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Hyuntae Na

and 2 more

Crystallographic B-factors provide direct dynamical information on the internal mobility of proteins that is closely linked to function, and are also widely used as a benchmark in assessing elastic network models. A significant question in the field is: what is the exact amount of thermal vibrations in protein crystallographic B-factors? This work sets out to answer this question. First, we carry out a thorough, statistically sound analysis of crystallographic B-factors of over 10,000 structures. Second, by employing a highly accurate all-atom model with the well-known CHARMM force field, we obtain computationally the magnitudes of thermal vibrations of nearly 1,000 structures. Our key findings are: (i) the magnitude of thermal vibrations, surprisingly, is nearly protein-independent, as a corollary to the universality in vibrational spectra of globular proteins established earlier; (ii) the magnitude of thermal vibrations is small, less than 0.1 Å2 at 100 K; (iii) the percentage of thermal vibrations in B-factors is the lowest at low resolution and low temperature (<10%) but increases to as high as 60% for structures determined at high resolution and at room temperature. The significance of this work is that it provides for the first time, using an extremely large dataset, a thorough analysis of B-factors and their thermal and static disorder components. The results clearly demonstrate that structures determined at high resolution and at room temperature have the richest dynamics information. Since such structures are relatively rare in the PDB database, the work naturally calls for more such structures to be determined experimentally.
Dylan K Wainwright et al. indicated high-performance Tuna platform for designing autonomous underwater vehicles [1]. Although their research will be useful, they should focus on the role of fins. Vadim Pavlov, et al. described hydraulic control of tuna fins [2]. During the late 18th century, wing designs were based on anatomical studies on dolphins, trout and tuna by the “father of aerodynamics”, Sir George Cayley [3,4]. Fish that are adapted for fast swimming, like tuna, are generally fusiform in shape and this is considered an efficient, hydrodynamic shape [5,6]. The hydraulic-fin-manufacture utilized multiple small fins instead of large hydraulic fins through the experiment for adopting better boat stabilizers [7]. By using two, four or six smaller active fins grouped together, the more small fins system produces better results without causing drag and slowing boats [7]. Tuna has such efficient hydrodynamic multiple small fins including 1st dorsal fin, 2nd dorsal fin, finlets, caudal fin, pelvic fin, pectoral fin, and anal fin. Every tuna fin may have the special role for better performance in stabilization of any vehicles.References:1. Dylan K Wainwright and George V Lauder 2020 Bioinspir. Biomim.15 0350072. Vadim Pavlov, et al., Hydraulic control of tuna fins: A role for the lymphatic system in vertebrate locomotion, Science, 21 Jul 2017, Vol.357, Issue 6348, pp.310-3143. Bio-mimetic Drag Reduction – Part 2: Aero- and Hydrodynamics, March 31, 2012http://aerospaceengineeringblog.com/bio-mimetic-drag-reduction-2/4. https://en.wikipedia.org/wiki/George_Cayley5. Eric Pickhartz, The ‘Tuna Robot’ is the Navy’s Newest Underwater Drone, July 4, 2014http://www.wideopenspaces.com/tuna-robot-navys-newest-underwater-drone/6. Kirk Janowiak, Are fish aerodynamic?, Jan 12, 2015https://www.quora.com/Are-fish-aerodynamic7. High-Performance Active Fin Stabilizers Improve Boat Speed and Performance, Feb 21, 2017http://www.gyrogalestabilizers.com/high-performance-active-fin-stabilizers-improve-boat-speed-performance/

