From NAFLD to NASH: Understanding the spectrum of non-alcoholic liver diseases and their consequences.

Non-alcoholic fatty liver disease (NAFLD) has become one of the most frequent chronic liver diseases worldwide in recent decades. Metabolic diseases like excessive blood glucose, central obesity, dyslipidemia, hypertension, and liver function abnormalities cause NAFLD. NAFLD significantly increases the likelihood of liver cancer, heart disease, and mortality, making it a leading cause of liver transplants. Non-alcoholic steatohepatitis (NASH) is a more advanced form of the disease that causes scarring and inflammation of the liver over time and can ultimately result in cirrhosis and hepatocellular carcinoma. In this review, we briefly discuss NAFLD's pathogenic mechanisms, their progression into NASH and afterward to NASH-related cirrhosis. It also covers disease epidemiology, metabolic mechanisms, glucose and lipid metabolism in the liver, macrophage dysfunction, bile acid toxicity, and liver stellate cell stimulation. Additionally, we consider the contribution of intestinal microbiota, genetics, epigenetics, and ecological factors to fibrosis progression and hepatocellular carcinoma risk in NAFLD and NASH patients.

Exosomal miR-122, miR-128, miR-200, miR-298, and miR-342 as novel diagnostic biomarkers in NAFL/NASH: Impact of LPS/TLR-4/FoxO3 pathway.

Nonalcoholic fatty liver disease (NAFLD) is a common liver disorder affecting a quarter of the global residents. Progression of NAFL into nonalcoholic steatohepatitis (NASH) may cause cirrhosis, liver cancer, and failure. Gut microbiota imbalance causes microbial components translocation into the circulation, triggering liver inflammation and NASH-related fibrosis. MicroRNAs (miRNAs) regulate gene expression via repressing target genes. Exosomal miRNAs are diagnostic and prognostic biomarkers for NAFL and NASH liver damage. Our work investigated the role of the gut microbiota in NAFLD pathogenesis via the lipopolysaccharide/toll-like receptor 4/Forkhead box protein O3 (LPS/TLR-4/FoxO3) pathway and certain miRNAs as noninvasive biomarkers for NAFL or its development to NASH. miRNA expression levels were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 50 NAFL patients, 50 NASH patients, and 50 normal controls. Plasma LPS, TLR-4, adiponectin, peroxisome proliferator-activated receptor γ (PPAR-γ), and FoxO3 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). In NAFL and NASH patients, miR-122, miR-128, FoxO3, TLR-4, LPS, and PPAR-γ were upregulated while miR-200, miR-298, miR-342, and adiponectin were downregulated compared with the normal control. The examined miRNAs might distinguish NAFL and NASH patients from the normal control using receiver operating characteristic analysis. Our study is the first to examine these miRNAs in NAFLD. Our findings imply that these are potentially promising biomarkers for noninvasive early NAFL diagnosis and NASH progression. Understanding the LPS/TLR-4/FoxO3 pathway involvement in NAFL/NASH pathogenesis may aid disease management.

Selenium nanoparticles enhance the efficacy of homologous vaccine against the highly pathogenic avian influenza H5N1 virus in chickens.

A proper vaccination against avian influenza viruses in chicken can significantly reduce the risk of human infection. Egypt has the highest number of recorded humans highly pathogenic avian influenza (HPAI)-H5N1 infections worldwide despite the widespread use of homologous vaccines in poultry. Enhancing H5N1 vaccine efficacy is ultimately required to better control HPAI-H5N1. The aim of this study is to boost chicken immunity by combined with inactivated HPAI-H5N1 with selenium nanoparticles (SeNPs). The chickens groups 1-3 were fed diets supplemented with SeNPs concentrations (0.25, 0.5, and 1 mg/kg) for 3 weeks and then vaccinated (inactivated HPAI-H5N1). while groups 4,5 and 6 were fed with SeNPs free diets and administered with 0.5 ml of the vaccine combined with 0.02, 0.06, and 0.1 mg/dose of SeNPs and then all groups were challenged with homologous virus 3 weeks post-vaccination (WPV). Group 7, 8 were used as control positive and negative respectively. At 4, 5, and 6 WPV, antibody titer was considerably higher in the group fed a meal supplemented with 1 mg SeNPs/kg. In contrast, both methods of SeNPs supplementation significantly increased the Interleukin 2 (IL2), Interleukin 6 (IL6), and Interferon γ (IFNγ) expressions in the blood cells in a dose-dependent manner, with a higher expression observed in the group that was vaccinated with 0.1 mg/dose. After the challenge, all groups that received SeNPs via diet or vaccines dose showed significant reduction in viral shedding and milder inflammation in lung, trachea, spleen, and liver in addition to higher expression of IL2, IL6, and IFNγ, with the highest expression observed in the group that was vaccinated with 0.1 mg/dose compared the plain vaccinated group. The groups of 1 mg SeNPs/kg and combined vaccinated with 0.1 mg/dose showed the best vaccine efficacy. However, the group vaccinated with 0.1 mg/dose showed the earliest reduction in viral shedding. Overall, SeNPs supplementation in the diet and the administration of the vaccine formula with SeNPs could enhance vaccine efficacy and provide better protection against HPAI-H5N1 in chickens by enhancing cellular immunity and reducing inflammation. We recommend using SeNPs as a vaccine combination or feeding with diet to increase the immunity and vaccine efficacy against H5N1.

