Tracheal Bleeding Research Articles

First Reported Case of Anaphylaxis to Nebulized Tranexamic Acid in a Pediatric Patient: A Rare but Critical Event.

Background: Tranexamic acid (TXA) is a medication used to treat or prevent excessive blood loss due to certain medical conditions. It has a low side effect profile and is safe to administer in most instances. Anaphylaxis cases due to intravenous TXA have been reported in the literature. We report the first pediatric case of anaphylaxis due to the use of nebulized TXA. Case Presentation: A 2-year-old boy with cerebral palsy, epilepsy, and tracheostomy was hospitalized with pneumonia. On the fourth day of hospitalization, the patient started bleeding from the trachea. Nebulized TXA was started to reduce tracheal bleeding. Anaphylaxis developed 5 min after administration of nebulized TXA. Subsequently, the patient was successfully treated with adrenaline, intravenous fluids, antihistamines, and steroids. Conclusion: Nebulized TXA is increasingly used off-label. Although it has a safe profile, side effects such as anaphylaxis may occur rarely. It is essential to recognize the symptoms of anaphylaxis when using nebulized TXA.

Comparison of Endotracheal Tube Cuff Pressure change between Supine prone and Supine – Knee Chest Position in Lumbar Disc Surgery

Background: In rare instances, massive over inflation of the cuff may lead to acute complications such as tracheal bleeding or rupture. This may be associated with post-operative complications like sore throat hoarseness of voice. The purpose of this study was to evaluate the ETT cuff pressure changes between supine to prone and supine to knee chest position in lumber disc surgery. Materials & Methods: Sixty patients, aged between 18 to 60 years of either sex, belonging to American Society of Anaesthesiology (ASA) physical status I to II undergoing elective lumbar disc surgery under general anaesthesia either in prone position or in knee-chest position were considered for this study. The patients were randomly allocated into two groups of 30 patients each. Group “p” was undergone operation in prone position and group “k” undergone operation in knee-chest position. The patients were connected to standard monitoring system such as non-invasive blood pressure (NIBP), electrocardiogram (ECG), pulse oxymeter, and capnometer. All patients were pre-medicated with inj. glycopyrrolate 0.2 mg and inj. fentanyl 2µg/kg iv 5-6 minutes before induction of anaesthesia and were pre-oxygenated with 100% oxygen for atleast 3 minutes. All the patients were induced with inj. propofol 2.5 mg/kg i.v. followed by inj. rocuronium at a dose of 1.2 mg/kg for facilitating tracheal intubation with reinforced ETT. The ETT size selected for men and women were 8.0-8.5 mm ID and 7.0- 7.5 mm ID (Mallinckrodt) respectively. Results: Group k patients showed higher cuff pressure change from 25 to 39.97cm of H2O compared to group p from 25 to 30.47 cm of H2O after change of position only. There was statistically significant different found between groups Sore throat was found significantly higher in group k compared to group p (20% vs 16.67%). Conclusion: The cuff pressure of the endotracheal tube should be monitored and managed properly after the position change from supine to prone and prone to knee chest position.

Tracheo-innominate fistula as a late complication of prolonged intubation in a patient with mycobacterium tuberculosis: a case report

BackgroundThe tracheo-innominate fistula is a rare and potentially life-threatening entity that occurs in approximately less than 1% of patients after a tracheostomy. It occurs when the anterior wall of the trachea erodes and comes into contact with the posterior wall of the innominate artery or brachiocephalic trunk due to excessive pressure from the hyperinflation of the cuff over the mucosa, creating a fistulous tract. Clinically, it manifests as massive tracheal bleeding that puts the patient's life at imminent risk.Case presentationWe present the case of a 60-year-old Latin American male patient with a history of SARS CoV-2 pneumonia approximately 4 months earlier, who required prolonged orotracheal intubation and tracheostomy due to subglottic stenosis, which required tracheal dilations. The patient was admitted to the emergency department due to hemoptysis associated with hemodynamic instability and later on presented with massive tracheal bleeding. The chest-CT angiography evidenced a tracheo-innominate fistula that required surgical management. A concomitant Mycobacterium Tuberculosis infection was also diagnosed during his hospitalization.ConclusionsThere are currently many gaps in our knowledge about the tracheo-innominate fistula, mainly in terms of its incidence following the SARS-CoV-2 pandemic, as well as the role that concomitant infections and their treatments, such as tuberculosis, play in the development of these events. During the pandemic, the cases of intubated patients and patients with tracheostomies increased, giving way to new and unexpected complications, we have yet to study in depth.

Early postoperative complications following tracheotomy: Does suturing technique influence outcomes?

