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591 result(s) for "Schreiber, Martin A."
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Rationale for the clinical use of adipose-derived mesenchymal stem cells for COVID-19 patients
In late 2019, a novel coronavirus (SARS-CoV-2) emerged in Wuhan, capital city of Hubei province in China. Cases of SARS-CoV-2 infection quickly grew by several thousand per day. Less than 100 days later, the World Health Organization declared that the rapidly spreading viral outbreak had become a global pandemic. Coronavirus disease 2019 (COVID-19) is typically associated with fever and respiratory symptoms. It often progresses to severe respiratory distress and multi-organ failure which carry a high mortality rate. Older patients or those with medical comorbidities are at greater risk for severe disease. Inflammation, pulmonary edema and an over-reactive immune response can lead to hypoxia, respiratory distress and lung damage. Mesenchymal stromal/stem cells (MSCs) possess potent and broad-ranging immunomodulatory activities. Multiple in vivo studies in animal models and ex vivo human lung models have demonstrated the MSC’s impressive capacity to inhibit lung damage, reduce inflammation, dampen immune responses and aid with alveolar fluid clearance. Additionally, MSCs produce molecules that are antimicrobial and reduce pain. Upon administration by the intravenous route, the cells travel directly to the lungs where the majority are sequestered, a great benefit for the treatment of pulmonary disease. The in vivo safety of local and intravenous administration of MSCs has been demonstrated in multiple human clinical trials, including studies of acute respiratory distress syndrome (ARDS). Recently, the application of MSCs in the context of ongoing COVID-19 disease and other viral respiratory illnesses has demonstrated reduced patient mortality and, in some cases, improved long-term pulmonary function. Adipose-derived stem cells (ASC), an abundant type of MSC, are proposed as a therapeutic option for the treatment of COVID-19 in order to reduce morbidity and mortality. Additionally, when proven to be safe and effective, ASC treatments may reduce the demand on critical hospital resources. The ongoing COVID-19 outbreak has resulted in significant healthcare and socioeconomic burdens across the globe. There is a desperate need for safe and effective treatments. Cellular based therapies hold great promise for the treatment of COVID-19. This literature summary reviews the scientific rationale and need for clinical studies of adipose-derived stem cells and other types of mesenchymal stem cells in the treatment of patients who suffer with COVID-19.
A high ratio of plasma and platelets to packed red blood cells in the first 6 hours of massive transfusion improves outcomes in a large multicenter study
In trauma, most hemorrhagic deaths occur within the first 6 hours. This study examined the effect on survival of high ratios of fresh frozen plasma (FFP) and platelets (PLTs) to packed red blood cells (PRBCs) in the first 6 hours. Records of 466 massive transfusion trauma patients (≥10 U of PRBCs in 24 hours) at 16 level 1 trauma centers were reviewed. Transfusion ratios in the first 6 hours were correlated with outcome. All groups had similar baseline characteristics. Higher 6-hour ratios of FFP:PRBCs and PLTs:PRBCs lead to improved 6-hour mortality (from 37.3 [in the lowest ratio group] to 15.7 [in the middle ratio group] to 2.0% [in the highest ratio group] and 22.8% to 19.0% to 3.2%, respectively) and in-hospital mortality (from 54.9 to 41.1 to 25.5% and 43.7% to 46.8% to 27.4%, respectively). Initial higher ratios of FFP:PRBCs and PLTs:PRBCs decreased overall PRBC transfusion. The early administration of high ratios of FFP and platelets improves survival and decreases overall PRBC need in massively transfused patients. The largest difference in mortality occurs during the first 6 hours after admission, suggesting that the early administration of FFP and platelets is critical.
Traumatic diaphragmatic injury in the American College of Surgeons National Trauma Data Bank: a new examination of a rare diagnosis
Traumatic diaphragmatic injury (TDI) is a rarely diagnosed injury in trauma. Previous studies have been limited in their evaluation of TDI because of small population size and center bias. Although injuries may be suspected based on penetrating mechanism, blunt injuries may be particularly difficult to detect. The American College of Surgeons National Trauma Data Bank is the largest trauma database in the United States. We hypothesized that we could identify specific injury patterns associated with blunt and penetrating TDIs. We examined demographics, diagnoses, mechanism of injury, and outcomes for patients with TDI in 2012 as this is the largest and most recent dataset available. Comparisons were made using chi-square or independent samples t test. There were a total of 833,309 encounters in the National Trauma Data Bank in 2012. Three thousand eight hundred seventy-three patients had a TDI (.46%). Of those, 1,240 (33%) patients had a blunt mechanism and 2,543 (67%) had a penetrating mechanism. Patients with blunt TDI were older (44 ± 19 vs 31 ± 13 years, P < .001), had a higher injury severity score (33 ± 14 vs 24 ± 15, P < .001), and a higher mortality rate (19.8% vs 8.8%, P < .001). Compared with patients with penetrating injuries, those with blunt TDI were more likely to have injuries to the thoracic aorta (2.9% vs .5%, P < .001), lung (48.7% vs 28.1, P < .001), bladder (5.9% vs .7%, P < .001), and spleen (44.8% vs 29.1%, P < .001). Penetrating TDI was associated with liver and hollow viscus injuries. Diaphragmatic injury is an uncommon but significant diagnosis in trauma patients. Blunt injuries may be more likely to be occult; however, a pattern of associated injuries to the aorta, lung, spleen, and bladder should prompt further workup for TDI.