Intra-operative ultrasound: does it improve the results of percutaneous repair of acute Achilles tendon rupture?

PURPOSE: Percutaneous repair is a good option for acute Achilles tendon rupture. Although it overcomes the complications of open technique, it carries the risk of sural nerve injury and inadequate repair. In this study, we explore if the use of intra-operative ultrasound with percutaneous technique has any advantageous effect on final results of repair. METHODS: This is a prospective randomized study done between May 2014 and December 2020. It included 91 patients with complete acute Achilles tendon rupture distributed in 2 groups with homogenous clinical and demographic data. Group A (n = 47) included those managed by percutaneous repair with assistant of an intra-operative ultrasound. Group B (n = 44) included those done without the assistant of ultrasound. Post-operative evaluation was done clinically by the American Orthopedic Foot and Ankle Society score, calf muscle circumference and single heel rise test and radiologically by Magnetic Resonance Image. RESULTS: Patients of both groups reported continuous improvement of the American Orthopedic Foot and Ankle Society score with time. However, patient of group A recorded better functional outcome score at 3 months postoperatively. We recorded longer operative time in group A than those in group B. Continuous improvement of maximum calf circumference was observed in both groups. Satisfactory healing was noticed to happen faster in patients of group A than those of group B. We recorded two cases of re-rupture and two cases of sural nerve injury in group B with no reported complication in group A. CONCLUSION: The use of an intra-operative ultrasound with percutaneous repair of acute rupture of Achilles tendon can improve the quality of repair as evidenced by quicker satisfactory healing and earlier regain of activity. Also, it can help in proper localization of sural nerve in relation to lateral edge of Achilles tendon. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT04935281.

Efficacy of oxytocics on reducing intraoperative blood loss during abdominal myomectomy: A systematic review and meta-analysis of randomized placebo-controlled trials.

OBJECTIVE: To conduct a systematic review and meta-analysis on the efficacy of oxytocics administration (oxytocin and carbetocin) on reducing intraoperative bleeding during abdominal myomectomy. METHODS: PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar databases were searched from inception until March 2021. Only randomized placebo-controlled trials (RCTs) were considered. The included RCTs were evaluated for risk of bias. The main outcome measures were mean intraoperative blood loss (ml), mean duration of hospital stay (day), mean operation time (min), mean difference of postoperative hemoglobin (g/dl), mean difference of postoperative hematocrit (%), and rate of blood transfusion (%). Pooled outcomes were summarized as risk ratio (RR) or mean difference (MD) with their 95% confidence interval (CI) in a random-effects model. RESULTS: Seven RCTs met the inclusion criteria (n=758 patients; 329 patients per group). Compared with control group, oxytocin and carbetocin resulted in a significantly lower intraoperative blood loss (MD=-281.08 ml, 95% CI [-400.63, -161.53], p<0.001), hospital stay (MD=-0.21 days, 95% CI [-0.31, -0.10], p<0.001), and need for blood transfusion (RR=0.32, 95% CI [0.22, 0.46], p<0.001). Subgroup analysis revealed that oxytocin, but not carbetocin, correlated with a reduced mean difference of postoperative hemoglobin (MD=0.60 g/dl, 95% CI [0.24 to 0.96], p=0.001), postoperative hematocrit (MD=2.29%, 95% CI [1.06, 3.52], p<0.001), and operation time (MD=-14.66 min, 95% CI [-21.04, -8.25], p<0.001) compared with control group. CONCLUSION: Among women undergoing abdominal myomectomy, administration of oxytocin and carbetocin correlated with several beneficial clinical outcomes, such as reduced intraoperative blood loss, hospital stay, and blood transfusion requirement.

