Impact of Bone Morphogenetic Protein 7 and Prostaglandin receptors on osteoblast healing and organization of collagen.

PURPOSE: This study seeks to investigate the impact of co-administering either a Prostaglandin EP2 receptor agonist or an EP1 receptor antagonist alone with a low dose BMP7 on in vitro healing process, collagen content and maturation of human osteoblasts. METHODOLOGY: Human osteoblast cells were used in this study. These cells were cultured and subjected to different concentrations of Prostaglandin EP2 receptor agonist, EP1 receptor antagonist, BMP7, Control (Ct) (Vehicle alone), and various combinations treatments. Cell viability at 24, 48 and 72 hours (h) was evaluated using the XTT assay. A wound healing assay was conducted to observe the migration ability of human osteoblast cells. Additionally, Sirius red staining and Fourier-Transform Infrared Spectroscopy Imaging (FT-IR) was employed to analyze various parameters, including total protein concentration, collagen production, mature collagen concentration, and mineral content. RESULTS: The combination of low dose BMP7 and Prostaglandin EP2 receptor agonist resulted to the lowest cell viability when compared to both the Ct and individual treatments. In contrast, the Prostaglandin EP1 receptor antagonist alone showed the highest cellular viability at 72 h. In the wound healing assay, the combined treatment of low dose BMP7 with the Prostaglandin EP2 receptor agonist and EP1 receptor antagonist showed a decrease in human osteoblast healing after 24 h. Analysis of FT-IR data indicated a reduction in total protein content, collagen maturity, collagen concentration and mineral content in combination treatment compared to the single or Ct treatments. CONCLUSION: The combination of a Prostaglandin EP2 receptor agonist or an EP1 receptor antagonist when combined with low dose BMP7 significantly hinders both human osteoblast healing and collagen maturity/concentration in comparison to low dose BMP7 treatment alone.

Circulation of foot-and-mouth disease serotypes, risk factors, and their effect on hematological and biochemical profiles among cattle and buffalo in Quetta, Balochistan, Pakistan.

Background and Aim: Foot-and-mouth disease (FMD) is an infectious disease of cloven-hoofed animals, including buffalo, cattle, sheep, goats, and pigs, causing major economic losses to the local farmers and, overall, to the national economy of the country. This study aimed to detect FMDV serotypes in year-round FMD outbreaks, hematological and biochemical changes, and oxidative stress in FMDV-infected cattle and buffaloes in the district of Quetta, Balochistan, Pakistan, and the socioeconomic impact of FMD outbreaks on farmers. Materials and Methods: We conducted a cross-sectional study in the district of Quetta, Balochistan, Pakistan, where FMD virus (FMDV) serotypes were detected by enzyme-linked immunosorbent assay (ELISA). Hematological, biochemical, and oxidative analyses were performed by analyzing the blood of FMDV-infected and non-infected animals. Information on the associated risk factors was obtained through a structured questionnaire by interviewing farmers in each FMD-affected farm. Results: Thirty-four out of 38 farms (89%, 95% confidence interval [CI]: 75%-97%) were positive for FMD by ELISA. Higher FMD infection was detected in farms with a herd size of <50 animals (50%, 17/34), followed by >100 animals (32%, 11/34) and 51-100 animals (18%, 6/34). Fifty-seven percent (114/200, 95% CI: 50%-64%) of animals were positive for FMD. Of these, 61% (69/114) were cattle and 39% (45/114) were buffalo. FMD positivity was higher in females (86%, 98/114) than in males (14%, 16/114) and higher in animals older than 2 years of age (52%, 59/114). On average, farmers lose U.S. dollars 3000 annually due to FMD outbreaks. Animals infected with FMDV had significantly (p ≤ 0.05) white blood cell counts and significantly (p ≤ 0.05) lower hemoglobin and total protein concentrations in buffalo and cattle, whereas infected cattle showed significantly (p ≤ 0.05) lower albumin levels. Globulin levels were lower in buffaloes infected. Alanine aminotransferase levels were lower in infected cattle (p ≤ 0.05). Creatinine levels were higher in infected buffalo (p ≤ 0.05). Urea and phosphorus concentrations were higher in FMDV-infected cattle and buffalo (p ≤ 0.05). Calcium levels were lower in infected cattle and buffalo (p ≤ 0.05). Catalase enzyme activity in infected cattle and buffaloes was significantly lower (p < 0.05). Lipid peroxidation was significantly higher in FMDV-infected cattle and buffalo (p ≤ 0.05). Conclusion: This study confirmed serotype O circulation among cattle and buffalo in year-long FMD outbreaks in the Quetta District of Balochistan. Blood analysis identified a parameter deviated from the normal level due to FMDV infection. In addition, the outbreak of FMD has a significant negative economic impact on livestock farmers.

