Video capsule endoscopy for previous overt obscure gastrointestinal bleeding in patients using anti‐thrombotic drugs

Background and Aim: Little is known about the causes of overt obscure gastrointestinal bleeding (OGIB) in patients using anti‐thrombotic therapy. We aimed to describe video capsule endoscopy (VCE) findings and to identify factors associated with positive findings in these patients. Methods: We carried out a retrospective study of 56 patients who underwent VCE for evaluation of previous overt OGIB during anti‐thrombotic therapy. VCE studies were re‐evaluated by a gastroenterologist blinded to clinical details. Clinical data included in the multivariate analysis were sex, age, indication for and type of anti‐thrombotic therapy, hemodynamic instability on admission, type of blood loss, hemoglobin on admission, use of a proton pump inhibitor, NSAID use, time between bleeding episodes and VCE, and whether or not anti‐thrombotic therapy was resumed before the VCE study. Results: A probable cause for gastrointestinal bleeding was identified in 28 (50%) of the 56 studies. Angiodysplasia was found in 19 patients. Twenty‐two studies showed a possible cause in the small bowel. Multivariate logistic regression analysis showed that reinstitution of anti‐thrombotic therapy before VCE was carried out was the only independent predictor of positive VCE findings (OR: 8.61, 95% CI: 1.20–60.42, P = 0.032). Conclusions: Small intestinal angiodysplasia was the most common cause for overt OGIB. Reinstitution of withdrawn anti‐thrombotic drugs before the VCE examination was carried out was associated with positive VCE findings in multivariate analysis.     

A Large Retroperitoneal Encapsulation of Bile from a Spontaneous Perforation of the Common Bile Duct

We report a patient with spontaneous rupture of the common bile duct. This is an extremely rare condition which produces free leakage of bile into the peritoneal cavity. There has been no previous report concerning the formation of a large retroperitoneal encapsulation of bile. The preoperative diagnosis in our patient was very difficult and endoscopic retrograde pancreatocholangiography and cystography by ultrasound guidance were helpful.     

Restriction of cell lysis by homologous complement: II. Protection of erythrocytes against lysis by newly activated complement

Our previous work revealed that homologous complement (C) was ineffective in lysing antibody-sensitized erythrocytes (EA) even at high concentrations. It was also shown that activation of complement on homologous EA resulted in the binding of C9 and the formation of EA bearing complement proteins C1 through C9 (EAC1-9), yet few hemolytic sites were formed. Instead, as shown here, the formation of homologous EAC1-9 caused the cells to become resistant to lysis even by heterologous complement during a second incubation. In contrast, when homologous EAC1-8 were produced by incubating EA with C9-depleted serum, such intermediates were not protected against lysis by heterologous complement during a second incubation. Furthermore, homologous C9 on EAC1-9 was able to reduce the hemolytic efficiency of heterologous complement without blocking C activation and the formation of new C5b-9 complexes. Protection was not modified when homologous EAC1-9 were produced in one step, by incubation of EA with serum, or sequentially by adding C9 to EAC1-8. The minimum number of 9-sites required to confer a protective effect on EAC1-9 was less than 200 per cell. Thus, in addition to its known effect in heterologous cell killing, homologous C9 is capable of protecting homologous cells against inadvertent complement lysis.     

Successful defibrotide treatment of a patient with veno-occlusive disease after living-donor liver transplantation: A case report

Rationale:Veno-occlusive disease (VOD) is characterized by painful hepatomegaly, ascites, weight gain, and jaundice with nonthrombotic, fibrous obliteration of the centrilobular hepatic veins. VOD after liver transplantation is a rare complication, with an incidence of approximately 2%; however, it can be life-threatening in severe cases. The precise etiology and mechanism of VOD after liver transplantation remains unclear. Acute cellular rejection, antibody-mediated rejection, and treatment with tacrolimus or azathioprine may be associated with the development of VOD after liver transplantation. Additionally, the optimal treatment of VOD after liver transplantation has not yet been established and focuses on supportive care. Defibrotide is an anti-ischemic and antithrombotic drug with no systemic anticoagulant effects. Moreover, only a few reports have investigated the use of defibrotide for VOD after liver transplantation, which has shown promising results.Patient concerns:A 39-year-old woman with primary biliary cholangitis underwent living-donor liver transplantation at our center. She experienced right upper quadrant pain with increased ascites, pleural effusion, and weight gain on postoperative day 14.Diagnoses:Imaging and pathological tests showed no evidence of rejection or vessel complications. VOD was diagnosed clinically based on the findings of weight gain, ascites, jaundice, and pathological biopsy.Interventions:Defibrotid, 25 mg/kg/day, was administered intravenously for 21 days.Outcomes:She showed complete clinical resolution of the VOD.Lessons:Herein, we report a case of successful defibrotide treatment of VOD after living-donor liver transplantation.     

Restoration of Serotonin Neuronal Firing Following Long-Term Administration of Bupropion but Not Paroxetine in Olfactory Bulbectomized Rats

Background:

Olfactory bulbectomized rats generally manifest many of the neurochemical, physiological, and behavioral features of major depressive disorder in humans. Another interesting feature of this model is that it responds to chronic but not acute antidepressant treatments, including selective serotonin reuptake inhibitors. The purpose of the present study was first to characterize the firing activity of dorsal raphe serotonin neurons in olfactory bulbectomized rats and then examine the effects of 2 antidepressants, bupropion and paroxetine.

Methods:

Olfactory bulbectomy was performed by aspirating olfactory bulbs in anesthetized rats. Vehicle and drugs were delivered for 2 and 14 days via subcutaneously implanted minipumps. In vivo electrophysiological recordings were carried out in male anesthetized Sprague-Dawley rats.