Tracheotomy is one of the most commonly performed procedure by otolaryngologists, but no consensus exists on the effect of suturing techniques on postoperative complications. Stay sutures and Bjork flaps are utilized frequently for securing the tracheal incision to the neck skin in order to create a tract for recannulation. Retrospective cohort study of tracheotomies performed by Otolaryngology-Head and Neck Surgery providers (May 2014 to August 2020) was conducted to determine the effect of suturing technique on postoperative complications and patient outcomes. Patient demographics, medical comorbidities, indication for tracheostomy, and postoperative complications were analyzed with a statistical alpha set of .05. Out of 1395 total tracheostomies performed at our institution during the study period, 518 met inclusion criteria for this study. Three hundred and seventeen tracheostomies were secured by utilizing a Bjork flap, while 201 were secured with up and down stay sutures. Neither technique was noted to be more commonly associated with tracheal bleeding, infection, mucus plugging, pneumothorax, or false passage of the tracheostomy tube. One mortality was noted following decannulation during the study period. Though various techniques exist; adverse outcomes are not associated with the manner in which a new tracheostomy stoma is secured. Medical comorbidities and the indications for tracheostomy likely play a more significant role in postoperative outcomes and complications. Level 3.

Open Bedside Tracheostomy: Safe and Cost Saving but Underutilized Nationally.

To evaluate open bedside tracheostomy (OBT) and compare it with open operating room (OR) tracheostomy and bedside percutaneous dilatational tracheostomy (PDT) in complications and cost. To determine the tracheostomy practice patterns of academic otolaryngology programs. Retrospective cohort study and cross-sectional study. Public hospital and tertiary care hospital. Otolaryngology program directors were surveyed to determine their institutions' tracheostomy practice patterns and the factors preventing the implementation of open bedside tracheostomies. A retrospective chart review was done of tracheostomies performed at our institutions from 2009 to 2019 for prolonged mechanical ventilation. Complications, length of intubation, comorbidities, body mass index, demographics, mortality rates, and decannulation rates were recorded. A cost analysis between OBT and PDT was conducted. Data from 802 patients were analyzed for 449 OBTs, 206 PDTs, and 147 open OR tracheostomies. Complication rates were low. PDTs were more likely to have perioperative tracheal bleeding (P = .028) and mucus plugging (P = .006). OBTs were performed on sicker patients with a higher Charlson Comorbidity Index than PDT and OR tracheostomies. The cost of OBT was less than that of PDT. The survey response rate of tracheostomy practice patterns was 46%. The otolaryngologists at the responding programs all conducted OR tracheostomies, while 52.7% did OBTs and 30.9% PDTs. OBT can be done safely in patients with multiple comorbidities and has a cost that can be less than PDT. Despite these benefits, only 50% of academic institutions routinely performed OBT.

Pulmonary vein aneurysm in a New Zealand White rabbit: a case report

BackgroundPulmonary venous aneurysm (PVA) is a rare condition characterized by aneurysmal dilatation of the pulmonary vein in humans. The diagnosis is incidental usually as there are no clinical symptoms. This case report describes a histological diagnosis of PVA in a New Zealand White rabbit.Case presentationA 1.5-kg male New Zealand White rabbit was acclimatized in an animal room for 5 weeks until the experiment began. However, the rabbit was found dead, with signs of nasal hemorrhage. Necropsy revealed tracheal and pulmonary hemorrhage, and the epistaxis had a pulmonary origin. PCR and ELISA to detect antigens and antibodies pertaining to the rabbit hemorrhagic disease virus showed negative results. Multiple ballooning lesions (50–200 μm size) in the pulmonary veins were observed on histological examination, and PVA was diagnosed. Death was attributed to a spontaneous rupture of the PVA and massive hemorrhage into the lung parenchyma that extended into the trachea and nasal passages.ConclusionsTo the author’s best knowledge, this is the first report of a PVA in a rabbit.

A Case of Newcastle disease from an outbreak in a commercial broiler farm in Mymensingh city, Bangladesh