Coagulopathy: Its Pathophysiology and Treatment in the Injured Patient
Hemorrhage continues to be one of the leading causes of death following trauma. Trauma patients are susceptible to the early development of coagulopathy and the most severely injured patients are coagulopathic on hospital admission. Hypothermia, acidosis, and dilution from standard resuscitation can worsen the presenting coagulopathy and perpetuate bleeding. Early identification of coagulopathy is dependent on clinical awareness and point of care laboratory values. Routinely used laboratory coagulation parameters fail to adequately describe this state. Thrombelastography is a test that can be done at the bedside and uses whole blood to provide a functional evaluation of coagulation. Rapid diagnosis of coagulopathy, followed by prevention or correction of hypothermia and acidosis should be a priority during the initial evaluation and resuscitation. Judicious use of resuscitation fluids and early replacement of coagulation factors will help prevent iatrogenic hemodilution. This review covers the pathophysiology as well as the clinical and laboratory diagnosis of coagulopathy. Prevention and treatment strategies are discussed, including early transfusion of coagulation factors during massive transfusion and the use of recombinant factor VIIa. Damage control resuscitation is briefly discussed, and it involves the combination of hypotensive resuscitation and hemostatic resuscitation. Finally, a description of the use of fresh whole blood in the military setting is included. Its use has been proven to be safe and beneficial in this setting and warrants further investigation as an adjunct to the management of civilian trauma patients.
Detection of neutralizing antibodies against multiple SARS-CoV-2 strains in dried blood spots using cell-free PCR
An easily implementable serological assay to accurately detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies is urgently needed to better track herd immunity, vaccine efficacy and vaccination rates. Herein, we report the Split-Oligonucleotide Neighboring Inhibition Assay (SONIA) which uses real-time qPCR to measure the ability of neutralizing antibodies to block binding between DNA-barcoded viral spike protein subunit 1 and the human angiotensin-converting enzyme 2 receptor protein. The SONIA neutralizing antibody assay using finger-prick dried blood spots displays 91–97% sensitivity and 100% specificity in comparison to the live-virus neutralization assays using matched serum specimens for multiple SARS-CoV-2 variants-of-concern. The multiplex version of this neutralizing antibody assay, using easily collectable finger-prick dried blood spots, can be a valuable tool to help reveal the impact of age, pre-existing health conditions, waning immunity, different vaccination schemes and the emergence of new variants-of-concern. Neutralizing antibodies are critical for conferring immunity against SARS-CoV-2. Here, Dahn et al. report a PCR assay termed SONIA (Split-Oligonucleotide Neighboring Inhibition Assay) for measuring neutralizing antibodies against multiple SARS-CoV-2 strains in fingerprick dried blood spot samples.
Management and outcome of pneumatosis intestinalis
Pneumatosis intestinalis (PI), infiltration of gas into the bowel wall, has traditionally been associated with immediate operative intervention and a high mortality rate. We retrospectively reviewed the diagnosis and management of pneumatosis in an attempt to characterize the disease, and examined management strategies. Ninety-seven patients had a computed tomography (CT) diagnosis of pneumatosis. The location of pneumatosis was as follows: 46% colon, 27% small bowel, 5% stomach, and 7% both small and large bowel. Fourteen patients also had portal venous gas and 6 (43%) of these patients died. Management strategy was non-operative in 52%, operative in 33%, and futile care in 15%. The overall mortality rate was 22% (16% operative, 6% non-operative, and 87% futile). Patients who died had a higher mean APACHE II score (25 vs 11, P <.001). Approximately 50% of patients with pneumatosis can be successfully managed non-operatively. The combination of PI and portal venous gas may confer a higher mortality rate.
