Incidence and Risk Factors of Thyroid Malignancy in Patients with Toxic Nodular Goiter.

Background: Although hyperfunctioning thyroid disorders were thought to be protective against malignancy, some recent studies reported a high incidence of incidentally discovered cancer in patients with hyperfunctioning benign thyroid disorders. We performed this study to estimate the incidence and predictors of malignant thyroid disease in patients with toxic nodular goiter (TNG). Patients and Methods. The data of 98 patients diagnosed with TNG were reviewed (including toxic multinodular goiter SMNG and single toxic nodule STN). The collected data included patients age, gender, systemic comorbidities, family history of thyroid malignancy, previous neck radiation, type of disease (multinodular or single), size of the dominant nodule by the US, operative time, and detection of significant lymph nodes during operation. Based on the histopathological analysis, the cases were allocated into benign and malignant groups. Results: Malignancy was detected in 21 patients (21.43%). Although age distribution was comparable between the two groups, males showed a significant increase in association with malignancy. Medical comorbidities and family history of cancer did not differ between the two groups. However, TMNG showed a statistically higher prevalence in the malignant group. Operative data, including operative time and lymph node detection, were comparable between the two groups. On regression analysis, both male gender and TMNG were significant predictors of malignancy. Conclusion: The presence of thyroid hyperfunction is not a protective factor against malignancy, as malignancy was detected in about 1/5 of cases. Male gender and TMNG were significant risk factors of malignancy in such patients.

Sevuparin for the treatment of acute pain crisis in patients with sickle cell disease: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: There are no approved treatments for vaso-occlusive crises in sickle cell disease. Sevuparin is a novel non-anticoagulant low molecular weight heparinoid, with anti-adhesive properties. In this study, we tested whether sevuparin could shorten vaso-occlusive crisis duration in hospitalised patients with sickle cell disease. METHODS: We did a multicentre, double-blinded, placebo-controlled, phase 2 study in 16 public access clinical hospitals in the Netherlands, Lebanon, Turkey, Bahrain, Oman, Saudi Arabia, and Jamaica. Patients aged 12-50 years with a diagnosis of sickle cell disease (types HbSS, HbSC, HbSß0-thalassaemia, or HbSß+-thalassaemia) on a stable dose of hydroxyurea, hospitalised with vaso-occlusive crisis for parenteral opioid analgesia with a projected stay of more than 48 h were included in the study. Patients were randomly assigned (1:1) using a computer-generated randomisation scheme to receive sevuparin (18 mg/kg per day) or placebo (NaCl, 0·9% solution) intravenously for 2-7 days until vaso-occlusive crisis resolution. All individuals involved in the trial were masked to treatment allocation. The analysis was done in the intention-to-treat population. The primary endpoint was time to vaso-occlusive crisis resolution defined as freedom from parenteral opioid use (in preceding 6-10 h); and readiness for discharge as judged by the patient or physician. The trial is registered with ClinicalTrials.gov, NCT02515838. FINDINGS: Between Oct 7, 2015, and Feb 10, 2019, 144 patients were randomly assigned and administered sevuparin (n=69) or placebo (n=75). The median age was 22·2 years (range 12·2-33·6), 104 (72%) 144 were adults (18 years or older), and 90 (63%) were male and 54 (37%) were female. The intention-to-treat analysis for the primary endpoint showed no significant difference in median time to vaso-occlusive crisis resolution between the sevuparin and placebo groups (100·4 h [95% CI 85·5-116·8]) vs 86·4 h [70·6-95·1]; hazard ratio 0·89 [0·6-1·3]; p=0·55). Serious adverse events occurred in 16 (22%) of 68 patients in the sevuparin group and in 21 (22%) of patients in the placebo group. The most frequent treatment-emergent adverse events were pyrexia (17 [25%] in the sevuparin group vs 17 [22%] in the placebo group), constipation (12 [18%] vs 17 [22%]), and decreased haemoglobin (18 [26%] vs 9 [12%]). There were no deaths in the sevuparin group and there was one (1%) death in the placebo group after a hyper-haemolytic episode due to alloimmunisation. INTERPRETATION: This result, as well as the results seen in other clinical studies of inhibitors of adhesion in sickle cell disease, suggest that selectin-mediated adhesion might be important in the initiation, but not maintenance of vaso-occlusion, indicating that strategies to treat vaso-occlusive crises differ from strategies to prevent this complication. FUNDING: Modus Therapeutics.

