Studies in Asia have questioned the dictum that signet ring cell carcinoma (SRC) has a worse prognosis than other forms of gastric cancer. Our study determined differences in presentation and ...outcomes between SRC and gastric adenocarcinoma (AC) in the United States.
The National Cancer Institute Surveillance, Epidemiology, and End Results database was reviewed for SRC and AC from 2004 to 2007.
We reviewed 10,246 cases of patients with gastric cancer, including 2,666 of SRC and 7,580 of AC. SRC presented in younger patients (61.9 v 68.7 years; P < .001) and less often in men (52.7% v 68.7%; P < .001). SRC patients were more frequently black (11.3% v 10.9%), Asian (16.4% v 13.2%), American Indian/Alaska Native (0.9% v 0.8%), or Hispanic (23.3% v 14.0%; P < .001). SRC was more likely to be stage T3-4 (45.8% v 33.3%), have lymph node spread (59.7% v 51.8%), and distant metastases (40.2% v 37.6%; P < .001). SRC was more likely to be found in the lower (30.7% v 24.2%) and middle stomach (30.6% v 20.7%; P < .001). Median survival was not different between the two (AC, 14.0 months v SRC, 13.0 months; P = .073). Multivariable analyses demonstrated SRC was not associated with mortality (hazard ratio HR, 1.05; 95% CI, 0.96 to 1.11; P = .150). Mortality was associated with age (HR, 1.01; 95% CI, 1.01 to 1.02; P < .001), black race (HR, 1.10; 95% CI, 1.01 to 1.20; P = .026), and tumor grade. Variables associated with lower mortality risk included Asian race (HR, 0.83; 95% CI, 0.77 to 0.91; P < .001) and surgery (HR, 0.37; 95% CI, 0.34 to 0.39; P < .001).
In the United States, SRC significantly differs from AC in extent of disease at presentation. However, when adjusted for stage, SRC does not portend a worse prognosis.
Background Thrombosis of the HeartMate II (HM2 Thoratec Corporation, Pleasanton, CA) is a potentially devastating complication. While attention has been focused on anticoagulation strategies to ...prevent this complication, the impact of surgical technique has not been assessed. Methods Patients undergoing HM2 implantation at two institutions were reviewed. Pump thrombosis (PT) was defined as a clinical syndrome that included more than 30% elevation in pump power, more than 30% elevation in lactate dehydrogenase, and greater than 20% decrease in hemoglobin with the presence of thrombus in the HM2 stator or rotor, or both, at explant or autopsy. A blinded clinician reviewed dimensions and angles of the HM2 obtained from chest x-ray films. Patients demonstrating PT were compared with patients having normal function. Results Of the 49 patients reviewed, 11 (22.4%) displayed evidence of PT at a median of 42 days after HM2 implantation. Patient with PT had greater acute angulation of the HM2 inflow cannula immediately postoperatively (48.2 ± 6.8 versus 65.4 ± 9.2 degrees, p < 0.001) and after 30 days (50.1 ± 8.0 versus 65.1 ± 9.9 degrees, p < 0.001). Pump pocket depth was lower in the PT group immediately after HM2 implantation (107.0 ± 41.9 versus 144.3 ± 20.3 cm, p < 0.001) and after 30 days (86.0 ± 39.1 versus 113.1 ± 25.4 cm, p = 0.02). Patients with evidence of PT did not have a decrease in end-diastolic diameter (76 ± 9 versus 70 ± 15 mm, p = 0.24) whereas patients in the normal function group had effective remodeling of the left ventricle (70 ± 10 versus 56 ± 12 mm, p = 0.01). Conclusions Meticulous surgical technique, which necessitates creating an adequately sized pump pocket and appropriately directing the inflow cannula at the time of operation, may reduce the risk of PT.
