Inhibition of the JAK/STAT pathway with baricitinib reduces the multiple organ dysfunction caused by hemorrhagic shock in rats

Objective: The aim of this study was to investigate (a) the effects of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway inhibitor (baricitinib) on the multiple organ dysfunction syndrome (MODS) in a rat model of hemorrhagic shock (HS) and (b) whether treatment with baricitinib attenuates the activation of JAK/STAT, NF-κB and NLRP3 caused by HS. Background: Post-traumatic MODS, which is in part due to excessive systemic inflammation, is associated with high morbidity and mortality. The JAK/STAT pathway is a regulator of numerous growth factor and cytokine receptors and, hence, is considered a potential master regulator of many inflammatory signaling processes. However, its role in trauma-hemorrhage is unknown. Methods: An acute HS rat model was performed to determine the effect of baricitinib on MODS. The activation of JAK/STAT, NF-κB and NLRP3 pathways were analyzed by western blotting in the kidney and liver. Results: We demonstrate here for the first time that treatment with baricitinib (during resuscitation following severe hemorrhage) attenuates the organ injury and dysfunction and the activation of JAK/STAT, NF-κB and NLRP3 pathways caused by HS in the rat. Conclusions: Our results point to a role of the JAK/STAT pathway in the pathophysiology of the organ injury and dysfunction caused by trauma/hemorrhage and indicate that JAK inhibitors, such as baricitinib, may be repurposed for the treatment of the MODS after trauma and/or hemorrhage.

Acute hemorrhage and death in calves following chlorophacinone exposure

Three calves were submitted to the Iowa State University Veterinary Diagnostic Laboratory for diagnostic evaluation following an abrupt increase in morbidity and mortality in a calf herd associated with epistaxis and widespread hemorrhage. Each of the submitted calves had moderate-to-severe hemorrhage within various tissues and body cavities, including the thymus, subcutaneous region of the neck, mediastinum, lungs, pericardial sac, heart, spleen, perirenal fat, urinary bladder, and skeletal muscle, including the diaphragm. An anticoagulant rodenticide screen was performed on the livers of each calf. Significant concentrations of chlorophacinone were detected at 4.2, 3.6, and 2.9 ppm in liver. Multiple piles and an open pail of white powdery material were present within the facility in which the calves were housed and were identified as the sources of chlorophacinone. Acute hemorrhage and death occurred in fourteen 1.5-mo-old, crossbred calves following ingestion of the vitamin K antagonist chlorophacinone.

Bronchopneumonia by Streptococcus equi subsp. zooepidemicus in a horse with inhalation of pine branch of Araucaria angustifolia

ABSTRACT: Respiratory problems due to tracheobronchial foreign bodies (FBs) are unusual in horses; although equines kept in pastures eventually inhale FBs, as conifer twigs of Araucaria angustifolia. A 1,5-year-old Criolle foal was presented with hemoptysis, dyspnea, restlessness and fever (40.9 ºC rectal temperature). Complete blood count showed intense neutropenia, monocytosis, thrombocytopenia and hypoproteinemia. Treatment was carried out but no clinical improvement was observed. At the post-mortem examination, marked amount of dark red liquid was observed in the thoracic cavity (hemothorax). The lung parenchyma was diffusely consolidated, predominantly in the cranioventral area, associated with mild pleural fibrin deposition. The right primary bronchus was obliterated by a Araucaria angustifolia pine branch measuring 18 cm in length, with adjacent darkened areas (lung consolidation). Microscopically, there was diffuse necrosis with severe hemorrhage in the lungs, associated with marked neutrophilic inflammatory infiltrate, numerous coccoid bacterial aggregates, and fibrinous pleuritis. Additionally, there was diffuse alveolar edema and multifocal thrombosis. Lung fragments were submitted for bacterial culture and mixed bacterial growth was observed with a predominance of Streptococcus equi subsp. zooepidemicus. Inhalation of branches is not commonly reported in horses, but it must be included in the differential diagnoses of pneumonia, and attention should be taken when allowing horses to graze in areas where the plant occurs.

Uterine Artery Embolization Combined with Subsequent Suction Evacuation as Low-Risk Treatment for Cesarean Scar Pregnancy

Objective: The aim of this study is to propose a standardized management of care for patients diagnosed with cesarean scar pregnancy (CSP). There are two types of CSP: Type 1 (on the scar) vs. type 2 (in the niche). To date there is no international standard to predict the extent of invasion or the optimal management of CSP. Materials and methods: We used intramuscular methotrexate injection followed by uterine artery embolization combined with suction evacuation as a conservative approach for the treatment of seven patients diagnosed with CSP. Our inclusion criteria, to be satisfied simultaneously, were established as follows: (1) patients with CSP; (2) early gestational age ≤ 9 weeks, and (3) written consent of the proposed treatment of the patient. Results: This course of treatment produced a positive outcome in all cases. We did not have any complications (e.g., emergency hysterectomy, perforation of the uterine cavity, severe hemorrhage, or endometritis) during the procedures or in the follow-up. The most important predictors of successful management are early diagnosis of CSP and orientation of the invasive trophoblast opposite to the scar. Conclusions: The main finding from this series of cases is that associating systemic methotrexate and uterine artery embolization provides efficient and low-risk management of CSP. This treatment regime is adequate for both types of CSPs. We consider that early localization diagnosis of pregnancy following a cesarean delivery is mandatory for CSP morbidity prevention.

