Carotid web catheter angiography hemodynamic parameters.

BACKGROUND: Carotid web (CaW)-related contrast stagnation on digital subtraction angiography (DSA) may be a marker supporting the pathophysiological theory of stasis and thrombosis/embolization. We aim to assess the correlation between DSA hemodynamic parameters with CT angiography (CTA) structural measurements and clinical characteristics. METHODS: Cross-sectional analysis of consecutive patients with CaW who underwent CTA+DSA. DSA-derived hemodynamic parameters were calculated based on a region of interest at the carotid bulb (time-density curves; TDC). The correlation between duration of contrast stagnation with CaW structural features and with clinical characteristics was evaluated with a mixed effects model. RESULTS: Sixty patients of mean±SD age 52.2±10.3 years were included, of whom 38 (63.3%) were women, 51 (85%) were black, and 59 (98.3%) had symptomatic lesions. The median CaW base was 2.46 mm (range 1.95-3.76), length 2.7 mm (range 2.15-3.96), thickness (length/base) 1.05 (IQR 0.81-1.36), caudal angle 31.93° (IQR 22.35-43.58), mean±SD distal angle 66.91±15.84°, pocket area 1.62 mm² (0.96-1.62), and pocket perimeter 6.03±2.6 mm. The TDC consistently showed an initial fast decay from the peak concentration followed by a plateau with a negative exponential pattern. The median stagnation time from peak density to 80% contrast clearance was 2.91 s (range 1.81-4.94). No significant associations were observed between the stagnation time and CaW CTA structural measurements (length/base/thickness, caudal and cranial angles web surface angles, web pocket area/perimeter) or clinical characteristics. CONCLUSIONS: A negative exponential pattern in the DSA contrast clearance of the CaW pocket was observed. There were no morphological or clinical features clearly associated with the duration of contrast stagnation on DSA. The hemodynamic disruption caused by CaW and its thrombotic risk may not be appropriately measured by contrast stagnation time.

Development and validation of a SCORing systEm for pre-thrombectomy diagnosis of IntraCranial Atherosclerotic Disease (Score-ICAD).

BACKGROUND: Early identification of intracranial atherosclerotic disease (ICAD) may impact the management of patients undergoing mechanical thrombectomy (MT). We sought to develop and validate a scoring system for pre-thrombectomy diagnosis of ICAD in anterior circulation large vessel/distal medium vessel occlusion strokes (LVOs/DMVOs). METHODS: Retrospective analysis of two prospectively maintained comprehensive stroke center databases including patients with anterior circulation occlusions spanning 2010-22 (development cohort) and 2018-22 (validation cohort). ICAD cases were matched for age and sex (1:1) to non-ICAD controls. RESULTS: Of 2870 MTs within the study period, 348 patients were included in the development cohort: 174 anterior circulation ICAD (6% of 2870 MTs) and 174 controls. Multivariable analysis ß coefficients led to a 20 point scale: absence of atrial fibrillation (5); vascular risk factor burden (1) for each of hypertension, diabetes, smoking, and hyperlipidemia; multifocal single artery stenoses on CT angiography (3); absence of territorial cortical infarct (3); presence of borderzone infarct (3); or ipsilateral carotid siphon calcification (2). The validation cohort comprised 56 ICAD patients (4.1% of 1359 MTs): 56 controls. Area under the receiver operating characteristic curve was 0.88 (0.84-0.91) and 0.82 (0.73-0.89) in the development and validation cohorts, respectively. Calibration slope and intercept showed a good fit for the development cohort although with overestimated risk for the validation cohort. After intercept adjustment, the overestimation was corrected (intercept 0, 95% CI -0.5 to -0.5; slope 0.8, 95% CI 0.5 to 1.1). In the full cohort (n=414), ≥11 points showed the best performance for distinguishing ICAD from non-ICAD, with 0.71 (95% CI 0.65 to 0.78) sensitivity and 0.82 (95% CI 0.77 to 0.87) specificity, and 3.92 (95% CI 2.92 to 5.28) positive and 0.35 (95% CI 0.28 to 0.44) negative likelihood ratio. Scores ≥12 showed 90% specificity and 63% sensitivity. CONCLUSION: The proposed scoring system for preprocedural diagnosis of ICAD LVOs and DMVOs presented satisfactory discrimination and calibration based on clinical and non-invasive radiological data.