Long-term effects of one-anastomosis gastric bypass on liver histopathology in NAFLD cases: a prospective study.

PURPOSE: Weight reduction can effectively improve nonalcoholic fatty liver disease (NAFLD), which is a constant companion of severe obesity. This study aimed to determine the effect of one-anastomosis gastric bypass (OAGB) on pathological liver changes in severely obese cases with NAFLD. METHODS: The present prospective research comprised 67 subjects with morbid obesity scheduled for OAGB during the period from February 2015 to August 2018. Clinical, biological, and histologic data were evaluated pre and 15 months postoperatively. RESULTS: Fifteen months after surgery, a considerable reduction was noted in the grades of fat deposition, liver cell ballooning, and lobular inflammatory changes, in addition to the total NAS score. Fifteen months after surgery, nonalcoholic steatohepatitis (NASH) disappeared in 42% of the patients. A significant regression of fibrosis stage occurred after surgery in 79.1% of patients (p < 0.001). After surgery, patients had substantial reductions in aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, HbA1c, total cholesterol, and Low-density lipoprotein (p < 0.001, for all comparisons). Diabetes mellitus, hypertension, and dyslipidemia resolved in 54%, 59%, and 69% of the patients, respectively. CONCLUSION: OAGB resolved NASH from nearly 42% of patients and reduced the histological features of NAFLD 15 months after surgery. Bariatric procedures might be adopted as a therapeutic modality in severely obese cases with NAFLD after the failure of lifestyle modifications.

Impact of laparoscopic sleeve gastrectomy on fibrosis stage in patients with child-A NASH-related cirrhosis.

PURPOSE: Bariatric surgery can improve non-alcoholic fatty liver disease (NAFLD). Yet data on the effect on fibrosis are insufficient and controversial. This work endeavored to evaluate the safety of laparoscopic sleeve gastrectomy (LSG) in cases that have compensated non-alcoholic steatohepatitis (NASH)-related cirrhosis and its impact on fibrosis stage. METHODS: The current prospective work involved 132 cases with Child-A NASH-related cirrhosis suffering from morbid obesity scheduled for LSG. They were subjected to preoperative assessment, wedge biopsy, and ultrasound-guided true-cut liver biopsy after 30 months. Patients were included if proved to have F4 fibrosis initially. The liver condition was assessed based on the NALFD Activity Score (NAS). The primary outcome measure was the impact of LSG on fibrosis stage and its relation to weight loss. RESULTS: The analysis included only 71 patients who completed the 30-month follow-up period. By the end of the follow-up interval, there was a substantial weight loss with a reasonable resolution of comorbidities. The median NAS decreased significantly from 6 (1-8) to 3 (0-6) after surgery. Fibrosis score regressed to F2 in 19 patients (26.8%) and F3 in 29 (40.8%). Patients with improved scores had a significantly higher amount of weight loss (p < 0.001). Improvement was more frequent in males (p = 0.007). By 30 months after treatment, 53.8% of cases with borderline NASH and 36.8% of those with probable NASH showed complete resolution, and 44.7% of patients with NASH showed improvement. Steatosis improved in 74.6% of patients (p < 0.001). CONCLUSION: In patients with NASH-related liver cirrhosis of Child class A, LSG may be a secure approach for the management of morbid obesity. It has a long-term benefit for both obesity and liver condition with significant improvement of steatosis, steatohepatitis, and fibrosis.

Redo pelvic fracture urethral injury repair: The case for tadalafil.