Treatment of tibial shaft nonunion with a retained nail in morbidly obese patients.

PURPOSE: Morbid obesity is a rising worldwide health problem. Tibial shaft nonunion with retained intramedullary nail (IMN) in the morbidly obese is a challenging orthopaedic problem. Prolonged immobilization carries a significant risk of complications. This study aimed to investigate whether decortication and cancellous bone grafting with the application of a circular external fixator (CEF) over the preexisting IMN can achieve fracture union and avoid serious complications. METHODS: We retrospectively reviewed 27 consecutive morbidly obese patients treated for tibial diaphysis aseptic nonunion after failed IMN. All cases were treated with osteoperiosteal decortication, cancellous bone grafting, and fixation with CEF over the IMN. Peri-operative multidisciplinary patient evaluation included internal medicine, cardiology, chest, vascular surgery, and anesthesia consultations. The union rate, bone results, functional results, and complications were recorded. RESULTS: The mean age of the patients was 37.9 years. The mean BMI was 45.8. Sixteen cases (59.3%) were treated for hypertrophic nonunion, while 11 cases (40.7%) were treated for atrophic nonunion. Seven cases (25.9%) had open initial injury, 14 cases (51.9%) had associated comorbidities, and seven cases (25.9%) were smokers. Twenty-six cases united. The mean time to union was 5.2 months. Bone results and functional results were good to excellent in 96.3% of the cases. We recorded 25 complications in 21 patients. However, most of the complications were minor. CONCLUSION: Decortication and cancellous bone grafting with the application of CEF over the preexisting nail is a safe and reliable treatment method for aseptic tibial shaft nonunion with retained IMN in morbidly obese patients.

Tibial Tray with a Stem: Does It Have Any Role in Primary Cemented Total Knee Replacement?

Over many decades, total knee replacement (TKR) has become the ideal treatment option for advanced arthritis. Many designs were introduced to increase the stability of the tibial tray, hence the longevity of the prosthesis. This retrospective study was performed on 168 patients who received NexGen cemented primary total knee either with standard tibial tray (group A) or tibial tray with an intramedullary stem (group B) between May 2008 and May 2017. We reviewed all preoperative and postoperative clinical and radiological data retrospectively. In addition, a prospective clinical and radiological reassessment was done. Our aim was to answer the following questions: (1) Is there any difference between both groups in regard to clinical and radiological results? (2) Is there any difference in the revision rate? (3) Is there a role of using stemmed tibial tray in primary TKR? Better results were recorded in obese and severely obese patients having stemmed cemented tibial tray and so for patients with marked and severe preoperative varus angle. Our recommendations are to use cemented tibial tray with a stem in complicated primary surgery without fear of adverse effects on short and intermediate terms of follow-up.

Trans-calcaneal retrograde nailing for secondary-displaced traumatic ankle fractures in diabetics with insensate feet: a less-invasive salvage-arthrodesis technique.

PURPOSE: Secondary displacement of traumatic ankle fractures with subsequent soft-tissue breakdown is a troublesome issue after inappropriate conservative treatment among non-compliant diabetic patients with severe peripheral neuropathy. This study was conducted to evaluate the results of a less-invasive arthrodesis procedure as an alternative to osteosynthesis in these complex scenarios. METHODS: A total of 46 diabetics, who underwent fluoroscopy-assisted trans-calcaneal retrograde nailing-based ankle arthrodesis between 2012 and 2018 for salvaging secondary-displaced diabetic ankle fractures in their insensate feet, were evaluated in this retrospective study. All fractures were associated with uninfected mechanical ulcers overlying malleoli, without Charcot changes, after failed conservative cast immobilization. The patients (mean age: 52.52 ± 3.70 years; 18 males; 46 feet) were evaluated radiologically for union and clinically for limb salvage, modified American Orthopedic Ankle and Foot Scale (AOAFS), and the overall subjective patients' satisfaction. RESULTS: The mean follow-up was 29.5 ± 3.1 months. All ulcers have healed with local care only with 100% limb salvage. Four patients experienced minor wound healing problems at posterior heel, and another one developed acute Charcot changes that was successfully managed by offloading and repeat surgery. Forty patients (86.96%) had fully consolidated fusions with a mean time to fusion 15.78 ± 2.58 weeks, while the other six cases had stable fibrous-union. At the final follow-up, the mean modified-AOFAS was 76.85 ± 6.0 from 86 total points. All, but four patients (91.30%) were completely satisfied while the other four patients were partially satisfied. CONCLUSIONS: The presented less-invasive arthrodesis technique is reproducible and effective alternative for salvaging unstable diabetic ankle fractures in the insensate feet when standard surgical procedures would be more risky. LEVEL OF EVIDENCE: IV, retrospective case series.

