Compassionate use of convalescent plasma for treatment of moderate and severe pneumonia in COVID-19 patients and association with IgG antibody levels in donated plasma.

BACKGROUND: We assessed outcome of patients with moderate and severe COVID-19 following treatment with convalescent plasma (CP) and the association with IgG levels in transfused CP. METHODS: A prospective cohort study. Primary outcome was improvement at day 14 defined as alive, not on mechanical ventilation, and moderate, mild, or recovered from COVID-19. Antibody levels in CP units were unknown at the time of treatment. IgG against the spike protein S1 was subsequently measured by ELISA. Neutralizing antibodies titers were determined in a subset. Outcome was assessed in relation to the mean antibody level transfused to the patients (≤4.0 versus >4.0). FINDINGS: Of 49 patients, 11 (22.4%) had moderate, 38 (77.6%) had severe disease, 28 were ventilated. At day 14, 24 (49.0%) patients improved, 9 (18.4%) died, and 13 (26.5%) were ventilated. In 14/98 (14.3%) CP units IgG was < 1.1 (cutoff calibration) and in 60 (61.2%) ≤4.0. IgG level and neutralizing antibody titer were correlated (0.85 p < 0.001). In patients receiving ≤4.0 antibody levels, 11/30 improved (36.7%) versus 13/19 (68.4%) in patients receiving >4.0 odds ratio (OR) 0.267 [95% confidence interval (CI) 0.079-0.905], P = 0.030. In patients diagnosed >10 days prior to treatment, 4/14 (22.4%) improved in the ≤4.0 antibody group, versus 6/7 (85.7%) in the >4.0 antibody group, OR 0.048 (95% CI, 0.004-0.520), P = 0.007. No serious adverse events were reported. INTERPRETATION: Treatment with CP with higher levels of IgG against S1 may benefit patients with moderate and severe COVID-19. IgG against S1 level in CP predicts neutralization antibodies titers.

Sepsis, septic shock, and fatal exertional heat stroke.

Exertional heat stroke (EHS) is a clinical syndrome of hyperthermia, encephalopathy, and multiorgan dysfunction that can be irreversible and fatal. While prompt recognition and immediate, aggressive total body cooling can prevent progression of the clinical syndrome, even a short delay can exacerbate the effects of hyperthermia-induced changes. EHS is linked to an inflammatory response that is akin to the systemic inflammatory response syndrome (SIRS). However because EHS is not a common problem in most hospital intensive care units and is not in the usual list of SIRS causes, it may be overlooked easily. Furthermore normalizing the body temperature of patients with EHS, especially when hyperthermia recognition and total body cooling are delayed, may not prevent SIRS and its clinical consequences. This narrative review focuses on the inflammatory response behind the pathway leading to EHS-associated organ pathology and recommends a new insight to possible clinical interventions beyond whole body cooling.

Severe acidosis does not predict fatal outcomes in intensive care unit patients: a retrospective analysis.

PURPOSE: Severe acidosis is a potentially life-threatening acid-base imbalance. The outcome of patients with severe acidosis has only been anecdotally described. We therefore assessed the discharge rate of such patients from the intensive care unit (ICU) and survival time after the event. METHODS: A retrospective evaluation of medical records of patients admitted to the ICU of Tel Aviv Medical Center between 2005 and 2010, in whom arterial blood pH less than 6.8 was documented during their ICU stay, was performed. RESULTS: Twenty-eight patients were suitable for study entry. Septic shock was the most common underlying medical condition (33%). Nine (32.1%) patients were either discharged alive or survived for at least 30 days in the ICU after their arterial blood pH measurement was less than 6.8. More than a quarter of the patients with life-threatening acidosis (n = 8; 28.6%) were discharged home and returned to their prehospitalization daily activity. Mean follow-up period for these patients was 132 ± 111 weeks. Multivariate analysis identified hyperkalemia, Acute Physiology and Chronic Health Evaluation II score, and Glasgow Coma Scale as determinants for ICU death after severe acidosis. CONCLUSIONS: A significant number of patients can outlast severe acidosis and return to their prehospitalization status. Larger studies are needed to define the patient population most likely to benefit from aggressive resuscitation efforts during severe acidosis.

Low plasma C-reactive protein level as an early diagnostic tool for heatstroke vs central nervous system-associated infection in the ED.