Early technique switch following failed passes during mechanical thrombectomy for ischemic stroke: should the approach change and when?

BACKGROUND: Fast and complete reperfusion in endovascular therapy (EVT) for ischemic stroke leads to superior clinical outcomes. The effect of changing the technical approach following initially unsuccessful passes remains undetermined. OBJECTIVE: To evaluate the association between early changes to the EVT approach and reperfusion. METHODS: Multicenter retrospective analysis of prospectively collected data for patients who underwent EVT for intracranial internal carotid artery, middle cerebral artery (M1/M2), or basilar artery occlusions. Changes in EVT technique after one or two failed passes with stent retriever (SR), contact aspiration (CA), or a combined technique (CT) were compared with repeating the previous strategy. The primary outcome was complete/near-complete reperfusion, defined as an expanded Thrombolysis in Cerebral Infarction (eTICI) of 2c-3, following the second and third passes. RESULTS: Among 2968 included patients, median age was 66 years and 52% were men. Changing from SR to CA on the second or third pass was not observed to influence the rates of eTICI 2c-3, whereas changing from SR to CT after two failed passes was associated with higher chances of eTICI 2c-3 (OR=5.3, 95% CI 1.9 to 14.6). Changing from CA to CT was associated with higher eTICI 2c-3 chances after one (OR=2.9, 95% CI 1.6 to 5.5) or two (OR=2.7, 95% CI 1.0 to 7.4) failed CA passes, while switching to SR was not significantly associated with reperfusion. Following one or two failed CT passes, switching to SR was not associated with different reperfusion rates, but changing to CA after two failed CT passes was associated with lower chances of eTICI 2c-3 (OR=0.3, 95% CI 0.1 to 0.9). Rates of functional independence were similar. CONCLUSIONS: Early changes in EVT strategies were associated with higher reperfusion and should be contemplated following failed attempts with stand-alone CA or SR.

Competitive leptomeningeal flow impact on thrombectomy reperfusion grade rating.

BACKGROUND: Competitive leptomeningeal flow (CLF) can be observed immediately after mechanical thrombectomy (MT) reperfusion with retrograde contrast clearing of the distal leptomeningeal branches from non-contrast opacified flow through different vascular territories. We aim to evaluate the frequency of the CLF phenomenon, to determine if it has an association with the degree of leptomeningeal collateral status, and to understand the potentia impact it may have on the final expanded Treatment in Cerebral Ischemia (eTICI) score rating. METHODS: Retrospective analysis of a prospective MT database spanning November 2020 to December 2021. Consecutive cases of intracranial internal carotid (i-ICA) or middle cerebral artery (MCA) M1 occlusions were included. CLF was defined by the observation of retrograde clearing of distal MCA branches that were previously opacified by antegrade reperfusion. The clearance of the distal branches is presumed to occur due to CLF via non-contrast opacified posterior cerebral artery or anterior cerebral artery flow. The washout was considered CLF if it cleared abruptly with or without forward reconstitution of antegrade opacification. RESULTS: A total of 125 patients met the inclusion criteria. The median age was 64 years (IQR 52.5-75) and 64 (51%) were men. The baseline median National Institutes of Health Stroke Scale score was 17 (IQR 12-22) and the Alberta Stroke Program Early CT Score was 9 (IQR 8-10). Median last known well time to puncture was 7 hours (IQR 4-13.1) and 30.4% received tissue plasminogen activator. Final eTICI 2c-3 was achieved in 80%. CLF was present in 32 (25.6%) patients, who had comparable baseline characteristics to patients without CLF. Twelve (37.5%) patients had regional CLF and 20 (62.5%) had focal CLF. The CLF arm had better leptomeningeal single-phase CTA collaterals than the non-CLF arm (P=0.01). The inter-rater agreement for the eTICI score was moderate when CLF was present and strong in its absence (Krippendorf's alpha=0.65 and 0.81, respectively). There was minimal agreement (Kappa=0.3) for the presence versus absence of CLF between the two operators, possibly related to reader experience. CONCLUSION: CLF was observed in 32% of patients, was associated with better collateral flow, and impacted the reported procedural eTICI rating.