The effect of surgical technique, age, and Trisomy 21 on early outcome of surgical management of complete atrioventricular canal defect.

BACKGROUND: The optimal timing, surgical technique, and the influence of Trisomy 21 on the outcome of surgical repair of Complete Atrioventricular Canal Defect remains uncertain. We reviewed our experience in the repair of CAVC to identify the influence of these factors on operative outcomes. METHODS: A prospective study included 70 patients, who underwent repair of CAVC at our institute between July, 2016 and October, 2019. Primary endpoint was mortality and the secondary endpoint was a degree of left atrioventricular valve regurgitation. RESULTS: No significant difference was noted between patients operated on, at the first 6 months of age versus later, regarding mortality or LAVV regurgitation. Surgical repair by modified single-patch technique showed a significant reduction in bypass time (71.13 ± 13.507 min versus 99.19 ± 27.092 min, p-value = 0.001). Compared to closure of cleft only, posterior annuloplasty used for repair of LAVV resulted in significant reduction in the occurrence of post-operative valve regurgitation during the early period (LAVV 2 + 43 versus 7 %, p-value = 0.03) and at 6 months of follow-up (LAVV 2 + 35.4 versus 0 %, p-value = 0.01), respectively. CONCLUSIONS: Early intervention, in the first 6 months in patients with CAVC by surgical repair gives comparable acceptable results to later repair; Trisomy 21 was not found to be a risk factor for early intervention. Repair of common AV valve by cleft closure with posterior LAVV annuloplasty showed better results with a significant decrease in post-operative LAVV regurgitation and early mortality in comparison to the closure of cleft only.

Antioxidant and anti-apoptotic prophylactic effect of silymarin against lead-induced hepatorenal toxicity in rats.

This study assessed prophylactic potentials of silymarin against lead-induced hepatorenal toxicity in rats with the respect to its antioxidant and anti-apoptotic activities. Forty male albino rats were distributed into four groups. Control group is provided with distilled water. Lead acetate group was given lead acetate (100 mg/kg bwt) orally for 10 weeks. The third and fourth groups administered silymarin at doses of 50 or 100 mg/kg bwt, respectively, 1 h before administration of lead acetate for 10 weeks. Lead acetate altered liver structure and function that represented by significant elevation of the activities of serum aspartate and alanine aminotransferases and serum levels of urea and creatinine. Hepatic and renal tissues' malondialdehyde concentrations were increased, while reduced glutathione content and superoxide dismutase and catalase activities were reduced in the lead acetate group. Also, lead acetate increased caspase-3 mRNA expression and inhibited alpha-fetoprotein mRNA expression in hepatic tissues, as well as it altered liver and kidney tissues' architectures. In contrast, silymarin ameliorated in a dose dependent mannar the toxic effects of lead acetate on the liver and kidneys through modulation of lead acetate which altered liver and kidney function and structures via reducing lipid oxidation and pathological changes of hepatic and renal tissue structure, improving antioxidant defense system of liver and kidneys, and decreasing pro-apoptotic gene expression in hepatic tissue. This study indicated that silymarin ameliorated lead acetate-induced hepatorenal toxicity via its antioxidant and cytoprotective potentials.

Medical therapy options for endometriosis related pain, which is better? A systematic review and network meta-analysis of randomized controlled trials.

