Deep Dissecting Hematoma Requiring Surgical Removal During Veno-Venous Extracorporeal Membrane Oxygenation Management: A Case Report.

Deep dissecting hematoma (DDH) is a disease in which minor trauma leads to the formation of an extensive hematoma. If left untreated, this can result in significant skin necrosis. Therefore, early treatment following a precise diagnosis is essential. However, the complexity of the disease may require differentiating it from soft tissue infections. A 58-year-old man with severe coronavirus disease 2019 (COVID-19) pneumonia developed skin complications such as purpura and blisters on his right upper extremity while undergoing veno-venous extracorporeal membrane oxygenation (VV-ECMO). We initially suspected a soft tissue infection or venous perfusion defect caused by the VV-ECMO cannula; however, these conditions were not observed. After making an exploratory incision, we diagnosed the patient with DDH and performed hematoma removal and skin grafting. The initial symptoms of DDH include erythema, swelling, and pain. It is important to differentiate DDH from soft tissue infections, especially necrotizing fasciitis, which is a more urgent condition. Because a surgical incision is necessary for the diagnosis and treatment of DDH, we do not hesitate to perform an exploratory incision to prevent skin necrosis, thereby contributing to early healing.

Simplifying vasectomy reversal without compromising outcomes: a single-surgeon series.

Background: In vasovasostomy (VV) surgery, the micro-surgical technique has consistently been shown to provide superior outcomes to both macroscopic and loupe-assisted techniques, with large studies showing overall patency rates of ~86% and pregnancy rates of ~52%. However, the question of whether a single- or double-layer anastomosis offers the best outcomes remains contentious, and despite the popularity of the two-layer technique, a meta-analysis suggests little difference in outcomes. This study records the outcomes of a single-surgeon series of a simplified single-layer technique, along with the comparative outcomes and predictive factors. Methods: A retrospective analysis of 237 consecutive patients undergoing microsurgical vasectomy reversal between 2010 and 2022 in a single institution was performed. A microsurgical, single-layer, six-point, 8-0 nylon anastomosis was performed with macroscopic intra-operative assessment of vasal fluid. An ipsilateral vasoepididymostomy (VE) was only performed in cases of complete absence of vasal fluid or the presence of toothpaste-like discharge (bilateral VE were excluded from this series). Semen analysis was performed 3 months postoperatively to assess for the presence of motile sperm. Results: A total of 237 men underwent microsurgical vasectomy reversal over a 12-year period. The median age of men at vasectomy was 34 years. The median age at vasectomy reversal was 42 years. The median obstructive interval was 7.3 years. An overall patency rate of 85.8% was achieved (motile sperm present), with 53.8% having a sperm count greater than 15 million/mL on initial 3-month assessment. For obstructive intervals of <3, 3-8, 9-14, and ≥15 years, there were declining patency rates of 96.3%, 90.5%, 80.0%, and 74.1%, respectively (P=0.04). These are the equivalent outcomes to published high-volume two-layer studies. We found no difference between patency rates of VV performed on the straight vas vs. the convoluted vas, and no difference when only one side could be re-anastomosed (20 patients). Conclusions: Using a micro-surgical technique in high volume, similar outcomes can be achieved from a simplified single-layer VV technique with fewer sutures, as compared to the more complex two-layer techniques described. We postulate that this may be due to reduced ischaemia relating to fewer sutures and less tissue-handling. Given the associated time and cost savings, as well as the easier learning curve involved, we would advocate the use of this technique in routine VV practise.

Use of Extracorporeal Membrane Oxygenation for Patients with Coronavirus Disease 2019 Infection.

The coronavirus disease 2019 (COVID-19) pandemic was a cataclysmic event that infected over 772 million and killed over 6.9 million people worldwide. The pandemic pushed hospitals and society to their limits and resulted in incredibly severe respiratory disease in millions of people. This severe respiratory disease often necessitated maximum medical therapy, including the use of extracorporeal membrane oxygenation. While our understanding of COVID-19 and its treatment continue to evolve, we review the current evidence to guide the care of patients with severe COVID-19 infection.

Utilisation and outcomes of a mobile (ambulance and air transport) venovenous extracorporeal membrane oxygenation (VV-ECMO) program in Poland during the COVID-19 pandemic - a retrospective, two-centres, case-series study.

