The diagnostic utility of FIB-4 as a non-invasive tool for liver fibrosis scoring among NAFLD patients: a retrospective cross-sectional study.

OBJECTIVE: Liver biopsy is the gold standard method to evaluate patients with non-alcoholic fatty liver disease (NAFLD). However, due to its several limitations and complications, a reliable and non-invasive marker is required to assess liver fibrosis. In this study, we compared the performance of the FIB-4 index [based on age, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels and platelets count] with the Scheuer scoring system of liver biopsies to evaluate the diagnostic utility of FIB-4 among NAFLD patients with different liver fibrosis severities. PATIENTS AND METHODS: A cross-sectional study was conducted at An-Najah National University Hospital (NNUH) in Palestine. The FIB-4 index was calculated using laboratory data for 128 NAFLD patients who underwent liver biopsies between November 2014 and July 2022. The results of FIB-4 were compared with the Scheuer scoring system of liver biopsies (using F0, F1+F2, F3+F4) to determine the sensitivity and specificity of FIB-4 in detecting and staging liver fibrosis. RESULTS: Out of 128 patients involved in our study, 49 of them had advanced fibrosis according to liver biopsy (F3+F4), where their FIB-4 indices showed 87% sensitivity at 1.45 cut off point and 87% specificity at 3.25 cut off point. CONCLUSIONS: The FIB-4 index may be used as a screening tool in the primary care setting. To raise awareness of liver diseases, this non-invasive, inexpensive, simple, and quick marker could identify people in need of further liver fibrosis evaluation and diagnosis.

The effect of irisin on the ultrastructure of the thoracic aorta in rat: A morphometric study.

BACKGROUND: One of the most recent hormones to be identified and isolated is irisin, extracted from mouse skeletal muscle in 2012. Irisin has been proven to alter blood pressure, which has an impact on blood vessels, enhance endothelial functions, and prevent injury to endothelial cells. The current study aimed to study the effect of irisin on the ultrastructure of the rat thoracic aorta using the transmission electron microscope (TEM). MATERIALS AND METHODS: Twenty female rats were recruited for this study and divided into a control group (non-injected), and four experimental groups (injected groups) each consisting of 4 rats. The experimental groups were injected intraperitoneally with different doses of irisin (250ng/mL, 500ng/mL, 1000ng/mL, and 2000ng/mL) twice a week for 4weeks. Then, the descending thoracic aorta of all experimental rats were resected and proceeded with imaging. RESULTS: The results of this study showed a change in the thickness of the tunica intima, internal elastic lamina, elastic lamellae, and external elastic lamina concerning increasing injected irisin concentration. While there was a significant increase in the thickness of tunica media (P<0.0001) and smooth muscle cells (P<0.05). Also, the results showed a significant increase in the number of elastic lamellae in the tunica media (P<0.0001). CONCLUSION: Irisin had a major impact on the elasticity of the rat thoracic aorta wall, suggesting that it influences the growth factors of the wall and activates smooth muscle cells in addition to endothelial cells.

Comparative study of two different computer-controlled local anesthesia injection systems in children: a randomized clinical trial.

PURPOSE: To compare pain perception associated with two computer-controlled local anesthesia devices, the WAND™ STA (Milestone Scientific Inc., Livingston, NJ, USA) and the Calaject (Rønvig dental MFG, Daugaard, Denmark) in young children. METHODS: A split-mouth randomized clinical trial comprising 30 patients, aged 6-12 years, received randomly, in two separate sessions, a local anesthesia injection in the maxillary using either the wand STA or the Calaject. Pain perception was evaluated using the patient's heart rate, an 11-point numerical scale (NRS), and the Sound, Eye, and Motor (SEM) body movements. Statistical difference was set at p = 0.05. Repeated measures analysis of variance were conducted to compare the mean pulse for Calaject and STA at different times. It was followed by univariate analysis and Bonferroni multiple comparisons tests. Wilcoxon tests were performed to compare NRS, SEM, and injection duration between Calaject and STA. RESULTS: There was no significant statistical difference between Calaject and STA in pulse rate before injection (p = 0.720), during injection (p = 0.767), and after injection (p = 0.757). The mean NRS score was significantly greater with STA in comparison with Calaject (p = 0.017). The mean SEM score was also significantly greater with STA in comparison with Calaject (p = 0.002). However, the mean duration was significantly longer with Calaject (p = 0.001). CONCLUSIONS: Calaject was more effective than STA in reducing pain perception associated with periapical injection in young children.