Our objective was to assess and rank different pharmacological interventions for relieving endometriosis-related pain. We conducted an online bibliographic search in different databases from their inception until March 2019. We included randomized controlled trials (RCTs) that assessed different medical therapies in the management of endometriosis-related pain. We applied this network meta-analysis (NMA) based on the frequentist approach using statistical package "netmeta" (version 1.0-1) in R software. Our main outcomes were the change in severity of pelvic pain, dysmenorrhea score, non-menstrual pelvic pain score, and dyspareunia score. Overall, 36 RCTs were included in this study (patients no. = 7942). Dienogest (0.94), combined hormonal contraceptives (CHCs) (0.782), and elagolix (0.38) were the highest-ranked interventions for reducing the severity of pelvic pain at three months, while at six months, gonadotropin-releasing hormone (GnRH) analogues (0.75), levonorgestrel-releasing intrauterine system (LNG-IUS) (0.73), and dienogest (0.65) were linked to more reduction in pelvic pain. The ranking p-score showed that GnRH analogues was the highest-ranked treatment for reducing dysmenorrhea at 3 months (1.00), while CHCs were the highest-ranked treatment at 6 months (0.97), followed by GnRH analogues (0.89). GnRH analogues (0.63) and elagolix (0.54) at three months while desogestrel (0.94) and CHCs (0.91) at six months were the highest-ranked treatment to reduce non-menstrual pelvic pain. GnRH analogues and elagolix were the highest-ranked pharmacologic therapies for reducing dyspareunia. In conclusion, CHCs, GnRH analogues, progesterone, and elagolix were the best approaches in reducing the pain of endometriosis.

Dual Mobility Cup: Does It Improve Patient's Satisfaction After Total Hip Arthroplasty? A Prospective Comparative Randomized Study.

INTRODUCTION: Despite the great success of total hip arthroplasty (THA), many patients were fairly dissatisfied after surgery. Therefore, patient-reported outcome measures have become of an utmost importance in assessing the results after joint replacement. This study was conducted to compare the postoperative patient-reported satisfactions after implantation of two commonly used THA designs. METHODS: Of 180 patients, who initially fulfilled the study selection criteria and received cementless THA, 165 patients were finally eligible and enrolled in this prospective comparative randomized study. All surgeries were carried out between 2010 and 2018. Two groups of homogenous demographic and clinical data were present. Group A patients (n = 80) were treated by large head THA, whereas group B (n = 85) received dual mobility cup designs. The Western Ontario McMaster Universities Osteoarthritis Index and visual analog scale were used for clinical evaluation. The degree of improvement that the patient expected and hoped before undergoing their surgeries was estimated using the score of the new knee society. The self-administered patient satisfaction scale was used to record the levels of patient satisfaction after surgery, and their values were statistically analyzed in relation to preoperative expectation scores (ie, score of the new knee society) and different clinical and sociodemographic variables. RESULTS: After a mean follow-up of 79 ± 4.13 months (range 24 to 96 months), both groups recorded a significant improvement (P < 0.05) in Western Ontario McMaster Universities Osteoarthritis Index and visual analogue scale scores. Patients of group B were significantly more satisfied (P < 0.05) than those of group A up to the first postoperative year. Certain studied variables were linked to superior satisfaction results among group B at the last follow-up. CONCLUSIONS: Dual mobility THA provides better patient satisfaction than their standard large head alternatives specifically among elderly patients, socially unsupported individuals, farmers, heavy manual workers, and those with high levels of expectations. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT04333316.

Cytotoxicity of Chitosan Ultrafine Nanoshuttles on the MCF-7 Cell Line as a Surrogate Model for Breast Cancer.

