Temporal-spatial organ response after blast-induced experimental blunt abdominal trauma.

Abdominal trauma (AT) is of major global importance, particularly with the increased potential for civil, terroristic, and military trauma. The injury pattern and systemic consequences of blunt abdominal injuries are highly variable and frequently underestimated or even missed, and the pathomechanisms remain still poorly understood. Therefore, we investigated the temporal-spatial organ and immune response after a standardized blast-induced blunt AT. Anesthetized mice were exposed to a single blast wave centered on the epigastrium. At 2, 6, or 24 h after trauma, abdominal organ damage was assessed macroscopically, microscopically, and biochemically. A higher degree of trauma severity, determined by a reduction of the distance between the epigastrium and blast inductor, was reflected by a reduced survival rate. The hemodynamic monitoring during the first 120 min after AT revealed a decline in the mean arterial pressure within the first 80 min, whereas the heart rate remained quite stable. AT induced a systemic damage and inflammatory response, evidenced by elevated HMGB-1 and IL-6 plasma levels. The macroscopic injury pattern of the abdominal organs (while complex) was consistent, with the following frequency: liver > pancreas > spleen > left kidney > intestine > right kidney > others > lungs and was reflected by microscopic liver and pancreas damages. Plasma levels of organ dysfunction markers increased during the first 6 h after AT and subsequently declined, indicating an early, temporal impairment of the function on a multi-organ level. The established highly reproducible murine blunt AT, with time- and trauma-severity-dependent organ injury patterns, systemic inflammatory response, and impairment of various organ functions, reflects characteristics of human AT. In the future, this model may help to study the complex immuno-pathophysiological consequences and innovative therapeutic approaches after blunt AT.

Feasibility Analysis of Ultrasound-Guided Placement of Tunneled Hemodialysis Catheters.

Introduction: Radiographic fluoroscopy is the current standard for placement of tunneled central venous catheters (CVCs) for hemodialysis. Radiographic fluoroscopy requires structural and personnel infrastructure and exposes the patient to ionizing radiation. Here, we investigate the feasibility of solely ultrasound-guided placement of tunneled central venous dialysis catheters (USCVCs). Methods: We evaluated prospectively collected single-center data regarding safety and catheter function of 134 consecutive patients who underwent USCVC implantation between 2020 and 2021. We used the inset guidewire to visualize the position of the catheter tip. In the case of inadequate visibility by ultrasound, we used intracardiac electrocardiography (ECG) recording or agitated saline. A total of 1844 catheter days were assessed. The optimal CVC position was defined as being within the upper right atrium (URA) and middle to deep right atrium. Results: Of the 134 USCVCs, 87% were placed on the right side. The primary success rate for optimal tip position and catheter function was 98%. Of the USCVCs, 97% were placed solely by ultrasound. Regarding positioning, 6% were in the vena cava superior zone, 70% in the URA and 24% in the middle to deep right atrium, resulting in a rate of 94% with optimal positioning. Effective blood flow averaged 292 ± 39 ml/min. There were no immediate procedure-associated complications. Conclusion: Placement of CVC for hemodialysis solely by ultrasound is an effective alternative to fluoroscopy-assisted placement.

An unusual presentation of invasive Fusarium aortitis in a patient who is immunocompromised: A case report.

Fusarium (F.) species are ubiquitous filamentous fungi that may cause various opportunistic infections, especially in patients who are immunocompromised. A rare manifestation of disseminated fusariosis affects the aortic valve and results in invasive aortitis, which poses a significant challenge for clinicians in diagnosis and treatment. Here, we report a case of a patient, aged 54 years, who is immunocompromised, presenting initially with Fusarium keratitis and chorioretinitis in both eyes and a new endovascular aortic mass. Positron emission tomography/computed tomography was performed, suggesting aortitis. Transoesophageal echocardiography and electrocardiogram-guided computed tomography-angiography confirmed a large intraluminal mass in the ascending aorta. The aortic mass and a part of the ascending aorta were resected surgically, and a filamentous fungus with the microscopic features of the genus Fusarium was isolated and later identified molecularly as F. petroliphilum. The course of the treatment was complicated by perioperative cerebral embolization and mesenteric ischemia. These complications could be attributed to a preoperatively existing occlusion of the superior and inferior mesenteric artery and a subtotal stenosis of the celiac trunk. This case report describes a rare manifestation of disseminated fusariosis, frequently characterized by protracted clinical courses with poor prognosis. Fusariosis may manifest at different sites at different times or persist as a long-lasting disease with reactivation. This case highlights the importance of the interdisciplinary approach for effectively treating invasive mycoses.