OBJECTIVE: To define the role of tadalafil in improving outcomes of redo urethroplasty for pelvic fracture urethral injury (PFUI). PFUI is common in developing countries, invariably as a result of road traffic trauma. Repair is complex, and redo cases are even more challenging. MATERIAL AND METHODS: This was a longitudinal prospective nonrandomized study between 2017 and 2019. Men undergoing redo-urethroplasty were nonrandomized into two groups. Group 1 received tadalafil 5 mg the next day after surgery and continued for 3 months, and group 2 did not receive tadalafil. Inclusion criteria were patients undergoing redo-urethroplasty willing to trial low-dose tadalafil post-operatively. Exclusion criteria were <18 years, females, primary cases, and complex cases such as recto-urethral fistula. Average follow-up was 19.5 months. RESULTS: Sixty patients were enrolled (29 in group 1 and 31 in group 2). Mean age was 31 years. These patients had 1-3 prior failed urethroplasties. Most required step 3 anastomotic urethroplasty (68.3%). Success was defined as absence of symptoms and no need for surgical intervention. Failure was defined as redo urethroplasty or >1 endoscopic intervention. Primary success was 83.3%. Success with tadalafil was 96.6%, compared to 71.0% in the non-Tadalafil group (P » .0008). Only one patient on tadalafil failed, compared with nine in the non-tadalafil group. Secondary success rate was defined as the need for a single subsequent endoscopic intervention and was 93.3%. CONCLUSION: In our series, there was improved outcome with using tadalafil in patients having redo urethroplasty for PFUI. Further trials should be done to evaluate the use in all PFUI cases.

Effect of Bariatric Surgery on the Cardiovascular System in Obese Cases with Pulmonary Hypertension.

INTRODUCTION AND AIM: Recently, the incidence of obesity has been rising exponentially. Clinical studies have demonstrated that different subtypes of pulmonary hypertension (PH) are linked to obesity. The current work mainly aims to assess the impact of laparoscopic sleeve gastrectomy (LSG) on PH in a cohort of obese cases. PATIENTS AND METHODS: The present prospective work included 37 obese cases with PH for whom LSG was done. Only cases with PH and presurgical right ventricular systolic pressure (RVSP) ≥ 35 mmHg using Doppler echocardiogram were enrolled. Fifteen months later, patients were reassessed regarding new weight and BMI in addition to changes in RVSP. RESULTS: At the end of follow-up, the average BMI improved from 45.8 + 3.9 to 33.8 + 2.5 Kg/m2 (p value < 0.001). Improved right ventricular (RV) size compared to baseline echo was observed in 20 patients. RV size decreased from 2.68 + 0.44 cm to 2.34 + 0.36 cm (p value < 0.001). Notable decrease of PH to less than 30 mmHg occurred in 33 patients. Mean RVSP decreased from 39.62 + 2.1 to 31.81 + 3.1 mmHg (p value < 0.001). LSG significantly decreased the requirements for PH drugs and supplemental oxygen therapy. CONCLUSION: The current work suggests that LSG-induced weight loss may result in a considerable decrease in pulmonary pressures as well as RV size with a concurrent resolution of other metabolic comorbidities.

Long-Term Changes in Leptin, Chemerin, and Ghrelin Levels Following Roux-en-Y Gastric Bypass and Laparoscopic Sleeve Gastrectomy.

AIM: Published reports showed conflicting results regarding the sustained alterations in leptin, chemerin, and ghrelin concenratios after metabolic surgery. Therefore, we performed the present work to contrast the alterations in leptin, chemerin, and ghrelin levels one year after Roux-en-Y gastric bypass (RYGB) versus laparoscopic sleeve gastrectomy (LSG). METHODS: The present research is a prospective, comparative one that followed 100 cases for whom RYGB or LSG was done. We assessed the serum values of adiposity-associated mediators, including adipokcytokines (leptin and active chemerin) and gastrointestinal hormones (total ghrelin). The primary outcome in the present study was the alterations in leptin, chemerin, and ghrelin values at 12 months after RYGB and LSG. RESULTS: The serum leptin level decreased significantly in the LSG group with a mean change of - 170.8 ± 29.4 ng/mL (p < 0.001). Similarly, the serum leptin concentration decreased significantly in the RYGB group, with a mean change of - 165.42 ± 53.4 (p < 0.001). In addition, the mean reduction in baseline chemerin levels 12 months after the operation was considerable in the LSG cohort (- 23.24 ± 9.5 ng/mL) and RYGB group (- 22.12 ± 15.9 ng/mL). The ghrelin values demonstrated a notable reduction in the LSG cohort (- 0.083 ± 0.11 pg/mL) and RYGB group (- 0.068 ± 0.097 pg/mL). However, the changes in the three hormones were not substantially different between both groups (p > 0.05). CONCLUSION: Both RYGB and LSG result in a considerable, comparable decrease in the postoperative serum concentrations of leptin, chemerin, and ghrelin.