AIM: This study aimed to explore an affordable technique for the fabrication of Chitosan Nanoshuttles (CSNS) at the ultrafine nanoscale less than 100 nm with improved physicochemical properties, and cytotoxicity on the MCF-7 cell line. BACKGROUND: Despite several studies reported that the antitumor effect of CS and CSNS could achieve intracellular compartment target ability, no enough information is available about this issue and further studies are required to address this assumption. OBJECTIVES: The objective of the current study was to investigate the potential processing variables for the production of ultrafine CSNS (less than; 100 nm) using Box-Behnken Design factorial design (BBD). This was achieved through a study of the effects of processing factors, such as CS concentration, CS/TPP ratio, and pH of the CS solution, on PS, PDI, and ZP. Moreover, the obtained CSNS was evaluated for physicochemical characteristics, morphology. In addition, hemocompatibility and cytotoxicity using Red Blood Cells (RBCs) and MCF-7 cell lines were investigated. METHODS: Box-Behnken Design factorial design (BBD) was used in the analysis of different selected variables. The effects of CS concentration, sodium tripolyphosphate (TPP) ratio, and pH on particle size, Polydispersity Index (PDI), and Zeta Potential (ZP) were measured. Subsequently, the prepared CS nanoshuttles were exposed to stability studies, physicochemical characterization, hemocompatibility, and cytotoxicity using red blood cells and MCF-7 cell lines as surrogate models for in vivo study. RESULT: The present results revealed that the optimized CSNS has ultrafine nanosize, (78.3 ± 0.22 nm), homogenous with PDI (0.131 ± 0.11), and ZP (31.9 ± 0.25 mV). Moreover, CSNS has a spherical shape, amorphous in structure, and physically stable. Moreover, CSNS has biological safety as indicated by a gentle effect on red blood cell hemolysis, besides, the obtained nanoshuttles decrease MCF-7 viability. CONCLUSION: The present findings concluded that the developed ultrafine CSNS has unique properties with enhanced cytotoxicity, thus promising for use in intracellular organelles drug delivery.

In Vitro Release of 5-Fluorouracil and Methotrexate from Different Thermosensitive Chitosan Hydrogel Systems.

5-Fluorouracil is a member of cytotoxic drugs with poor selectivity to cancer cells. Currently, systemic administration of this anti-cancer drug (oral or injection) exposes normal tissues to the drug-induced toxicity. Nowadays, attention has been greatly directed towards in situ gel-forming systems that can be injected into the affected tissues in its sol form with a minimally invasive technique. More specifically, chitosan hydrogel systems were in focus due to their antibacterial effect as well as their biodegradable, biocompatible, and mucoadhesive properties. In the present work, 5-fluorouracil was loaded on various thermosensitive chitosan hydrogel systems cross linked with different linking agents like ß-glycerophosphate, pluronic F127, and hydroxyapatite. Also, methotrexate was added to 5-fluorouracil in order to gain its previously reported synergistic effects. Firstly, a compatibility study was performed using UV-spectrophotometric, infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) techniques to exclude the possibility of any physical or chemical interactions between the selected drugs and excipients. The prepared hydrogel systems were characterized for their physicochemical properties including organoleptic, pH, syringeability and injectability, viscosity, and gelation temperature (Tgel) by various analysis techniques. Moreover, the in vitro release behavior of 5-fluorouracil and methotrexate was determined with a modified analytical method. The results indicated that chitosan hydrogel system cross-linked with a combination of ß- glycerophosphate, and 10 % pluronicF127 (F4) showed the most suitable physicochemical properties and release profile. Accordingly, this formula can be considered as a missionary system for localized sustained delivery of cytotoxic drugs.

Role of Oral Tramadol 50 mg in Reducing Pain During Colposcopy-Directed Cervical Biopsy: A Randomized Controlled Trial.

OBJECTIVE: The aim of the study was to assess safety and efficacy of 50-mg tramadol in reducing patient-perceived pain during colposcopy. MATERIAL AND METHODS: We conducted a randomized double-blind placebo-controlled trial in the colposcopy unit of a tertiary referral hospital, Cairo, Egypt, from April 2018 to October 2018. Our primary outcome was pain during colposcopy-guided ectocervical punch biopsy. Our secondary outcomes were pain during speculum insertion, acetic acid application, Lugol iodine application, endocervical curettage (ECC), endocervical brushing, 10-minute postprocedure, and additional analgesia requirement. Pain was assessed using 10-cm visual analog scale. RESULTS: One hundred fifty women were randomized into 2 groups: tramadol group (n = 75) received oral 50-mg tramadol tablets, and control group (n = 75) received placebo tablets. Both groups showed no significant difference in anticipated pain score (p = .56), pain scores during speculum insertion (p = .70), application of acetic acid (p = .40), and Lugol iodine (p = .79). However, the mean pain scores were significantly lower in tramadol group compared with placebo at ectocervical biopsy (p = .001), ECC (p = .001), endocervical brushing (p = .001), and 10 minutes after colposcopy (p = .001). Need for additional analgesia was significantly lower in tramadol group (p = .03). CONCLUSIONS: Oral tramadol 50 mg significantly reduces pain perception during colposcopy-guided ectocervical biopsy, ECC, endocervical brushing, and 10 minutes after colposcopy with tolerable adverse effects.