INTRODUCTION: Many patients required mechanical ventilation support due to severe COVID-19 pneumonia. A significant proportion of mechanically ventilated patients also required venovenous extracorporeal membrane oxygenation (VV-ECMO) due to refractory hypoxemia. A high demand for VV-ECMO support during the pandemic was challenging due to many factors, including limited resources and lack of established transfer protocols. This study aims to present the organisation and outcomes of a mobile VV-ECMO program in two high-volume centres in Poland during the COVID-19 pandemic. MATERIAL AND METHODS: This retrospective, two-centre case series study, which lasted 36 months, was conducted between March 10, 2020, and January 31, 2023. The data of all patients transferred using venovenous extracorporeal membrane oxygenation (VV-ECMO) were analysed, including five women in the perinatal period with severe respiratory failure attri-buted to the COVID-19 virus. The analysis encompassed baseline patient demographics, Sequential Organ Failure Assessment (SOFA) scores, admission laboratory parameters, ECMO therapy, duration of mechanical ventilation, and patient survival to ICU discharge. RESULTS: We assessed 86 patients who met the ELSO inclusion criteria and were transported during VV-ECMO support. Mortality in the analysed group was high (80.3%). Despite high mortality, VV-ECMO appeared to be a safe procedure in COVID-19 patients with severe ARDS. No complications were noted in more than half of the analysed procedures. Despite the above, many severe complications were observed, including stroke or cerebral haemorrhage (9.8%) and limb or gut ischemia (1.6%). The most common problems co-existing with VV-ECMO treatment were bleeding complications (34.4%). CONCLUSIONS: The ICU mortality rate among patients requiring VV-ECMO for COVID-19 in high-volume ECMO centres was high but not associated with the type of transportation.

VV-ECMO in critical COVID-19 obese patients: a cohort study.

BACKGROUND: Obesity causes significant difficulties in successful extracorporeal membrane oxygenation (ECMO) support and may interfere with patient outcomes. During the COVID-19 pandemic, we experienced an increased number of obese patients supported with ECMO in our intensive care unit due to severe illness in this population. METHODS: We designed a single-center retrospective study to identify prognostic factors for 180-day survival in obese critical COVID-19 patients receiving venovenous ECMO (VV-ECMO). We included adult critical COVID-19 patients on VV-ECMO, who were obese and overweight (according to the World Health Organization) and admitted to a tertiary hospital's intensive care unit from April 1, 2020, to May 31, 2022. Univariate logistic regression analysis was performed to assess differences in 180-day mortality. RESULTS: Forty-one patients were included. The median age was 55 (IQR 45-60) years, and 70.7% of the patients were male. The median body mass index (BMI) was 36 (IQR 31-42.5) kg/m2; 39% of patients had a BMI ≥ 40 kg/m2. The participants had 3 (IQR 1.5-4) days of mechanical ventilation prior to ECMO, and 63.4% were weaned from VV-ECMO support after a median of 19 (IQR 10-34) days. The median ICU length of stay was 31.9 (IQR 17.5-44.5) days. The duration of mechanical ventilation was 30 (IQR 19-49.5) days. The 180-day mortality rate was 41.5%. Univariate logistic regression analysis revealed that a higher BMI was associated with greater 180-day survival (OR 1.157 [1.038-1.291], p = 0.009). Younger age, female sex, less invasive ventilation time before ECMO, and fewer complications at the time of ECMO cannulation were associated with greater 180-day survival [OR 0.858 (0.774-0.953), p 0.004; OR 0.074 (0.008-0.650), p 0.019; OR 0.612 (0.401-0.933), p 0.022; OR 0.13 (0.03-0.740), p 0.022), respectively]. CONCLUSION: In this retrospective cohort of critical COVID-19 obese adult patients supported by VV-ECMO, a higher BMI, younger age, and female sex were associated with greater 180-day survival. A shorter invasive ventilation time before ECMO and fewer complications at ECMO cannulation were also associated with increased survival.

A Novel Model of Venovenous Extracorporeal Membrane Oxygenation in Rats with Femoral Cannulation and Insights into Hemodynamic Changes.