The endothelial glycocalyx (EGX) contributes to the permeability barrier of vessels and regulates the coagulation cascade. EGX damage, which occurs in numerous disease states, including sepsis and ...trauma, results in endotheliopathy. While influenza and other viral infections are known to cause endothelial dysfunction, their effect on the EGX has not been described. We hypothesized that the H1N1 influenza virus would cause EGX degradation. Human umbilical vein endothelial cells (HUVECs) were exposed to varying multiplicities of infection (MOI) of the H1N1 strain of influenza virus for 24 hours. A dose-dependent effect was examined by using an MOI of 5 (n = 541), 15 (n = 714), 30 (n = 596), and 60 (n = 653) and compared to a control (n = 607). Cells were fixed and stained with FITC-labelled wheat germ agglutinin to quantify EGX. There was no difference in EGX intensity after exposure to H1N1 at an MOI of 5 compared to control (6.20 vs. 6.56 Arbitrary Units (AU), p = 0.50). EGX intensity was decreased at an MOI of 15 compared to control (5.36 vs. 6.56 AU, p<0.001). The degree of EGX degradation was worse at higher doses of the H1N1 virus; however, the decrease in EGX intensity was maximized at an MOI of 30. Injury at MOI of 60 was not worse than MOI of 30. (4.17 vs. 4.47 AU, p = 0.13). The H1N1 virus induces endothelial dysfunction by causing EGX degradation in a dose-dependent fashion. Further studies are needed to characterize the role of this EGX damage in causing clinically significant lung injury during acute viral infection.
The goal of this study was to determine if IL-22:Fc would Acute Respiratory Distress Syndrome (ARDS).
No therapies exist for ARDS and treatment is purely supportive. Interleukin-22 (IL-22) plays an ...integral component in recovery of the lung from infection. IL-22:Fc is a recombinant protein with a human FC immunoglobulin that increases the half-life of IL-22.
ARDS was induced in C57BL/6 mice with intra-tracheal lipopolysaccharide (LPS) at a dose of 33.3 or 100 ug. In the low-dose LPS group (LDG), IL-22:FC was administered via tail vein injection at 30 minutes (n = 9) and compared to sham (n = 9). In the high-dose LPS group (HDG), IL-22:FC was administered (n = 11) then compared to sham (n = 8). Euthanasia occurred after bronchioalveolar lavage (BAL) on post-injury day 4.
In the LDG, IL-22:FC resulted in decreased protein leak (0.15 vs. 0.25 ug/uL, p = 0.02). BAL protein in animals receiving IL-22:Fc in the HDG was not different. For the HDG, animals receiving IL-22:Fc had lower BAL cell counts (539,636 vs 3,147,556 cells/uL, p = 0.02). For the HDG, IL-6 (110.6 vs. 527.1 pg/mL, p = 0.04), TNF-α (5.87 vs. 25.41 pg/mL, p = 0.04), and G-CSF (95.14 vs. 659.6, p = 0.01) levels were lower in the BAL fluid of IL-22:Fc treated animals compared to sham.
IL-22:Fc decreases lung inflammation and lung capillary leak in ARDS. IL-22:Fc may be a novel therapy for ARDS.
Hemorrhagic shock has recently been shown to cause shedding of a carbohydrate surface layer of endothelial cells known as the glycocalyx. This shedding of the glycocalyx is thought to be a mediator ...of the coagulopathy seen in trauma patients. Clinical studies have demonstrated increases in shed glycocalyx in the blood after trauma, and animal studies have measured glycocalyx disruption in blood vessels in the lung, skeletal muscle, and mesentery. However, no study has measured glycocalyx disruption across a wide range of vascular beds to quantify the primary locations of this shedding.
In the present study, we used a rat model of hemorrhagic shock and resuscitation to more comprehensively assess glycocalyx disruption across a range of organs. Glycocalyx disruption was assessed by fluorescent-labeled wheat germ agglutinin or syndecan-1 antibody staining in flash frozen tissue.
We found that our model did elicit glycocalyx shedding, as assessed by an increase in plasma syndecan-1 levels. In tissue sections, we found that the greatest glycocalyx disruption occurred in vessels in the lung and intestine. Shedding to a lesser extent was observed in vessels of the brain, heart, and skeletal muscle. Liver vessel glycocalyx was unaffected, and kidney vessels, including the glomerular capillaries, displayed an increase in glycocalyx. We also measured reactive oxygen species (ROS) in the endothelial cells from these organs, and found that the greatest increase in ROS occurred in the two beds with the greatest glycocalyx shedding, the lungs, and intestine. We also detected fibrin deposition in lung vessels following hemorrhage-resuscitation.