Background Newcastle disease (ND) is a contagious and often deadly viral disease caused by the Newcastle disease virus (NDV), affecting a wide variety of domestic and wild birds. The outbreak of this fatal disease is one of the greatest constraints to the expansion of poultry farms, resulting in significant financial losses. Here we report the clinical and pathological features of a ND case from an outbreak in a commercial broiler farm. Materials and Methods A broiler farm with a population of 850 birds aged 27 days reported the death of 100 chickens within 4 days of the onset of the disease in 2019. For investigation, one dead chicken was brought to the department of pathology, Bangladesh Agricultural University, Mymensingh. The case history was recorded, and an autopsy was performed. Portion of the samples were kept in 10% neutral buffered formalin for histopathological study. Results The morbidity and mortality rates were reported to be 17.65% and 11.47%, respectively. Recorded clinical history were depression, off-feed, huddling, gasping, ruffled feathers, greenish diarrhea, soiled vent and the birds were unvaccinated. On external examination, the birds appeared dehydrated, dyspneic and had nasal exudates, ruffled feathers, and soiled vents. Autopsy exhibited prominent gross lesions in the trachea, lungs, proventriculus, gizzard, intestine, cecal tonsil, liver, spleen and cloacal bursa. Grossly, tracheal hemorrhage, severe congestion in the lungs, pin point hemorrhages on the tip of the proventriculur glands, hemorrhage in the cecal tonsil, button-like ulceration in the intestine and mottled spleen were suggestive of ND. Histopathologically, severe enteritis, necrotic mass in the cecal tonsil and proventriculus, lymphoid depletion in the spleen supported the infection of NDV. The clinicopathological findings of the ND outbreak in broiler farm confirmed that it was velogenic viscerotropic in nature. Conclusion ND in commercial flocks remains a threat to the poultry industry in Bangladesh. Implementation of strict biosecurity, husbandry practice and effective vaccination are required to prevent diseases and improve economic stability.

A Phase 2 Study to Test the Feasibility, Safety and Efficacy of the Addition of Blinatumomab to the Interfant06 Backbone in Infants with Newly Diagnosed KMT2A-Rearranged Acute Lymphoblastic Leukemia. a Collaborative Study of the Interfant Network

▪Background:Infant acute lymphoblastic leukemia (ALL) is a rare disease with dismal outcome. While outcomes for older children have improved, with event-free survival (EFS) currently above 85%, newly diagnosed infants (<1 year of age) with KMT2A-rearranged ALL have an 1-year EFS of 54.8% (SE 2.3) and a 3-year EFS of 39.6% (SE 2.3) (48% and 23% for medium risk (MR) and high risk (HR) patients, respectively). Ninety percent of all relapses occur during treatment, 66% within one year of diagnosis. Survival after relapse is only 20%. Intensifying chemotherapy with the Interfant06 protocol has not improved the outcome for infant ALL over the last two decades (Pieters et al., JCO 2019), hence there is an urgent need to improve upfront treatment. We studied the safety and efficacy of blinatumomab, a bispecific T-cell engager antibody targeting CD19, in infants with newly diagnosed KMT2A-r ALL.Methods:We conducted a prospective, single-arm, international, multicenter, phase 2 study. Newly diagnosed patients <1 year of age with KMT2A-r ALL treated according to the Interfant06 protocol and with a M1/M2 marrow at the end of induction (EOI) were eligible to receive one course of blinatumomab (15ug/m 2/day, 28 day continuous infusion) after induction (Figure 1). Minimal residual disease (MRD) was measured at EOI (TP2), during blinatumomab (TP blina1 day15 and TP blina2 day29), before MARMA (TP4) and OCTADAD/hematopoietic stem cell transplant (HSCT) (TP5), and at the start of maintenance (TP6) using MLL and/or Ig/TCR polymerase chain reaction. HR KMT2A-r infant ALL was defined as age <6 months at diagnosis AND white blood cell count≥300x10 9/L and/or poor prednisone response. All other KMT2A-r patients were classified as MR. MR patients with MRD levels >0.05% before OCTADAD and all HR patients in complete remission were eligible for HSCT. (Serious) Adverse Events ((S)AEs) were collected from the start of blinatumomab until the next treatment block. Outcome data were compared to historical controls.Results:Twenty-eight patients were enrolled. Baseline characteristics are shown in Table 1. The median follow-up was 11 months (range 1.5-33 months). All patients received the full course of blinatumomab without treatment interruptions. Seven SAEs were reported during blinatumomab (3 fever, grade 1 and 4 infections, grade 3-4). None of the patients experienced neurological (S)AEs. In total, 70 AEs were reported, the most frequent grade >3 adverse events were febrile neutropenia (n= 2), anemia (n=5), and elevated GGT (n=2). MRD negative complete response occurred in 54% (n=15/28) at TP blina1, as well as at TP blina2 (after 2 and 4 weeks of blinatumomab, Table 2), which tended to be higher compared to the end of consolidation in Interfant06 (40%, p=0.16). There were 89% (25/28) of patients who were MRD negative or not quantifiable (<0.05%) at TP blina2. None of the MR patients had an indication for HSCT based on high MRD before OCTADAD, compared to 20% in Interfant06, however one patient was transplanted per investigator's discretion. All MR patients who continued chemotherapy became MRD negative during further treatment. MRD negative complete response at the end of blinatumomab was more frequently found in MR compared to HR patients (68% vs 22%, p=0.0418) and in patients with low MRD at EOI (<0.05%) compared to patients with high MRD at EOI (76% vs 18 %, p=0.0056). The 1-year EFS was 96.2% (SE 3.8). One death in first complete remission (CR1) occurred just before HSCT, which was not blinatumomab related (tracheal bleeding due to a tracheal cannula). One MR patient with high MRD at EOI had a combined CD19 positive relapse in the bone marrow and CNS at the end of maintenance, and is in continuous CR2 after HSCT.Conclusion:This is the first trial to use blinatumomab in infants with newly diagnosed KMT2A-r ALL. Blinatumomab added to the Interfant06 backbone was very well tolerated, and has promising efficacy in terms of a high rate of complete MRD response and short term EFS. Longer follow-up is awaited, but the low relapse rate after blinatumomab is remarkable, given that in historical controls relapses occur frequently and early, during therapy. Given these findings, blinatumomab will be implemented for all infants with newly diagnosed KMT2A-r ALL in the next Interfant21 protocol. [Display omitted] DisclosuresNysom: Y-mAbs: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: teaching; EUSA Pharma: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees, Other: teaching. Biondi: Amgen: Honoraria; Incyte: Consultancy, Other: Advisory Board; Bluebird: Other: Advisory Board; Novartis: Honoraria; Colmmune: Honoraria. OffLabel Disclosure:Investigational use of blinatumomab