Rescue intracranial stenting for failed posterior circulation thrombectomy: analysis from the Stenting and Angioplasty in NeuroThrombectomy (SAINT) study.

BACKGROUNDS: Recent trials have shown improved outcomes after mechanical thrombectomy (MT) for vertebrobasilar occlusion (VBO) stroke. However, there is a paucity of data regarding safety and outcomes of rescue intracranial stenting (RS) after failed MT (FRRS+) for posterior circulation stroke. We sought to compare RS to failed reperfusion without RS (FRRS-). METHODS: This is a retrospective analysis of the Stenting and Angioplasty in NeuroThrombectomy (SAINT) study, a multicenter collaboration involving prospectively collected databases. Patients were included if they had posterior circulation stroke and failed MT. The cohort was divided into two groups: FRRS+ and FRRS- (defined as modified Thrombolysis In Cerebral Infarction (mTICI) score 0-2a). The primary outcome was a shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included mRS 0-2 and mRS 0-3 at 90 days. Safety measures included rates of symptomatic intracranial hemorrhage (sICH), procedural complications, and 90-day mortality. Sensitivity and subgroup analyses were performed to identify outcomes in a matched cohort and in those with VBO, respectively. RESULTS: A total of 152 failed thrombectomies were included in the analysis. FRRS+ (n=84) was associated with increased likelihood of lower disability (acOR 2.24, 95% CI 1.04 to 4.95, P=0.04), higher rates of mRS 0-2 (26.8% vs 12.5%, aOR 4.43, 95% CI 1.22 to 16.05, P=0.02) and mRS 0-3 (35.4% vs 18.8%, aOR 3.13, 95% CI 1.08 to 9.10, P=0.036), and lower mortality (42.7% vs 59.4%, aOR 0.40, 95% CI 0.17 to 0.97, P=0.04) at 90 days compared with FRRS- (n=68). The rates of sICH and procedural complications were comparable between the groups. Sensitivity and subgroup analyses showed similar results. CONCLUSION: In patients with posterior circulation stroke who had failed MT, RS resulted in better functional outcomes with comparable safety profile to procedure termination.

Evaluation of ultrathin semirigid ureteroscopy in terms of efficiency and cost compared to flexible ureteroscopy in treating proximal ureteric stones: a prospective randomized multicenter study.

PURPOSE: To investigate the outcome and cost-effectiveness of ultrathin 6-7.5-Fr semirigid ureteroscopy in treating proximal ureteric stones compared to flexible ureteroscopy. METHODS: Two hundred and twenty patients with a solitary proximal ureteric stone were eligible for ureteroscopy (stone size = 1-2 cm). Patients were randomly subdivided into two groups: Group I included 105 patients who underwent ultrathin semirigid ureteroscopy and group II included 115 patients who underwent flexible ureteroscopy. Both groups were compared regarding successful stone access, operation time, reoperation rates, the financial cost to stone-free, complications, and stone clearance at 4 and 8 weeks. RESULTS: Groups I and II had no significant differences regarding patient demographics, stone criteria, and hospitalization time. In contrast, the mean operative time was significantly longer in group II (p < 0.001). The overall scope-to-stone access rate was 89.5%. It was 87.6% compared to 91.3% (p = 0.32), while the stone-free rate was 81.9% versus 87.8% (p = 0.22) for groups I and II, respectively. Intraoperative and postoperative complications were statistically insignificant between the study groups. The cost/person in Egyptian pounds was 8619 ± 350 in group I, compared to 17,620 ± 280 in group II (p < 0.001); similarly, the cost to attain the stone-free rate was 8950 ± 720 in group I compared to 17,950 ± 500 in group II. CONCLUSION: Ultrathin semirigid ureteroscopy is safe, durable, and considered a cost-effective method for treating upper ureteric calculi compared to the flexible ureteroscopy and could be considered a first treatment option in developing countries.