We conclude that the endothelium in the lungs and intestine are particularly susceptible to the oxidative stress of hemorrhage-resuscitation, as well as the resulting glycocalyx disruption. Thus, these two vessel beds may be important drivers of coagulopathy in trauma patients.
Background International Society of Heart and Lung Transplantation guidelines for adult heart transplantation (HT) suggest a donor to recipient body weight ratio (WR) of greater than 0.8. For female ...to male transplants, a WR of greater than 0.9 is recommended. Methods The United Network for Organ Sharing database was examined for adult HT from 1999 to 2011. Controls with a WR of 0.9 or greater (normal donor to recipient weight ratio) were compared with patients with a WR of 0.6 to 0.89 (WRL) and a WR of less than 0.59 (WRVL). The primary measured outcome was survival. Results Of the 21,928 patients undergoing HT, 14,592 (66.6%) were performed with a normal donor to recipient weight ratio, 7212 (32.9%) were performed with WRL, and 124 (0.6%) were performed with WRVL. In male donor to male recipient, male donor to female recipient, and female donor to female recipient HT, the use of WRL did not influence median survival ( P = .3621) and was not associated with increased mortality ( P = .7273). In female donor to male recipient HT, WRL was associated with decreased median survival (435 days, P = .0241) and was associated with increased mortality (hazard ratio, 1.201; P = .0383). Conclusions HT can be safely performed using WRL donors between sex-matched and male to female transplants. However, in female to male transplants, WRL donors are associated with decreased survival. Although clinical circumstances will guide decision making, consensus criteria may be revisited to liberalize the pool of acceptable donors in an era of unprecedented donor shortage.
Background
We aimed to systematically review the clinical and laboratory features of patients with the multisystem inflammatory syndrome in pediatrics diagnosed during the COVID-19 pandemic.
Data ...sources
A literature search in Web of Science, PubMed, Scopus, and Science Direct was made up to June 29, 2020.
Results
Analysis of 15 articles (318 COVID-19 patients) revealed that although many patients presented with the typical multisystem inflammatory syndrome in pediatrics, Kawasaki-like features as fever (82.4%), polymorphous maculopapular exanthema (63.7%), oral mucosal changes (58.1%), conjunctival injections (56.0%), edematous extremities (40.7%), and cervical lymphadenopathy (28.5%), atypical gastrointestinal (79.4%) and neurocognitive symptoms (31.8%) were also common. They had elevated serum lactic acid dehydrogenase, D-dimer, C-reactive protein, procalcitonin, interleukin-6, troponin I levels, and lymphopenia. Nearly 77.0% developed hypotension, and 68.1% went into shock, while 41.1% had acute kidney injury. Intensive care was needed in 73.7% of cases; 13.2% were intubated, and 37.9% required mechanical ventilation. Intravenous immunoglobulins and steroids were given in 87.7% and 56.9% of the patients, respectively, and anticoagulants were utilized in 67.0%. Pediatric patients were discharged after a hospital stay of 6.77 days on average (95% CI 4.93–8.6).
Conclusions
Recognizing the typical and atypical presentation of the multisystem inflammatory syndrome in pediatric COVID-19 patients has important implications in identifying children at risk. Monitoring cardiac and renal decompensation and early interventions in patients with multisystem inflammatory syndrome is critical to prevent further morbidity.
