Severe Coronavirus Disease 2019 (COVID-19) is Associated With Elevated Serum Immunoglobulin (Ig) A and Antiphospholipid IgA Antibodies.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) frequently entails complications that bear similarities to autoimmune diseases. To date, there are little data on possible immunoglobulin (Ig) A-mediated autoimmune responses. Here, we aim to determine whether COVID-19 is associated with a vigorous total IgA response and whether IgA antibodies are associated with complications of severe illness. Since thrombotic events are frequent in severe COVID-19 and resemble hypercoagulation of antiphospholipid syndrome, our approach focused on antiphospholipid antibodies (aPL). METHODS: In this retrospective cohort study, clinical data and aPL from 64 patients with COVID-19 were compared from 3 independent tertiary hospitals (1 in Liechtenstein, 2 in Switzerland). Samples were collected from 9 April to 1 May 2020. RESULTS: Clinical records of 64 patients with COVID-19 were reviewed and divided into a cohort with mild illness (mCOVID; 41%), a discovery cohort with severe illness (sdCOVID; 22%) and a confirmation cohort with severe illness (scCOVID; 38%). Total IgA, IgG, and aPL were measured with clinical diagnostic kits. Severe illness was significantly associated with increased total IgA (sdCOVID, P = .01; scCOVID, P < .001), but not total IgG. Among aPL, both cohorts with severe illness significantly correlated with elevated anticardiolipin IgA (sdCOVID and scCOVID, P < .001), anticardiolipin IgM (sdCOVID, P = .003; scCOVID, P< .001), and anti-beta 2 glycoprotein-1 IgA (sdCOVID and scCOVID, P< .001). Systemic lupus erythematosus was excluded from all patients as a potential confounder. CONCLUSIONS: Higher total IgA and IgA-aPL were consistently associated with severe illness. These novel data strongly suggest that a vigorous antiviral IgA response, possibly triggered in the bronchial mucosa, induces systemic autoimmunity.

Factors associated with intravenous lidocaine in pediatric patients undergoing laparoscopic appendectomy - a retrospective, single-centre experience.

BACKGROUND: Due to its potential beneficial effects, intra- and postoperative application of intravenous lidocaine has become increasingly accepted over the last couple of years, e.g. in patients undergoing laparoscopic surgical procedures. Based on its beneficial properties, lidocaine was introduced to the standard of care for all pediatric laparoscopic procedures in our institution in mid-2016. In contrast to adult care, scarce data is available regarding the use of perioperative intravenous lidocaine administration in children undergoing laparoscopic procedures, such as an appendectomy. METHODS: Retrospective analysis of all pediatric patients undergoing laparoscopic appendectomy at the University Children's Hospital Zurich in 2016. Perioperative data, as recorded in the electronic patient data management system, were evaluated for any signs of systemic lidocaine toxicity (neurological and cardiovascular), behavioral deterioration, as well as for hemodynamic instability. Additionally, the incidence of postoperative nausea and vomiting, administration of pain rescue medication, time to hospital discharge and to first bowel movement, as well as any postoperative complications were recorded. Starting on 01/07/2016, all patients undergoing laparoscopic surgery received intravenous lidocaine (1.5 mg/kg body weight (BW) bolus after induction of anesthesia followed by continuous infusion of 1.5 mg/kgBW/h). These patients were then compared to children without lidocaine administration who had undergone laparoscopic appendectomy between 01/01/2016 and 30/06/2016. RESULTS: Data of 116 patients was analyzed. Of these, 60 patients received lidocaine. No signs of systemic toxicity, neurologic impairment or circulatory disturbances were noted in any of these patients. A (non-significant) difference in the incidence of emergence delirium was observed (0 cases in the lidocaine group vs. 4 cases in the control group, p = 0.05). CONCLUSION: This retrospective analysis did not reveal any adverse effects in pediatric patients receiving intravenous lidocaine for laparoscopic appendectomy under general anesthesia. However, further trials investigating beneficial effects as well as pharmacokinetic properties of intravenous lidocaine in children are required.