Psoriasis paradox-infliximab-induced psoriasis in a patient with Crohn's disease: a case report and mini-review.

Biologic drugs are therapeutic modalities designed to inhibit specific cytokine signaling pathways. The introduction of these drugs in the management of autoimmune diseases has dramatically changed the treatment paradigm of chronic systemic immune-mediated inflammatory disorders. However, despite their overall acceptable safety profiles, paradoxical reactions have been reported in some real-life cases including case studies and clinical trials. In this study, we report a patient with Crohn's disease who developed infliximab-induced psoriasis vulgaris after starting infliximab treatment. In this case, infliximab was discontinued, and low-dose steroids and subcutaneous methotrexate were introduced to control both his psoriasis and bowel condition with satisfying responses.

Factors associated with infrainguinal bypass graft patency at 1-year; a retrospective analysis of a single centre experience.

INTRODUCTION: The aim of this study was to identify factors associated with primary graft patency 1 year following open lower limb revascularisation (LLR) at a tertiary referral vascular service. METHODS: A retrospective analysis of patients undergoing infra-inguinal bypass surgery between January 2016 and May 2017 at a tertiary vascular centre (St Mary's Hospital, London) was performed. Data regarding patient demographics, comorbidities, type of operation and post-operative anti-thrombotic strategy were collected. Quality of run-off score was assessed from pre-operative imaging. RESULTS: Seventy-seven cases were included in the analysis. Overall, the primary patency rate at 1-year was 63.6% (n = 49/77) and the secondary patency rate was 67.5% (n = 52/77). Independent variables with statistically significant inferior patency rates at 1-year were (1) bypasses with below knee targets (p = 0.0096), (2) chronic limb threatening ischaemia indication (p = 0.038), (3) previous ipsilateral revascularisation (p < 0.001) and (4) absence of hypertension history (p = 0.041). There was also a trend towards significance for American Society of Anesthesiologists (ASA) grade (p = 0.06). Independent variables with log-rank test p values of <0.1 were included in a Cox proportional hazards model. The only variable with a statistically significant impact on primary patency rates was previous open or endovascular ipsilateral revascularisation (HR 2.44 (1.04-5.7), p = 0.04). CONCLUSION: At 1-year follow-up, previous ipsilateral revascularisation was the most significant factor in affecting patency rates. Patients in this subgroup should therefore be deemed high-risk, which should be reflected in the informed consent and peri-operative management.

Barriers to Completing Therapy for Hepatitis C with Direct-Acting Antivirals: A Real-Life Experience from a Single Treatment Center in Egypt.

