-8 cm H2 O, the new paradigm in chest drain management following thoracoscopic lung resection?

BACKGROUND: Chest drain suction of -20 cm H2 O has been used universally after lung resection. After introducing new guidelines,-8 cm H2 O was used routinely for all non-pneumonectomy, thoracoscopic lung resections. We conducted a review to determine outcomes and safety. METHODS: After introduction of the guidelines data were collected in the study institutions' thoracic surgical database and subsequently analysed. RESULTS: A total of 155 patients underwent thoracoscopic lung resection. Mean patient age was 61.5 ± 13.6 years. Video-assisted thoracoscopic surgery was performed in 92.2% (144/155) of patients and robotically-assisted thoracoscopic surgery was performed in 7.8% (12/155) of patients. Lobectomy was performed in 56.8% (88/155) of patients, segmentectomy was performed in 11.6% (18/155) of patients and wedge resection was performed in 31.6% (49/155) of patients. Median ICC duration time was 1 day (IQR 1-3). Median length of stay was 3 days (IQR 2-6). For patients undergoing lobectomy median ICC time was 2 days (IQR 1-4.5) and median length of stay was 3.5 days (IQR 2-7), for segmentectomy median ICC time was 1 day (IQR 1-5) and median length of stay was 2 days (IQR 1-5) and for wedge resection median ICC time was 1 day (IQR 1-1) and median admission time was 2 days (IQR 1-4). CONCLUSION: A suction level -8 cm H2 O is safe to use for thoracoscopic lung resections from day 0 post-operatively. A dedicated, prospective study comparing levels of suction should be performed.

Long-term outcomes of pulmonary metastasectomy: a multicentre analysis.

BACKGROUND: Many extrapulmonary neoplasms metastasize to the lungs. We conducted a retrospective review of all patients who underwent pulmonary metastasectomy for oligometastatic disease at two centres in order to determine long-term outcomes. METHODS: The study institutions' thoracic surgery databases were searched for all patients who underwent pulmonary metastasectomy from 2000 to 2017. RESULTS: There were a total of 476 patients who underwent pulmonary metastasectomy. Mean age at time of surgery was 57.2 ± 15.9 years. Mean number of pulmonary lesions was 1.9 ± 1.6. Mean disease-free interval (DFI) was 3.6 ± 4.3 years. The most common primary neoplasms were colorectal cancer (CRC) in 35.1% (167/476), sarcoma in 23.9% (114/476), melanoma in 16.2% (77/478), renal cell carcinoma (RCC) in 7.3% (35/476) and germ cell tumour (GCT) in 4.4% (21/476). Hospital mortality was 0.4% (2/476). Mean follow-up time was 3.8 ± 2.9 years. Survival was 88.9% (95% confidence interval 85.77-91.5) at 1 year and 49.6% (95% confidence interval 44.4-54.6) at 5 years. On multivariate Cox-regression analysis GCT (P = 0.004), CRC (P = 0.03), DFI of 36+ months (P = 0.007), R0 resection (P = 0.002) and non-anatomical, sub-lobar (wedge) resection (P = 0.002) were protective against mortality. CONCLUSION: Pulmonary metastasectomy is associated with survival of 50% at 5-year follow-up. DFI of over 36 months, R0 resections, lesions resectable by wedge resection rather than anatomic resection and GCT and CRC primary cancers were associated with improved survival.

Perioperative Anesthetic and Transfusion Management of Veno-Venous Extracorporeal Membrane Oxygenation Patients Undergoing Noncardiac Surgery: A Case Series of 21 Procedures.