Yanan Sun

and 5 more

E,E-2,4-hexadienal is probably a precursor of secondary organic aerosol (SOA) and plays an important role in the atmospheric chemistry. Its main degradation routs are the reactions with OH, Cl, NO3 as well as photolysis. Atmospheric hydroxyl radical, as the most important oxidant, generally controls the removal of volatile organic compounds (VOCs) in the atmosphere. Thus, the quantum chemical calculations are used to investigate the reaction mechanism of E,E-2,4-hexadienal with hydroxyl radical, which would give better understanding for the main degradation products. The reaction paths of E,E-2,4-hexadienal with OH radical have been calculated accurately at the BMC-CCSD//M06-2X/6-311G (d, p) level at atmospheric pressure and room temperature. There are six hydrogen abstraction and four carbon addition paths at the first stages of this reaction. Due to the low energy barrier and reaction exotherm, the ten paths would contribute to the total reaction. Furthermore, the peroxy (RO2) and alkoxy (RO) radicals from the most important adduct IM1(CH3CHOHCHCH=CHCHO) would be formed in the atmospheric environment. The reaction mechanism of the peroxy radical (CH3CHOHCHO2CH=CHCHO) with NO, NO2, HO2, and self-reaction have been studied by using the same quantum chemical methods. And the reaction paths of alkoxy radical (CH3CHOHCHOCH=CHCHO) have been also originally studied. The subsequent reactions play a key role in the cycling of atmospheric radicals, production of ozone, and SOA formation. What’s more, the reaction mechanism of this study accords with the reported experimental observations.

Shahid Dar

and 2 more

Globally, urban wetlands are facing immense pressure of land use land cover changes (LULCCs) and associated water quality degradation that is severely affecting the trophic status of these pristine ecosystems. This study analyzed water quality degradation resulting due to the land system changes in the vicinity of Khushalsar, an urban wetland, in Srinagar city from 1980-2017. The analysis of satellite data indicated that the wetland has lost ~18.1 ha from 1980-2017. During the same period the urban area within the wetland increased from 0.2% to 16.5%. The land cover changes assessed in the immediate vicinity of wetland indicated an increase of 119% in built-up and 62.8% in roads. The analysis of surface water quality of the wetland showed much greater degradation of Khushalsar wetland. The Trophic State Index (TSI) ranged from 73.4-84.6 thereby indicating the hyper-eutrophic nature of the wetland. A snapshot of comparative water quality data from 2002-2018 revealed that the mean concentration of NO3–N increased from 219-433 µg L-1 and total phosphorus (TP) increased from 135.4-1236 µg L-1 indicative of continuous nutrient enrichment. Hierarchical cluster analysis (HCA) clustered 8 sampling sites into 4 groups based on likeness of water quality characteristics. Similarly, discriminant analysis (DA) showed the formation of similar patterns of clusters, authenticating the outcomes of HCA. Wilk’s λ quotient dispersion highlighted the role of nutrients and ions in the development of clusters. Principal component analysis (PCA) formed three principal components (PC’s) accounting for a cumulative variance of 90.61%.

Masroor Sharfi

and 5 more

Here we report an extremely rare case of congenitally corrected transposition of great arteries (CCTGA) associated with Interrupted aortic arch (IAA) type A and ventricular septal defect (VSD) in a preterm baby. Antenatally diagnosed as large VSD and severe Coarctation of aorta. Echocardiogram done revealed that left ventricle with the mitral valve lay on the right side in continuation with the venous right atrium and was connected to the pulmonary artery. The right ventricle lay on the left in continuation with the arterial left atrium and was connected to the aorta. Smallish transverse arch with Interruption of aorta below the left subclavian artery. Large VSD with bidirectional shunt. Small PDA with restrictive right to left flow. As far we know, only one similar case was reported earlier by Cottrell, at el. (4). At that time the initial diagnosis was done by cardiac angiography as 2D color echocardiography was not available at their center, after one year they were able to use echocardiogram and same diagnosis was confirmed. In our case despite the complex anatomy we were able to diagnose our case by 2D color Echocardiogram. The Echocardiogram images and loops were so clear and confirmative that no other cardiac imaging was required. Baby was stable clinically on prostaglandin and underwent successful aortic arch repair (end to end anastomosis) and PA banding. We believe that Echocardiography still is a basic tool for diagnosis of complex congenital cardiac anomalies specially in centers where other higher diagnostic modalities are still not available.