INTRODUCTION: Interferon-based therapies against the hepatitis C virus had a poor adherence profile. On the other hand, new direct-acting antivirals (DAAs) are orally administered medications, show high efficacy against the hepatitis C virus in addition to a high safety profile. Therefore, adherence to this treatment is expected to improve. Assessment for treatment adherence is mandatory to assess the feasibility of achieving viral hepatitis elimination. AIM: The study aims to assess the adherence rate and causes of non-adherence in Egyptian hepatitis C patients who received interferon-free treatment regimens. METHODS: Retrospective data analysis for 668 hepatitis C patient's records from August 2014 to October 2019 was done. Assessment of treatment adherence was done by revising the records and phone calls. However, 172 patients were excluded due to the absence of contact data. Rest of patients (n = 496) was categorized into 2 groups: Adherent (n = 432) and non-adherent (n = 64). For whom comparative analysis was done. RESULTS: The adherent group (87%) achieved 100 % sustained virological response after 12 weeks (SVR 12). Non-adherence was reported in 12.9% of patients. Low awareness was the main cause of non-adherence (43.75%). BMI was the only significant risk factor for poor adherence (P = .04). Other Patient demographics, clinical, and laboratory data didn't show any significant differences between both groups. CONCLUSION: Interferon-free regimens are tolerable. Raising awareness is mandatory for proper treatment adherence and, subsequently, good clinical outcomes.

Laparoscopic Roux-en-Y Gastric Bypass After Failed Vertical Banded Gastroplasty: 2-Year Follow-up of 102 Patients.

BACKGROUND: Vertical banded gastroplasty (VBG) is now discarded from being a restrictive procedure for morbid obesity due to its many drawbacks, doubtful efficacy, and lots of post-operative complications. Roux-en-Y gastric bypass (RYGB) is the most commonly performed procedure for VBG revision. So we aimed at reporting our experience in conversional RYGB for a failed VBG. MATERIAL AND METHODS: Analyzing follow-up records of 102 patients who underwent revisional RYGB after failed VBG in the period from April 2014 to January 2018. RESULTS: A total of 102 laparoscopic revisions of failed VBGs to RYGB were performed. The mean operating time was 161.9 min ±29.2 and the mean length of the hospital stay was 1.5 days ±1.2. Fourteen patients (13%) developed early post-operative complications (gastrojejunostomy leak 5; bleeding 9). Four patients (4.7%) developed late complications (Port site hernia 2; internal hernia 1; Stomal ulcer 1). The mean BMI pre-RYGB was 46.6 ± 5.9 kg/m2, and the mean %EBWL (percent excess body weight lost) of the patients at 12 and 24 months post-revision were 56.2% and 64.3%, respectively. Our patients had immediate post-revision resolution of VBG-related complications like dysphagia and vomiting. We also report improvement in all obesity-related health problems with (75.7%) complete remission rate and (24.3%) partial remission or improvement rate of diabetes mellitus. CONCLUSION: Conversion of VBG to RYGB is a feasible procedure and is associated with acceptable early morbidity rates and reduced lengths of hospitalization also it provides acceptable weight loss and improvement in obesity-related health problems. Graphical Abstract.

Diagnostic accuracy of acoustic radiation force impulse elastography (ARFI) in comparison to other non-invasive modalities in staging of liver fibrosis in chronic HCV patients: single-center experience.

PURPOSE: To evaluate the reliability of ARFI elastography for liver fibrosis staging and compare it to other non-invasive assessment of hepatic fibrosis (FIB-4 and APRI) in chronic HCV (CHC) patients. METHODS: A single-center, prospective study included 2103 CHC patients. Liver stiffness (LS) was evaluated by TE and ARFI elastography. FIB-4 and APRI were calculated. The area under the receiver-operating characteristic curve (AUROCs) was used to assess the diagnostic performance of ARFI elastography for staging of liver fibrosis using TE as a reference standard. RESULTS: The best cut off values of ARFI elastography for diagnosis of ≥ F2, ≥ F3and F4 were 1.36 m/s, 1.45 m/s, and 1.7 m/s with AUROCs of 0.89, 0.94 and 0.95, respectively. ARFI elastography cut offs are lower in patients with normal ALT level compared to those with ALT level (1.1-< 3 ULN) and those with ALT level ≥ 3ULN (1.35 m/s vs 1.39 m/s vs 1.54 for F ≥ 2, 1.44 m/s vs 1.58 m/s vs 1.6 m/s for F3, 1.69 m/s, 1.84 m/s, 1.86 m/s for F4). FIB-4 (0.82-0.86) and APRI (0.78-0.82) yielded lower AUC in prediction of significant fibrosis and cirrhosis than ARFI elastography (0.89-0.95). CONCLUSION: ARFI elastography is a reliable method for non-invasive staging of liver fibrosis in CHC patients when compared to TE with a good diagnostic performance comparable to FIB-4 and APRI scores for the prediction of significant fibrosis and cirrhosis.