Thrombelastography-identified coagulopathy is associated with increased morbidity and mortality after traumatic brain injury
The purpose of this study was to determine the relationship between coagulopathy and outcome after traumatic brain injury. Patients admitted with a traumatic brain injury were enrolled prospectively and admission blood samples were obtained for kaolin-activated thrombelastogram and standard coagulation assays. Demographic and clinical data were obtained for analysis. Sixty-nine patients were included in the analysis. A total of 8.7% of subjects showed hypocoagulability based on a prolonged time to clot formation (R time, > 9 min). The mortality rate was significantly higher in subjects with a prolonged R time at admission (50.0% vs 11.7%). Patients with a prolonged R time also had significantly fewer intensive care unit–free days (8 vs 27 d), hospital-free days (5 vs 24 d), and increased incidence of neurosurgical intervention (83.3% vs 34.9%). Hypocoagulability as shown by thrombelastography after traumatic brain injury is associated with worse outcomes and an increased incidence of neurosurgical intervention.
Circulation first – the time has come to question the sequencing of care in the ABCs of trauma; an American Association for the Surgery of Trauma multicenter trial
Background The traditional sequence of trauma care: Airway, Breathing, Circulation (ABC) has been practiced for many years. It became the standard of care despite the lack of scientific evidence. We hypothesized that patients in hypovolemic shock would have comparable outcomes with initiation of bleeding treatment (transfusion) prior to intubation (CAB), compared to those patients treated with the traditional ABC sequence. Methods This study was sponsored by the American Association for the Surgery of Trauma multicenter trials committee. We performed a retrospective analysis of all patients that presented to trauma centers with presumptive hypovolemic shock indicated by pre-hospital or emergency department hypotension and need for intubation from January 1, 2014 to July 1, 2016. Data collected included demographics, timing of intubation, vital signs before and after intubation, timing of the blood transfusion initiation related to intubation, and outcomes. Results From 440 patients that met inclusion criteria, 245 (55.7%) received intravenous blood product resuscitation first (CAB), and 195 (44.3%) were intubated before any resuscitation was started (ABC). There was no difference in ISS, mechanism, or comorbidities. Those intubated prior to receiving transfusion had a lower GCS than those with transfusion initiation prior to intubation (ABC: 4, CAB:9, p  = 0.005). Although mortality was high in both groups, there was no statistically significant difference (CAB 47% and ABC 50%). In multivariate analysis, initial SBP and initial GCS were the only independent predictors of death. Conclusion The current study highlights that many trauma centers are already initiating circulation first prior to intubation when treating hypovolemic shock (CAB), even in patients with a low GCS. This practice was not associated with an increased mortality. Further prospective investigation is warranted. Trial registration IRB approval number: HM20006627. Retrospective trial not registered.
Achieving Hemostasis With Topical Hemostats: Making Clinically and Economically Appropriate Decisions in the Surgical and Trauma Settings
Achieving hemostasis is a crucial focus of clinicians working in surgical and trauma settings. Topical hemostatic agents—including mechanical hemostats, active hemostats, flowable hemostats, and fibrin sealants—are frequently used in efforts to control bleeding, and new options such as hemostatic dressings, initially used in combat situations, are increasingly being used in civilian settings. To achieve successful hemostasis, a number of vital factors must be considered by surgeons and perioperative nurses, such as the size of the wound; bleeding severity; and the efficacy, possible adverse effects, and method of application of potential hemostatic agents. Understanding how and when to use each of the available hemostatic agents can greatly affect clinical outcomes and help to limit the overall cost of treatment.
Chitosan based advanced hemostatic dressing is associated with decreased blood loss in a swine uncontrolled hemorrhage model
The purpose of this study was to compare standard gauze (SG) and advanced hemostatic dressings in use by military personnel in a no-hold model. A randomized, controlled trial was conducted using 36 swine. Animals underwent femoral arteriotomy, followed by 60 seconds of uncontrolled hemorrhage. After hemorrhage, packing with 1 of 3 dressings—SG, Combat Gauze (CG), or Celox Rapid gauze (XG)—and a 500-mL bolus of Hextend were initiated. Pressure was not held after packing, and animals were followed for 120 minutes. Physiologic parameters were monitored continuously, and electrolyte and hematologic laboratory assessments were performed before injury and 30 and 120 minutes after injury. Dressing failure was determined if bleeding occurred outside the wound. All animals survived to study end. Baseline characteristics were similar between groups. No statistical difference was seen in initial blood loss or dressing success rate (SG, 10 of 12; CG, 10 of 12; and XG, 12 of 12). Secondary blood loss was significantly less with XG (median, 12.8 mL; interquartile range, 8.8 to 39.7 mL) compared with SG (median, 44.7 mL; interquartile range, 17.8 to 85.3 mL; P = .02) and CG (median, 31.9 mL; interquartile range, 18.6 to 69.1 mL; P = .05). Packing time was significantly shorter with XG (mean, 37.1 ± 6.2 seconds) compared with SG (mean, 45.2 ± 6.0 seconds; P < .01) and CG (mean, 43.5 ± 5.6 seconds; P = .01). XG demonstrated shorter application time and decreased secondary blood loss in comparison with both SG and CG. These differences may be of potential benefit in a care-under-fire scenario.