O que mudou entre os períodos de pico e de platô durante a primeira onda do SARS-CoV-2? Estudo multicêntrico português em unidades de cuidados intensivos / What changed between the peak and plateau periods of the first COVID-19 pandemic wave? A multicentric Portuguese cohort study in intensive care

RESUMO Objetivo: Analisar e comparar as características de pacientes críticos com a COVID-19, a abordagem clínica e os resultados entre os períodos de pico e de platô na primeira onda pandêmica em Portugal. Métodos: Este foi um estudo de coorte multicêntrico ambispectivo, que incluiu pacientes consecutivos com a forma grave da COVID-19 entre março e agosto de 2020 de 16 unidades de terapia intensiva portuguesas. Definiram-se as semanas 10 - 16 e 17 - 34 como os períodos de pico e platô. Resultados: Incluíram-se 541 pacientes adultos com mediana de idade de 65 [57 - 74] anos, a maioria do sexo masculino (71,2%). Não houve diferenças significativas na mediana de idade (p = 0,3), no Simplified Acute Physiology Score II (40 versus 39; p = 0,8), na pressão parcial de oxigênio/fração inspirada de oxigênio (139 versus 136; p = 0,6), na terapia com antibióticos na admissão (57% versus 64%; p = 0,2) ou na mortalidade aos 28 dias (24,4% versus 22,8%; p = 0,7) entre o período de pico e platô. Durante o período de pico, os pacientes tiveram menos comorbidades (1 [0 - 3] versus 2 [0 - 5]; p = 0,002); fizeram mais uso de vasopressores (47% versus 36%; p < 0,001) e ventilação mecânica invasiva na admissão (58,1% versus 49,2%; p < 0,001), e tiveram mais prescrição de hidroxicloroquina (59% versus 10%; p < 0,001), lopinavir/ritonavir (41% versus 10%; p < 0,001) e posição prona (45% versus 36%; p = 0,04). Entretanto, durante o platô, observou-se maior uso de cânulas nasais de alto fluxo (5% versus 16%; p < 0,001) na admissão, remdesivir (0,3% versus 15%; p < 0,001) e corticosteroides (29% versus 52%; p < 0,001), além de menor tempo de internação na unidade de terapia intensiva (12 versus 8 dias; p < 0,001). Conclusão: Houve mudanças significativas nas comorbidades dos pacientes, nos tratamentos da unidade de terapia intensiva e no tempo de internação entre os períodos de pico e platô na primeira onda da COVID-19.

ABSTRACT Objective: To analyze and compare COVID-19 patient characteristics, clinical management and outcomes between the peak and plateau periods of the first pandemic wave in Portugal. Methods: This was a multicentric ambispective cohort study including consecutive severe COVID-19 patients between March and August 2020 from 16 Portuguese intensive care units. The peak and plateau periods, respectively, weeks 10 - 16 and 17 - 34, were defined. Results: Five hundred forty-one adult patients with a median age of 65 [57 - 74] years, mostly male (71.2%), were included. There were no significant differences in median age (p = 0.3), Simplified Acute Physiology Score II (40 versus 39; p = 0.8), partial arterial oxygen pressure/fraction of inspired oxygen ratio (139 versus 136; p = 0.6), antibiotic therapy (57% versus 64%; p = 0.2) at admission, or 28-day mortality (24.4% versus 22.8%; p = 0.7) between the peak and plateau periods. During the peak period, patients had fewer comorbidities (1 [0 - 3] versus 2 [0 - 5]; p = 0.002) and presented a higher use of vasopressors (47% versus 36%; p < 0.001) and invasive mechanical ventilation (58.1 versus 49.2%; p < 0.001) at admission, prone positioning (45% versus 36%; p = 0.04), and hydroxychloroquine (59% versus 10%; p < 0.001) and lopinavir/ritonavir (41% versus 10%; p < 0.001) prescriptions. However, a greater use of high-flow nasal cannulas (5% versus 16%, p < 0.001) on admission, remdesivir (0.3% versus 15%; p < 0.001) and corticosteroid (29% versus 52%, p < 0.001) therapy, and a shorter ICU length of stay (12 days versus 8, p < 0.001) were observed during the plateau. Conclusion: There were significant changes in patient comorbidities, intensive care unit therapies and length of stay between the peak and plateau periods of the first COVID-19 wave.