Objective Bridge to transplantation patients with continuous flow left ventricular assist devices (cfLVADs) are assigned United Network for Organ Sharing status 1A or 1B priority while awaiting ...orthotopic heart transplantation. We investigated the influence of cfLVAD on the waitlist times and organ allocation. Methods The United Network for Organ Sharing database was examined from 2005 to 2012 for patients with cfLVAD and pulsatile flow LVAD (pLVAD). These 2 cohorts were compared with patients who did not receive LVAD. Results Of 16,476 total orthotopic heart transplantations, 3270 (19.8%) were performed on patients with an LVAD as a bridge to transplantation. The cfLVAD group had the longest total waitlist time (259.6 days) compared with the pLVAD (134.6 days) and non-LVAD (121.7 days) groups ( P < .001). The cfLVAD group spent more time in status 1A (44.7 days) than did the pLVAD (32.1 days) and non-LVAD (16.4 days) cohorts ( P < .001). The median waitlist survival was better for the cfLVAD group (1234.0 days) than in the pLVAD (441.0 days) and non-LVAD (471.0 days) groups ( P < .001). The cfLVAD recipients were older, had a greater body mass index, and more often had diabetes than did pLVAD and non-LVAD patients. The cfLVAD cohort received hearts from older, more often male donors, with a greater body mass index. Post-transplant survival was not significantly different among the 3 groups on Kaplan-Meier analysis ( P = .12). Conclusions Despite being older, less favorable recipients, the cfLVAD patients spent more time in status 1A and had greater waitlist survival. This might allow cfLVAD patients to receive preferred donor hearts, which might allow for better post-transplant survival.
Background This study was performed to evaluate the effect of socioeconomic status (SES) on outcomes after cholecystectomy. Study Design The National Inpatient Sample (NIS) database (2005-2011) was ...queried for patients undergoing cholecystectomy. Clinically relevant variables were used to examine clinical characteristics, postoperative complications, and mortality. SES was investigated by examining income quartile. Results Over 2 million patients underwent cholecystectomy during this period. They were divided into quartiles by SES. The lowest cohort was younger (50 years, p<0.001) and had the lowest Charlson Comorbidity Index (2.08, p<0.001). This cohort was more likely African American (15.8%, p < 0.001) and more likely to have Medicaid (19.2%, p<0.001). Using split-sample validation and multivariate analysis, lower SES, Charlson comorbidity Index and Medicaid recipients were associated with increased mortality. Conclusions Patients with Medicaid and lower SES had poorer outcomes after cholecystectomy.
Background Lung transplantation using grafts from donors with a history of heavy smoking (>20 pack-years) is thought to confer worse prognosis. We attempt to determine if adult, double-lung ...transplantation can be safely performed with lungs from heavy-smoking donors (HSD). Methods The United Network for Organ Sharing (UNOS) database was examined for adult, double-lung transplants from 2005 to 2011. Results Of 5,900 double-lung transplants, 766 (13.0%) were from HSDs. The two groups were similar in recipient age (49.8 vs 50.5 years, p = 0.15), male sex (56.9% vs 56.5%, p = 0.87), and lung allocation score (45.8 vs 44.9, p = 0.18). Recipients of lungs from HSDs had lower forced expiratory volume in 1 second (FEV1 ; 34.3 vs 36.1% predicted, p = 0.04), longer ischemic time (5.75 vs 5.58 hours, p = 0.01), less human leukocyte antigen mismatch (4.51 vs 4.62, p = 0.01), and lower class I plasma reactive antigens (2.64 vs 3.69%, p = 0.001). HSDs were older (40.9 vs 32.6 years, p < 0.001) and less likely male (51.7 vs 59.7%, p < 0.001). Recipients of lungs from HSDs had longer median length of stay (18.0 vs 17.0 days, p < 0.001). Freedom from bronchiolitis obliterans syndrome ( p = 0.09), decrement in FEV1 ( p = 0.12), peak FEV1 (79.8% vs 79.0%, p = 0.51), and median survival (2,043 vs 1,928 days, p = 0.69) were not different. On multivariate analysis, HSD lungs were not associated with death (hazard ratio, 1.003; 95% confidence interval, 0.867 to 1.161, p = 0.96). Death was associated with donor age, ischemic time, race mismatch, mechanical ventilation, and extracorporeal membranous oxygenation before transplantation. Conclusions Double-lung transplantation can be safely performed with lungs from donors with a heavy smoking history.
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