Partial and simultaneous remission of nephritis and autoimmune hemolytic anemia in patients with lupus after treatment with biological agent: a case report

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease, systemic, of unknown cause and autoimmune nature. It features variable prognosis, depending on the affected organ or system. The renal impairment is the condition most often related to morbidity and mortality. This manuscript aims to contribute to the further evidence that early diagnosis of lupus associated with quickly aggressive therapy could increase the success outcome rate. Also, immediate recognition of therapeutic failures and change the treatment strategy must be applied. In this regard, a new therapeutic option seems to be the biological drug rituximab described in this study and which it is emphasised because of its possible and still supposed ability to act as a rescue agent for nephritis and hemolytic lupus anaemia, simultaneously, with effectiveness and safety. This article presents the case of female lupus patient with both severe refractory hematologic disorder and renal impairment, which had an evolution of the simultaneous restoration of urine output, and clinical and laboratory improvement of autoimmune anaemia after rituximab administration. The persistence of renal damage could not be ruled out, so the response to treatment was considered to be partialO Lúpus Eritematoso Sistêmico (LES) é uma doença inflamatória crônica, sistêmica, de causa desconhecida e de natureza autoimune. Apresenta prognóstico variável, dependente do órgão ou sistema acometido, sendo o comprometimento renal uma das condições mais frequentemente relacionadas à morbimortalidade. O presente manuscrito propõe-se a contribuir como mais um indício de que o diagnóstico precoce e a terapia agressiva inicial, no lúpus, elevam sobremaneira o índice de sucesso clinico. Falhas no tratamento devem ser reconhecidas de imediato, com rápida mudança de estratégia, quando necessário. Neste sentido, uma nova opção terapêutica parece ser o agente biológico rituximab, descrito neste estudo e para o qual é dada ênfase devido à sua possível e ainda suposta capacidade de atuar como agente de resgate para a nefrite e para a anemia hemolítica lúpicas, simultaneamente, com efetividade e segurança. Apresenta-se o caso de paciente lúpica com acometimento renal e hematológico grave e refratário, que evoluiu simultaneamente com restabelecimento do débito urinário e melhora clínico-laboratorial da anemia autoimune após administração de rituximab, resposta considerada parcial, posto que a existência de dano renal persistente não pode ser descartad

International Union of Angiology (IUA) consensus paper on imaging strategies in atherosclerotic carotid artery imaging: From basic strategies to advanced approaches

Cardiovascular disease (CVD) is the leading cause of mortality and disability in developed countries. According to WHO, an estimated 17.9 million people died from CVDs in 2019, representing 32% of all global deaths. Of these deaths, 85% were due to major adverse cardiac and cerebral events. Early detection and care for individuals at high risk could save lives, alleviate suffering, and diminish economic burden associated with these diseases. Carotid artery disease is not only a well-established risk factor for ischemic stroke, contributing to 10%–20% of strokes or transient ischemic attacks (TIAs), but it is also a surrogate marker of generalized atherosclerosis and a predictor of cardiovascular events. In addition to diligent history, physical examination, and laboratory detection of metabolic abnormalities leading to vascular changes, imaging of carotid arteries adds very important information in assessing stroke and overall cardiovascular risk. Spanning from carotid intima-media thickness (IMT) measurements in arteriopathy to plaque burden, morphology and biology in more advanced disease, imaging of carotid arteries could help not only in stroke prevention but also in ameliorating cardiovascular events in other territories (e.g. in the coronary arteries). While ultrasound is the most widely available and affordable imaging methods, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), their combination and other more sophisticated methods have introduced novel concepts in detection of carotid plaque characteristics and risk assessment of stroke and other cardiovascular events. However, in addition to robust progress in usage of these methods, all of them have limitations which should be taken into account. The main purpose of this consensus document is to discuss pros but also cons in clinical, epidemiological and research use of all these techniques

Strengthening therapeutic adherence and pharmacovigilance to antimalarial treatment in Manaus, Brazil: a multicomponent strategy using mHealth