The role of levonorgestrel intra-uterine system in the management of adenomyosis: A systematic review and meta-analysis of prospective studies.

INTRODUCTION: The levonorgestrel intrauterine system (LNG-IUS) is a long-acting hormone-releasing uterine device that has many non-contraceptive benefits. The study aims to assess the safety and efficacy of LNG-IUS in the management of adenomyosis. MATERIAL AND METHODS: We searched the following bibliographic databases: MEDLINE via PubMed, SCOPUS, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and Google Scholar for the relevant studies which used LNG-IUS in management of patients with clinically or ultrasonographic diagnosed adenomyosis.The main outcome measures are pain score at the end of follow-up, bleeding, symptomatic relief, uterine volume (mL), endometrial thickness (mm) and/or hemoglobin level. RESULTS: Ten prospective studies (patients n = 551) were included. The overall effect estimates showed that the LNG-IUS led to significant reductions in pain score after 12 months (standardized mean difference [SMD[ -3.87, 95% confidence interval [CI] -5.51 to -2.23, P < .001), 24 months (SMD -5.56, 95% CI -9.80 to -1.32, P = .01) and 36 months of insertion (SMD -3.81, 95% CI -4.27 to -3.36, P < .001). Similarly, the Pictorial Blood Assessment Chart (PBAC) showed significant reduction up to 36 months after LNG-IUS insertion (SMD -2.32, 95% CI -2.91 to -1.73, P < .001). The LNG-IUS led to significant reductions in the uterine volume 12 months (SMD -.60, 95% CI -0.88 to -.31, P < .001) and 36 months after insertion (SMD -0.42, 95% CI -0.69 to -0.14, P = .003). CONCLUSIONS: LNG-IUS is a promising and effective option for the management of adenomyosis. Its use effectively reduced the severity of symptoms, uterine volume and endometrial thickness, and improved laboratory outcomes.

Developed simvastatin chitosan nanoparticles co-crosslinked with tripolyphosphate and chondroitin sulfate for ASGPR-mediated targeted HCC delivery with enhanced oral bioavailability.

Simvastatin (SV) repurposing has emerged as an alternative approach for the treatment of cancer. In this study, SV chitosan nanoparticles co-crosslinked with tripolyphosphate and chondroitin sulfate (SVCSChSNPs) were developed in order to maximize SV therapeutic efficiency. The hepatic targeting was realized using N-acetylgalactosamine (GalNAc) residues of ChS, which can be identified by the ASGPR receptors specifically expressed in hepatocytes. SV was repurposed as an anticancer agent against hepatocellular carcinoma (HCC). NPs were fabricated by the ionic gelation method, and the formulation variables (CS concentration, CS:ChS ratio, and CS solution pH) were optimized using a three-factor, three-level Box-Behnken design. The optimized NPs were investigated for particle size, size distribution, zeta potential, morphology, in vitro cytotoxicity, apoptotic effects against human hepatocellular carcinoma HepG2 cells, and detection of intracellular localization. The NPs were further evaluated for in vitro release behavior of SV and pharmacokinetics using Wister albino rats. Transmission electron microscopy (TEM) imaging showed a spherical shape with regular surface NPs of < 100 nm diameter. In vitro cytotoxicity testing showed that the SVCSChSNPs exhibited greater inhibition of proliferation in HepG2 cells and high cellular uptake through ASGPR-mediated endocytosis. The in vitro dissolution profile was 2.1-fold greater than that of pure SV suspension. Furthermore, in vivo oral pharmacokinetics revealed that the obtained NPs enhanced the bioavailability of SV by up to 2- and 1.6-fold for SV and SVA, respectively, compared to the pure SV suspension. These findings demonstrated that hepatic-targeted CSChSNPs delivering SV could potentially serve as a promising platform for HCC and other liver-related diseases.

Vaginal Dinoprostone in Reducing Pain Perception During Diagnostic Office Hysteroscopy in Postmenopausal Women: A Randomized, Double-Blind, Placebo-Controlled Trial.