Yi Du

and 3 more

Preferential flow plays an important role in soil water retention, movement, and solute transport. Heterogeneity, uncertainty, and the scale of preferential flow are the focus of the current research. The multi-index method and preferential flow classification method were used to identify and quantify preferential characteristics and flow types at three points on a slope in the upstream portion of a drinking water supply area. Results show that the infiltration depth of the preferential flow on the hillslope is about 400 mm. The preferential flow fraction of the stain profile ranges from 56.6 to 74.8%. The result of multi-index evaluation indicates that the weight of the peak value of the stained area and coefficient of variation are the two indexes that have a greater influence on the preferential flow. Regarding the difference in preferential flow at different slope positions, the peak value of the stained area at mid-slope is higher and the coefficient of variation is lower, indicating that the preferential flow at mid-slope is more developed than upslope and downslope. The results of the quantitative analysis of preferential flow types indicate that the dyeing depth can be divided into three parts with dividing points at 100 and 275 mm due to the distribution of the stain width. The main flow type is macropore flow, especially macropore flow with mixed interaction, accounting for 49.8, 52.2, and 61.3% of the flow types at upslope, mid-slope, and downslope locations, respectively. The interaction between macropores gradually decreases with increasing soil depth and increasing elevation. As for the factors influencing preferential flow type, correlation analysis found that the higher the soil moisture content, the stronger the interaction between macropores. Influenced by bulk density, saturated conductivity, and porosity, matrix flow in the soil is relatively stable with a depth of approximately 10 cm. The study results can provide a reference for subsequent research on the preferential infiltration mechanism at different slope positions and the transport characteristics of water and nutrients.

chunyuan wang

and 6 more

Drought is one of the most significant natural disasters in the arid and semi-arid areas of China. The growth stages of populations or plant organs often differ in how they respond to drought and other adversities. At present, little is known about size- and leaf age-dependent differences in the mechanisms of shrubs-related drought resistance in China’s deserts. We studied Artemisia ordosica Krasch to evaluate its photosynthesis responses to drought stress. A field experiment conducted in Mu Us Desert, Ningxia, China. Rainfall was manipulated by installing outdoor shelters, with four rainfall treatments applied to 12 plots (each 5  5 m). There were four precipitation levels CK (ambient), -30%, -50%, -70%, each with three replications. Taking individual crown size as the dividing basis, the responses of the plants’ photosynthetic systems to drought were measured at different growth stages, i.e. large-sized (>1 m2), medium-sized (0.25-1 m2), small-sized (<0.25 m2). In the meanwhile, leaves were divided into mature leaves and new ones for separately measurement. Our results showed that (1) under drought stress, the transfer efficiency of light energy captured by antenna pigments to the PSII reaction center decreased, and the heat dissipation capacity increased simultaneously. To resist the photosynthetic system damage caused by drought, A. ordosica enhanced free radical scavenging by activating the antioxidant enzyme system. (2) The threshold for a reduction in rainfall was 70%; beyond this value, the adaptive regulation of the photosynthetic system in A. ordosica failed. (3) The growth stages and leaves age led to differences in the photosynthetic system reaction to drought. Small A. ordosica plants could not withstand severe drought stress (70% rainfall reduction), whereas large A. ordosica individuals could absorb deep soil water to ensure their survival. Under mild drought stress, tender (younger) leaves had a greater ability to resist drought than older leaves, whereas the latter were more resistant to drought under severe stress.

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Wahaj Munir

and 3 more

Background: Acute type A aortic dissection (ATAAD), is a surgical emergency often requiring intervention on the aortic root. There is much controversy regarding root management; aggressively pursuing a root replacement, versus more conservative approaches to preserve native structures. Methods: Electronic database search we performed through PubMed, Embase, SCOPUS, google scholar and Cochrane identifying studies that reported on outcomes of surgical repair of ATAAD through either root preservation or replacement. The identified articles focused on short- and long-term mortalities, and rates of re-operation on the aortic root. Results: There remains controversy on replacing or preserving aortic root in ATAAD. Current evidence supports practice of both trends following an extensive decision-making framework, with conflicting series suggesting favourable results with both procedures as the approach that best defines higher survival rates and lower perioperative complications. Yet, the decision to perform either approach remains surgeon decision and bound to the extent of the dissection and tear entries in strong correlation with status of the aortic valve and involvement of coronaries in the dissection. Conclusions: There exists much controversy regarding fate of the aortic root in ATAAD. There are conflicting studies for impact of root replacement on mortality, whilst some study’s report no significant results at all. There is strong evidence regarding risk of re-operation being greater when root is not replaced. Majority of these studies are limited by the single centred, retrospective nature of these small sample sized cohorts, further hindered by potential of treatment bias.