Meningioangiomatosis with Skull Erosion.

Meningioangiomatosis (MA) is a rare, poorly studied brain hamartomatous lesion, the etiology of which is not fully elucidated. It typically involves the leptomeninges, extending to the underlying cortex, characterized by small vessel proliferation, perivascular cuffing, and scattered calcifications. Given its close proximity to, or direct involvement of, the cerebral cortex, MA lesions typically manifest in younger patients as recurrent episodes of refractory seizures, comprising approximately 0.6% of operated-on intractable epileptic lesions. Due to the absence of characteristic radiological features, MA lesions constitute a significant radiological challenge, making them easy to miss or misinterpret. Although MA lesions are rarely reported with still-unknown etiology, it is prudent to be aware of these lesions for prompt diagnosis and management to avoid morbidity and mortality associated with delayed diagnosis and treatment. We present a case of a young patient with a first-time seizure caused by a right parieto-occipital MA lesion that was successfully excised via an awake craniotomy, achieving 100% seizure control.

Primary Cutaneous T-Cell/Histiocyte-Rich B-Cell Lymphoma: A Case Report and Literature Review.

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a lymphoproliferative disorder in which the majority of cells are reactive T cells with only a minor population of neoplastic large B cells. THRLBCL is a very rare lymphoma, and most cases are nodal THRLBCL; an extranodal case of THRLBCL presenting primarily on the skin is an extremely rare occurrence with only a few cases reported in the literature. Here, we report a case of a primary cutaneous THRLBCL in a 41-year-old Saudi male who presented unusually with multiple skin lesions. He was successfully treated with electron beam radiotherapy and had a complete resolution with no recurrence as of his 24-month follow-up.

MITOCHONDRIA: The dual function of the transient receptor potential melastatin 2 channels from cytomembrane to mitochondria.

Mitochondria are closely related to oxidative stress and play an important role in maintaining cell functional homeostasis and meeting cell energy demand. The transient receptor potential melastatin 2 (TRPM2) channel affects the occurrence and progression of diseases by regulating mitochondrial function. TRPM2 channel promotes Ca2+ influx to affect 18 kDa translocator protein (TSPO), mitochondrial membrane potential (MMP), reactive oxygen species (ROS), adenosine triphosphate (ATP) production, and mitochondrial autophagy. The mechanism of Ca2+ influx into the mitochondria by TRPM2 is abundant. Interestingly, the TRPM2 channel inhibits the production of mitochondrial ROS in cancer cells and promotes the production of mitochondrial ROS in normal cells, which induces cell death in normal cells but proliferation in cancer cells. TRPM2 can be a potential target for the treatment of various diseases due to its role as a molecular link between mitochondria and Ca2+ signals.

Effect of metformin as an adjuvant therapy to letrozole on estradiol and other biomarkers involved in the pathogenesis of breast cancer in overweight and obese postmenopausal women: a pilot study.