Coagulopathy Secondary to Chronic Hepatopathy in Three Lizards

Liver disease is prevalent in reptiles, but the understanding of the secondary consequences of liver disease in reptile patients is far from understood. This case series details three lizards that developed coagulopathy secondary to hepatopathies. Two green iguanas (Iguana iguana) both diagnosed with severe hepatic fibrosis experienced coagulopathies—one with fatal exsanguination from a broken toenail and the second case with acute pulmonary hemorrhage. A Mali uromastyx (Uromastyx maliensis) diagnosed with severe hepatic lipidosis experienced acute severe respiratory distress secondary to acute tracheal hemorrhage. The occurrence of pulmonary or tracheal hemorrhage in two patients appears notable, however, more cases are needed to determine significance. All three cases had hepatopathies diagnosed by computed tomography, prior to the coagulation related complications. Based upon the cases presented here, it is recommended that coagulopathic sequelae of liver disease be considered in lizards with hepatopathies.

Phase Ib study of BI 836880 (VEGF/Ang2 nanobody) plus ezabenlimab (BI 754091; anti-PD-1 antibody) in patients (pts) with solid tumors.

2579 Background: In preclinical studies, the combination of anti-VEGF/Ang2 and anti-PD-1 therapy has been shown to promote an immunopermissive state, which is supportive of T-cell-mediated tumor cell destruction. BI 836880 is a humanized bispecific nanobody that targets VEGF and Ang2, and ezabenlimab (BI 754091) is an anti-PD-1 antibody. Phase I studies investigating each as monotherapies have reported safety and preliminary antitumor activity. This ongoing Phase Ib study is evaluating the combination of BI 836880 and ezabenlimab in pts with advanced solid tumors. In Part 1 (dose escalation), the combination was feasible in pts with advanced NSCLC, with a recommended Phase II dose (RP2D) of BI 836880 720 mg + ezabenlimab 240 mg IV q3w. Here, we report updated results from Part 2 (expansion phase), which is assessing the antitumor activity and safety of the RP2D. Methods: Seven cohorts are currently recruiting pts in Part 2: metastatic (m) NSCLC after checkpoint inhibitor (CPI) monotherapy (Cohort A); mNSCLC after chemotherapy (CT) + CPI (Cohort B); mSCLC after CT ± CPI (Cohort C); 1st and 2nd recurrences of glioblastoma (GBM; Cohort D); immunotherapy-resistant m-melanoma (Cohort E); hepatocellular carcinoma (HCC) after prior sorafenib or lenvatinib ± CPI (Cohort F); and previously untreated/unresectable HCC (Cohort G). Primary endpoint is objective response rate (complete response + partial response [PR]). Results: As of January 2021, 196 pts have received BI 836880 plus ezabenlimab (14 in Part 1, 182 in Part 2 [Cohort A, 26; B, 30; C, 19; D, 31; E, 32; F, 28; G, 16]). 134 (68%) pts were male, median age was 63 years and 102 (52%) had prior CPI use. Any grade and ≥G3 adverse events (AEs; any cause) were reported by 160 (82%) and 62 (32%) pts, most commonly (all%/≥G3%) hypertension (20/8), asthenia (20/3), diarrhea, decreased appetite, and nausea (all 11/1). 95 (48%) pts had a drug-related AE, most commonly hypertension and asthenia (both 11%). 6 pts had a G4 AE (non-related: hyperkalemia + cardiac arrest, laryngospasm, gastrointestinal perforation; drug-related: anaphylactic reaction, acute pancreatitis, transaminases increased); 8 pts had a G5 AE (non-related: general physical health deterioration, epilepsy, hemoptysis, cardio-respiratory arrest, hepatic failure, intracranial hemorrhage, COVID-19 pneumonia; drug-related tracheal hemorrhage). 30 (15%) pts had immune-related AEs (3% ≥G3), including hypothyroidism (3%). 11 (6%) pts had an AE leading to discontinuation. Overall, 145 pts were evaluable for response: 9 pts achieved confirmed PR (2 pts in Part 1 and 7 in Part 2 [NSCLC, n = 3; SCLC, n = 1; GBM, n = 1; melanoma, n = 1; and 2nd-line HCC, n = 1]), 87 pts had stable disease and 49 pts had progressive disease. 111 pts remain on treatment. Conclusions: BI 836880 plus ezabenlimab had a manageable safety profile. The combination showed preliminary antitumor activity in a range of tumor types. Clinical trial information: NCT03468426.

