The challenges in the treatment of large burned and polytraumatized patients with arterial thrombosis in the lower limb during the COVID-19 pandemic: a case report

Introduction: The COVID-19 pandemic spread rapidly worldwide, bringing the need for emergency actions to control the disease at the collective and individual level. Thus, the Division of Plastic Surgery and Burns of the largest hospital complex in Latin America was physically aimed at the infected. In this context, we find the challenges of treating a large burned and polytraumatized patient, who presented arterial thrombosis in the lower limb, a rare complication associated with the thermal burn. All treatment was performed in a hospital not specialized in trauma care. Case Report: Case Report: Male patient, 18 years old, without comorbidities, with predominantly third-degree burns of 50% of body surface burned and severe neurotrauma. He presented arterial thrombosis in his right leg 24 hours after the burn. The patient underwent limb amputation and serial surgical interventions for debridement and skin grafting. Despite the prevention protocols, the patient was infected by COVID-19 during hospitalization. Conclusion: This case focuses on a rare complication related to burn injury, which does not yet have diagnostic criteria and defined prophylactic measures. Besides, the COVID-19 pandemic has impacted various health services areas, and it is essential to share knowledge during this pandemic by seeking adaptations to the crisis situation

Efeito do óxido nitroso sobre o consumo de fentanil em pacientes queimados submetidos à troca de curativo

ResumoJustificativa e objetivosOs ferimentos térmicos e a manipulação das áreas lesadas são causas importantes de dor em pacientes vítimas de queimaduras, necessitando que estes pacientes sejam constantemente submetidos a anestesias gerais para a troca do curativo. O óxido nitroso (N2O) tem propriedades analgésicas e sedativas, sendo capaz de fácil utilização e de ampla disponibilidade. Com isto, objetivou‐se avaliar o efeito analgésico da administração de N2O associado ao fentanil em pacientes queimados, durante a troca de curativo.MétodoApós aprovação pela comissão de ética institucional, foram avaliados 15 pacientes adultos, vítimas de queimaduras com necessidade de troca diária de curativo. A analgesia do paciente foi controlada pelo uso de fentanil 0,0005% administrado por bomba de infusão sob demanda, intravenosa. De maneira aleatória, em um dos dias foi associada mistura de N2O a 65% em oxigênio (O2) sob máscara com fluxo de 10 L/min (grupo N2O) e no outro dia apenas O2 sob o mesmo fluxo (grupo controle).ResultadosNão se observou diminuição significativa da dor no grupo N2O em relação ao grupo controle. A dor na EAV antes da troca do curativo foi de 4,07 e 3,4; respectivamente nos grupos N2O e controle. Quanto à dor ao término da troca de curativo, os pacientes do grupo N2O referiram dor intensidade 2,8; enquanto no grupo controle foi de 2,87. Não houve diferença significativa de consumo de fentanil em ambos os grupos.ConclusõesA associação de N2O não foi eficaz na redução no consumo de opióides durante a troca de curativos.AbstractBackground and objectivesThermal injuries and injured areas management are important causes of pain in burned patients, requiring that these patients are constantly undergoing general anesthesia for dressing change. Nitrous oxide (N2O) has analgesic and sedative properties; it is easy to use and widely available. Thus, the aim of this study was to evaluate the analgesic effect of N2O combined with fentanyl in burned patients during dressing change.MethodAfter approval by the institutional Ethics Committee, 15 adult burned patients requiring daily dressing change were evaluated. Patient analgesia was controlled with fentanyl 0.0005% administered by intravenous pump infusion on‐demand. Randomly, in one of the days a mixture of 65% N2O in oxygen (O2) was associated via mask, with a flow of 10 L/min (N2O group) and on the other day only O2 under the same flow (control group).ResultsNo significant pain reduction was seen in N2O group compared to control group. VAS score before dressing change was 4.07 and 3.4, respectively, in N2O and control groups. Regarding pain at the end of the dressing, patients in N2O group reported pain severity of 2.8; while the control group reported 2.87. There was no significant difference in fentanyl consumption in both groups.ConclusionsThe association of N2O was not effective in reducing opioid consumption during dressing changes

Abordagem farmacocinética-farmacodinâmica (PK/PD) na avaliação da efetividade do Meropenem em pacientes sépticos queimados adolescentes versus adultos jovens / PK/PD approach to evaluate Meropenem effectiveness in critically ill burn adolescents versus young adults undergoing therapy of septic shock