PURPOSES: Heatstroke (HS) is a life-threatening condition, manifested by systemic inflammation and multiorgan failure. Rapid recognition and treatment are life saving. We report a laboratory-oriented characterization of HS by low plasma C-reactive protein (CRP) level and propose its usefulness in distinguishing this type of hyperpyrexia from central nervous system-associated high core temperature. METHODS: After institutional review board approval, records of patients admitted to general intensive care unit between August 2008 and September 2011 with core temperature 39.0°C or higher due to HS or meningoencephalitis (ME) were reviewed. Patients' demographics, CRP on admission and 24 to 48 hours later, serum creatinine, creatine phosphokinase, platelets count, international normalized ratio, alanine transaminase, serum pH, and lactate levels were retrieved. RESULTS: Thirty-six patients were admitted to the intensive care unit with high core temperature: 19 patients, aged 21 to 85 years, had HS; 17 individuals, aged 22 to 81 years, had ME. None of the HS individuals had infection. Twelve HS patients were previously healthy; in 13 patients, the event occurred postexercise. Mean admission CRP levels was 2.1 ± 3.3 mg/L in the HS group compared with 129 ± 84 mg/L in the ME patients (P < .0001); mean 24- to 48-hour CRP levels were 14.6 ± 16.8 vs 139 ± 98 mg/L, respectively (P < .0001). There were no clinically significant differences between the groups regarding laboratory parameters indicative of end-organ damage. Six HS patients underwent computed tomography and/or lumbar puncture before starting intensive cooling, due to misdiagnosis; 5 of them died subsequently. CONCLUSIONS: Low serum CRP levels characterize non-central nervous system-associated HS. This available laboratory test could identify noninfectious hyperthermic patients upon admission, saving precious time until treatment and avoiding unnecessary diagnostic tests.

Vipera aspis venom reduces lethality and down-regulates tumor necrosis factor-alpha in a rat model of LPS-induced sepsis.

OBJECTIVES: Sepsis and septic shock are major causes of morbidity and mortality in critically-ill patients. Sepsis constitutes the systemic response to infection, that is predominantly mediated by the pro-inflammatory cytokines TNF-alpha and IL-1beta. Hence, cytokine modulation provides a promising target for the treatment of sepsis. In this work we evaluated the effect of a low-dose Vipera aspis venom (VAV) vaccine on survival and cytokine serum levels in a rat model of lipopolysaccharide (LPS)-induced septic shock. METHODS: Adult male Wistar rats were given either VAV vaccine or saline, and 2 weeks later half of each group received LPS challenge, and were monitored for mortality, cytokine levels, blood count and chemistry. RESULTS: Survival rate was significantly higher in venom-treated, compared to non-vaccinated septic rats. Furthermore, VAV treatment significantly reduced LPS-associated TNF-alpha and LDH, without affecting IL-6 and IL-10 levels, and modified WBC and platelet counts. CONCLUSIONS: Our data suggest that sub-toxic doses of VAV have a protective effect against LPS-induced septic shock that may be mediated, at least partially, by the modulated TNF-alpha activity. This study thus offers a novel therapeutic approach for the attenuation of bacteremia-induced septic shock through the modulation of a central pro-inflammatory cytokine by VAV vaccination in mammals.

Donor recruitment and selection for adult-to-adult living donor liver transplantation in urgent and elective circumstances.