INTRODUCTION: Metformin may provide a therapeutic benefit in different types of malignancy. PURPOSE: We aimed at evaluating the effect of metformin as an adjuvant therapy to letrozole on estradiol and other biomarkers involved in the pathogenesis of breast cancer in overweight and obese postmenopausal women. METHODS: Seventy-five postmenopausal stages II-III breast cancer female patients were assessed for eligibility in an open-labeled parallel pilot study. Forty-five patients met the inclusion criteria and were assigned into three arms: the lean arm (n = 15) women who received letrozole 2.5 mg/day, the control arm (n = 15) overweight/obese women who received letrozole 2.5 mg/day, and the metformin arm (n = 15) overweight/obese women who received letrozole 2.5 mg/day plus metformin (2000 ± 500 mg/day). The intervention duration was 6 months. Blood samples were obtained at baseline and 6 months after intervention for the measurement of serum estradiol, leptin, osteocalcin levels, fasting blood glucose concentration, and serum insulin. RESULTS: After the intervention and as compared to the control arm, the metformin arm showed a significantly lower ratio to the baseline (significant reduction) for estradiol (p = 0.0433), leptin (p < 0.0001), fasting blood glucose (p = 0.0128), insulin (p = 0.0360), osteocalcin serum levels (p < 0.0001), and the homeostatic model assessment of insulin resistance "HOMA-IR" value (p = 0.0145). There was a non-significant variation in the lactate ratio to the baseline among the three study arms (p = 0.5298). CONCLUSION: Metformin may exert anti-cancer activity by decreasing the circulating estradiol, leptin, and insulin. Metformin might represent a safe and promising adjuvant therapy to letrozole in overweight/obese postmenopausal women with breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05053841/Registered September 23, 2021 - Retrospectively.

Snake Venom: A Promising Source of Neurotoxins Targeting Voltage-Gated Potassium Channels.

The venom derived from various sources of snakes represents a vast collection of predominantly protein-based toxins that exhibit a wide range of biological actions, including but not limited to inflammation, pain, cytotoxicity, cardiotoxicity, and neurotoxicity. The venom of a particular snake species is composed of several toxins, while the venoms of around 600 venomous snake species collectively encompass a substantial reservoir of pharmacologically intriguing compounds. Despite extensive research efforts, a significant portion of snake venoms remains uncharacterized. Recent findings have demonstrated the potential application of neurotoxins derived from snake venom in selectively targeting voltage-gated potassium channels (Kv). These neurotoxins include BPTI-Kunitz polypeptides, PLA2 neurotoxins, CRISPs, SVSPs, and various others. This study provides a comprehensive analysis of the existing literature on the significance of Kv channels in various tissues, highlighting their crucial role as proteins susceptible to modulation by diverse snake venoms. These toxins have demonstrated potential as valuable pharmacological resources and research tools for investigating the structural and functional characteristics of Kv channels.

Scutellarein attenuates atopic dermatitis by selectively inhibiting transient receptor potential vanilloid 3 channels.

BACKGROUND AND PURPOSE: Atopic dermatitis (AD) is one of the most common chronic inflammatory cutaneous diseases with unmet clinical needs. As a common ingredient found in several medicinal herbs with efficacy on cutaneous inflammatory diseases, Scutellarein (Scu) has been shown to possess anti-inflammatory and anti-proliferative activities. We aimed to evaluate the therapeutic efficacy of Scu against AD and its underlying molecular mechanism. EXPERIMENTAL APPROACH: Efficacy of Scu on AD was evaluated in 2,4-dinitrofluorobenzene (DNFB) and carvacrol-induced dermatitis mouse models. Cytokine mRNA and serum IgE levels were examined using qPCR and ELISA, respectively. Voltage clamp recordings were used to measure currents mediated by transient receptor potential (TRP) channels. In silico docking, site-direct mutagenesis, and covalent modification were used to explore the binding pocket of Scu on TRPV3. KEY RESULTS: Subcutaneous administration of Scu efficaciously suppresses DNFB and carvacrol-induced pruritus, epidermal hyperplasia and skin inflammation in wild type mice but has no additional benefit in Trpv3 knockout mice in the carvacrol model. Scu is a potent and selective TRPV3 channel allosteric negative modulator with an apparent affinity of 1.18 µM. Molecular docking coupled with site-direct mutagenesis and covalent modification of incorporated cysteine residues demonstrate that Scu targets the cavity formed between the pore helix and transmembrane helix S6. Moreover, Scu attenuates endogenous TRPV3 activity in human keratinocytes and inhibits carvacrol-induced proliferative and proinflammatory responses. CONCLUSION AND IMPLICATIONS: Collectively, these data demonstrate that Scu ameliorates carvacrol-induced skin inflammation by directly inhibiting TRPV3, and TRPV3 represents a viable therapeutic target for AD treatment.