Matthew Sussman

and 9 more

The recognition of fibrinolysis phenotypes in trauma patients has led to a reevaluation of antifibrinolytic therapy (AF). Many cardiac patients also receive AF, however the distribution of fibrinolytic phenotypes in that population is unknown. The purpose of this study was to fill that gap. Methods: Data were retrospectively reviewed from 78 cardiac surgery patients. Phenotypes were defined as hypofibrinolytic (LY30 <0.8%), physiologic (LY30 0.8-3.0%) and hyperfibrinolytic (LY30 >3%). Continuous variables were expressed as M ± SD or median (interquartile range). Results: The study population was 65±10 yrs old, 74% male, average body mass index of 29±5 kg/m2. Fibrinolytic phenotypes were distributed as physiologic=45%, hypo=32% and hyper = 23%. There was no obvious effect of age, gender, race, or ethnicity on the distribution of fibrinolysis phenotypes; 47% received AF. The time with chest tube during post-operative recovery was longer in those who received AF (4[3,5] days) vs no AF (3[2,4] days), P=0.037). All cause morbidity occurred in 51% of patients who received AF vs 25% with no AF (p=0.017). However, with AF vs no AF, apparent differences in median chest tube output (1379 vs 820ml, p=0.075), hospital LOS (13 vs 10 days, P=0.873), estimated blood loss (1100 vs 775 ml, P=0.127), units of transfused RBCs (4 vs 2], P=0.152) or all-cause mortality (5.4% [2/37] vs 10% [4/41], P=0.518) were not statistically significant. Conclusion: This is the first description of three distinctly different fibrinolytic phenotypes in cardiac surgery patients. In this population, the use of AF was associated with increased morbidity.

Arushi Singh

and 6 more

Background: Ibrutinib is associated with atrial fibrillation (AF), though echocardiographic predictors of AF have not been studied in this population. We sought to determine whether left atrial (LA) strain on transthoracic echocardiography could identify patients at risk for developing ibrutinib-related atrial fibrillation (IRAF). Methods: We performed a retrospective review of 66 patients who had an echocardiogram prior to ibrutinib treatment. LA strain was measured with TOMTEC Imaging Systems, obtaining peak atrial longitudinal strain (PALS) and peak atrial contraction strain (PACS) on 4-chamber and 2-chamber views. Statistical analysis was performed with Chi-square analysis, T-test, or binomial regression analysis, with a p-value < 0.05 considered statistically significant. Results: Twenty-two patients developed IRAF (33%). Age at initiation of ibrutinib was significantly associated with IRAF (65.1 years vs. 74.1 years, p = 0.002). Mean ibrutinib dose was lower among patients who developed IRAF (388.2 ± 121.7 vs. 448.6 ± 88.4, p = 0.025). E/e’ was significantly higher among patients who developed IRAF (11.5 vs. 9.3, p = 0.04). PALS was significantly lower in patients who developed AF (30.3% vs. 36.3%, p = 0.01). On multivariate regression analysis, age, PALS and PACS were significantly associated with IRAF. On multivariate regression analysis, only PACS remained significantly associated with IRAF while accounting for age. Conclusions: Age, ibrutinib dose, E/e’, and PALS on pre-treatment echocardiogram were significantly associated with development of IRAF. On multivariate regression analyses, age, PALS and PACS remained significantly associated with IRAF. Impaired LA mechanics add to the assessment of patients at risk for IRAF