The application of venovenous (VV) extracorporeal membrane oxygenation (ECMO) has gained wide acceptance for the treatment of acute severe respiratory failure. Since no rat model of VV ECMO therapy with femoral drainage has yet been described, although this cannulation strategy is commonly used in humans, this study aimed to establish such a model. Twenty male Lewis rats were randomly assigned to receive a sham procedure or VV ECMO therapy. After the inhalative induction of anesthesia, animals were intubated and the vascular accesses were placed surgically. While venous drainage was achieved through a modified multi-orifice 18 G cannula that was placed in the inferior vena cava through the femoral vein over a guide wire with an ultra-flexible tip, the venous return was realized via a shortened 20 G cannula into the jugular vein. Hemodynamic data were obtained from a tail artery and left ventricular pressure-volume catheter. Repetitive blood gas analyses were carried out, and systemic inflammation was measured using an enzyme-linked immunosorbent assay. While animals in the ECMO group showed adequate oxygenation and decarboxylation, there was no evidence of recirculation. VV ECMO therapy increased stroke volume (SV), cardiac output (CO), and left ventricular end-diastolic volume (LVEDV). ECMO-induced inflammation was reflected in increased levels of tumor necrosis factor alpha. However, no differences in interleukins 6 and 10 were seen. This study describes a frequently used cannulation strategy in humans for a rat model of VV ECMO. Despite successful oxygenation and decarboxylation, the oxygenated blood may reduce pulmonary vascular resistance and lead to an increased LVEDV, which is associated with increased SV and CO. This model allows us to answer research questions about topics such as intestinal microcirculation in further studies.

Role of age as eligibility criterion for ECMO in patients with ARDS: meta-regression analysis.

BACKGROUND: Age as an eligibility criterion for V-V ECMO is widely debated and varies among healthcare institutions. We examined how age relates to mortality in patients undergoing V-V ECMO for ARDS. METHODS: Systematic review and meta-regression of clinical studies published between 2015 and June 2024. Studies involving at least 6 ARDS patients treated with V-V ECMO, with specific data on ICU and/or hospital mortality and patient age were included. The search strategy was executed in PubMed, limited to English-language. COVID-19 and non-COVID-19 populations were analyzed separately. Meta-regressions of mortality outcomes on age were performed using gender, BMI, SAPS II, APACHE II, Charlson comorbidity index or SOFA as covariates. RESULTS: In non-COVID ARDS, the meta-regression of 173 studies with 56,257 participants showed a significant positive association between mean age and ICU/hospital mortality. In COVID-19 ARDS, a significant relationship between mean age and ICU mortality, but not hospital mortality, was found in 103 studies with 21,255 participants. Sensitivity analyses confirmed these findings, highlighting a linear relationship between age and mortality in both groups. For each additional year of mean age, ICU mortality increased by 1.2% in non-COVID ARDS and 1.9% in COVID ARDS. CONCLUSIONS: The relationship between age and ICU mortality is linear and shows no inflection point. Consequently, no age cut-off can be recommended for determining patient eligibility for V-V ECMO.

A rare case of spontaneous hemoperitoneum in a bone marrow transplant recipient on VV-ECMO.

A 53-year-old man with acute myeloid leukemia received an allogeneic hematopoietic cell transplant (HCT) from a matched unrelated donor. One month after his transplantation, he developed ARDS requiring initiation of VV-ECMO. He suffered from pancytopenia, managed with frequent transfusions, granulocyte-colony stimulating factor (G-CSF) and weekly thrombopoietin receptor agonist. On ECMO day 17, the patient developed severe hypotension after insertion of a chest tube for a large right-sided pneumothorax. CT angiography of the abdomen showed hemoperitoneum. Exploratory laparotomy revealed approximately 4 L of blood and a ruptured splenic hilum. A splenectomy was performed. Unfortunately, the patient continued to require multiple daily blood products and his condition continued to decline despite two reoperations. His family chose to discontinue ECMO and he passed away peacefully. Spontaneous splenic rupture after GM-CSF has never been reported in patients on VV-ECMO. This manuscript reviews the literature regarding the pathophysiology and clinical manifestation of this rare occurrence.