Essential Conditions for the Full Synergy of Probability of Occurrence Distributions.

In this contribution, we specify the conditions for assuring the validity of the synergy of the distribution of probabilities of occurrence. We also study the subsequent restriction on the maximal extension of the strict concavity region on the parameter space of Sharma-Mittal entropy measures, which has been derived in a previous paper in this journal. The present paper is then a necessary complement to that publication. Some applications of the techniques introduced here are applied to protein domain families (Pfam databases, versions 27.0 and 35.0). The results will show evidence of their usefulness for testing the classification work performed with methods of alignment that are used by expert biologists.

Cytokine Adsorption Therapy during Extracorporeal Membrane Oxygenation in Adult Patients with COVID-19.

Respiratory failure and systemic inflammation are paramount features of severe SARS-CoV-2 disease (COVID-19). Extracorporeal membrane oxygenation (ECMO) therapy has a potential role in patients with refractory disease. An inflammatory response due to blood contact with hemofilters, functioning as a synergic inflammatory stimulus, can lead to a hyperinflammatory state, relatable to cytokine release syndromes. After the first patient succumbed to a refractory vasodilatory shock believed to be due to hyperinflammatory state, a strategy of blood purification through cytokine adsorption therapy (CAT) with CytoSorb® was designed. In this case series, the authors describe the initial experience with such strategy. CAT was employed with no direct complications and helped controlling the inflammatory state, with all patients halting vasopressor support in 72 h and biomarker levels (C-reactive protein, ferritin, and interleukin-6) showing negative trends in most patients. Analysis of inflammatory biomarkers evolution highlighted 2 biomarker profiles related to the presence or absence of superinfection at the time of CAT implementation. In this case series of severe COVID-19 patients, 3 patients died - irreversible lung fibrosis, complications of critical hypoxemia before ECMO induction and complications of systemic anticoagulation were the causes. This case series aimed to contribute to the body of evidence substantiating CAT utilization in hyperinflammatory patients, namely, COVID-19 patients requiring ECMO rescue.

What changed between the peak and plateau periods of the first COVID-19 pandemic wave? A multicentric Portuguese cohort study in intensive care. / O que mudou entre os períodos de pico e de platô durante a primeira onda do SARS-CoV-2? Estudo multicêntrico português em unidades de cuidados intensivos.

OBJECTIVE: To analyze and compare COVID-19 patient characteristics, clinical management and outcomes between the peak and plateau periods of the first pandemic wave in Portugal. METHODS: This was a multicentric ambispective cohort study including consecutive severe COVID-19 patients between March and August 2020 from 16 Portuguese intensive care units. The peak and plateau periods, respectively, weeks 10 - 16 and 17 - 34, were defined. RESULTS: Five hundred forty-one adult patients with a median age of 65 [57 - 74] years, mostly male (71.2%), were included. There were no significant differences in median age (p = 0.3), Simplified Acute Physiology Score II (40 versus 39; p = 0.8), partial arterial oxygen pressure/fraction of inspired oxygen ratio (139 versus 136; p = 0.6), antibiotic therapy (57% versus 64%; p = 0.2) at admission, or 28-day mortality (24.4% versus 22.8%; p = 0.7) between the peak and plateau periods. During the peak period, patients had fewer comorbidities (1 [0 - 3] versus 2 [0 - 5]; p = 0.002) and presented a higher use of vasopressors (47% versus 36%; p < 0.001) and invasive mechanical ventilation (58.1 versus 49.2%; p < 0.001) at admission, prone positioning (45% versus 36%; p = 0.04), and hydroxychloroquine (59% versus 10%; p < 0.001) and lopinavir/ritonavir (41% versus 10%; p < 0.001) prescriptions. However, a greater use of high-flow nasal cannulas (5% versus 16%, p < 0.001) on admission, remdesivir (0.3% versus 15%; p < 0.001) and corticosteroid (29% versus 52%, p < 0.001) therapy, and a shorter ICU length of stay (12 days versus 8, p < 0.001) were observed during the plateau. CONCLUSION: There were significant changes in patient comorbidities, intensive care unit therapies and length of stay between the peak and plateau periods of the first COVID-19 wave.