James Hummel

and 1 more

We thank Medina et al. for their interest in our recent work on QTc prolongation associated with treatment of COVID-19 patients with hydroxychloroquine and azithromycin. As they appropriately point out in their letter, genetic variation is likely a significant determinant of QT prolongation in the population at large and in COVID-19 patients specifically. While drugs causing acquired long QT syndrome and torsades de pointes are generally blockers of IKr, repolarization results from the aggregate of multiple inward and outward currents. Patients with sub-clinical defects in any of these ion channels can have normal or only slightly prolonged baseline QT intervals, but may possess decreased repolarization reserve leading to an exaggerated response to IKr blockade (1).  In our study, a baseline QTc of > 460 ms was associated with excessive QTc prolongation, and this likely represents a group of patients with sub-clinical cardiac ion channel mutations (so called “first hit”) (2). We also agree that many patients with latent mutations demonstrate a normal baseline QT, which gets prolonged with the addition of a drug or a change in the clinical condition “second hit” (3). The patients in our study who exhibited QTc prolongation were generally acutely ill, and displayed “multiple hits” that led to QTc prolongation and it is certainly plausible that many may have had sub-clinical cardiac ion mutations. We therefore wholeheartedly agree that pharmacogenetics should be considered in studies of drug-induced QT prolongation, however this information is rarely available to include for acutely ill patients. And while it makes sense to obtain genetic profiles prior to administration of QT-prolonging medications, that can only be performed in the elective outpatient setting, while taking into consideration medical, ethical and social issues related to asymptomatic genetic screening (e.g. cost, reimbursement, informed consent, etc…). There is significant interest in building genomic databases, and when this becomes a reality for the population at large we believe that genetic information should certainly be included in studies of QT prolongation.Roden DM Long QT syndrome: reduced repolarization reserve and the genetic link. J Intern Med. 2006 Jan; 259(1):59-69.Napolitano C, Schwartz PJ, Brown AM, et al. Evidence for a cardiac ion channel mutation underlying drug-induced QT prolongation and life-threatening arrhythmias. J Cardiovasc Electrophysiol. 2000;11:691–6Sauer AJ and Newton-Cheh C. Clinical and genetic determinants of torsade de pointes risk. Circulation. 2012;125:1684-94.

Roberto CHIESA

and 3 more

During the first phase of COVID-19 pandemic in Italy, several strategies have been taken to deal with the pandemic outbreak. The Regional Authority of Lombardy remodeled the hospitalization system in order to allocate appropriate resources to treat COVID-19 patients and to identify “Hub/Spoke” hospitals for highly specialized medical activities. The Hubs hospitals were required to guarantee full time evaluation of all patients presenting with cardiovavascular diseases with an independent pathway for patients with suspect or confirmed COVID-19 infection. San Raffaele Hospital was identified as Hub for cardiovascular emergencies and the Vascular Surgery Department was remodeled to face this epidemic situation. Surgical treatment was reserved only to symptomatic, urgent or emergent cases. Large areas of the hospital were simultaneously reorganized to assist COVID-19 patients. During this period, 135 patients were referred to San Raffaele Vascular Surgery Department. COVID-19 was diagnosed in 24 patients and, among them, acute limb ischemia was the most common cause of admission. At this time, the COVID-19 trend is in decline in Italy and the local authorities reorganized the health care system in order to return to normal activities avoiding new escalations of COVID-19 cases. Several strategies have been taken to ensure the safety of the San Raffaele hospital, and maintaining potentially suspected patients with COVID-19 separated from other patients. The aim of this paper is to report the remodeling of the Vascular Surgery Department of San Raffaele Hospital as regards the strategies of preparation, escalation, de-escalation and return to normal activities during the COVID-19 pandemic.