A Deep Learning Framework for Predicting Patient Decannulation on Extracorporeal Membrane Oxygenation Devices: Development and Model Analysis Study.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a therapy for patients with refractory respiratory failure. The decision to decannulate someone from extracorporeal membrane oxygenation (ECMO) often involves weaning trials and clinical intuition. To date, there are limited prognostication metrics to guide clinical decision-making to determine which patients will be successfully weaned and decannulated. OBJECTIVE: This study aims to assist clinicians with the decision to decannulate a patient from ECMO, using Continuous Evaluation of VV-ECMO Outcomes (CEVVO), a deep learning-based model for predicting success of decannulation in patients supported on VV-ECMO. The running metric may be applied daily to categorize patients into high-risk and low-risk groups. Using these data, providers may consider initiating a weaning trial based on their expertise and CEVVO. METHODS: Data were collected from 118 patients supported with VV-ECMO at the Columbia University Irving Medical Center. Using a long short-term memory-based network, CEVVO is the first model capable of integrating discrete clinical information with continuous data collected from an ECMO device. A total of 12 sets of 5-fold cross validations were conducted to assess the performance, which was measured using the area under the receiver operating characteristic curve (AUROC) and average precision (AP). To translate the predicted values into a clinically useful metric, the model results were calibrated and stratified into risk groups, ranging from 0 (high risk) to 3 (low risk). To further investigate the performance edge of CEVVO, 2 synthetic data sets were generated using Gaussian process regression. The first data set preserved the long-term dependency of the patient data set, whereas the second did not. RESULTS: CEVVO demonstrated consistently superior classification performance compared with contemporary models (P<.001 and P=.04 compared with the next highest AUROC and AP). Although the model's patient-by-patient predictive power may be too low to be integrated into a clinical setting (AUROC 95% CI 0.6822-0.7055; AP 95% CI 0.8515-0.8682), the patient risk classification system displayed greater potential. When measured at 72 hours, the high-risk group had a successful decannulation rate of 58% (7/12), whereas the low-risk group had a successful decannulation rate of 92% (11/12; P=.04). When measured at 96 hours, the high- and low-risk groups had a successful decannulation rate of 54% (6/11) and 100% (9/9), respectively (P=.01). We hypothesized that the improved performance of CEVVO was owing to its ability to efficiently capture transient temporal patterns. Indeed, CEVVO exhibited improved performance on synthetic data with inherent temporal dependencies (P<.001) compared with logistic regression and a dense neural network. CONCLUSIONS: The ability to interpret and integrate large data sets is paramount for creating accurate models capable of assisting clinicians in risk stratifying patients supported on VV-ECMO. Our framework may guide future incorporation of CEVVO into more comprehensive intensive care monitoring systems.

New Insights into Hepatic and Intestinal Microcirculation and Pulmonary Inflammation in a Model of Septic Shock and Venovenous Extracorporeal Membrane Oxygenation in the Rat.

Treatment of critically ill patients with venovenous (V-V) extracorporeal membrane oxygenation (ECMO) has gained wide acceptance in the last few decades. However, the use of V-V ECMO in septic shock remains controversial. The effect of ECMO-induced inflammation on the microcirculation of the intestine, liver, and critically damaged lungs is unknown. Therefore, the aim of this study was to measure the hepatic and intestinal microcirculation and pulmonary inflammatory response in a model of V-V ECMO and septic shock in the rat. Twenty male Lewis rats were randomly assigned to receive V-V ECMO therapy or a sham procedure. Hemodynamic data were measured by a pressure-volume catheter in the left ventricle and a catheter in the lateral tail artery. Septic shock was induced by the intravenous infusion of lipopolysaccharide (1 mg/kg). During V-V ECMO therapy, rats received lung-protective ventilation. The hepatic and intestinal microcirculation was assessed by micro-lightguide spectrophotometry after median laparotomy for 2 h. Systemic and pulmonary inflammation was measured by enzyme-linked immunosorbent assays of plasma and bronchoalveolar lavage (BAL), respectively, which included tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-10, C-X-C motif ligand 2 (CXCL2), and CXCL5. Reduced oxygen saturation and relative hemoglobin concentration were measured in the hepatic and intestinal microcirculation during treatment with V-V ECMO. These animals also showed increased systolic, mean, and diastolic blood pressures. While no differences in left ventricular ejection fraction were observed, animals in the V-V ECMO group presented an increased heart rate, stroke volume, and cardiac output. Blood gas analysis showed dilutional anemia during V-V ECMO, whereas plasma analysis revealed a decreased concentration of IL-10 during V-V ECMO therapy, and BAL measurements showed increased concentrations of TNF-α, CXCL2, and CXCL5. Rats treated with V-V ECMO showed impaired microcirculation of the intestine and liver during septic shock despite increased blood pressure and cardiac output. Despite lung-protective ventilation, increased pulmonary inflammation was recognized during V-V ECMO therapy in septic shock.