BACKGROUND: Adult-to-adult living donor liver transplantation is becoming an alternative to cadaveric transplantation in urgent and elective settings. Donor selection crucially affects donor safety and recipient outcome. OBJECTIVE: To present our algorithm of urgent and elective donor selection. METHODS: Urgent selection is expeditious and protocol-based. Elective selection permits a comprehensive process. Both include medical, psychosocial and surgical-anatomic evaluations. Liver volumes and vascular anatomy are evaluated with computerized tomographic angiography. Informed consent is obtained after painstaking explanations. Independent institutional committees review and approve all cases. RESULTS: Between July 2003 and June 2004 we evaluated 43 potential live donors for 12 potential recipients (fulminant hepatic failure, n = 5; chronic end-stage liver disease, n = 6; primary graft non-function, n = 1). Thirty-three candidates (76%) were excluded due to blood type incompatibility (n = 14, 42%), incompatible anatomy (n = 8, 24%)--including problematic volume distribution (n = 2) or vascular anatomy (n = 6)--psychosocial issues (n = 4, 12%), or medical co-morbidity (n = 7, 22%). Five recipients (FHF, n = 4; chronic ESLD, n = 1) were successfully transplanted from living donors. In the acute setting, two patients (FHF, PGNF) died in the absence of an appropriate donor (cadaveric or living donor). In the elective group, one patient died of unexpected variceal bleeding and one received a cadaveric graft just before the planned living donor transplantation was performed. One candidate was transplanted overseas and two cases are scheduled. The ratio of compatibility for donation was 34% (10/29) for blood type-compatible candidates. CONCLUSIONS: Donor selection for living donor liver transplantation is a complex, labor-intensive multidisciplinary process. Most exclusions are due to blood type incompatibility or anatomic details. Psychosocial aspects of these donations warrant special attention.

Characteristics of road traffic accidents treated in an urban trauma center.

BACKGROUND: Road traffic accidents are the leading cause of accidental injury and death for persons under the age of 35. The medical literature presents surprisingly little information on the general characteristics of such accidents in the urban setting. OBJECTIVES: To characterize RTA patients arriving at an urban trauma center. METHODS: We prospectively examined the charts of all patients admitted to the Tel Aviv Sourasky Medical Center due to RTA injuries during two periods in 1995. RESULTS: Of the 1,560 patients examined, the male:female ratio was 1:1 and median age was 27 years (47% aged 20-30 years); 51% of the accidents took place between 8 a.m. and 4 p.m. and on working week days; automobiles comprised 47.1% of the vehicles involved, motorized two-wheel vehicles 37.1%, bicycles 3.8%, and pedestrians 12%. The Glasgow Coma Scale was 15 on arrival in 98.7% of the patients. The trunk was the most commonly injured body part (84.7%); whiplash injury to the neck was diagnosed in 343 patients (22%), and brain concussion in 183 (11.7%). Computed tomography studies were performed in 34 patients (2.2%). The vast majority of patients (1,438, 92.2%) was discharged home; 14 (0.9%) were admitted to the intensive care unit, and 2 (0.13%) died during hospitalization. The average time spent in the emergency department in the morning shift was 2.1 hours. CONCLUSIONS: We could identify distinguishing factors of this population: equal gender distribution, peak RTA incidence in the young adult working population during working hours, automobile drivers being the most injured subgroup, a disproportionate number of motorcycle and motor scooter involvement, and a relatively extensive amount of time and resources spent treating these injuries despite their generally minor nature.

Initial experience with urgent adult-to-adult living donor liver transplantation in fulminant hepatic failure.

BACKGROUND: The prognosis of patients with fulminant hepatic failure without timely liver transplantation is dismal. Given the limited availability of cadaveric organs for urgent transplantation in Israel, adult-to-adult living donor segmental liver transplantation may be the only alternative. OBJECTIVES: To report our initial experience with urgent lifesaving LDLT in this unique scenario. METHODS: Three adult patients with FHF (two of unknown etiology, one with paracetamol intoxication) were transferred from other institutions and admitted to our intensive care unit. Initial treatment and monitoring included intracranial pressure monitoring and hepatic dialysis using the Molecular Adsorbent Recirculating System. Expeditious potential donor selection included medical, psychosocial and surgical evaluation. Liver volume and vascular anatomic compatibility were assessed with computed tomography angiography. RESULTS: Between July and October 2003 we performed three procedures of urgent adult-to-adult LDLT. The donors (two uncles, one sister) underwent hepatic resection (two right lobes, one left lateral segment) and recovered well. The recipients underwent total hepatectomy with caval preservation, followed by lobar grafting. All recipients recovered and are alive with good liver function and without any neurologic complications. CONCLUSIONS: Urgent adult-to-adult living donor segmental liver transplantation can be performed safely and timely as a lifesaving procedure in the setting of comatose patients with FHF.

Exposure to extremely high concentrations of carbon dioxide: a clinical description of a mass casualty incident.