Revisiting the anatomy of the cephalic vein, its origin, course and possible clinical correlations in relation to the anatomical snuffbox among Jordanian.

BACKGROUND: The cephalic vein is one of the most distinguished superficial veins of the upper limb. Its clinical value lies in venous access. There is little known about the variation of its formation in relation to the anatomical snuffbox. Hence, anatomical variants in the origin of the cephalic vein are important in clinical practice. Subsequently, this study was designed to examine the variation of the cephalic vein formation in relation to the anatomical snuffbox. MATERIALS AND METHODS: A cross-sectional study of 438 subjects (722 hands), was prepared to study the cephalic vein among Jordanian students and staff of one of the major governmental Medical College in Jordan, by using infrared illumination system. The obtained data was analysed according to; gender, sidedness, and handedness. RESULTS: Four sites for the formation of the cephalic vein in relation to the anatomical snuffbox were found. There was a significant relation between gender and sidedness, and the sites of formation of the cephalic vein (p < 0.0001 and p = 0.048, respectively). CONCLUSIONS: For the first time this study identified different sites for the formation of the cephalic vein in relation to the anatomical snuffbox. However, regardless of its sites of formation, the cephalic vein was running in 98% of the examined hands in the anatomical snuffbox.

Medicine in motion: Opportunities, challenges and data analytics-based solutions for traditional medicine integration into western medical practice.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional pharmacopeias have been developed by multiple cultures and evaluated for efficacy and safety through both historical/empirical iteration and more recently through controlled studies using Western scientific paradigms and an increasing emphasis on data science methodologies for network pharmacology. Traditional medicines represent likely sources of relatively inexpensive drugs for symptomatic management as well as potential libraries of new therapeutic approaches. Leveraging this potential requires hard evidence for efficacy that separates science from pseudoscience. MATERIALS AND METHODS: We performed a review of non-Western medical systems and developed case studies that illustrate the epistemological and practical translative barriers that hamper their transition to integration with Western approaches. We developed a new data analytics approach, in silico convergence analysis, to deconvolve modes of action, and potentially predict desirable components of TM-derived formulations based on computational consensus analysis across cultures and medical systems. RESULTS: Abstraction, simplification and altered dose and delivery modalities were identified as factors that influence actual and perceived efficacy once a medicine is moved from a non-Western to Western setting. Case studies on these factors highlighted issues with translation between non-Western and Western epistemologies, including those where epistemological and medicinal systems drive markets that can be epicenters for zoonoses such as the novel Coronavirus. The proposed novel data science approach demonstrated the ability to identify and predict desirable medicinal components for a test indication, pain. CONCLUSIONS: Relegation of traditional therapies to the relatively unregulated nutraceutical industry may lead healthcare providers and patients to underestimate the therapeutic potential of these medicines. We suggest three areas of emphasis for this field: First, vertical integration and embedding of traditional medicines into healthcare systems would subject them to appropriate regulation and evidence-based practice, as viable integrative implementation mode. Second, we offer a new Bradford-Hill-like framework for setting research priorities and evaluating efficacy, with the goal of rescuing potentially valuable therapies from the nutraceutical market and discrediting those that are pseudoscience. Third, data analytics pipelines offer new capacity to generate new types of TMS-inspired medicines that are rationally-designed based on integrated knowledge across cultures, and also provide an evaluative framework against which to test claims of fidelity and efficacy to TMS made for nutraceuticals.