OBJETIVO: Analisar e comparar as características de pacientes críticos com a COVID-19, a abordagem clínica e os resultados entre os períodos de pico e de platô na primeira onda pandêmica em Portugal. MÉTODOS: Este foi um estudo de coorte multicêntrico ambispectivo, que incluiu pacientes consecutivos com a forma grave da COVID-19 entre março e agosto de 2020 de 16 unidades de terapia intensiva portuguesas. Definiram-se as semanas 10 - 16 e 17 - 34 como os períodos de pico e platô. RESULTADOS: Incluíram-se 541 pacientes adultos com mediana de idade de 65 [57 - 74] anos, a maioria do sexo masculino (71,2%). Não houve diferenças significativas na mediana de idade (p = 0,3), no Simplified Acute Physiology Score II (40 versus 39; p = 0,8), na pressão parcial de oxigênio/fração inspirada de oxigênio (139 versus 136; p = 0,6), na terapia com antibióticos na admissão (57% versus 64%; p = 0,2) ou na mortalidade aos 28 dias (24,4% versus 22,8%; p = 0,7) entre o período de pico e platô. Durante o período de pico, os pacientes tiveram menos comorbidades (1 [0 - 3] versus 2 [0 - 5]; p = 0,002); fizeram mais uso de vasopressores (47% versus 36%; p < 0,001) e ventilação mecânica invasiva na admissão (58,1% versus 49,2%; p < 0,001), e tiveram mais prescrição de hidroxicloroquina (59% versus 10%; p < 0,001), lopinavir/ritonavir (41% versus 10%; p < 0,001) e posição prona (45% versus 36%; p = 0,04). Entretanto, durante o platô, observou-se maior uso de cânulas nasais de alto fluxo (5% versus 16%; p < 0,001) na admissão, remdesivir (0,3% versus 15%; p < 0,001) e corticosteroides (29% versus 52%; p < 0,001), além de menor tempo de internação na unidade de terapia intensiva (12 versus 8 dias; p < 0,001). CONCLUSÃO: Houve mudanças significativas nas comorbidades dos pacientes, nos tratamentos da unidade de terapia intensiva e no tempo de internação entre os períodos de pico e platô na primeira onda da COVID-19.

Alternative Entropy Measures and Generalized Khinchin-Shannon Inequalities.

The Khinchin-Shannon generalized inequalities for entropy measures in Information Theory, are a paradigm which can be used to test the Synergy of the distributions of probabilities of occurrence in physical systems. The rich algebraic structure associated with the introduction of escort probabilities seems to be essential for deriving these inequalities for the two-parameter Sharma-Mittal set of entropy measures. We also emphasize the derivation of these inequalities for the special cases of one-parameter Havrda-Charvat's, Rényi's and Landsberg-Vedral's entropy measures.

Senile Systemic Amyloidosis: An Underdiagnosed Disease.

Senile systemic amyloidosis is caused by a non-mutated form of transthyretin with the heart being the major organ involved. This infiltrative cardiomyopathy usually presents as slowly progressive heart failure. An 82-year-old female patient was admitted for newly diagnosed heart failure. A year later she presented with decompensated heart failure and syncope. Inpatient work-up showed persistently elevated troponin and N-terminal-pro BNP levels, rapid progression to severe left ventricular concentric hypertrophy, and sinus pauses on the Holter. Cardiac MRI revealed diffuse late gadolinium enhancement in the left ventricle. The demonstration of amyloid protein with the clinical findings and complementary investigations allowed for the diagnosis of senile systemic amyloidosis. LEARNING POINTS: Senile systemic amyloidosis is a rare disease with a common clinical presentation that is probably underdiagnosed in patients with heart failure with preserved systolic function.A new unexplained heart failure diagnosis, increased ventricular wall thickness and particularly low voltage on the ECG should raise the suspicion of cardiac amyloidosis.Histopathological evidence of amyloid deposition elsewhere and typical advanced imaging features can support the diagnosis, rendering endomyocardial biopsy no longer mandatory.