Long-Term Outcome of LVAD in Duchenne Population with End Stage Cardiomyopathy

Purpose The aim of this study was to report the effect of long-term use of VAD in patients affected by Duchenne Muscular Distrophy and end stage cardiomyopathy (DMD-DCM). Methods We collected data of end stage DMD-DCM patients who were implanted with LVAD in our center (group 1) and the ones in regular follow-up because not eligible for LVAD implantation (group 2). Each patient of group 1 underwent extensive pre-operative assessment, in-hospital treatment and was enrolled in a dedicated DMD heart failure (HF) clinic during the post-discharge period. Patients of group 2 were followed in a dedicated DMD HF clinic or as inpatient in case of need of inotropic support. All data during long-term follow-up were recorded including echocardiography, ECG examination, laboratory blood tests, BNP dosing and assessment of nutritional status and respiratory function. Survival of the groups was represented by Kaplan Meier analysis and compared by log rank. Results A total of eight DMD-DCM patients (group 1) were implanted with LVAD and treated at our center during the period from 2011 until 2018 (mean age at implantation was 16.9 ± 2.9 years)¸whilst 4 patients (group 2) were not eligible for LVAD implantation. At the time of the last follow-up, 4 out of 8 patients were alive and 2 out of 8 patients did not have post-operative complications. The most prominent complications were bleeding and infections with one episode of acute heart failure that was successfully treated. The principal causes of 3 deaths at the median follow-up of 22 months were sepsis, tracheal bleeding, and cerebral hemorrhage. After one year from implantation we noticed a significant decrease in heart rate (p=0.002), in LV volumes and diameters (LVEDD p=0.03, LVESD p=0.02, EDV p=0.01 and ESV p=0.02) together with a significant increase in ejection fraction (p=0.0036). However, relative wall thickness did not change over time, showing an eccentric remodeling pattern before and after LVADs. Analysis on short and long-term follow-up showed significant improvement of survival in DMD patients treated with LVAD compared to the group that was not implanted (log rank Conclusion Our data showed that cardiac atrophy is persistent in Duchenne cardiomyopathy despite the improvement of LV function. LVAD improved outcomes in patients with LVAD when compared to those without.

Evaluation of Endovascular Intervention for Tracheo-Innominate Artery Fistula: A Systematic Review

While the standard of care for suspected tracheo-innominate artery fistula (TIF) necessitates sternotomy, perioperative mortality remains high. Endovascular interventions have been attempted, but reports have been anecdotal. The aim of this systematic review was to evaluate the outcomes of endovascular management of TIF by pooling the existing evidence. An electronic database search of Ovid MEDLINE, Scopus, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Controlled Trials Register was performed to identify all studies examining endovascular treatment of TIF. Patients greater than 14 years of age who underwent endovascular intervention for TIF were included. 25 studies consisting of 27 patients met the inclusion criteria. 48.1% (13/27) of patients were male and median age was 39.0 [IQR 16.0, 47.5] years. Tracheostomy was present in 96.3% (26/27) of cases. Median duration from tracheostomy to TIF presentation was 2.2 months [0.5, 42.5]. On presentation, 84.6% (22/26) had tracheal hemorrhage, and 22.8% (6/27) were hemodynamically unstable. 96.3% (26/27) underwent covered stent graft placement while 1 patient (3.8%) had coil embolization. 18.5% (5/27) of patients required repeat endovascular intervention for recurrent bleeding, while 11.1% (3/27) required rescue sternotomy. Median hospital length of stay was 30 days [16.0, 46.5], and overall mortality was 29.6% (8/27) with a median follow-up time of 5 months [1.2, 11.5]. While uncommon, endovascular treatment of TIF may be a feasible alternative to sternotomy. The approach may be useful in those who are unable to undergo surgery or are likely to have adhesions from prior chest operations.