Clinical reports on unintentional mass exposure to extreme concentrations of carbon dioxide are rare. We describe an industrial incident caused by a container of liquid carbon dioxide that was unintentionally opened in an enclosed working environment. Twenty-five casualties reached our emergency department. Symptoms included dyspnea, cough, dizziness, chest pain, and headache. ECGs (n=15) revealed ST-segment changes in 2 (13.3%) patients, atrial fibrillation in 2 patients, and non-Q wave myocardial infarction in 1 patient. Chest radiographs (n=22) revealed diffuse or patchy alveolar patterns, consistent with pneumonitis, in 6 (27%) patients and pulmonary edema in 2 (9%) patients. Eleven (44%) patients were admitted to the hospital: 8 were discharged 24 hours later and the others within 8 days. No patient died. Exposure to high concentrations of carbon dioxide resulted in significant but transient cardiopulmonary morbidity with no mortality when victims were promptly evacuated and given supportive therapy. Cardiac complications were frequently observed and should be actively sought.

Middle cerebral artery flow velocity decreases and electroencephalogram (EEG) changes occur as acute hypercapnia reverses.

OBJECTIVE: To define the changes in middle cerebral artery flow velocity (Vmca) and the electroencephalogram (EEG) during rapid reduction in arterial carbon dioxide (PCO2) from acute hypercapnia. DESIGN. Human volunteer study. SETTING: University-affiliated hospital experimental laboratory. PARTICIPANTS: Nine healthy volunteers aged 25-35 years. INTERVENTIONS: Subjects rebreathed exhaled gas from a bag pre-filled with 5% carbon dioxide (CO2) in oxygen, up to an end-tidal CO2 of 10% or to the limit of discomfort, when they were disconnected. MEASUREMENTS AND RESULTS: Middle cerebral artery blood flow velocity was continuously measured by transcranial Doppler ultrasound, quantitative EEG was recorded and hemodynamics were monitored non-invasively. Vmca closely correlated with end-tidal CO2 changes (r=0.65, p<0.001). When rebreathing ceased, there was a rapid decline in end-tidal CO2 and in Vmca to baseline within 42+/-14 s, followed by a rapid further decline in both variables to below baseline. End-tidal CO2 reached a nadir of 4.4+/-1.1% at 146+/-79 s, with Vmca decreasing to 37+/-10 cm/s at 104+/-65 s (a 40% reduction and 31% below basal values). Electroencephalogram alpha activity significantly decreased and delta activity increased during hypercapnia. During subsequent hypocapnia, delta activity decreased back to baseline, while alpha activity increased, but remained below baseline. CONCLUSIONS: These findings demonstrate the rapid changes occurring in cerebral blood flow during rapid declines in arterial CO2 and the consequent potential for producing brain ischemia and hemodynamic alterations if inadvertent hyperventilation occurs following institution of mechanical ventilation for acute hypercapnia.

Intensive care in a field hospital in an urban disaster area: lessons from the August 1999 earthquake in Turkey.

OBJECTIVE: To describe our experience with the implementation of intensive care in the setting of a field hospital, deployed to the site of a major urban disaster. DESIGN: Description of our experience during mission to Turkey; conclusions regarding implementation of intensive care at disaster sites. SETTING: Military Field Hospital at Adapazari in Turkey. PATIENTS: Civilian patients admitted for care at the field hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: On August 17, 1999 a major earthquake occurred in western Turkey, causing approximately 16,000 fatalities and leaving >44,000 injured. Approximately 66,000 buildings were severely damaged or destroyed. A medical unit of the Israeli Defense Forces Medical Corps, consisting of 23 physicians, 13 nurses, nine paramedics, 13 medics, laboratory and roentgen technicians, pharmacists, and associated support personnel, were sent to Adapazari in Turkey. The field hospital treated approximately 1,200 patients over a period of 2 wks, 70 surgical operations were performed, 20 babies were delivered, and a variety of medical, surgical, orthopedic, and pediatric/neonatal care was provided. The 12-bed intensive care unit operated by the unit, was staffed by three physicians and eight nursing/paramedic personnel. Patient mix was: a total of 63 patients, among them five with major trauma, 20 with acute cardiac disease, 15 patients with various acute medical conditions, and 11 surgical and postoperative patients. Three patients were intubated and mechanically ventilated (one cardiogenic pulmonary edema and two major trauma). The intensive care unit provided the following functions to the field hospital: care of the critically ill and injured, preparation for and implementation of transportation of such patients, pre- and postoperative care for major surgical procedures, expertise, and equipment for the care of very ill patients throughout the field hospital. CONCLUSIONS: In suitable circumstances, an intensive care capability should be an integral part of medical expeditions to major disasters.