Exploring physical performance using basic fitness test among collegiate students.

OBJECTIVE: To determine the effect of recreational status, body weight and risk factors on physical fitness of general students and on agility of physical therapy students. METHODS: The cross-sectional study was conducted at Taibah University, Medina, Kingdom of Saudi Arabia, from November 2018 to April 2019, and comprised general and physical therapy students from the College of Medical Rehabilitation Sciences. Data was obtained related to risk factors, like overweight, smoking and recreational status. Upper body strength, agility and endurance were measured using flexed-arm hang, 11x10 shuttle sprint test, and 1000-meter run test respectively. Data was analysed using SPSS 23. RESULTS: Of the 50 subjects, 30(60%) were physical therapy students and 20(40%) were general students. Overall mean age of the sample was 21.54±1.83 years (range: 18-26), and mean body mass index was 23.34±3.37kg/m2 (range: 16.8-29.4kg/m2). The mean values for overweight status and number of risk factors were significantly different for the shuttle-sprint test (p<0.05), but were non-significant for the recreational status (p>0.05). All the assessed variables had non-significant association (p>0.05) in terms of flexed-arm hang test. Overall, 29(58%) subjects could not complete the 1000-meter run test, and 44(88%) found it a strong exertion. Conclusions: Unhealthy lifestyle significantly impaired physical fitness. gain by the diabetics.

Long-Term Success Durability of Transurethral Resection of Ejaculatory Duct in Treating Infertile Men with Ejaculatory Duct Obstruction.

Objectives: The current study aimed to evaluate the long-term outcomes of TURED (transurethral resection of the ejaculatory duct) in treating male infertility due to ejaculatory duct obstruction (EDO) to the short-term follow-up. Methods: From 2000 to 2010, we retrospectively reviewed 30 men with infertility resulting from EDO who underwent TURED. Information on preoperative evaluation of patients was collected from the medical records. Standardized semen analysis was performed 6 weeks, 3 months, and 12 months postoperatively, as well as after a 7-year follow-up. Results: The average age of patients was 35.5 ± 2.6. All patients had low ejaculate volume and normal range of the mean serum hormone levels (gonadotropins and testosterone). Transrectal ultrasonography (TRUS) assessment revealed midline cysts in 46.7% (n = 14 cases), a seminal vesicle dilatation in 83.3% (25/30 cases), and ejaculatory duct dilatation in 76.7% (23/30 patients). In addition, two patients (6.6%) underwent MRI pelvis to confirm equivocal EDO by TRUS. After short-term and long-term follow-up, semen parameters improved significantly in 90% of cases vs 63.3% of cases, respectively, with statistically insignificant differences in all parameters (p ≥ 0.1). Based on subgroup analysis, semen parameters improved in all partial EDO and cystic EDO cases vs complete EDO and noncystic EDO, respectively. Spontaneous pregnancies were achieved in 10 (33.3%) vs 8 (26.6%) cases after short and long term, respectively. Regarding post-TURED complications, we reported 23.3% (n = 7). Conclusion: TURED is an effective treatment for EDO. It significantly improves all semen parameters and improves the symptoms related to EDO after short and long-term follow-up.