Anticoagulation Management in Severe Coronavirus Disease 2019 Patients on Extracorporeal Membrane Oxygenation

ObjectiveTo explore special coagulation characteristics and anticoagulation management in extracorporeal membrane oxygenation (ECMO)–assisted patients with coronavirus disease 2019 (COVID-19).DesignSingle-center, retrospective observation of a series of patients.ParticipantsLaboratory-confirmed severe COVID-19 patients who received venovenous ECMO support from January 20–May 20, 2020.InterventionsThis study analyzed the anticoagulation management and monitoring strategies, bleeding complications, and thrombotic events during ECMO support.Measurements and Main ResultsEight of 667 confirmed COVID-19 patients received venovenous ECMO and had an elevated D-dimer level before and during ECMO support. An ECMO circuit pack (oxygenator and tubing) was replaced a total of 13 times in all 8 patients, and coagulation-related complications included oxygenator thrombosis (7/8), tracheal hemorrhage (5/8), oronasal hemorrhage (3/8), thoracic hemorrhage (3/8), bleeding at puncture sites (4/8), and cannulation site hemorrhage (2/8).ConclusionsHypercoagulability and secondary hyperfibrinolysis during ECMO support in COVID-19 patients are common and possibly increase the propensity for thrombotic events and failure of the oxygenator. Currently, there is not enough evidence to support a more aggressive anticoagulation strategy.

A Rare Case of Rectal Gastrointestinal Stromal Tumor Associated with Parapharyngeal Metastasis

Background: Gastrointestinal stromal tumors are the most frequent mesenchymal tumors and represent 1- 3% of all digestive neoplasms. Their incidence is 0.68 per 10,000 people. GISTs originate from the interstitial cells of Cajal, which are known as the gastrointestinal pacemaker, and carry mutations in the KIT gene in 95% of those affected. GISTs occur mainly in the middle-aged and rarely under the age of 40. The main age of presentation is 64 years old. The most common site of metastasis is the liver (65%), and exceptionally the bone (3%). Discussion: Rectal GISTs represent 5 to 15% of all GISTs. They are usually asymptomatic and discovered incidentally. Surgical resection with curative intent is the standard treatment for localized GISTs. Complete excision of the tumor is the most significant factor related to the outcome and can be accomplished in 40- 60% of cases. For borderline or unresectable lesions, neoadjuvant treatment with anti-tyrosine kinase (imatinib) should be considered. Imatinib is considered to be a relatively safe treatment and is generally well-tolerated by patients. Overall, the five-year survival rate is 90% for low-grade GIST, but the prognosis is worse for high-grade tumors (&lt; 20%). Bone metastasis is a rare site of GIST metastases and usually presents itself during disease relapse. We present a rare case of a patient with an oligometastatic with pelvic bone lesion rectal GIST who developed parapharyngeal metastasis infiltrating C3 with airway compromise. Unfortunately, the patient passed away after massive tracheal bleeding. Conclusion: Bone metastasis from GIST is uncommon. The development of dyspnea and hoarseness should prompt the diagnosis of potential life-threatening complications such as parapharyngeal metastasis.

Extracorporeal Life Support in Hemorrhagic Conditions: A Systematic Review.

Extracorporeal life support (ECLS) is indicated in refractory acute respiratory or cardiac failure. According to the need for anticoagulation, bleeding conditions (e.g., in trauma, pulmonary bleeding) have been considered a contraindication for the use of ECLS. However, there is increasing evidence for improved outcomes after ECLS support in hemorrhagic patients based on the benefits of hemodynamic support outweighing the increased risk of bleeding. We conducted a systematic literature search according to the PRISMA guidelines and reviewed publications describing ECLS support in hemorrhagic conditions. Seventy-four case reports, four case series, seven retrospective database observational studies, and one preliminary result of an ongoing study were reviewed. In total, 181 patients were identified in total of 86 manuscripts. The reports included patients suffering from bleeding caused by pulmonary hemorrhage (n = 53), trauma (n = 96), postpulmonary endarterectomy (n = 13), tracheal bleeding (n = 1), postpartum or cesarean delivery (n = 11), and intracranial hemorrhage (n = 7). Lower targeted titration of heparin infusion, heparin-free ECLS until coagulation is normalized, clamping of the endotracheal tube, and other ad hoc possibilities represent potential beneficial maneuvers in such conditions. Once the patient is cannulated and circulation restored, bleeding control surgery is performed for stabilization if indicated. The use of ECLS for temporary circulatory or respiratory support in critical patients with refractory hemorrhagic shock appears feasible considering tailored ECMO management strategies. Further investigation is needed to better elucidate the patient selection and ECLS management approaches.