Clinical concentrations of morphine are cytotoxic on proliferating human fibroblasts in vitro.

BACKGROUND: Morphine and other opioids are routinely used systemically and as wound infusions in the postoperative period. Their effect on wound and fracture healing remains unclear. OBJECTIVE: The primary outcome was to assess the potential cytotoxicity of clinically relevant concentrations of morphine on human fibroblasts. DESIGN: Laboratory in-vitro study. SETTING: Institute of Physiology, Zurich Center for Integrative Human Physiology, University of Zurich. MATERIALS: Monolayers of human fibroblasts. INTERVENTION(S): Exposure of human fibroblast monolayers to several concentrations of morphine, for different periods of time, with and without an artificially induced inflammatory process. MAIN OUTCOME MEASURES: Cell count, cell viability, cell proliferation and apoptosis. RESULTS: A concentration, time and exposure-dependent cytotoxic effect of morphine-mediated apoptosis was observed. Simulated inflammatory conditions seemed to lessen toxic effects. CONCLUSION: Cytotoxic effects of morphine are exposure, time and concentration dependent. Simulating aspects of inflammatory conditions seems to increase resistance to morphine cytotoxicity especially in the presence of higher concentration and longer exposure times.

Intrathecal hyperbaric 2% prilocaine versus 0.4% plain ropivacaine for same-day arthroscopic knee surgery: a prospective randomized double-blind controlled study.

BACKGROUND: Short-duration spinal anesthesia is a good option for ambulatory knee surgery. Hyperbaric 2% prilocaine has short onset and rapid recovery times and, therefore, may be well suited in this setting. The aim of this study was to compare the times to reach motor block, motor block resolution, and discharge from the postanesthesia care unit (PACU) between hyperbaric 2% prilocaine and 0.4% plain ropivacaine. METHODS: In this prospective randomized double-blind study, 140 patients (ages 18-80 yr and American Society of Anesthesiologists physical status I-II) scheduled for elective unilateral arthroscopic knee surgery lasting < 45 min were allocated to either 3 mL of 2% prilocaine (60 mg) or 3 mL of 0.4% plain ropivacaine (12 mg). Time to reach complete recovery of motor block, time to reach criteria for discharge, as well as side effects up to 48 hr after discharge were recorded. RESULTS: The median (interquartile range [IQR]) time to recovery from the motor block was faster in the 2% prilocaine group compared with the 0.4% ropivacaine group (180 [169-240] min vs 240 [180-300] min, respectively; median difference, 60 min, 95% confidence interval (CI), 23 to 97 min; P = 0.036). The median [IQR] time to reach discharge criteria was similar between the two groups (330 [295-365] min vs, 335 [290-395] min; median difference 5 min, 95% CI, -25 to 35 min; P = 0.330). The incidence of side effects was low and similar in both groups. No case of transient neurologic symptoms occurred in either group. CONCLUSION: The recovery of motor block was faster after intrathecal administration of hyperbaric 2% prilocaine compared with 0.4% plain ropivacaine; however, discharge time was similar between the two groups. Both drugs showed a similar risk profile.

Human amniotic membranes as an allogenic biological dressing for the treatment of burn wounds: Protocol for a randomized-controlled study.

Background: Burn wounds pose significant challenges in medical treatment due to their devastating nature and resource-intensive requirements. Temporary coverage of burn wounds using synthetic or biological dressings allows for reepithelization before definitive skin grafting. Allogenic skin grafts have been widely used but come with drawbacks such as rejection and disease transmission. The use of amniotic membranes (AMs) offers a promising alternative for temporary coverage, as they possess biological properties that promote faster healing and improved scar quality. The various components of the amniotic membrane, including pluripotent stem cells, extracellular matrix proteins, and regenerative factors, contribute to cell growth, migration, and differentiation, as well as preservation of the original epithelial phenotype. Objective: Reliable information on the treatment of burn wounds with AM is needed. The knowledge gained in this project may help to include this advantageous modern concept of biological dressings in clinical practice. The purpose of this study is to use human amniotic membranes from our in hospital laboratory, as an allogenic biological dressing after enzymatic debridement in superficial partial thickness, deep partial thickness or full thickness burn wounds. Methods: We will include 30 patients in a randomized-controlled trial with each patient receiving the study intervention and the control intervention. Two 7 × 7 cm burn wound areas will be compared regarding percentage of skin graft take, healing time, healing percentage value and total healing time. Human amniotic membranes will be compared to allogenic skin grafts.