High sustained virologic response rate using generic directly acting antivirals in the treatment of chronic hepatitis C virus Egyptian patients: single-center experience.

BACKGROUND: Hepatitis C virus (HCV) is a major health problem in Egypt, with a high prevalence of genotype 4. AIM: This study aimed to evaluate the safety and efficacy of generic sofosbuvir (SOF) plus generic daclatasvir (DAC) with or without ribavirin in the treatment of Egyptian chronic HCV patients compared with the use of brand drugs. MATERIALS AND METHODS: An observational study that included 234 Egyptian chronic HCV patients was carried out. Patients were classified into two groups: group A (101 patients) received brand SOF 400 mg plus brand DAC 60 mg and group B (134 patients) received generic SOF 400 mg plus generic DAC 60 mg with or without ribavirin for 12 weeks. The end point was a sustained virological response at 12 weeks after treatment. RESULTS: Thirty-eight (37.2%) patients in group A were treatment experienced compared with 12 (9.02%) patients in group B; there were 39 (38%) cirrhotic patients in group A and 22 (16.5%) cirrhotic patients in group B. In group A, 50% of patients received ribavirin, while in group B, 42.1% of patients received ribavirin. All patients were followed up; all of them attended their week 12 post-treatment visit with negative HCV RNA, with achievement of sustained virological response at 12 in 100% of patients receiving generic drugs (group B) and 99% of patients receiving brand drugs (group A). Generic SOF and DAC were well tolerated, with mild adverse events including fatigue and headache. CONCLUSION: Use of generic SOF and DAC with or without ribavirin is an extremely effective and a well-tolerated treatment for Egyptian chronic HCV patients.

Improvement of liver stiffness measurement, acoustic radiation force impulse measurements, and noninvasive fibrosis markers after direct-acting antivirals for hepatitis C virus G4 recurrence post living donor liver transplantation: Egyptian cohort.

Progression of recurrent hepatitis C is accelerated in liver transplant (LT) recipients. Direct-acting antivirals (DAAs) have recently emerged as a promising therapeutic regimen for the treatment of hepatitis C virus infection. Rates of sustained virological response (SVR) have drastically improved since the introduction of DAAs. The aim is to elucidate the changes in liver stiffness measurement (LSM) by transient elastography (TE) as well as acoustic radiation force impulse (ARFI) elastography and fibrosis scores after DAA treatment in LT recipients with hepatitis C virus recurrence. A single-center, prospective study including 58 LT recipients with hepatitis C recurrence who received different sofosbuvir-based treatment regimens. Transient elastography and ARFI elastography values were recorded as well as fibrosis 4 score (FIB-4) and aspartate aminotransferase-to-platelet ratio index were calculated at baseline and SVR at week 24 (SVR24). The outcome was improvement in LSM and at least a 20% decrease in LSM at SVR24 compared with baseline. The sustained virological response was 98.1%. There was improvement of platelet counts, alanine aminotransferase, and aspartate aminotransferase, which in turn caused improvement in fibrosis scores at SVR24. LSM by TE and ARFI elastography decreased from the baseline median value of 6.3 kPa (interquartile range [IQR]; 4.6 to 8.8 kPa) and 1.28 m/s (IQR; 1.07 to 1.53 m/s) to an SVR24 median value of 6.2 kPa (IQR; 4.85 to 8.9 kPa) and 1.12 (IQR; 0.97 to 1.30 m/s), respectively. Logistic regression analysis showed that baseline viral load was the only significant predictor of improvement in LS after DAA therapy at SVR24. Sofosbuvir-based treatment resulted in an early improvement in parameters of liver fibrosis in post-LT patients with hepatitis C recurrence.