Jose Lemus Calderon

and 5 more

INTRODUCTION: The SARS-CoV-2 coronavirus pandemic has caused more than fifteen million infections worldwide. Our aim is to investigate the differentiating characteristics in asthmatic patients with SARS-CoV-2 infection in the community of Castilla la Mancha. METHODS: We used the Savana® software and its algorithm based on Big Data and artificial intelligence, performed a retrospective search of the diagnoses of COVID 19 and asthma in the digitized medical records with positive RT-PCR results for SARS-CoV-2, and analysed the demographic characteristics, comorbidities, hospitalization data and deaths. RESULTS: 6,310 patients with positive RT-PCR for SARS-CoV-2 were selected, of which 577 had a diagnosis of asthma with a prevalence of 9.14%. The mean age in SARS-CoV-2 (SC2) was 59 ±19 years of age and in SARS-CoV2-asthma (SC2-A) 55 ±20 years of age. SC2 included 2983 (41%) men and 3327 (59%) women, while SC2-A included 198 (31%) men and 379 (69%) women. High blood pressure (BP) was the most common comorbidity in both groups (51%). 2,164 SC2 (34.2%) and 131 SC2-A (22.7%) required hospitalization with an asthma prevalence of 6.05%. 250 SC2 (3.96%) and 21 SC2-A (3.64%) died. CONCLUSION: The prevalence of asthma in our SARS-CoV-2 positive RT-PCR population was 9.14% and 6.05% in hospitalized patients. HBP is the most frequent comorbidity in both groups, and smoking is the only one with significant differences, more frequent in asthmatics. Mortality is lower in patients with asthma
Drug hypersensitivity reactions (DHRs) represent a global threat to healthcare systems due to their incidence, with a significant increase over last years1. DHR figures are overestimated in the general population since less than 40% of cases initially labelled as allergic can be confirmed as such when evaluated in an allergy unit2. Achieving an accurate diagnosis is complex and time consuming; besides, tests must be tailored to specific clinical manifestations and underlying mechanisms and will depend on the culprit drugs. Diagnosis often requires performing drug provocation tests (DPTs), which are especially problematic for severe reactions, making management of these patients challenging and expensive for the health care system.Clinically, DHRs are classified into immediate and non-immediate, based on the time interval between drug exposure and onset of the symptoms3. The most severe immediate reaction is anaphylaxis. This issue of the journal has been dedicated o drug hypersensitivity, which is becoming a major public health issue during the last decade, especially with the introduction of biologicals to medicine. Bilo et al. 4 evaluated the anaphylaxis mortality rate in Italy from 2004 to 2016 and found an average mortality rate for definite anaphylaxis (ICD-10 code) of 0.51 per million population per year, mostly due to the use of medications (73.7%), although in 98% of the cases culprit drugs were not identified. Regarding non-immediate reactions, one of the most challenging diagnoses is drug reaction with eosinophilia and systemic symptoms (DRESS), which is sometimes difficult, at an early stage, due to overlapping clinical symptoms with maculopapular exanthema (MPE). Pedruzzi et al. 5 identified 7 microRNAs (miRNAs) that correctly classified DRESS or MPE patients and were associated with keratinocyte differentiation/skin inflammation, type I IFN pathway viral replication, ATP-binding cassette transporters, and T lymphocyte polarisation, being all of them potential biomarkers. Non-immunologically mediated adverse reactions, such as attention-deficit/hyperactivity disorder (ADHD) are reported by Fuhrmannet al. 6 in association with systemic H1-antihistamines administration in school-age children, especially the 1st generation agents.The mechanism underlying DHR and the reason why patients treated with the same drug develop a tolerance response or an immediate or non-immediate DHR is not completely understood (Figure 1). Therefore, the prediction of who may experience a DHR, and if so, in what form, remains clinically obscure for most drugs. Goh SJR et al. 7 elegantly analyse this complexity, using non-immediate reactions to penicillins as a model. They focus on the understanding of the role of nature of the lesional T cells, the characterisation of drug-responsive T cells isolated from patient blood, and the potential mechanisms by which penicillins enter the antigen-processing and presentation pathway to stimulate these deleterious responses.Regarding specific drugs involved in allergy, betalactam antibiotics (BL) are the most frequent culprit, being many reactions mediated by IgE. This type of reaction varies among patients, with some reacting only to one BL and others to several of them; it tends to change over time and differs between European countries, depending on BL consumption. Nowadays, amoxicillin (AX), alone or in combination with the β-lactamase inhibitor clavulanic acid (CLV), is the most often prescribed BL worldwide (Figure 2) and the most common elicitor of reactions in both children and adults. It is unclear why patients after the administration of AX-CLV develop selective hypersensitivity to AX, while tolerating CLV and vice-versa. Ariza et al. 8 generated drug-specific T-cell clones from AX- or CLV-selective immediate hypersensitivity patients and found that both AX- and CLV-specific clones were generated irrespective of whether AX or CLV was the culprit, although a higher secretion of Th2 cytokines (IL-13 and IL-5) was detected when clones were activated with the culprit BL compared with clones stimulated with the tolerated BL, in which higher secretion of Th1 cytokines (IFN-γ) was observed. Regarding selective non-immediate reactions to CLV, Copaescu A et al. 9 report on a cohort of patients with a history of non-immediate reaction to CLV, who demonstrated a delayed intradermal skin test response to CLV, 17% were allergic to both CLV and ampicillin, and 83% were selective reactors with good tolerance to AX. IFN-γ release enzyme-linked immunospot (ELISpot) was performed giving a sensitivity of 33%. Other drugs such as sulphonamides, either antibiotic or non-antibiotics are important triggers of non-immediate DHRs. Vilchez-Sanchez et al. 10 showed that lymphocyte transformation tests (LTT) can help avoid the performance of DPT with a sensitivity of 75%, a specificity of 100%, and negative and positive predictive values of 72.7% and 100%, respectively.There has been a great expansion in the use of biological agents (mainly monoclonal antibodies (mAbs)), and they have greatly improved the treatment landscape of hemato-oncologic, autoimmune, inflammatory and rheumatologic diseases. In parallel, the incidence rate of reported DHRs associated with these products has increased considerably within the last years, ranging from mild to life-threatening. Yang BC et al. 11 recommend risk stratification as the first step for managing patients with DHRs to these drugs. In cases with negative skin test and mild reactions, DPT is an option, and in moderate or severe reactions, desensitisation becomes the preferred approach. In cases with positive skin test, desensitisation is the recommended course of action, especially when there is no alternative medication. Desensitisation is also widely used in the management of immediate hypersensitivity reactions to chemotherapy agents, such as platinums. There is suspicion about the presence of a longer memory of tolerance in subsequent desensitisation protocols partially resembling the regulatory tolerance mechanisms induced by allergen immunotherapy. Tüzer et al. 12 demonstrate the possible role of IL-10 in desensitisation with platinums, as they found a dynamic change in serum IL-10 levels observed as an increase during desensitisation and a decrease in between the protocols.Finally, a wide spectrum of drugs has been considered for treatment of coronavirus disease 2019 (COVID-19) and all of them can potentially induce DHRs. Gelincik A et al .13 reviewed DHRs in COVID-19 times to these drugs, with knowledge mainly coming from previous clinical experience in patients not infected with COVID-19. As in other viral infections, skin symptoms, including exanthemas, may appear during the evolution of the disease, leading to differential diagnosis with DHRs. Whether COVID-19 can aggravate T–cell mediated DHRs reactions as some viruses is at present unknown.We can conclude that new drugs are continuously introduced into the markets and confirmed as inducers of hypersensitivity reactions. We still do not completely understand the mechanisms underlying many of these reactions and further studies for improving diagnostic and management are needed even in classic and well-studied drugs as BLs.Abbreviations: AX: Amoxicillin; CLV: Clavulanic acid; COVID-19: Coronavirus disease 2019; DHR: Drug hypersensitivity reactions; DPT: Drug provocation tests; DRESS: Drug reaction with eosinophilia and systemic symptoms; ELISpot: enzyme-linked immunospot; LTT: Lymphocyte transformation tests; MPE: Maculopapular exanthema.