Predictors of early recipient mortality after living donor liver transplantation in a tertiary care center in Egypt.

BACKGROUND: Living donor liver transplantation (LDLT) has evolved into a widely accepted therapeutic option. Many different risk factors may affect early mortality after LDLT. OBJECTIVES: Analyze risk factors that can affect early (<6 months) mortality of patients after LDLT in a single center. DESIGN: Retrospective chart review of patients who underwent LDLT. SETTING: University hospital. PATIENTS AND METHODS: Adult cirrhotic patients who underwent LDLT were classified by early (first 6 months) or late mortality. A full pre, intra- and post-operative evaluation had been done on all patients including a full history, examination and investigations to identify risk factors that might affect mortality post-LDLT. MAIN OUTCOME MEASURES: Determination of pre-, intra- or postoperative factors that might affect recipient mortality post-LDLT. SAMPLE SIZE: 123. RESULTS: Pre-operative factors that increased early mortality in a univariate analysis were higher model for end-stage liver disease (MELD) scores, lower graft-recipient weigh ratio (GRWR), older donor age, and recurrent spontaneous bacterial peritonitis. Intraoperative factors included more transfusion units of blood, plasma, platelets and cryoprecipitate, a longer time for cold and warm ischemia, and a longer anhepatic phase among others. Postoperative factors included a longer ICU or hospital stay and abnormal postoperative laboratory data. In the final logistic regression model, the most significant factors were pre-operative GRWR, length of hospital stay, units of intraoperative blood transfusion, postoperative alanine aminotransferase, postoperative total leukocyte count, and MELD score. CONCLUSION: LDLT outcomes might be improved by attempting to resolve clinical factors that have been identified as contributors to early post-LDLT mortality. LIMITATIONS: More risk factors, such as those relevant to patient portal vein hemodynamics, should be included in an analysis of predictors of early mortality. CONFLICT OF INTEREST: None.

Study of changes of obesity-related inflammatory cytokines after laparoscopic sleeve gastrectomy.

BACKGROUND: Chronic inflammation in adipose tissue may play a substantial role in the pathogenesis of obesity-related metabolic disorders. The present study aims to evaluate the changes in adipocytokines, bile acids, fibroblast growth factor 19 (FGF-19) and pro-inflammatory cytokines 6 months after laparoscopic sleeve gastrectomy (LSG). METHODS: This prospective study included 75 obese patients with body mass index >35 kg/m2 who underwent LSG. All patients were recruited preoperatively and followed up post-operatively at 6 months, with laboratory assessment of their cytokines including adiponectin, leptin, resistin, bile acid, interleukin (IL)-6, IL-8, tumour necrosis factor-α, monocyte chemotactic protein-1, high-sensitivity C-reactive protein, plasminogen activator inhibitor-1, serum amyloid-A and FGF-19. RESULTS: There were statistically highly significant changes regarding anthropometric parameters (weight, body mass index and waist-to-hip ratio), blood glucose and lipid profile as well as liver enzymes at 6 months post-sleeve gastrectomy. The present study showed that the levels of serum adiponectin and FGF-19 significantly increased at 6 months of follow-up after surgery (P < 0.001), while the levels of serum leptin, resistin, high-sensitivity C-reactive protein, plasminogen activator inhibitor-1 and serum amyloid-A significantly decreased at 6 months of follow-up after surgery (P < 0.001). There were no significant differences regarding serum bile acid, IL-6, IL-8, tumour necrosis factor-α and monocyte chemotactic protein-1. CONCLUSION: Weight loss after LSG is associated with significant improvement of the adipokine levels towards anti-diabetic and anti-inflammatory profiles. Future studies should use a larger sample size and longer follow-up periods.