Introdução: O meropenem é um carbapenêmico largamente prescrito aos pacientes sépticos em terapia intensiva com infecções graves causadas por patógenos hospitalares Gram-negativos Enterobacteriaceae (EB) e Non Enterobacteriaceae (NEB) CIM>2 mg/L. As alterações fisiopatológicas que ocorrem nestes pacientes pela síndrome da resposta inflamatória sistêmica decorrente do choque séptico podem causar profundas modificações na farmacocinética impactando o desfecho clínico desejado. Racional do estudo: O objetivo deste estudo foi investigar se o alvo terapêutico foi atingido na fase precoce do choque séptico nos pacientes grandes queimados pela comparação de adolescentes aos adultos jovens em terapia intensiva recebendo o meropenem no regime empírico recomendado. Casuística e Métodos: A aprovação ética foi obtida sob registro CAAE 07525118.3.0000.0068. Incluíram-se 14 pacientes grandes queimados 11M/3F com função renal preservada, após acidente com fogo ou alta voltagem (11/3). Os pacientes incluídos foram distribuídos em dois grupos: G1-Adolescentes, G2-Jovens adultos, sendo que as características dos pacientes, G1/G2 foram 16/24 anos, 60/70 kg, 42/35 % superfície corpórea total queimada, medianas. A lesão inalatória ocorreu em 9/14; a ventilação mecânica e o uso de vasopressor foram requeridos em 13/14 pacientes em choque séptico recebendo meropenem 1g q8h através de infusão estendida de 3 horas. As culturas foram coletadas imediatamente antes do início da terapia antimicrobiana. Apenas duas amostras de sangue (2 mL/cada) foram coletadas em momentos estratégicos para a dosagem sérica do meropenem no steady state, realizada por cromatografia líquida. Os resultados da farmacocinética obtidos para os pacientes foram comparados aos dados reportados para voluntários sadios. O alvo PK/PD de 100%f?T>CIM foi considerado para a avaliação da efetividade do meropenem. Resultados: Os resultados obtidos no presente estudo evidenciaram níveis de vale semelhantes nos dois grupos de pacientes investigados, que receberam a mesma dose de 3g diários. Ressalta-se que a farmacocinética do meropenem evidenciou alteração nos dois grupos de pacientes pela comparação dos dados obtidos aos reportados em voluntários sadios. Por outro lado, evidenciou-se diferença significativa entre grupos relacionada ao aumento da meia vida biológica e do volume aparente de distribuição. Evidenciou-se redução da depuração total corporal, apesar da função renal preservada ocorrer em todos os pacientes sépticos investigados. A cura clínica ocorreu para os pacientes, a partir dos isolados de Gram-negativos susceptíveis (CIM até 2mg/L) Enterobacteriaceae (EB) e Non-Enterobacteriaceae (NEB), sendo garantida para os pacientes com isolados de susceptibilidade intermediária até CIM 4mg/L, apesar da cobertura ter sido atingida pelo meropenem para todos os pacientes dos dois grupos. Conclusão: Não se registrou diferença entre grupos com relação à cobertura do meropenem, apesar das alterações registradas entre grupos na farmacocinética do carbapenêmico. Finalmente, a abordagem PK/PD baseada na dosagem sérica realizada em tempo real se mostrou importante ferramenta para acessar a efetividade do antimicrobiano nos pacientes sépticos, permitindo ainda a alteração precoce de conduta médica, de forma a se atingir o desfecho clínico desejado

A Single Dose of a Hybrid hAdV5-Based Anti-COVID-19 Vaccine Induces a Long-Lasting Immune Response and Broad Coverage against VOC

Most approved vaccines against COVID-19 have to be administered in a prime/boost regimen. We engineered a novel vaccine based on a chimeric human adenovirus 5 (hAdV5) vector. The vaccine (named CoroVaxG.3) is based on three pillars: (i) high expression of Spike to enhance its immunodominance by using a potent promoter and an mRNA stabilizer; (ii) enhanced infection of muscle and dendritic cells by replacing the fiber knob domain of hAdV5 by hAdV3; (iii) use of Spike stabilized in a prefusion conformation. The transduction with CoroVaxG.3-expressing Spike (D614G) dramatically enhanced the Spike expression in human muscle cells, monocytes and dendritic cells compared to CoroVaxG.5 that expressed the native fiber knob domain. A single dose of CoroVaxG.3 induced a potent humoral immunity with a balanced Th1/Th2 ratio and potent T-cell immunity, both lasting for at least 5 months. Sera from CoroVaxG.3-vaccinated mice was able to neutralize pseudoviruses expressing B.1 (wild type D614G), B.1.117 (alpha), P.1 (gamma) and B.1.617.2 (delta) Spikes, as well as an authentic P.1 SARS-CoV-2 isolate. Neutralizing antibodies did not wane even after 5 months, making this kind of vaccine a likely candidate to enter clinical trials.Fil: López, M. Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Vinzon, Sabrina Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Cafferata, Eduardo Gustavo Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Nuñez, Felipe. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Soto, Ariadna Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Sanchez Lamas, Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Afonso, María Jimena. Fundación Instituto Leloir; ArgentinaFil: Aguilar Cortes, Diana Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Rios, Gregorio David. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Maricato, Juliana T.. Universidade Federal de Sao Paulo; BrasilFil: Torres Braconi, Carla. Universidade Federal de Sao Paulo; BrasilFil: Barbosa da Silveira, Vanessa. Universidade Federal de Sao Paulo; BrasilFil: Montes de Andrade, Tatiane. Universidade Federal de Sao Paulo; BrasilFil: Carvalho de Souza Bonetti, Tatiana. Universidade Federal de Sao Paulo; BrasilFil: Ramos Janini, Luiz M.. Universidade Federal de Sao Paulo; BrasilFil: Castello Girão, Manoel J. B.. Universidade Federal de Sao Paulo; BrasilFil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Ortega, Hugo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Berguer, Paula Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentin

Characterization of Oxidative Guanine Damage and Repair in Mammalian Telomeres

8-oxo-7,8-dihydroguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) are among the most common oxidative DNA lesions and are substrates for 8-oxoguanine DNA glycosylase (OGG1)–initiated DNA base excision repair (BER). Mammalian telomeres consist of triple guanine repeats and are subject to oxidative guanine damage. Here, we investigated the impact of oxidative guanine damage and its repair by OGG1 on telomere integrity in mice. The mouse cells were analyzed for telomere integrity by telomere quantitative fluorescence in situ hybridization (telomere–FISH), by chromosome orientation–FISH (CO–FISH), and by indirect immunofluorescence in combination with telomere–FISH and for oxidative base lesions by Fpg-incision/Southern blot assay. In comparison to the wild type, telomere lengthening was observed in Ogg1 null (Ogg1−/−) mouse tissues and primary embryonic fibroblasts (MEFs) cultivated in hypoxia condition (3% oxygen), whereas telomere shortening was detected in Ogg1−/− mouse hematopoietic cells and primary MEFs cultivated in normoxia condition (20% oxygen) or in the presence of an oxidant. In addition, telomere length abnormalities were accompanied by altered telomere sister chromatid exchanges, increased telomere single- and double-strand breaks, and preferential telomere lagging- or G-strand losses in Ogg1−/− mouse cells. Oxidative guanine lesions were increased in telomeres in Ogg1−/− mice with aging and primary MEFs cultivated in 20% oxygen. Furthermore, oxidative guanine lesions persisted at high level in Ogg1−/− MEFs after acute exposure to hydrogen peroxide, while they rapidly returned to basal level in wild-type MEFs. These findings indicate that oxidative guanine damage can arise in telomeres where it affects length homeostasis, recombination, DNA replication, and DNA breakage repair. Our studies demonstrate that BER pathway is required in repairing oxidative guanine damage in telomeres and maintaining telomere integrity in mammals

Search for CP violation in D+→ϕπ+ and D+s→K0Sπ+ decays

A search for CP violation in D + → ϕπ + decays is performed using data collected in 2011 by the LHCb experiment corresponding to an integrated luminosity of 1.0 fb−1 at a centre of mass energy of 7 TeV. The CP -violating asymmetry is measured to be (−0.04 ± 0.14 ± 0.14)% for candidates with K − K + mass within 20 MeV/c 2 of the ϕ meson mass. A search for a CP -violating asymmetry that varies across the ϕ mass region of the D + → K − K + π + Dalitz plot is also performed, and no evidence for CP violation is found. In addition, the CP asymmetry in the D+s→K0Sπ+ decay is measured to be (0.61 ± 0.83 ± 0.14)%

Measurement of the Bs0→J/ψKS0B_s^0\to J/\psi K_S^0 branching fraction

The $B_s^0\to J/\psi K_S^0$ branching fraction is measured in a data sample corresponding to 0.41$fb^{-1}$ of integrated luminosity collected with the LHCb detector at the LHC. This channel is sensitive to the penguin contributions affecting the sin2$\beta$ measurement from $B^0\to J/\psi K_S^0$ The time-integrated branching fraction is measured to be $BF(B_s^0\to J/\psi K_S^0)=(1.83\pm0.28)\times10^{-5}$. This is the most precise measurement to date

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Differential branching fraction and angular analysis of the decay B0→K∗0μ+μ−

The angular distribution and differential branching fraction of the decay B 0→ K ∗0 μ + μ − are studied using a data sample, collected by the LHCb experiment in pp collisions at s√=7 TeV, corresponding to an integrated luminosity of 1.0 fb−1. Several angular observables are measured in bins of the dimuon invariant mass squared, q 2. A first measurement of the zero-crossing point of the forward-backward asymmetry of the dimuon system is also presented. The zero-crossing point is measured to be q20=4.9±0.9GeV2/c4 , where the uncertainty is the sum of statistical and systematic uncertainties. The results are consistent with the Standard Model predictions