Meilin Schaap

and 4 more

Introduction: To evaluate the long-term (5 years) effects of perioperative briefing and debriefing on team climate. We explored the barriers and facilitators of the performance of perioperative briefing and debriefing to explain its effects on team climate and to make recommendations for further improvement of surgical safety tools. Methods: A mixed-method evaluation study was carried out among surgical staff at a tertiary care university hospital with 593-bed capacity in the Netherlands. Thirteen surgical teams were included. Team climate inventory and a standardised evaluation questionnaire were used to measure team climate (primary outcome) and experiences with perioperative briefing and debriefing (secondary outcome), respectively. Thirteen surgical team members participated in a semi-structured interview to explore barriers and facilitators of the performance of perioperative briefing and debriefing. Results: The dimension ‘participative safety’ increased significantly 5 years after the implementation of perioperative briefing and debriefing (p = 0.02 (95% confidence interval 1.18–9.25)). Perioperative briefing and debriefing was considered a useful method for improving and sustaining participative safety and cooperation within surgical teams. The positive aspects of briefing were that shared agreements made at the start of the day and that briefing enabled participants to work as a team. Participants were less satisfied regarding debriefing, mostly due to the lack of a sense of urgency and a lack of a safe culture for feedback. Briefing and debriefing had less influence on efficiency. Conclusions: Although perioperative briefing and debriefing improves participative safety, the intervention will become more effective for maintaining team climate when teams are complete, irrelevant questions are substituted by customised ones and when there is a safer culture for feedback.

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