Mfsd2b and Spns2 are essential for maintenance of blood vessels during development and protection of anaphylaxis

Sphingosine-1-phosphate (S1P) is a potent lipid mediator that is secreted by several cell types to induce signaling. We recently showed that Mfsd2b is an S1P transporter from hematopoietic cells, which contributes approximately 50% plasma S1P. To further determine the sources of plasma S1P, here, we report the characterizations of compound deletions of Mfsd2b and Spns2, another S1P transporter from endothelial cells. Global deletion of Mfsd2b and Spns2 (gDKO) resulted in embryonic lethality between E13.5 and E14.5 with severe hemorrhage that largely recapitulated the phenotypes from global S1P1 knockout mice, indicating that together with Mfsd2b, Spns2 also provides embryonic source of S1P for S1P1 stimulation. The hemorrhagic phenotypes in gDKO embryos were accompanied by increased angiogenesis and defects of tight junction proteins, indicating that S1P from Mfsd2b and Spns2 is essential for blood vessel integrity and maturation. The various sources of S1P in postnatal stages are yet to be fully understood. Postnatal ablation of S1P synthesis enzymes using Mx1Cre shows that Mx1Cre-sensitive cells provide most of plasma S1P. Interestingly, we showed that compound postnatal deletion of Mfsd2b and Spns2 using Mx1Cre (ctDKO-Mx1Cre) resulted in maximal reduction of 80% plasma S1P. Thus, a small amount of plasma S1P is supplied from other sources independent of Mfsd2b and Spns2. Nevertheless, the vasculature in the lung of ctDKO-Mx1Cre mice was compromised. Furthermore, ctDKO-Mx1Cre mice also exhibited severe susceptibility to anaphylaxis, indicating that S1P from Mfsd2b and Spns2 is indispensable during vascular stress. Together, our results show that Mfsd2b and Spns2 provide a critical source of S1P for embryonic development and they also provide a majority of plasma S1P for vascular homeostasis.

Development of a Clamping Device for Tensile Testing of Intracranial Flow Diverter Stents

The main danger of a brain aneurysm (a sack-like bulge on the vessel wall) is that in the event of a rupture a severe hemorrhage can occur which may cause death. However, if doctors have tools at their disposal, such as numerical models and simulations for analyzing patient-specific blood vessels, they could use them to decide if a particular treatment is necessary and if so, when. For such models, the different mechanical characteristics of the flow control devices are the input data. Several of these mechanical properties of the devices, such as modulus of elasticity and tensile strength, are determined by tensile testing. In the course of our research, we have developed a clamping device suitable for uniaxial tensile testing of flow diverter stents.

Efficacy and Safety of Whole Blood Transfusion in Non-Trauma Patients

Whole blood (WB) transfusion for trauma patients with severe hemorrhage has demonstrated early successful outcomes compared to conventional component therapy. The objective of this study was to demonstrate WB transfusion in the non-trauma patient. Consecutive adult patients receiving WB transfusion at a single academic institution were reviewed from February 2018 to January 2020. Outcomes measured were mortality and transfusion-related reactions. A total of 237 patients who received WB were identified with 55 (23.2%) non-trauma patients. Eight patients (14.5%) received pre-hospital WB. The most common etiology of non-traumatic hemorrhage was gastrointestinal bleeding (43.6%, n = 24/55). Approximately half of the non-trauma patients (n = 28/55) received component therapy. Transfusion-related events occurred in 3 patients. This study demonstrated that non-trauma patients could receive WB transfusions safely with infrequent transfusion-related events. Future studies should focus on determining if outcomes are improved in non-trauma patients who receive WB transfusions and defining specific transfusion criteria for this population.

SURGICAL MANAGEMENT OF A MASSIVE CONGENITAL HEMANGIOMA OF THE TONGUE IN AN INFANT: A RARE CASE REPORT

Lesions involving the tongue may present with life threatening complications such as airway compromise and risk of severe hemorrhage. This paper reports the surgical management of a non-involuting massive congenital hemangioma of the tongue in an infant presenting with difficulty breathing, feeding and inability to close the mouth.