Amelioration of cyclophosphamide toxicity via modulation of metabolizing enzymes by avocado (Persea americana) extract.

OBJECTIVES: Cyclophosphamide (CPA) is highly effective in treating several human tumours and autoimmune disorders; but, it triggers deleterious side effects. Avocado, Persea americana (Mill.), is a widely consumed fruit with pronounced nutritional and medicinal value. Though many studies examined the protective mechanisms of natural products against CPA toxicity, almost none investigated the modulation of CPA metabolism as a potential underlying mechanism for protection. Here, we investigated the modulating effect of avocado extract (AE) on certain CPA metabolizing enzymes and its correlation with the extent of CPA-induced pulmonary toxicity and urotoxicity. METHODS: Rats received oral AE (0.9 g/kg body weight/day) 7 days before a single CPA injection (150 mg/kg body weight) and continued AE intake for 2, 7 or 28 days to study three phases of CPA-induced urotoxicity and pulmonary toxicity. KEY FINDINGS: CPA acutely elevated then reduced hepatic microsomal cytochrome P450 2B6 (CYP2B6) content and significantly suppressed bladder and lung glutathione-S-transferase activity. Furthermore, CPA elevated lung myeloperoxidase activity, DNA content and hydroxyproline level and bladder blood content. AE ameliorated CPA-induced derangements through suppression of CYP2B6 and myeloperoxidase and augmentation of glutathione-S-transferase activity in CPA-treated rats. CONCLUSIONS: AE modulation of CPA metabolizing enzymes and potential anti-inflammatory effect may mitigate CPA-induced toxicity.

Impact of FOXP1 rs2687201 genetic variant on the susceptibility to HCV-related hepatocellular carcinoma in Egyptians.

Hepatocellular carcinoma (HCC) constitutes a challenging health problem in Egypt due to the high incidence of hepatitis C virus (HCV) infection. Improved understanding of genetic mechanisms underlying the individual predisposition to HCC will lead to enhancements in the early diagnosis, treatment, and prevention of this disease. Transcription factor forkhead box P1 (FOXP1) is involved in the cellular processes of proliferation, differentiation, metabolism, and longevity. In addition, it has been implicated in hepatic tumorigenesis. The present study explored the association of C/A single-nucleotide polymorphism in the FOXP1 gene (rs2687201) with HCC susceptibility in HCV Egyptian patients. The study included 108 patients with HCV-dependant HCC, 86 HCV patients, and 80- age and gender-matched healthy controls. rs2687201 genotyping was performed by allelic discrimination method using TaqMan real-time PCR assays while FOXP1 gene expression and protein level were determined using qRT-PCR and enzyme-linked immunoassay, respectively. Our results revealed a significant association between FOXP1 rs2687201 and HCC risk where (A) allele was significantly more frequent in patients with HCC compared to controls (odds ratio [OR]: 1.88, 95% confidence interval [CI]: 1.17-3.04, p = 0.01) and to HCV patients (OR: 1.85, 95% CI: 1.62-2.94, p = 0.012). Furthermore, FOXP1 gene and protein expression levels were remarkably higher in (CA + AA) than in CC genotype carriers in a dominant model. The (CA + AA) genotype displayed a significantly shorter overall survival than the CC genotype in HCC patients. In conclusion, FOXP1 gene polymorphism rs2687201 is significantly associated with HCC, but not with HCV infection, in Egyptian patients.

Antepartum and postpartum changes in adipokines, endothelial dysfunction, inflammatory markers and other biochemical parameters in preeclamptic women: A prospective observational cohort study.