Quantifying Variation in Bacterial Reproductive Fitness: a High-Throughput Method.

To evaluate changes in reproductive fitness of bacteria, e.g., after acquisition of antimicrobial resistance, a low-cost high-throughput method to analyze bacterial growth on agar is desirable for broad usability. In our bacterial quantitative fitness analysis (BaQFA), arrayed cultures are spotted on agar and photographed sequentially while growing. These time-lapse images are analyzed using a purpose-built open-source software to derive normalized image intensity (NI) values for each culture spot. Subsequently, a Gompertz growth model is fitted to NI values, and fitness is calculated from model parameters. To represent a range of clinically important pathogenic bacteria, we used different strains of Enterococcus faecium, Escherichia coli, and Staphylococcus aureus, with and without antimicrobial resistance. Relative competitive fitness (RCF) was defined as the mean fitness ratio of two strains growing competitively on one plate.BaQFA permitted the accurate construction of growth curves from bacteria grown on semisolid agar plates and fitting of Gompertz models. Normalized image intensity values showed a strong association with the total CFU/ml count per spotted culture (P < 0.001) for all strains of the three species. BaQFA showed relevant reproductive fitness differences between individual strains, suggesting substantially higher fitness of methicillin-resistant S. aureus JE2 than Cowan (RCF, 1.58; P < 0.001). Similarly, the vancomycin-resistant E. faecium ST172b showed higher competitive fitness than susceptible E. faecium ST172 (RCF, 1.59; P < 0.001). Our BaQFA method allows detection of fitness differences between bacterial strains and may help to estimate epidemiological antimicrobial persistence or contribute to the prediction of clinical outcomes in severe infections.IMPORTANCE Reproductive fitness of bacteria is a major factor in the evolution and persistence of antimicrobial resistance and may play an important role in severe infections. With a computational approach to quantify fitness in bacteria growing competitively on agar plates, our high-throughput method has been designed to obtain additional phenotypic data for antimicrobial resistance analysis at a low cost. Furthermore, our bacterial quantitative fitness analysis (BaQFA) enables the investigation of a link between bacterial fitness and clinical outcomes in severe invasive bacterial infections. This may allow future use of our method for patient management and risk stratification of clinical outcomes. Our proposed method uses open-source software and a hardware setup that can utilize consumer electronics. This will enable a wider community of researchers, including those from low-resource countries, where the burden of antimicrobial resistance is highest, to obtain valuable information about emerging bacterial strains.

Dynamic optic nerve sheath diameter changes upon moderate hyperventilation in patients with traumatic brain injury.

BACKGROUND: Sonographic assessment of optical nerve sheath diameter (ONSD) has the potential for non-invasive monitoring of intracranial pressure (ICP). Hyperventilation (HV) -induced hypocapnia is used in the management of patients with traumatic brain injury (TBI) to reduce ICP. This study investigates, whether sonography is a reliable tool to detect dynamic changes in ONSD. METHODS: This prospective single center trial included patients with TBI and neuromonitoring within 36 h after injury. Data collection and ONSD measurements were performed at baseline and during moderate HV for 50 min. Patients not suffering from TBI were recruited as control group. RESULTS: Ten patients with TBI (70% males, mean age 35 ± 14 years) with a median of first GCS of 5.9 and ten control patients (40% males, mean age 45 ± 16 years) without presumed intracranial hypertension were included. During HV, ICP decreased significantly (p < .0001) in the TBI group. An ONSD response was found for HV (p = .05). CONCLUSION: We observed a dynamic decrease of ONSD during moderate HV. This suggests a potential use of serial ONSD measurements when applying HV in cases of suspected intracranial hypertension.