Feasibility of laser-guided percutaneous pedicle screw placement in the lumbar spine using a hybrid-OR.

PURPOSE: Innovations in intraoperative imaging lead to major changes in orthopaedic surgery. In our setting, a 3D flat-panel c-arm (Artis zeego) is mounted on a robotic arm offering an integrated aiming tool (Syngo iGuide). Our aim was to investigate the feasibility of Syngo iGuide for pedicle screw placement in comparison with fluoroscopic screw implantation. METHODS: In 10 lumbar models, 100 screws were implanted. In 5 models, a standard fluoroscopic technique was used. Syngo iGuide was used in all other models. Afterwards, CT-scans were performed and screw accuracy was investigated. RESULTS: The procedure time for the new technique was significantly longer in comparison with the standard technique. The post-operative CT showed the same accuracy in both groups. CONCLUSIONS: Syngo iGuide proofed feasible for percutaneous implantation of pedicle screws in anatomic models. Syngo iGuide can be a help for screw implantation in difficult anatomic regions without the need of an additional navigation system.

[Introduction of the photoselective vaporization of the prostate in an outpatient setting: Outcomes after the first 100 cases]. / Introduction de la photovaporisation de prostate en ambulatoire : résultats sur les 100 premiers patients.

BACKGROUND AND OBJECTIVES: Our objective was to describe the progressive introduction of photoselective vaporization of the prostate (PVP) in an academic department of urology in an outpatient care setting and report our outcomes after the first 100 cases. PATIENTS AND METHODS: Since May 2014, XPS GreenLight™ (Boston Scientific-AMS, USA) PVP in the treatment of benign prostatic hyperplasia was introduced in our department. A prospective local registry was opened to collect patients' demographics, preoperative characteristics and surgical outcomes including operative time, length of stay, catheterization time, and postoperative complications as well as functional outcomes. We also assessed limitations to the outpatient care setting. RESULTS: Conversion to TURP was reported in 6 % for uncontrolled bleeding. Overall, 21 % patients needed more than 1-day catheterization. After 6 months of follow-up, 3 patients (prostate volume 50, 117, and 178mL) had reintervention (second PVP). Ninety days' complications were reported to be up to 6 % (3 urinary obstructions, 1 prostatitis, 1 transfusion and a severe sepsis). After 8 months, an 80 % plateau of outpatient care setting was achieved. Anesthesiologists counter-indicated outpatient care in 59 % of the cases. CONCLUSIONS: A progressive introduction of the PVP in an outpatient care setting is associated with a low complication rate. A plateau was achieved in less than 100 procedures. The major limitation of the outpatient care setting was patients' competitive comorbidities and not disease characteristics. LEVEL OF EVIDENCE: 4.

Sub-clinical left ventricular diastolic dysfunction in early stage of chronic obstructive pulmonary disease.

Sub-clinical cardiac dysfunction may be significantly associated with chronic obstructive pulmonary disease (COPD) with a different degree of severity. In a cross-sectional design we aimed to evaluate the frequency of left ventricular diastolic dysfunction (LVdd) and its correlation with lung function, pulmonary arterial pressure and systemic inflammation in a selected population of COPD at an early stage of their disease. Fifty-five COPD patients with no clinical signs of cardiovascular dysfunction were recruited and compared to 40 matched healthy controls. All the subjects underwent pulmonary function testing, doppler echocardiography, and interleukin-6 blood sampling. Presence of LVdd was defined according to the significant change in both the ratio between early and late diastolic transmitral flow velocity (E/A ratio), isovolumetric relaxation time (IVRT), and deceleration time (DT). The frequency of LVdd was higher in the COPD group (70.9 percent) compared to controls (27.5 percent). In these patients decreased E/A ratio, and prolonged IVRT and DT clearly pointed to left ventricular filling impairment, a condition we found to be especially severe in those patients suffering from lung static hyperinflation as expressed by inspiratory-to-total lung capacity ratio (IC/TLC) <0.25. Circulating levels of interleukin-6 were also higher among COPD patients compared to controls. The results of the present study suggest that subclinical left ventricular filling impairment is frequently found in COPD patients at the earlier stage of the disease even in the absence of any other cardiovascular dysfunction. Doppler echocardiography may help the early identification of LVdd in COPD patients.