OBJECTIVES: To analyze the perioperative management of veno-venous extracorporeal membrane oxygenation (VV ECMO) in patients undergoing major noncardiac surgical procedures, which is poorly described in the literature. In doing so, perioperative challenges related to hemodynamic instability, impaired gas exchange, bleeding, and coagulopathy will be quantified. DESIGN: Retrospective, nonrandomized, observational study. SETTING: A single, university-affiliated, quaternary medical center. PARTICIPANTS: Fourteen patients who underwent 21 noncardiac surgical procedures during the period of January 1, 2014, through April 1, 2016. Approval for this study was obtained from the Duke University Medical Center Institutional Review Board (study Pro00072723). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty percent of subjects were alive at 1 year after ECMO cannulation. Anesthetic type was variable with an inhaled anesthetic utilized in 71.4% of events, a presurgical continuous sedative was continued in 81.0% of cases, fentanyl was utilized in 100% of encounters, and midazolam was utilized in 71.4% of encounters. Intraoperatively, 50% of encounters resulted in an oxygen desaturation with a peripheral oxygen saturation assessed by pulse oximetry (SpO2)<90%, and 15% of procedures resulted in a SpO2 <80%. A vasopressor, most commonly epinephrine, was used during 66.7% of procedures. Intraoperatively, blood was administered in 52.4% of procedures, fresh frozen plasma was administered in 23.8% of procedures, and platelets were administered in 28.6% of procedures. Hemoglobin levels remained stable throughout the perioperative period, averaging 9.5 g/dL preoperatively, 9.7 g/dL immediately postoperatively, and 9.5 g/dL 24 hours after surgery. CONCLUSIONS: VV ECMO patients can be anesthetized using either inhalational or intravenous anesthetics. Patient hemodynamics, oxygenation, and decarboxylation require frequent interventions, but can typically be optimized to meet clinically acceptable thresholds.

Homografts versus stentless bioprosthetic valves in the pulmonary position: a multicentre propensity-matched comparison in patients younger than 20 years.

OBJECTIVES: The aim of this study was to compare the performance of pulmonary homografts with stentless bioprosthetic valves [Medtronic Freestyle™ (Medtronic, Minneapolis, MN, USA)] in the pulmonary position in patients with congenital heart disease (CHD) younger than 20 years. METHODS: Between January 2000 and December 2017, 215 patients were retrospectively identified from hospital databases in 3 congenital heart centres in Australia. Valve performance was evaluated using standard criteria. Propensity score matching was used to balance the 2 treatment groups. RESULTS: Freedom from reintervention for patients who received a pulmonary homograft (n = 163) was 96%, 88% and 81% at 5, 10 and 15 years and for patients who received a Freestyle™ valve (n = 52) was 98%, 89% and 31% at 5, 10 and 15 years, respectively. Freedom from structural valve degeneration for patients with a homograft was 92%, 87% and 77% at 5, 10 and 15 years and for patients with a Freestyle valve was 96%, 80% and 14% at 5, 10 and 15 years, respectively. In the first 10 years, there was no difference in outcomes [reintervention hazard ratios (HR) = 0.69, 95% confidence intervals (CI) (0.20-2.42), P = 0.56; structural valve degeneration HR = 0.92 (0.34-2.51), P = 0.87]. After 10 years, the recipients of the Freestyle valves were at higher risk of both outcomes [reintervention HR = 7.89; 95% CI (2.79-22.34), P < 0.001; structural valve degeneration HR = 7.41 (2.77-19.84), P < 0.001]. The findings were similar when analysed by implantation in the orthotopic position and in the propensity-matched groups. CONCLUSIONS: The Freestyle stentless bioprosthetic valve is a comparable alternative to cryopreserved pulmonary homografts up to 10 years after implantation when implanted in an orthotopic pulmonary position in patients younger than 20 years with CHD.

An anti-apoptotic peptide improves survival in lethal total body irradiation.