Synchronous presentation of two rare forms of extrapulmonary tuberculosis.

Tuberculosis (TB) remains one of the leading infectious causes of death throughout the world. Extrapulmonary forms, namely adrenalitis and prostatitis, are rare presentations of TB and pose a difficult diagnostic challenge, given their non-specific manifestations. The authors present a case of a 42-year-old man with long-standing symptoms of fatigue, anorexia, weight loss, nightly fever and sudoresis. He also suffered from sporadic vomiting and episodic hypotension, and had skin hyperpigmentation, as well as frequent urination, perineal discomfort and pain at ejaculation. Laboratory investigation confirmed primary adrenal failure. On CT scan there were two hypodense right adrenal nodules and bilateral lung condensations with a tree-in-bud pattern. Another hypodense nodule was seen in the prostate. TB was diagnosed by isolatingMycobacterium tuberculosisfollowing cultures of bronchoalveolar lavage, bronchial secretions, urine and ejaculate. Antibacillary treatment resolved the infectious lesions but the patient remained on corticosteroid replacement therapy for ongoing adrenal failure.

Exertional heat stroke and acute liver failure: a late dysfunction.

Heat stroke (HS) is defined as a severe elevation of core body temperature along with central nervous system dysfunction. Exertional heat stroke (EHS) with acute liver failure (ALF) is a rare condition. The authors report the case of a 25-year-old man with a history of cognitive enhancers' intake who developed hyperthermia and neurological impairment while running an outdoor marathon. The patient was cooled and returned to normal body temperature after 6 h. He subsequently developed ALF and was transferred to the intensive care unit. Over-the-counter drug intake may have been related to heat intolerance and contributed to the event. The patient was successfully treated with conservative measures. In the presence of EHS, it is crucial to act promptly with aggressive total body cooling, in order to prevent progression of the clinical syndrome. Liver function must also be monitored, since it can be a late organ dysfunction.

Malignant Otitis Externa and Stroke.

Malignant otitis externa (MOE) is an aggressive but benign entity which evolves into skull base osteomyelitis. An 81-year-old female patient was admitted for left hemiparesis and homonymous hemianopia. She complained of headache radiating to the right cervical area. A recent history of recurrent otitis media was present. Head and neck imaging showed an ischemic infarction (right temporo-occipital) and a parapharyngeal soft tissue mass originating in an external and medial ear infection. Culture samples revealed Pseudomonas aeruginosa infection leading to the diagnosis of Malignant otitis externa (MOE). Parenteral antibacterial therapy and hyperbaric oxygen therapy resulted in improvement. LEARNING POINTS: Malignant otitis externa is an aggressive and life-threatening disease which must be identified early and treated promptly for therapeutic success.Although starting as an outer ear infection (typically caused by Pseudomonas aeruginosa) local spread can involve noble head and neck structures leading to variable signs and symptoms.Modern imaging techniques can help define structure involvement (MRI) and may help identify disease activity and prognosis (nuclear medicine).

Sonographic assessment of vessel invasion by cervical masses in dogs / Avaliação ultrassonográfica da invasão vascular por massas cervicais em cães

Tumor invasion of the vessels displays both therapeutic and prognostic implications and represents a challenge for head and neck surgeons. Although previous research has shown that ultrasound can detect such invasions, accurate sonographic parameters to do so have not yet been established. We sought to determine sonographic criteria which are able to characterize these invasions. A high-resolution transducer was used to perform ultrasound examinations of 15 patients selected from a group with inconclusive radiography and computed tomography diagnosis. We found that encasement of the vessel, tumor immobility or fixation in the vessel wall, and narrowing and/or deformity of the lumen were the best criteria. Indeed, when loss of hyperechoic interface of the vessel wall was used as a single criterion it generated false positive results. This study shows that a combination of parameters can be used to provide the best sensitivity and specificity values to produce conclusive diagnosis of vessel invasion by tumors in the cervical region.