Impact of valvular thickness on stroke recurrence in medically treated patients with stroke.

BACKGROUND: It remains controversial whether left-sided valvular thickening (VaT) is a risk factor for ischemic stroke. Little is known about the relationship between VaT and the recurrent adverse event rate in medically treated patients with stroke. METHODS: We examined the outcomes of 627 noncardioembolic stroke patients who were double-blindly assigned to either warfarin or aspirin therapy and assessed VaT using transesophageal echocardiography. Endpoints were recurrent ischemic stroke or death from any cause. The Cox proportional hazards model was used to adjust for covariates. RESULTS: VaT was present in 57.3% of the patients (359/627), 34.6% (271/627) involving the aortic valve and 46.4% (291/627) involving the mitral valve. There was no difference in the time to primary endpoints between those with and without VaT of the aortic valve (p = 0.49; hazard ratio, HR: 1.17; 95% CI: 0.74-1.85; 2-year event rates: 18.9 vs. 13.2%) or mitral valve (p = 0.66; HR: 0.91; 95% CI: 0.60-1.38; 2-year event rates: 16.9 vs. 14.7%). Among the patients with VaT, there was no significant difference in the time to primary endpoints between those treated with warfarin and those with aspirin (p = 0.13, HR: 0.65, 95% CI: 0.37-1.14, 2-year event rates: 15.2 vs. 22.7% for the aortic valve; p = 0.22, HR: 0.70, 95% CI: 0.40-1.23, 2-year event rates: 14.2 vs. 19.6% for the mitral valve). CONCLUSIONS: VaT does not appear to increase recurrent adverse event rates in medically treated patients with ischemic stroke, regardless of warfarin or aspirin therapy.

The risk of radiocontrast nephropathy in patients with cirrhosis.

A retrospective case-control study was conducted to determine whether liver cirrhosis might be a risk factor for radiocontrast induced nephropathy as has been suggested. Data from 72 patients with cirrhosis and 72 patients without cirrhosis who all received 100-150 ml of low osmolality radiocontrast medium for abdominal or chest computerized tomography scan were reviewed. Blood urea nitrogen and creatinine were recorded before and 48-72 h after the administration of an intravenous radiocontrast agent. Acute renal failure developed in two patients with cirrhosis (2.8%) and one patient in the control group (1.4%). This difference was not significant. There was no significant change in blood urea nitrogen and creatinine in either group after radiocontrast injection. Both of the cirrhotic patients who developed radiocontrast induced nephropathy had received high-dose diuretics and were hypovolemic. We conclude that hepatic cirrhosis per se may not be a risk factor for radiocontrast-induced nephropathy.

Life-threatening hyperkalemia after intravenous labetolol injection for hypertensive emergency in a hemodialysis patient.

Intravenous labetolol, a nonselective alpha- and beta-blocking drug, is commonly used to treat severe hypertension. Nonselective beta-blockers can cause hyperkalemia, especially in patients with renal failure. One series reported 3 renal transplant patients who had hyperkalemia after labetolol infusion, but none of these patients developed any serious complication. We report a case of life-threatening hyperkalemia (serum [K+] 9.9 mEq/l) with ventricular tachycardia and hypotension in a patient on maintenance hemodialysis who received labetolol for a hypertensive emergency. Physicians should be aware of this potentially lethal complication, which is easily preventable.

Mechanisms of anticarcinogenic properties of curcumin: the effect of curcumin on glutathione linked detoxification enzymes in rat liver.