Characterisation of clinical manifestations and treatment strategies for invasive beta-haemolytic streptococcal infections in a Swiss tertiary hospital.

AIMS OF THE STUDY: Invasive streptococcal infections affect more than half a million patients worldwide every year and have a high lethality. Little is known about the epidemiology and microbiological characteristics of streptococcal infections in Switzerland. This case series study aims to describe the demographics, known risk factors for streptococcal skin and soft tissue infections, clinical presentations, treatment and outcomes of patients admitted to the University Hospital Zurich between 2000 and 2014 with invasive streptococcal infections caused by Streptococcus pyogenes (group A Streptococcus), Streptococcus dysgalactiae ssp. equisimilis or the Streptococcus anginosus group, as well as the microbiological characteristics of the clinical isolates. METHODS: Data collected retrospectively from patients hospitalised between 2000 and 2014 with invasive streptococcal infections were analysed. M protein gene (emm) typing of the bacterial clinical isolates was carried out according to the Centers for Disease Control and Prevention guidelines. RESULTS: A total of 86 patients with invasive beta-haemolytic streptococcal infections were included in this study, of which 49% presented with necrotising fasciitis (NF). The median age was 44 years and half were female. The most common risk factor was acute skin lesions. C-reactive protein levels were significantly higher in patients with NF, as were acute renal failure and distributive shock. Beta-lactam antibiotics were given to most patients, and intravenous immunoglobulins were given to 18% of patients within the first 24 hours. All patients suffering from NF underwent surgery. The overall case fatality rate was 8.1% at 30 days post admission. All Group A Streptococcus strains were susceptible to penicillin and clindamycin, and we found resistance to tetracycline in 11.9% of strains. The most common emm-type isolated was emm1 (44.4%). CONCLUSIONS: Invasive beta-haemolytic streptococcal infections, the most severe presentation of which is NF, remain a serious clinical issue and require rapid diagnosis and treatment. This is the first representative analysis monitoring clinical and microbiological characteristics of patients with a severe invasive beta-haemolytic streptococcal infection and treated in Zurich, Switzerland. In addition to the detailed reporting of various clinical and microbiological characteristics, we show that C-reactive protein levels, acute renal failure and distributive shock were higher in the patients with NF. We also found a low case fatality rate compared to other reports. The detailed clinical data and microbiological characteristics depicted in this study will lead to a better understanding of regional differences in severe invasive streptococcal infections.

The beach chair position for shoulder surgery in intravenous general anesthesia and controlled hypotension: Impact on cerebral oxygenation, cerebral blood flow and neurobehavioral outcome.

STUDY OBJECTIVES: The aim of this study was to assess the impact of intravenous general anesthesia and controlled hypotension on cerebral saturation (rScO2), cerebral blood flow measured as middle cerebral artery blood flow velocity (Vmax MCA) and neurobehavioral outcome in patients scheduled for shoulder surgery in beach chair position. DESIGN: Prospective, assessor-blinded observational study. SETTING: University hospital, shoulder surgery operating room. PATIENTS: Forty ASA I-II patients scheduled for shoulder surgery in beach chair position and controlled hypotension. INTERVENTIONS: Neurological and neurobehavioral tests were performed prior and the day after surgery. The baseline data for near-infrared spectroscopy, bispectral index, cerebral blood flow, PaCO2 and invasive blood pressure (radial artery) were taken prior anesthesia and after anesthesia induction, after beach chair positioning and all 20 min after surgery start until discharge of the patient. MEASUREMENTS: Neurological and neurobehavioral tests, cerebral saturation (rScO2) using near-infrared spectroscopy, BIS, cerebral blood flow using Doppler of the middle cerebral artery (Vmax MCA), PaCO2 and invasive blood pressure assessed at heart and at the external acoustic meatus level. MAIN RESULTS: The incidence of cerebral desaturation events (CDEs) was 25%. The blood pressure drop 5 min after beach chair position measured at the acoustic meatus level in the CDE group was higher compared to patients without CDEs (p = 0.009) as was the rScO2 (p = 0.039) and the Vmax MCA (p = 0.002). There were no neurological deficits but patients with CDEs showed a greater negative impact on neurobehavioral tests 24 h after surgery compared to patients without CDEs (p = 0.001). CONCLUSIONS: In ASA I-II patients intravenous general anesthesia and controlled hypotension in the beach chair position affects cerebral blood flow and cerebral oxygenation with impact on the neurobehavioral outcome.