Von Willebrand Factor Concentrate Administration for Acquired Von Willebrand Syndrome- Related Bleeding During Adult Extracorporeal Membrane Oxygenation

To review the use of Von Willebrand Factor (VWF) concentrate for treatment of acquired Von Willebrand syndrome (VWS)-related bleeding in adult extracorporeal membrane oxygenation (ECMO) patients and determine if it was associated with improved VWF laboratory parameters. Retrospective observational cohort study. Tertiary care academic medical center. Adult ECMO patients who received VWF concentrate for treatment of acquired VWS- related bleeding. None, observational study. Ten adult ECMO patients received VWF concentrate for treatment of bleeding with evidence of acquired VWS over a 15-month period. Six patients were on veno-arterial ECMO and 4 were on veno-venous ECMO. The most common site of bleeding was airway or tracheal bleeding. The mean dose of VWF concentrate was 41 IU/kg. Mean VWF antigen was 263 ± 93 IU/dL before treatment and 394 ± 54 after treatment. Mean ristocetin cofactor activity was 127 ± 47 IU/dL before treatment and 240 ± 33 after treatment. The mean VWF ristocetin cofactor activity antigen ratio increased from 0.52 ± 0.14 before treatment to 0.62 ± 0.04 after treatment. Four of 10 patients had complete resolution of their bleeding within 24 hours, and 6 of 10 had complete resolution of their bleeding within 2- to- 4 days. There were 3 patients who had thrombotic events potentially related to VWF concentrate administration. No patient had an arterial thrombosis, stroke, or myocardial infarction. VWF concentrate administration increases VWF function in adult ECMO patients, but also may be associated with increased thrombotic risk. Larger studies are needed to determine VWF concentrate's safety, efficacy, and optimal dosing in adult ECMO patients.

Successful respiratory management of a Marshall-Smith syndrome patient with a tracheo-innominate artery fistula

BackgroundTracheo-innominate artery fistula (TIF) is a life-threatening complication of tracheostomy. We describe perioperative management for innominate artery transection in a case with TIF.Case presentationA 4-year-old Japanese female with Marshal-Smith syndrome presented for management of TIF. She underwent tracheostomy at the age of 3 months and an uncuffed tracheostomy tube was inserted. One month before admission to our hospital, intermittent tracheal bleeding, suggesting TIF, occurred. Although we considered to change to a cuffed endotracheal tube, craniofacial abnormality suggested difficult oral intubation, and there was a possibility of rebleeding. Finally, innominate artery transection was performed under total intravenous anesthesia without changing the tracheostomy tube. Surgery completed uneventfully and she received mechanical ventilation under sedation for a day, followed by weaning without complications.ConclusionsA cuffed tracheostomy tube should have been inserted before surgery for effective hemostasis against sudden bleeding from TIF even though conversion to oral intubation was difficult.

Randomized phase III study of irinotecan/cisplatin (IP) versus etoposide/cisplatin (EP) for completely resected high-grade neuroendocrine carcinoma (HGNEC) of the lung: JCOG1205/1206.

9006 Background: In the WHO classification, small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are considered as high-grade neuroendocrine carcinoma (HGNEC) of the lung. Although there were no randomized trials evaluating adjuvant chemotherapy for patients (pts) with resected HGNEC, EP was considered to be a standard regimen for this population. A phase III study showed the superiority of IP to EP in pts with extensive stage SCLC (JCOG9511). Methods: Pts with completely resected HGNEC were randomized in a 1:1 ratio to receive either etoposide (100 mg/m2, days 1-3)/cisplatin (80 mg/m2, day 1) or irinotecan (60 mg/m2, days 1, 8, 15)/cisplatin (60 mg/m2, day 1), using the minimization method according to sex, pathologic stage, histology and institution. The primary endpoint was changed from overall survival (OS) to relapse-free survival (RFS) during the study period. We assumed a 3-year RFS of 59% of EP arm and 72% of IP arm (hazard ratio (HR) of 0.623). Planned sample size was 220 in total to give a power of 80% with a one-sided alpha of 5%, an accrual period of 6 years and a follow-up period of 3 years. Results: Between April 2013 and October 2018, 221 pts with a median age of 66 years, pathological stage I (54%), SCLC (53%), were randomly assigned to the EP arm (n = 111) or the IP arm (n = 110). In the second interim analysis, the predictive probability that IP would be superior to EP at the time of the primary analysis was 15.9%, which led to early termination of the trial. With a median follow-up of 24.1 months, 3-year RFS was 65.4% versus 69.0% with HR of 1.076 (95% CI, 0.666-1.738; log-rank test, one-sided P= 0.619). In the subgroup analyses of histology, 3-year RFS in SCLC was 65.2% versus 66.5% with HR of 1.029 (95% CI, 0.544-1.944), and 3-year RFS in LCNEC was 66.5% versus 72.0% with HR of 1.072 (95% CI, 0.517-2.222). Overall survival at 3 years was 84.1% versus 79.0% with HR of 1.539 (95% CI, 0.760-3.117). Proportions of treatment completion were 87.4% (EP) and 72.7% (IP). Incidences (EP/IP) of grade 3 or 4 febrile neutropenia (20.2/3.7%) or neutropenia (97.2/35.8%) were more common in EP. Grade 3 or 4 diarrhea (0.9/8.3%) or anorexia (6.4/11.1%) were more common in IP. One treatment-related death due to tracheal bleeding was observed in IP. Conclusions: This study failed to show the superiority of IP to EP in RFS for pts with completely resected HGNEC. EP is still a standard treatment for this population. Clinical trial information: UMIN000010298.