Curcumin, an antioxidant isolated from turmeric (curcuma longa), has been shown to attenuate chemical carcinogenesis in rodents. Previous studies have shown that curcumin causes an increase in glutathione S-transferase (GST) activity in rodent liver which may contribute to its anti-cancer and anti-inflammatory activities. Since the effects of curcumin on specific GST isozymes and other glutathione (GSH)-linked enzymes are incompletely defined, we have examined in the present studies the effect of curcumin on hepatic non-protein sulfhydryls and GSH-linked enzymes in male Sprague-Dawley rats. When rats were fed curcumin at doses from 1 to 500 mg kg-1 body weight daily for 14 days, the induction of hepatic GST activity towards 1-chloro-2,4-dinitrobenzene (CDNB) was found to be biphasic, with maximal induction of about 1.5 fold at the 25 to 50 mg kg-1 body weight dosage. At higher doses, a decrease was observed in the activity and in the rats treated with 500 mg kg-1 curcumin this activity was below the levels observed in controls. In contrast, GST activity towards 4-hydroxynonenal (4-HNE) increased in a saturable, dose dependent manner. Western-blot analyses of liver cytosols revealed that curcumin caused a dose dependent induction of rGST 8-8, an isozyme which is known to display the highest activity towards 4-HNE, a highly toxic product of lipid peroxidation. Glutathione peroxidase (GPx) activity towards cumene hydroperoxide in liver homogenate was also found to be increased in a saturable manner with respect to curcumin dose. Our results suggest that induction of enzymes involved in the detoxification of the electrophilic products of lipid peroxidation may contribute to the anti-inflammatory and anti-cancer activities of curcumin.

Pre-clinical Cushing's syndrome: an unexpected frequent cause of poor glycaemic control in obese diabetic patients.

OBJECTIVE: Autonomous cortisol secretion without clinical stigmata of Cushing's syndrome (CS) has been recently recognized and termed pre-clinical or sub-clinical CS. The common assumption is that CS is an extremely rare cause of uncontrolled diabetes; however, the prevalence of this entity has not been studied. We assessed the prevalence of pre-clinical CS among obese patients with uncontrolled diabetes. PATIENTS AND DESIGN: (1) In a retrospective analysis, the medical records of 63 patients with endogenous CS were reviewed. (2) In a cross-sectional study, 90 obese patients (BMI > 25 kg/m2) followed in a University Hospital and the local Health Fund endocrine and diabetes clinics, with poorly controlled diabetes (glycosylated haemoglobin > 9%), underwent an overnight 1 mg dexamethasone suppression. In patients with non-suppressible cortisol levels (> 140 nmol/l), Liddle's 2 and 8 mg dexamethasone suppression tests and imaging studies were performed. MEASUREMENTS: The prevalence of poorly controlled diabetes, the major presenting symptom of CS, was assessed in the retrospective analysis. The prevalence of "true' CS and the false positive rate in the overnight dexamethasone suppression test were calculated. The endocrine evaluation of the patients with pre-clinical CS and the effects of surgical cure on glycaemic control are described. RESULTS: In the retrospective analysis, 11 (17.5%) had diabetes and 2 (3.2%) lacked the classic physical characteristics of the syndrome. In the cross-sectional study, 4 patients failed to suppress plasma cortisol (< 140 nmol/l). In one patient the diagnosis of CS was not confirmed by a standard Liddle's test and was therefore considered false positive. In the other 3, the diagnosis of CS was confirmed (prevalence of 3.3%, 95% confidence interval 1-9%). In all other patients the overnight cortisol suppression test was normal (cortisol level 47.3 +/- 2.5 nmol/l (mean +/- SEM)). After surgical treatment of CS, glycaemic control was markedly improved in all 5 patients (2 from retrospective and 3 from cross-sectional studies). CONCLUSIONS: The prevalence of pre-clinical Cushing's syndrome in obese patients with poorly controlled diabetes appears to be considerably higher than previously believed. The overnight dexamethasone suppression test proved to be a simple, sensitive and highly specific screening test for Cushing's syndrome despite the presence of obesity and hyperglycaemia.

Pendred syndrome maps to chromosome 7q21-34 and is caused by an intrinsic defect in thyroid iodine organification.