Duration of Invasive Mechanical Ventilation before Veno-Venous ExtraCorporeal Membrane Oxygenation for Covid-19 related Acute Respiratory Distress Syndrome: The experience of a tertiary care center.

Background: Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO) is an efficient ventilatory support in patients with refractory Covid-19-related Acute Respiratory Distress Syndrome (ARDS), however the duration of invasive mechanical ventilation (IMV) before ECMO initiation as a contraindication is still controversial. The aim of this study was to investigate the impact of prolonged IMV prior to VV-ECMO in patients suffering from refractory Covid-19-related ARDS. Methods: This single-center retrospective study included all patients treated with VV-ECMO for refractory Covid-19-related ARDS between January 1, 2020 and May 31, 2022. The impact of IMV duration was investigated by comparing patients on VV-ECMO during the 7 days (and 10 days) following IMV with those assisted after 7 days (and 10 days). The primary endpoint was in-hospital mortality. Results: Sixty-four patients were hospitalized in the ICU for Covid-19-related refractory ARDS requiring VV-ECMO. Global in-hospital mortality was 55 %. Median duration of IMV was 4 [2; 8] days before VV-ECMO initiation. There was no significant difference in in-hospital mortality between patients assisted with IMV pre-VV-ECMO for a duration of ≤7 days (≤10 days) and those assisted after 7 days (and 10 days) ((p = 0.59 and p = 0.45). Conclusion: This study suggests that patients assisted with VV-ECMO after prolonged IMV had the same prognosis than those assisted earlier in refractory Covid-19-related ARDS. Therefore, prolonged mechanical ventilation of more than 7-10 days should not contraindicate VV-ECMO support. An individual approach is necessary to balance the risks and benefits of ECMO in this population.

The use of prone position ventilation in Danish patients with COVID-19-induced severe acute respiratory distress syndrome treated with veno-venous extracorporeal membrane oxygenation: A nationwide cohort study with focus on pulmonary effects.

BACKGROUND: Prone position ventilation (PPV) is recommended for patients with COVID-19 induced severe Adult Respiratory Distress Syndrome (ARDS) and is used for patients supported with V-V ECMO as well. The purpose of this study was to describe the use of PPV in these patients focusing on physiological effects with the hypothesis that PPV could reduce oxygen need and improve dynamic compliance. METHODS: This study was a nationwide retrospective analysis of all COVID-19 patients in Denmark from March 2020 - December 2021 with severe ARDS and need of V-V ECMO support. Data on the number of patients treated with PPV, number of PPV sessions, timing, the time spent in prone position, pulmonary physiological response types with analysis of variables affecting the response are reported. RESULTS: Out of 68 patients 44 were treated with 220 PPV sessions and a positive clinical response was observed in 80% of patients but only in 45% of sessions. On a single session level, increased compliance was observed in 38% and increased oxygenation in only 15% of 220 sessions, with within-patient heterogeneity. Higher dynamic compliance at the beginning of a PPV session was associated with a lower delta change in dynamic compliance during PPV. The response to a PPV session could not be predicted by the response in the prior session. Dynamic compliance did not change during the ECMO course. CONCLUSION: Eighty percent of patients responded positively during a PPV session, but this was not associated with overall pulmonary improvement. On a single patient level, responses were heterogenous and only 45% of sessions resulted in clinical improvement. Response in dynamic compliance was associated with starting values of compliance.

Arterial oxygen pressure during veno-venous extracorporeal membrane oxygenation may be increased by advancing the tip of the drainage cannula into the superior vena cava: a case report.

A simple and robust method for veno-venous extracorporeal membrane oxygenation (V-V ECMO) involves a drainage cannula into the inferior vena cava via the femoral vein (FV) and a reinfusion cannula into the right atrium (RA) via the internal jugular vein (IJV) (F-J configuration). However, with this method, the arterial oxygen (PaO2) is said to remain below 100 mmHg.Since recently, in our ICU, to prevent drainage failure, we apply a modification from the commonly practiced F-J configuration by advancing the tip of the drainage cannula inserted via the FV into the superior vena cava (SVC) and crossing the reinfusion cannula inserted via the IJV in the RA (F(SVC)-J(RA) configuration). We experienced that this modification can be associated with unexpectedly high PaO2 values, which here we investigated in detail.Veno-arteriovenous ECMO was induced in a 65-year-old male patient who suffered from repeated cardiac arrest due to acute respiratory distress syndrome. His chest X-ray images showed white-out after lung rest setting, consistent with near-absence of self-lung ventilation. Cardiac function recovered and the system was converted to F(SVC)-J(RA) configuration, after which both PaO2 and partial pressure of pulmonary arterial oxygen values remained high above 200 mmHg. Transesophageal echocardiography could not detect right-to-left shunt, and more efficient drainage of the native venous return flow compared to common F-J configuration may explain the increased PaO2.Although the F(SVC)-J(RA) configuration is a small modification of the F-J configuration, it seems to provide a revolutionary improvement in the ECMO field by combining robustness/simplicity with high PaO2 values.