Determinaram-se critérios ultrassonográficos capazes de caracterizar a invasão vascular por tumores em cães. Utilizaram-se transdutores de alta resolução para os exames ultrassonográficos realizados em 15 pacientes, selecionados de um grupo submetido previamente à radiografia e tomografia computadorizada, com resultados inconclusivos. Os melhores critérios encontrados foram: encarceramento do vaso, imobilidade do tumor ou aderência na parede vascular e estreitamento ou deformidade luminal. A perda de definição da interface hiperecoica da parede vascular quando foi usada como critério isolado produziu resultados falso positivos. O estudo demonstrou que uma combinação de parâmetros pode ser usada para aumentar a sensibilidade e especificidade diagnóstica, produzindo diagnósticos mais conclusivos e precisos pra definir a invasão vascular por tumores na região cervical ventral.

[Peritonitis in the neonatal period]. / Peritonite no período neonatal.

The authors report a case of 32-week-old newborn, admitted to the Intensive Care Unit for Newborns. Mechanical ventilation was needed from the first day of life. The patient was treated with indomethacin on the second day of life due to patent ductus arteriosus. On the seventh day pneumoperitoneum was diagnosed, emergency surgery was performed revealing perforation of Meckel's diverticulum. Perinatal asphyxia and indomethacin administration probably played an important role in this process.

[Nosocomial infection in a pediatric intensive care unit]. / Infecção nosocomial numa unidade de cuidados intensivos pediátricos.

UNLABELLED: Patients in intensive care units (ICU) are 3 to 4 times more prone to nosocomial infection (NI) than patients in general wards owing to the severity of their pathology and the frequent use of invasive procedures. The aim of this study was to establish the incidence of NI in an ICU and the associated risk factors. PATIENTS AND METHODS: During 18 months, all patients with severity scores III and IV (Clinical Classification System) were studied, (n = 575). The admissions were mainly due to accidents (24.7%), neurological (19.1%), surgical (17.2%), respiratory (11.1%) and infectious (7.0%) disease. The mean duration of stay was 2.4 days. The mortality was 5.2%. The evaluation protocol of these patients included determination of the PRISM score, registration of every invasive procedure and daily search for clinical and laboratory signs of infection. NI was defined according to the criteria of the Centers for Disease Control. Both the intrinsic and extrinsic risk factors were analysed and in the statistical analysis the null hypothesis was rejected at the significance level of p < 0.05. RESULTS: The incidence of NI was 7.6%. The infections occurred in the respiratory tract in 20 patients, bloodstream in 8, genito-urinary tract in 2, central nervous system in 2, skin in 2, gastrointestinal tract in 2, eyes in 1 and surgical wound in 1. There were isolates in 60.6%. The mean duration of stay was longer in patients with NI (9.8 versus 1.9). The factors most closely associated with NI were higher PRISM scores, malnutrition, immunodeficiency failure of 2 or more organs, administration of antibiotic since admission or corticosteroids and simultaneous use of 3 or more invasive procedures. The risk of pneumonia was significantly increased in patients with mechanical ventilation and all the patients with bacteremia had central venous catheters. The mortality was higher in the group with NI (18.2%) than in the group without NI (4.4%). CONCLUSIONS: The incidence of NI is acceptable in our ICU. The most frequent location was the respiratory tract (52.6%). The pathogens most frequently isolated in this ICU were Gram negative rods. The risk of NI increased in more debilitated patients with more severe disease who were administered antibiotic or corticosteroids and submitted to more invasive procedures.

[Adult type respiratory distress syndrome (ARDS) induced by hydrocarbons]. / Síndrome de dificuldade respiratória tipo adulto (ARDS) induzido por hidrocarbonetos.

The authors present a case of a child aged 32 months, victim of accidental ingestion of an unidentified hydrocarbon product. Sixteen hours following hospitalization, the patient began polypnea with progressive hypoxemia, with the radiograph showing ARDS pattern. Mechanical ventilation was initiated on the 2nd day of admission. During hospitalization the patient developed pneumomediastinum and bilateral pneumothorax which justified active drainage. Inspite of the initial poor prognosis, the patient improved, with no symptoms after discharge. The authors discuss certain theoretical considerations regarding hydrocarbon intoxication.