Long-Term Outcome of LVAD in Duchenne Population with End Stage Cardiomyopathy

The aim of this study was to report the effect of long-term use of VAD in patients affected by Duchenne Muscular Distrophy and end stage cardiomyopathy. We collected data of DMD patients with end-stage cardiomyopathy implanted with LVAD in our center (group 1) and the ones in regular follow-up not eligible for LVAD implantation (group 2). Each patient of group 1 underwent extensive pre-operative assessment, in-hospital treatment and was enrolled in a dedicated DMD HF (heart failure) clinic during the post-discharge period. Patients of group 2 were followed in a dedicated DMD HF clinic or as inpatient in case of need of inotropic support. During long-term follow-up all data were recorded including echocardiography, ECG examination, laboratory blood tests, and respiratory function. Survival was represented by Kaplan Meier analysis and compared by log rank. A total of 8 DMD patients (group 1) were implanted with LVAD and treated at our center during the period from 2011 until 2018 (mean age at implantation was 16.9 ± 2.9 years)¸ whilst 4 patients (group 2) were not eligible for LVAD implantation. At the time of the last follow-up, 4 out of 8 patients were alive and 2 out of 8 patients did not have post-operative complications. The principal causes of 3 deaths at the median follow-up of 22 months were sepsis, tracheal bleeding, and cerebral hemorrhage. After 1 year from implantation we noticed a significant decrease in heart rate (p=0.002), in LV volumes and diameters (LVEDD p=0.03, LVESD p=0.02, EDV p=0.01 and ESV p=0.02) and significant increase in ejection fraction (p=0.0036). However, relative wall thickness did not change over time, showing an eccentric remodeling pattern before and after LVADs. Analysis on short and long-term follow-up showed significant improvement of survival in DMD patients treated with LVAD compared to the group that was not implanted (log rank&lt0.001), with a 5-year increase in life expectancy. Our data showed that cardiac atrophy is persistent in Duchenne cardiomyopathy despite the improvement of EF due to a significant ventricular unloading coupled with chronic therapy. LVAD improved outcomes in patients with LVAD when compared to those without. An integration of outpatient DMD HF clinic and patient-centered palliative care will most likely increase the quality of life and delivery of care for this population.

Detection of new antibiotic resistance gene profile in Escherichia coli associated with avian leukosis virus infection from broiler chickens

The Escherichia coli (E. coli) is prevailing worldwide, but the epidemiology of E. coli infections feature regional distribution characteristics to some extent. E. coli, as a zoonotic pathogen, can be transferred from animals to humans through food chain or via contact with wounds, causing a public health risk. We reported the swelling of proventriculus and tracheal bleeding following the death in two broiler chickens (Gallus gallus domesticus) from Beijing, China. To investigate whether a virus was involved in the infection, Madin Darby Bovine Kidney (MDCK) cells were co-cultured with supernatants of proventriculus, trachea and spleen homogenates. The avian leucosis virus was detected in the samples of proventriculus and trachea, but the avian influenza virus, the Newcastle disease virus and the avian infectious laryngotracheitis virus were not detected. E. coli isolates were resistant to almost all the antimicrobial as tested except for the combinations of amoxicillin/clavulanic acid and sulfamethoxazole/trimethoprim. PCR tests demonstrated the presence of antibiotic resistance genes in these E. coli isolates and further research revealed a novel gene profile with the presence of CTX-M-1, gyrA, gyrB, oqxA, oqxB, parC and Sul2 antibiotic resistance genes in a strain isolated from a proventriculus sample. These results demonstrated that the presence of antibiotic resistant E. coli would not necessarily cause outbreak of large-scale disease. However, when the bacteria carrying new antibiotic resistance genes enter the environment, it may result in the development of more virulent strains which will potentially impact human and animal health.