STUDY OBJECTIVE: To evaluate the efficacy of vaginal dinoprostone in reducing pain perception during diagnostic office hysteroscopy (OH) in postmenopausal women. DESIGN: Randomized, double-blind controlled trial. SETTING: Tertiary university hospital. PARTICIPANTS: Postmenopausal patients scheduled for OH. INTERVENTIONS: Eligible participants were randomized in a 1:1 ratio to the dinoprostone and placebo groups. The severity of pain was assessed with a visual analog scale (VAS) ranging from 0, no pain to 10, worst pain during OH and 30 minutes after OH. MEASUREMENTS AND MAIN RESULTS: The difference in the intensity of pain using the VAS score during the procedure. One hundred women (50 in each arm) were included in the study. The mean VAS score during OH was significantly lower in the dinoprostone group compared with the placebo group (3.9 ± 0.8 vs 5.6 ± 0.7; p <.001). The passage of the hysteroscope through the cervical canal was easier in the dinoprostone group (62.4 ± 9.5 vs 42.8 ± 10.8; p <.001). The 2 groups were comparable in terms of the duration of the procedure (p = .91) and the rate of adverse effects. CONCLUSION: Vaginal dinoprostone is effective in relieving pain during diagnostic OH in postmenopausal women with few adverse effects.

The effect of mechanical cervical dilatation during scheduled cesarean section on the blood loss: a randomized controlled trial.

Objective: This study evaluates the effects of mechanical cervical dilatation during scheduled cesarean section (CS) on intra- and postoperative blood loss.Methods: A single-center randomized double-blind controlled trial (NCT03444792) conducted at a tertiary University Hospital in the period between 1 April 2017 and 31 March 2018 included all women scheduled for scheduled CS under spinal anesthesia if they met our inclusion criteria. Eligible participants were randomized to one of two groups. Group (I): Women with intraoperative cervical dilatation and Group (II): women with no intraoperative cervical dilatation. The primary outcome of this study was the mean volume of total blood loss during CS. The secondary outcomes included the mean reduction in the hemoglobin and hematocrit, the rate of primary postpartum hemorrhage, the duration of surgery, the duration of hospital stay, the rate of wound infection and endometritis.Results: No statistical significant difference between both study groups regarding the baseline characteristics. No significant difference in the intraoperative blood loss between both groups (p = .21); however, there was significantly more postoperative blood loss in group II (p = .001). The total blood loss was significantly higher in group II (912.6 ± 242.1 versus 845.8 ± 188.9 mL) in group I (p = .029). There were significantly lower postoperative hemoglobin and hematocrit levels in group II (p = .014 and .033 respectively). The mean duration of CS was significantly shorter in the cervical dilatation group (p = .002). No difference between both groups regarding the rate of postpartum hemorrhage (PPH) (p = .21), the duration of hospital stay (p = .17), the rate of wound infection (p = .32), the rate of endometritis (p = .82).Conclusions: Mechanical cervical dilatation during scheduled CS could be associated with lower postoperative blood loss, higher postoperative hemoglobin & hematocrit levels and shorter duration of CS.

Randomized controlled trial of the effect of bilateral uterine artery ligation during cesarean among women at risk of uterine atony.

OBJECTIVE: To assess the effectiveness of prophylactic bilateral uterine artery ligation (BUAL) in reducing the incidence of postpartum hemorrhage (PPH) during cesarean delivery among women at risk of uterine atony. METHODS: A randomized clinical trial at Cairo University Maternity Hospital, Egypt, from December 2017 to December 2018. Women at risk of uterine atony undergoing scheduled or emergency cesarean were randomized to two groups. In the BUAL group, women underwent BUAL before placental delivery; in the control group, women had cesarean delivery without BUAL. The primary outcome was the estimated blood loss during cesarean. RESULTS: Intraoperative blood loss during cesarean was significantly lower in the BUAL group than in the control group (523.4 ± 41.0 vs 619.6 ± 36.1 mL; P=0.003). Blood loss in the first 6 hours after cesarean was also significantly lower in the BUAL group than in the control group (246.1 ± 21.4 vs 326.1 ± 18.5 mL; P=0.006). There was no difference in operative time between the two groups (52.1 ± 6.1 vs 52.2 ± 6.8, P=0.880). CONCLUSION: BUAL during cesarean was found to be an effective method for decreasing blood loss during and after cesarean delivery among women at risk of uterine atony and subsequent PPH. CLINICALTRIALS.GOV: NCT03591679.