (1×10(9) colony-forming-units/dose), along with their normal diets, for a period of 120 days. Initially, the supplementation had a significant effect on the serum cholesterol levels of the suckling lambs, but the benefit was reduced after weaning. On slaughter at 120 days, the mean cholesterol concentrations in three cuts of lamb meat were reduced by over 20%, and that in the liver by ∼18%. In the Middle East where the consumption of lamb is high, this reduction could be beneficial for the consumer, and it is suggested that the potential value of probiotic cultures in ruminant nutrition merits further attention.