Exactly 100 years ago, in 1896, Pendred first described the association of congenital deafness with thyroid goitre (MM#274600). The incidence of Pendred syndrome is estimated at 7.5-10/100,000, and may be responsible for as much as 10% of hereditary deafness. The cause of the congenital deafness in Pendred syndrome is obscure, although a Mondini type malformation of the cochlea exists in some patients. The reason for the association between the thyroid and cochlear defects is similarly obscure, leading some investigators to suggest that the two recessive defects may be occurring together by chance in highly consanguineous families. An in vivo defect in thyroid iodine organification in Pendred syndrome patients has been reported. However, the molecular basis of this defect is unknown and the presence of an intrinsic thyroidal defect has not been conclusively demonstrated. We have adopted a genetic linkage study as a first step towards identifying the gene. The availability of an inbred Pendred syndrome kindred allowed us to utilize an efficient DNA pooling strategy to perform a genome-wide linkage search for the disease locus. In this way, we have mapped the disease locus to an approximately 9-cM interval between GATA23F5 and D7S687 on chromosome 7. In addition, we demonstrate an intrinsic thyroid iodine organification defect in a patient's thyroid cells as the cause of the thyroid dysfunction.

Hyperinsulinemic hypoglycemia of infancy (nesidioblastosis) in clinical remission: high incidence of diabetes mellitus and persistent beta-cell dysfunction at long-term follow-up.

In persistent hyperinsulinemic hypoglycemia of infancy (PHHI), the long term outcome of the disease is not well documented. Previous reports suggested that partial pancreatectomy in infants does not endanger future islet function. We evaluated endocrine pancreatic function in 14 PHHI patients 6.5-21 yr after diagnosis. Eight underwent early subtotal pancreatectomy, and 6 were medically treated; all were in clinical remission. Intravenous glucose tolerance and C-peptide suppression tests were performed, with multiple determinations of hormone levels. The insulin response to glucose was blunted in all pancreatectomized and in 2 conservatively treated patients. Glucose disposal was reduced in 6 pancreatectomized patients and in 2 medically treated subjects. Six of the pancreatectomized patients, including two with normal glucose disposal at first evaluation, developed overt diabetes during puberty. None in the medically treated group became diabetic; however, only 2 patients have reached puberty. C-Peptide suppression in response to hypoglycemia was inadequate in 4 of 5 pancreatectomized and 3 of 5 nonpancreatectomized patients studied. These results show that children with PHHI have impaired insulin responses to glucose and lack of suppressibility of endogenous insulin secretion several years after clinical remission. Thus, the beta-cell defect responsible for the disease in infancy is not corrected with time despite the disappearance of spontaneous hypoglycemia. Insulin secretion seems more disturbed in pancreatectomized patients; the majority develop insulin-requiring diabetes during puberty. An effort should be made to treat PHHI patients medically to avoid pancreatectomy; this may reduce the incidence of diabetes at puberty.

Intracellular Ca(2+)-containing vesicles in sickle cell disorders.

The frequency of red blood cells harboring Ca(2+)-containing vesicles was determined in patients with various sickle cell disorders; vesicles were identified by microscopy after the cells were stained with the fluorescent probe chlortetracycline. Specimens from 49 patients were studied. The highest frequencies of vesicle-containing cells were observed in samples from adults with homozygous sickle cell (SS) disease and in patients with S beta zero and SS(-alpha/alpha alpha) thalassemias. The frequency of cells with vesicles was less elevated in patients with SS(-alpha/-alpha) thalassemia and in patients with SS disease (Saudi Arabia high hemoglobin F), whereas a normal low frequency of positive cells was seen in patients with sickle cell-hereditary persistence of fetal hemoglobin and in patients with sickle trait. Deoxygenation induced an increase in the number of vesicle-containing cells that was proportional to the frequency of such cells in the oxygenated population. The frequency of Ca(2+)-containing vesicles in sickle red cells is associated with the clinical, hematologic, or clinical and hematologic severity of the sickle cell disorder.