Eculizumab in chemotherapy-induced thrombotic microangiopathy.

Thrombotic microangiopathy (TMA) is a rare but severe complication of tumors and their chemotherapeutic treatment. We report on two patients with chemotherapy-induced TMA who were successfully treated with a short course of the terminal complement inhibitor eculizumab. Both patients quickly achieved remission of microangiopathic hemolytic anemia and recovery of renal function. After withdrawal of eculizumab, remission was stable over an observation period of 47 months and 15 months, respectively. Our data show that eculizumab is effective in treating chemotherapy-induced TMA. Discontinuation of eculizumab is feasible once the complement-activating condition is controlled and the trigger is eliminated. Additional studies need to determine the optimal duration of complement-directed therapies and validate effective monitoring strategies after discontinuation of such therapy.

Thirty-eight-negative kinase 1 mediates trauma-induced intestinal injury and multi-organ failure.

Dysregulated intestinal epithelial apoptosis initiates gut injury, alters the intestinal barrier, and can facilitate bacterial translocation leading to a systemic inflammatory response syndrome (SIRS) and/or multi-organ dysfunction syndrome (MODS). A variety of gastrointestinal disorders, including inflammatory bowel disease, have been linked to intestinal apoptosis. Similarly, intestinal hyperpermeability and gut failure occur in critically ill patients, putting the gut at the center of SIRS pathology. Regulation of apoptosis and immune-modulatory functions have been ascribed to Thirty-eight-negative kinase 1 (TNK1), whose activity is regulated merely by expression. We investigated the effect of TNK1 on intestinal integrity and its role in MODS. TNK1 expression induced crypt-specific apoptosis, leading to bacterial translocation, subsequent septic shock, and early death. Mechanistically, TNK1 expression in vivo resulted in STAT3 phosphorylation, nuclear translocation of p65, and release of IL-6 and TNF-α. A TNF-α neutralizing antibody partially blocked development of intestinal damage. Conversely, gut-specific deletion of TNK1 protected the intestinal mucosa from experimental colitis and prevented cytokine release in the gut. Finally, TNK1 was found to be deregulated in the gut in murine and porcine trauma models and human inflammatory bowel disease. Thus, TNK1 might be a target during MODS to prevent damage in several organs, notably the gut.

Complement in Pancreatic Disease-Perpetrator or Savior?

The complement system is a major pillar of the humoral innate immune system. As a first line of defense against pathogens, it mediates early inflammatory response and links different branches of humoral and cellular immunity. Disorders affecting the exocrine pancreas, such as acute pancreatitis, potentially lead to a life-threatening systemic inflammatory response with aberrant activation of complement and coagulation cascades. Pancreatic proteases can activate key effectors of the complement system, which in turn drive local and systemic inflammation. Beyond that, the extent of pancreas-complement interaction covers complex pro- and anti-inflammatory mechanisms, which to this day remain to be fully elucidated. This review provides a comprehensive overview of the pathophysiological role of complement in diseases of the exocrine pancreas, based on existing experimental and clinical data. Participation of complement in acute and chronic pancreatitis is addressed, as well as its role in tumor immunology. Therapeutic strategies targeting complement in these diseases have long been proposed but have not yet arrived in the clinical setting.

Algorithm guided outlining of 105 pancreatic cancer liver metastases in Ultrasound.

Manual segmentation of hepatic metastases in ultrasound images acquired from patients suffering from pancreatic cancer is common practice. Semiautomatic measurements promising assistance in this process are often assessed using a small number of lesions performed by examiners who already know the algorithm. In this work, we present the application of an algorithm for the segmentation of liver metastases due to pancreatic cancer using a set of 105 different images of metastases. The algorithm and the two examiners had never assessed the images before. The examiners first performed a manual segmentation and, after five weeks, a semiautomatic segmentation using the algorithm. They were satisfied in up to 90% of the cases with the semiautomatic segmentation results. Using the algorithm was significantly faster and resulted in a median Dice similarity score of over 80%. Estimation of the inter-operator variability by using the intra class correlation coefficient was good with 0.8. In conclusion, the algorithm facilitates fast and accurate segmentation of liver metastases, comparable to the current gold standard of manual segmentation.