Results:

Following ablation of olfactory bulbs, the firing rate of serotonin neurons was decreased by 36%, leaving those of norepinephrine and dopamine neurons unchanged. In olfactory bulbectomized rats, bupropion (30mg/kg/d) restored the firing rate of serotonin neurons to the control level following 2- and 14-day administration and also induced an increase in the tonic activation of serotonin_1A receptors; paroxetine (10mg/kg/d) did not result in a return to normal of the attenuated firing of serotonin neurons in olfactory bulbectomized rats. In the hippocampus, although at a higher dose of WAY 100635 than that required in bupropion-treated animals, paroxetine administration also resulted in an increase in the tonic activation of serotonin_1A receptors.

Conclusions:

The present results indicate that unlike paroxetine, bupropion administration normalized serotonin neuronal activity and increased tonic activation of the serotonin_1A receptors in hippocampus.     

Percutaneous removal of common bile duct stones using a modified balloon technique

To evaluate the effectiveness of percutaneous removal of common bile duct (CBD) stones using a modified balloon technique (balloon catheter sphincteroplasty and expulsion of the stones using half-captured balloons within the sheath) in patients difficult to treat with endoscopy.Fifty patients underwent a modified balloon technique (balloon group), and 53 patients underwent CBD stone removal by the basket method (stone basket group) between 2016 and 2019. We compared the balloon and stone basket groups to evaluate the effectiveness of the modified balloon technique. Outcome variables such as demographics, technical success rates, procedural details, and complications were analyzed. Statistical analysis was performed using Student t test, Fisher exact test, or the χ² test.The technical success rate in the balloon group was 66% (33/50) in 1 session, 32% (16/50) in 2 sessions, and 2% (1/50) in 3 sessions. That of the stone basket group was 45% (24/53) in 1 session, 38% (20/53) in 2 sessions, and 17% (9/53) in 3 sessions.The total procedure time was significantly shorter in the balloon group (29.5 ± 15.1 minutes) than in the stone basket group (41.7 ± 20.2 minutes) (P < .01), whereas the number of stones was higher in the balloon group than in the stone basket group (P = .03). Maximal stone size, balloon size, pancreatitis, and hospitalization stay did not show statistical differences between the 2 groups. Most complications (9 patients, balloon group; 8 patients, stone basket group) were mild and transient. Major complications occurred in one patient in the stone basket group, who experienced hemobilia due to arterial injury caused by percutaneous transhepatic biliary drainage, which was treated by endovascular embolization without mortality.The modified balloon technique is an effective and safe treatment method for CBD stone removal in patients presenting difficulties in the endoscopic approach.     

Further delineation of the KBG syndrome caused by ANKRD11 aberrations

Loss-of-function variants in ANKRD11 were identified as the cause of KBG syndrome, an autosomal dominant syndrome with specific dental, neurobehavioural, craniofacial and skeletal anomalies. We present the largest cohort of KBG syndrome cases confirmed by ANKRD11 variants reported so far, consisting of 20 patients from 13 families. Sixteen patients were molecularly diagnosed by Sanger sequencing of ANKRD11, one familial case and three sporadic patients were diagnosed through whole-exome sequencing and one patient was identified through genomewide array analysis. All patients were evaluated by a clinical geneticist. Detailed orofacial phenotyping, including orthodontic evaluation, intra-oral photographs and orthopantomograms, was performed in 10 patients and revealed besides the hallmark feature of macrodontia of central upper incisors, several additional dental anomalies as oligodontia, talon cusps and macrodontia of other teeth. Three-dimensional (3D) stereophotogrammetry was performed in 14 patients and 3D analysis of patients compared with controls showed consistent facial dysmorphisms comprising a bulbous nasal tip, upturned nose with a broad base and a round or triangular face. Many patients exhibited neurobehavioural problems, such as autism spectrum disorder or hyperactivity. One-third of patients presented with (conductive) hearing loss. Congenital heart defects, velopharyngeal insufficiency and hip anomalies were less frequent. On the basis of our observations, we recommend cardiac assessment in children and regular hearing tests in all individuals with a molecular diagnosis of KBG syndrome. As ANKRD11 is a relatively common gene in which sequence variants have been identified in individuals with neurodevelopmental disorders, it seems an important contributor to the aetiology of both sporadic and familial cases.     

Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium

Confluent cultures of endothelial cells from human umbilical cord were used to study the effect of activated human protein C (APC) on the production of plasminogen activators, plasminogen activator-inhibitor, and factor VIII-related antigen. Addition of APC to the cells in a serum-free medium did not affect the production of tissue-type plasminogen activator (t-PA) or factor VIII-related antigen; under all measured conditions, no urokinase activity was found. However, less plasminogen activator-inhibitor activity accumulated in the conditioned medium in the presence of APC. This decrease was dose dependent and could be prevented by specific anti-protein C antibodies. No decrease was observed with the zymogen protein C or with diisopropylfluorophosphate-inactivated APC. APC also decreased the t-PA inhibitor activity in endothelial cell-conditioned medium in the absence of cells, which suggests that the effect of APC is at least partly due to a direct effect of APC on the plasminogen activator- inhibitor. High concentrations of thrombin-but not of factor Xa or IXa-- had a similar effect on the t-PA inhibitor activity. The effect of APC on the plasminogen activator-inhibitor provides a new mechanism by which APC may enhance fibrinolysis. The data suggest that activation of the coagulation system may lead to a secondary increase of the fibrinolytic activity by changing the balance between plasminogen activator(s) and its (their) fast-acting inhibitor.