Safety of Supraclavicular Approach for Dual-Lumen Catheter Placement in Veno-Venous Extracorporeal Membrane Oxygenation: A Case Report.

In veno-venous extracorporeal membrane oxygenation (V-V ECMO), the dual-lumen catheter (DLC) facilitates mobility, reduces recirculation, and mitigates the risk of infection. The right internal jugular vein (IJV) is the most common site for DLC insertion. Still, it is often unavailable for various reasons, including local infection, hematoma, or thrombus. A 64-year-old male patient with mantle lymphoma, which was in remission after autogenous blood transplantation, suffered lung damage and refractory pneumothorax from coronavirus disease 2019 (COVID-19) and required V-V ECMO treatment initiated on day 39. The patient was unable to be weaned off V-V ECMO due to uncontrolled high serum carbon dioxide (CO2) concentration and required long-term V-V ECMO treatment for more than 80 days. DLC placement was necessary to implement aggressive rehabilitation, reduce puncture site-induced infections, and reduce recirculation. On day 119, a supraclavicular approach was used for DLC placement under fluoroscopic guidance using ultrasound guidance because a thrombus in the right IJV prevented the DLC insertion at a usual puncture site. Rehabilitation was safely performed at a higher intensity than preoperatively of DLC insertion. Overall, the DLC catheter was maintained for more than 30 days until the patient died due to septic shock by an unknown focus on day 150, with no complications such as bleeding or infection. This case report highlights the significance of using the supraclavicular approach for DLC placement in V-V ECMO in cases where IJV is not possible due to thrombus presence. In conclusion, the supraclavicular approach is safe and feasible for V-V ECMO insertion as an alternative to the IJV.

A Case of COVID-19 Pneumonia Leading to Acute Respiratory Distress Syndrome (ARDS) and Multi-organ Failure Requiring Extracorporeal Membrane Oxygenation (ECMO) for Six Months and an Associated Critical Limb Ischemia.

This article presents the case of a 57-year-old woman with a history of rheumatoid arthritis who developed severe coronavirus disease 2019 (COVID-19) pneumonia that progressed to acute respiratory distress syndrome (ARDS) and multi-system organ failure. Despite initial slow progression and multiple hospital readmissions, her condition rapidly deteriorated, leading to full respiratory failure requiring intubation and ventilation. She was transferred to a specialized center where she underwent extracorporeal membrane oxygenation (ECMO) and hemodialysis for acute renal failure. Unfortunately, she remained dependent on ECMO for an extended period of six months. Although she made a gradual recovery, the prolonged critical care treatment resulted in critical ischemia of multiple extremities, necessitating a below-knee amputation (BKA) of her left lower extremity and transmetatarsal amputations of her right hand. This case reports one of the longest ECMO treatments for COVID-19 and associated comorbidities in the literature. Clinicians could include a longer duration of treatment and potential associated disabilities in the informed consent.

The impact of small movements with dual lumen cannulae during venovenous extracorporeal membrane oxygenation: A computational fluid dynamics analysis.