Cell penetrating peptides (CPPs) have been used to deliver the anti-apoptotic Bcl-xL-derived BH4 peptide to prevent injury-induced apoptosis both in vitro and in vivo. Here we demonstrate that the nuclear localization sequence (NLS) from the SV40 large T antigen has favorable properties for BH4 domain delivery to lymphocytes compared to sequences based on the HIV-1 TAT sequence. While both TAT-BH4 and NLS-BH4 protected primary human mononuclear cells from radiation-induced apoptotic cell death, TAT-BH4 caused persistent membrane damage and even cell death at the highest concentrations tested (5-10 microM) and correlated with in vivo toxicity as intravenous administration of TAT-BH4 caused rapid death. The NLS-BH4 peptide has significantly attenuated toxicity compared to TAT-BH4 and we established a dosing regimen of NLS-BH4 that conferred a significant survival advantage in a post-exposure treatment model of LD90 total body irradiation.

Pneumonia after cecal ligation and puncture: a clinically relevant "two-hit" model of sepsis.

Sepsis continues to be the primary cause of death among patients in surgical intensive care units. In many cases, death does not result from the initial septic event but rather from subsequent nosocomial infection with pneumonia being the most common etiology. In addition, most deaths in patients with sepsis occur after the first 72 h. By contrast, in most animal models of sepsis, most deaths occur within the first 72 h. The purpose of this study was to develop a clinically relevant "two-hit" model of sepsis that would reflect delayed mortality because of secondary nosocomial infection. The well-accepted and widely used cecal ligation and puncture (CLP) model was used as the "first hit". Pseudomonas aeruginosa or Streptococcus pneumoniae was used to induce pneumonia in mice 72 h after CLP as a "second hit." In this study, mortality in mice undergoing CLP followed by pneumonia was significantly higher than in mice receiving pneumonia or CLP alone. S. pneumoniae pneumonia after CLP resulted in a 95% mortality compared with a 20% mortality for pneumonia alone, P < 0.0001. Similarly, mortality of P. aeruginosa pneumonia after CLP (85%) was significantly higher than P. aeruginosa alone (20%), P < 0.0001. Mice undergoing CLP followed by P. aeruginosa pneumonia also had significantly higher levels of B- and T-cell apoptotic death. Finally, mice undergoing CLP followed by P. aeruginosa or S. pneumoniae pneumonia had significantly decreased concentrations of proinflammatory mediators monocyte chemoattractant protein-1 and interleukin (IL)-6 compared with mice undergoing CLP or pneumonia alone. In conclusion, a primary sublethal infection impairs the immune system thus rendering the host more susceptible to secondary infection and death. Double injury, that is, CLP followed by pneumonia, provides a useful tool in the study of sepsis, creating a prolonged period of infection as opposed to CLP alone. The extended duration of infection may lead to a better understanding of the mechanism of the immune dysregulation seen in clinical sepsis and therefore provides for evaluation of potential therapies that target specific stages of the immune response.

Adoptive transfer of apoptotic splenocytes worsens survival, whereas adoptive transfer of necrotic splenocytes improves survival in sepsis.

In sepsis, both necrotic and apoptotic cell death can occur. Apoptotic cells induce anergy that could impair the host response, whereas necrotic cells cause immune activation that might result in enhanced antimicrobial defenses. We determined whether adoptive transfer of apoptotic or necrotic cells impacted survival in a clinically relevant sepsis model. We also evaluated the effects of adoptive transfer of apoptotic or necrotic cells on the prototypical TH1 and TH2 cytokines IFN-gamma and IL-4, respectively. C57BL6/J mice had adoptive transfer of apoptotic (irradiated) or necrotic (freeze thaw) splenocytes. Controls received saline. Apoptotic cells greatly increased mortality, whereas necrotic splenocytes markedly improved survival, P < or = 0.05. The contrasting effects that apoptotic or necrotic cells exerted on survival were mirrored by opposite effects on splenocyte IFN-gamma production with greatly decreased and increased production, respectively. Importantly, either administration of anti-IFN-gamma antibodies or use of IFN-gamma knockout mice prevented the survival benefit occurring with necrotic cells. This study demonstrates that the type of cell death impacts survival in a clinically relevant model and identifies a mechanism for the immune suppression that is a hallmark of sepsis. Necrotic cells (and likely apoptotic cells) exert their effects via modulation of IFN-gamma