Aspectos sazonais da limitaçäo potencial por N, P, e Fe no litoplâncton da represa de Barra Bonita, rio Tietê, SP / Seasonal aspects of potential limitation by N, P, and Fe on phytoplankton in Barra Bonita reservoir (river Tietê, SP)

Experimentos de enriquecimento artificial e medidas de seus efeitos no fitoplâncton de superfície foram efetuados durante um ano. Após 3 a 10 dias de incubaçäo "in situ", as respostas medidas foram os teores de clorofila-a e feofitina, a produçäo primária pelo fitoplâncton de amostras enriquecidas e nutrientes inorgânicanicos dissolvidos remanescentes nos frascos. Durante todo o ciclo anual, o fosfato foi o nutriente estimulador do crescimento do fitopâncton (clorofila-a). A resposta à adiçäo de fosfato foi mais imediata (3§ dia) nos experimentos de março, abril-maio e setembro de l984 e janeiro de l985, ou ocorreu depois de um prazo maior (10§ dia) em junho e novembro de l984. A adiçäo de nitrato, mesmo em combinaçäo com fosfato, näo tem efeito estimulador. Desta forma, em todo o ano, o nitrogênio näo tem um papel importante na limitaçäo ao desenvolvimento do fitoplâncton. A açäo do ferro como agente estimulador é secundária

Diastematomielia.Relato de dois casos / Diastematomyelia. Report of 2 cases

Foram descritos dois casos de pacientes portadores de diastematomielia, ambos do sexo feminino, com idade de 5 e 11 anos.Apresentaram clinicamente dificuldade a deambulacao e ulceracao no halux. As alteracoes radiologicas consistiram basicamente de escoliose e alargamento do canal medular no segmento lombar acompanhado de esporao osseo na linha media

Principios fisicos e o controle da qualidade da imagem e da exposicao em mamografia. / Physical principles and the quality control of the image and the exposure in mammography

Mamografia e o mais eficiente metodo de se detectar alguns casos de cancer de mama antes de ser clinicamente palpavel. A qualidade de um sistema de imagem deve ser determinada pela habilidade de se detectar, nao somente massas de tecido mole, cisto ou tumores solidos mas, tambem, microcalcificacoes. Assim, o objetivo de qualquer sistema mamografico deve ser o de obter mamografias da melhor qualidade com os mais baixos indices de exposicao a radiacao. Neste trabalho foi utilizado o fantoma mamografico da Universidade de Wisconsin. Os resultados mostram imagens de boa qualidade com uma exposicao de 1,8R

Aneurismas imtracranianos gigantes multiplos (relato de um caso). / Multiple giant intracranial aneurysms case report)

Os autores apresentam um caso de aneurismas multiplos, em uma paciente de 54 anos, com historia de disturbios de visao ha um ano. A tomografia computadorizada mostrou lesao dupla, que nao podia ser definitivamente diferenciada de neoplasia, sobretudo meningioma. O diagnostico definitivo foi obtido com angiografia

[The electrocardiogram of the normal child]. / Electrocardiograma en el niño normal.

The EKG findings of 202 normal children, aged 1 month to 10 years were reviewed in order to determine criteria for diagnosis of ventricular hypertrophy. QRS voltage in right and left precordial leads are very variable and do not constitute adequate criteria for the diagnosis of ventricular hypertrophy the same is true with QRS duration, which increases progressively from 50 to 60 msec from the first to the fourth year of life, and to 70 msec over that age. The values found are smaller than those previously reported in the literature. Measurement of initial intrinsicoid deflection time in leads VI, aVF and V6 apparently have important clinical significance. This is a constant finding in normal hearts in lead VI, where deflection time is 18 to 20 msec. Therefore, times above 25 to 30 msec are sugestive of right ventricular hypertrophy when RBBB is not present. Intrinsicoid deflection time in lead V6 in children under one year of age was 20 msec, while between age one and ten it varied between 20 and 31 msec. Such variations show how left ventricular tissue increases after the first years of life, and also that times above 5 msec over those found for any age group are indicative of left ventricular hypertrophy.