Tumor necrosis factor as a mediator of cardiac toxicity following snake envenomation.

OBJECTIVE: To investigate the possible role of tumor necrosis factor in mediating cardiotoxicity following venom injection in a rat. DESIGN: A randomized controlled experimental study using a Langendorff isolated heart model. SETTING: Animal laboratory. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: The control group (n = 10) was injected with saline only. Each animal in the experimental groups 1-3 (n = 10 each) was injected with Vipera aspis venom 500 microg/kg intramuscularly. Group 1 animals received no additional substance beforehand, group 2 animals were injected intramuscularly with 250 microg of soluble tumor necrosis factor receptor (sTNF-R p55) 15 mins before the venom injection, and group 3 animals were injected intraperitoneally with 40 microg of anti-tumor necrosis factor 60 mins before the venom injection. MEASUREMENTS AND MAIN RESULTS: Cardiac performances were investigated following envenomation. Cardiac histology and myocardial tumor necrosis factor-RNA concentrations were assessed. Serum tumor necrosis factor concentrations rose and peaked 2 hrs following envenomation. A reduction in peak systolic pressures, maximum and minimum change in pressure over time, time-pressure integral, and coronary flow occurred in the venom-only-injected rats compared with controls, whereas blocking tumor necrosis factor activity prevented the deleterious cardiac effects of the envenomation. No histologic changes or increases in myocardial tumor necrosis factor-RNA concentrations were detected. CONCLUSION: These results strongly suggest that systemic release of tumor necrosis factor mediates cardiac toxicity following Vipera aspis envenomation.

Pulmonary oedema in SCUBA divers: pathophysiology and computed risk analysis.

SCUBA diving has become a popular sport, with an increasing number of people participating in it. Although it is an essentially very safe activity, several specific medical problems are associated with diving. The present paper addresses diving-related pulmonary oedema, which is a rarely reported condition. It has been described mostly in cold water diving, and its occurrence in warm water has not been documented before. We delineate the pathophysiology of this condition and its treatment, and use a novel computational model to analyse further the mechanisms leading to diving-related pulmonary oedema. A better understanding of diving-related pulmonary oedema may lead to earlier recognition and treatment, and, potentially, to its prevention. The physiological mechanisms likely to lead to diving-related pulmonary oedema are well recognized. Consequently, we could design and construct a bio-mechanical computer model of the alveolar septa to explore the pathophysiology of diving-related pulmonary oedema and the vulnerability of individual divers as they relate to some mechanical characteristics of their lung structure. The physiological mechanisms of diving-related pulmonary oedema and the results provided by the computational model successfully delineated the process. The model predicted that the risk of injury is significantly increased in individuals who have a stiffer lung parenchyma or lower lung compliance values.

Gray-white matter discrimination--a possible marker for brain damage in heat stroke?

INTRODUCTION/OBJECTIVE: Heat stroke (HS) is a common medical emergency which carries high morbidity and morality. This study was designed to describe the pattern of central nervous system (CNS) changes as detected by brain CT scan in a case series of six patients suffering from classical and exertional HS. METHODS AND PATIENTS: All the patients were admitted in critical condition during the heat wave in the summer of 1999 in Israel. Each was in deep coma with a measured core temperature of over 40 degrees C upon admission to the emergency department. RESULTS: Aggressive cooling measures decreased the core temperature to <38 degrees C within 30 min following admission. Two patients (33.3%) died. One of the survivors remained in a vegetative state. Brain CT studies carried out within 4 days of admission in all the patients revealed severe loss of gray-white matter discrimination (GWMD) without signs of acute bleed or significant focal lesion, findings that persisted in repeated brain CTs in one patient who remained in a vegetative state. DISCUSSION AND CONCLUSIONS: Loss of GWMD may represent an early and sensitive indication of severe brain damage in patients with severe HS. Further studies in larger groups of patients are warranted in order to determine whether the appearance of GWMD in brain CTs of patients with HS has prognostic value.