This study aimed at evaluating the role played by insulin resistance, lipid metabolism disorder, oxidative stress, resistin, vaspin, Interleukin-18 and asymmetric dimethyl arginine as a marker for endothelial dysfunction in the pathogenesis of preeclampsia. This prospective observational cohort study involved 60 women who were classified into: 20 non-pregnant women (group 1 or control group), 20 normally pregnant women (group 2) and 20 preeclamptic women (group 3) at their third trimester. The pregnant women were assessed at their third trimester and further re-evaluated four weeks after delivery. The assessment included demography, assessment of proteinuria and urinary protein to creatinine ratio, blood pressure measurement and assessment of fasting blood glucose, fasting insulin level, lipid panel and the circulating levels of malondialdehyde, resistin, vaspin, interleukin-18 and asymmetric dimethyl arginine. Preeclamptic women showed more atherogenic lipid profile, significantly higher Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and significantly elevated levels of malondialdehyde, resistin, vaspin and interleukin-18 than the other study groups. Serum asymmetric dimethyl arginine concentration showed non-significant difference among the three study groups. The levels of resistin and vaspin showed significant decrease four weeks postpartum in preeclamptic group. We concluded that, preeclampsia was associated with insulin resistance, dyslipidemia, oxidative stress, inflammation and significant changes in adipokines; resistin and vaspin. Furthermore, the significant increase in the serum levels of resistin and vaspin at the third trimester and their significant decline four weeks postpartum in preeclamptic group focus the attention on the role played by these adipokines in the pathogenesis of preeclampsia.

Autoimmunity roots of the thrombotic events after COVID-19 vaccination.

Although vaccination represents the most promising way to stop or contain the coronavirus disease 2019 (COVID-19) pandemic and safety and effectiveness of available vaccines were proven, a small number of individuals who received anti-SARS-CoV-2 vaccines developed a prothrombotic syndrome. Vaccine-induced immune thrombotic thrombocytopenia (VITT) can be triggered by the adenoviral vector-based vaccine, whereas lipid nanoparticle-mRNA-based vaccines can induce rare cases of deep vein thrombosis (DVT). Although the main pathogenic mechanisms behind this rare phenomenon have not yet been identified, both host and vaccine factors might be involved, with pathology at least in part being related to the vaccine-triggered autoimmune reaction. In this review, we are considering some aspects related to pathogenesis, major risk factors, as well as peculiarities of diagnosis and treatment of this rare condition.

Extended TIP vs. Standard TIP for primary distal hypospadias repair: randomized study for comparing functional and cosmetic outcomes.

OBJECTIVES: The aim of this study was to critically evaluate distal extension of the midline urethral plate incision, extended tubularized incised plate (e-TIP) technique, with the standard TIP and investigating predictors of functional and cosmetic success. METHODS: In a prospective study, consecutive patients with primary distal hypospadias presented for repair were randomized to undergo either extended TIP (e-TIP) or standard TIP (s-TIP) technique. Cosmetic outcome was evaluated postoperatively using Hypospadias-Objective-Penile-Evaluation (HOPE) score and measurement of ventral-glans-closure-length (VGCL) and meatal length (ML). Functional outcome was evaluated by maximal flow rate (Qmax), average flow rate (Qave), and postvoid residual urine (PVR). The effect of preoperative parameters on the outcome was assessed with regression analysis. RESULTS: In all 94 cases, out of 110 randomized, were available for analysis. Forty-six in e-TIP group and 48 cases in s-TIP group with comparable preoperative demographics. Median (inter-quartile range) of postoperative total HOPE-score was 57(45-60) vs. 55(44-60) for e-TIP and s-TIP (p < 0.001), respectively. The mean (SD) ratio of VGCL/ML was 87% (26) versus 46% (12) for e-TIP vs. s-TIP, respectively (p < 0.001). Both complications and functional outcomes were comparable. Urethral plate (UP) width and the use of e-TIP technique were significant predictors of successful cosmetic outcome in regression analysis (p = 0.019 and p = 0.001), respectively. CONCLUSION: Extension of midline urethral plate can potentially create a vertical slit-like meatus located at the glans tip without compromising the functional outcome, thus providing better cosmetic outcome compared with the standard technique. The UP width was a significant predictor of superior cosmetic outcome.