BACKGROUND AND OBJECTIVES: Venovenous Extracorporeal Membrane Oxygenation (VV ECMO) provides respiratory support to patients with severe lung disease failing conventional medical therapy. An essential component of the ECMO circuit are the cannulas, which drain and return blood into the body. Despite being anchored to the patient to prevent accidental removal, minor cannula movements are common during ECMO. The clinical and haemodynamic consequences of these small movements are currently unclear. This study investigated the risk of thrombosis and recirculation caused by small movements of a dual lumen cannula (DLC) in an adult using computational fluid dynamics. METHODS: The 3D model of an AVALON Elite DLC (27 Fr) and a patient-specific vena cava and right atrium were generated for an adult patient on ECMO. The baseline cannula position was generated where the return jet enters the tricuspid valve. Alternative cannula positions were obtained by shifting the cannula 5 and 15 mm towards inferior (IVC) and superior (SVC) vena cava, respectively. ECMO settings of 4 L/min blood flow and pulsatile flow at SVC and IVC were applied. Recirculation was defined as a scalar value indicating the infused oxygenated blood inside the drainage lumen, while thrombosis risk was evaluated by shear stress, stagnation volume, washout, and turbulent kinetic energy. RESULTS: Recirculation for all models was less than 3.1 %. DLC movements between -5 to 15 mm increased shear stress and turbulence kinetic energy up to 24.7 % and 11.8 %, respectively, compared to the baseline cannula position leading to a higher predicted thrombosis risk. All models obtained a complete washout after nine seconds except for when the cannula migrated 15 mm into the SVC, indicating persisting stasis and circulating zones. CONCLUSION: In conclusion, small DLC movements were not associated with an increased risk of recirculation. However, they may increase the risk of thrombosis due to increased shear rate, turbulence, and slower washout of blood. Developing effective cannula securement devices may reduce this risk.

The Recombinant Oncolytic Virus VV-GMCSF-Lact and Chemotherapy Drugs against Human Glioma.

Virotherapy is one of the perspective technologies in the treatment of malignant neoplasms. Previously, we have developed oncolytic vaccinia virus VV-GMCSF-Lact and its high cytotoxic activity and antitumor efficacy against glioma was shown. In this work, using immortalized and patient-derived cells with different sensitivity to VV-GMCSF-Lact, we evaluated the cytotoxic effect of chemotherapy agents. Additionally, we studied the combination of VV-GMCSF-Lact with temozolomide which is the most preferred drug for glioma treatment. Experimental results indicate that first adding temozolomide and then the virus to the cells is inherently more efficient than dosing it in the reverse order. Testing these regimens in the U87 MG xenograft glioblastoma model confirmed this effect, as assessed by tumor growth inhibition index and histological analysis. Moreover, VV-GMCSF-Lact as monotherapy is more effective against U87 MG glioblastoma xenografts comparing temozolomide.

Antibodies Induced by Smallpox Vaccination after at Least 45 Years Cross-React with and In Vitro Neutralize Mpox Virus: A Role for Polyclonal B Cell Activation?

AIMS: To evaluate whether antibodies specific for the vaccinia virus (VV) are still detectable after at least 45 years from immunization. To confirm that VV-specific antibodies are endowed with the capacity to neutralize Mpox virus (MPXV) in vitro. To test a possible role of polyclonal non-specific activation in the maintenance of immunologic memory. METHODS: Sera were collected from the following groups: smallpox-vaccinated individuals with or without latent tuberculosis infection (LTBI), unvaccinated donors, and convalescent individuals after MPXV infection. Supernatant of VV- or MPXV-infected Vero cells were inactivated and used as antigens in ELISA or in Western blot (WB) analyses. An MPXV plaque reduction neutralization test (PRNT) was optimized and performed on study samples. VV- and PPD-specific memory T cells were measured by flow cytometry. RESULTS: None of the smallpox unvaccinated donors tested positive in ELISA or WB analysis and their sera were unable to neutralize MPXV in vitro. Sera from all the individuals convalescing from an MPXV infection tested positive for anti-VV or MPXV IgG with high titers and showed MPXV in vitro neutralization capacity. Sera from most of the vaccinated individuals showed IgG anti-VV and anti-MPXV at high titers. WB analyses showed that positive sera from vaccinated or convalescent individuals recognized both VV and MPXV antigens. Higher VV-specific IgG titer and specific T cells were observed in LTBI individuals. CONCLUSIONS: ELISA and WB performed using supernatant of VV- or MPXV-infected cells are suitable to identify individuals vaccinated against smallpox at more than 45 years from immunization and individuals convalescing from a recent MPXV infection. ELISA and WB results show a good correlation with PRNT. Data confirm that a smallpox vaccination induces a long-lasting memory in terms of specific IgG and that antibodies raised against VV may neutralize MPXV in vitro. Finally, higher titers of VV-specific antibodies and higher frequency of VV-specific memory T cells in LTBI individuals suggest a role of polyclonal non-specific activation in the maintenance of immunologic memory.