Causative classification of river flood events.

A wide variety of processes controls the time of occurrence, duration, extent, and severity of river floods. Classifying flood events by their causative processes may assist in enhancing the accuracy of local and regional flood frequency estimates and support the detection and interpretation of any changes in flood occurrence and magnitudes. This paper provides a critical review of existing causative classifications of instrumental and preinstrumental series of flood events, discusses their validity and applications, and identifies opportunities for moving toward more comprehensive approaches. So far no unified definition of causative mechanisms of flood events exists. Existing frameworks for classification of instrumental and preinstrumental series of flood events adopt different perspectives: hydroclimatic (large-scale circulation patterns and atmospheric state at the time of the event), hydrological (catchment scale precipitation patterns and antecedent catchment state), and hydrograph-based (indirectly considering generating mechanisms through their effects on hydrograph characteristics). All of these approaches intend to capture the flood generating mechanisms and are useful for characterizing the flood processes at various spatial and temporal scales. However, uncertainty analyses with respect to indicators, classification methods, and data to assess the robustness of the classification are rarely performed which limits the transferability across different geographic regions. It is argued that more rigorous testing is needed. There are opportunities for extending classification methods to include indicators of space-time dynamics of rainfall, antecedent wetness, and routing effects, which will make the classification schemes even more useful for understanding and estimating floods. This article is categorized under:Science of Water > Water ExtremesScience of Water > Hydrological ProcessesScience of Water > Methods.

Cerebral oxygenation in the beach chair position for shoulder surgery in regional anesthesia: impact on cerebral blood flow and neurobehavioral outcome.

STUDY OBJECTIVE: Beach chair position is considered a potential risk factor for central neurological events particularly if combined with low blood pressure. The aim of this study was to assess the impact of regional anesthesia on cerebral blood flow and neurobehavioral outcome. DESIGN: This is a prospective, assessor-blinded observational study evaluating patients in the beach chair position undergoing shoulder surgery under regional anesthesia. SETTING: University hospital operating room. PATIENTS: Forty patients with American Society of Anesthesiologists classes I-II physical status scheduled for elective shoulder surgery. INTERVENTIONS: Cerebral saturation and blood flow of the middle cerebral artery were measured prior to anesthesia and continued after beach chair positioning until discharge to the postanesthesia care unit. The anesthesiologist was blinded for these values. Controlled hypotension with systolic blood pressure≤100mm Hg was maintained during surgery. MEASUREMENTS: Neurobehavioral tests and values of regional cerebral saturation, bispectral index, the mean maximal blood flow of the middle cerebral artery, and invasive blood pressure were measured prior to regional anesthesia, and measurements were repeated after placement of the patient on the beach chair position and every 20 minutes thereafter until discharge to postanesthesia care unit. The neurobehavioral tests were repeated the day after surgery. MAIN RESULTS: The incidence of cerebral desaturation events was 5%. All patients had a significant blood pressure drop 5 minutes after beach chair positioning, measured at the heart as well as the acoustic meatus levels, when compared with baseline values (P<.05). There was no decrease in either the regional cerebral saturation (P=.136) or the maximal blood flow of the middle cerebral artery (P=.212) at the same time points. Some neurocognitive tests showed an impairment 24 hours after surgery (P<.001 for 2 of 3 tests). CONCLUSIONS: Beach chair position in patients undergoing regional anesthesia for shoulder surgery had no major impact on cerebral blood flow and cerebral oxygenation. However, some impact on neurobehavioral outcome 24 hours after surgery was observed.