Background: Public health initiatives for improving adherence to primaquine based regimens and enhancing effective pharmacovigilance are needed to support the efforts for malaria elimination in real world conditions. Methods: A multicomponent patient-oriented strategy using a Smart Safety Surveillance (3S) approach including: (1) educational materials for treatment counselling and identification of warning symptoms of haemolytic anaemia; (2) an mHealth component using Short Message Service (SMS) treatment reminders and (3) development and implementation of follow-up phone surveys three days after treatment completion, using a web-based platform linked to the local information system of malaria. Adherence was measured using the Morisky Medication Adherence Scale. Self-reported events were registered using a structured questionnaire and communicated to the Brazilian Health Regulatory Agency. Results: Educational materials were disseminated to 5594 patients, of whom 1512 voluntarily entered the mHealth component through the local information system; 7323 SMS were sent, and 1062 participants completed a follow-up survey after treatment. The mean age of patients was 37.36 years (SD 13.65), 61.24% were male, 98.54% were infected with. Plasmodium vivax and 95.90% received a short regimen of chloroquine plus primaquine (CQ + PQ 7 days), as per malaria case management guidelines in Brazil. From the 1062 surveyed participants 93.31% were considered adherent to the treatment. Most of the patients (95.20%) reported at least one adverse event. Headache, lack of appetite and nausea/vomiting were the most frequently reported adverse events by 77.31%, 70.90% and 56.78% of the patients respectively. A quarter of the patients reported anxiety or depression symptoms; 57 (5.37%) patients reported 5 to 6 warning symptoms of haemolytic anaemia including jaundice and dark urine in 44 (4.14%). Overall, three patients presenting symptoms of haemolytic anaemia attended a hospital and were diagnosed with G6PD deficiency, and one had haemolysis. All of them recovered. Conclusions: Under real world conditions, a multicomponent patient-oriented strategy using information and communication technologies allowed health care providers to reinforce treatment adherence and enhance safety surveillance of adverse events associated with regimens using primaquine. Active monitoring through phone surveys also reduced under-reporting of ADRs. This approach is low-cost, scalable and able to support prioritized activities of the national malaria programme.Fil: Macías Saint Gerons, Diego. Universidad de Valencia; EspañaFil: Rodovalho, Sheila. Universidad Federal del Amazonas.; BrasilFil: Barros Dias, Ádila Liliane. Universidad Federal del Amazonas.; BrasilFil: Lacerda Ulysses de Carvalho, André. Pan American Health Organization; BrasilFil: Beratarrechea, Andrea Gabriela. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Monteiro, Wuelton Marcelo. Universidad Federal del Amazonas.; BrasilFil: Barata Machado, Myrna. State of Amazonas Health Surveillance Foundation; BrasilFil: Fernandes da Costa, Cristiano. State of Amazonas Health Surveillance Foundation; BrasilFil: Yoshito Wada, Marcelo. No especifíca;Fil: Maximiano Faria de Almeida, Márcia Helena. No especifíca;Fil: Silva de Matos Fonseca, Rayanne. Fundação de Medicina Tropical Dr. Heitor Vieira Dourado; BrasilFil: Mota Cordeiro, Jady Shayenne. Fundação de Medicina Tropical Dr. Heitor Vieira Dourado; BrasilFil: Rodrigues Antolini, Alinne Paula. No especifíca;Fil: Nepomuceno, João Altecir. No especifíca;Fil: Fleck, Karen. Brazilian Health Regulatory Agency; BrasilFil: Simioni Gasparotto, Fernanda. Brazilian Health Regulatory Agency; BrasilFil: Lacerda, Marcus. Fundação de Medicina Tropical Dr. Heitor Vieira Dourado; BrasilFil: Rojas Cortés, Robin. Pan American Health Organization; Estados UnidosFil: Pal, Shanthi Narayan. No especifíca;Fil: Porrás, Analía I.. Pan American Health Organization; Estados UnidosFil: Ade, María de la Paz. Pan American Health Organization; Estados UnidosFil: Castro, José Luis. Pan American Health Organization; Estados Unido

Immunolocalization of cell wall polymers in grapevine (Vitis vinifera) internodes under nitrogen, phosphorus or sulfur deficiency

Abstract The impact on cell wall (CW) of the deficiency in nitrogen (–N), phosphorus (–P) or sulphur (–S), known to impair essential metabolic pathways, was investigated in the economically important fruit species Vitis vinifera L. Using cuttings as an experimental model a reduction in total internode number and altered xylem shape was observed. Under –N an increased internode length was also seen. CW composition, visualised after staining with calcofluor white, Toluidine blue and ruthenium red, showed decreased cellulose in all stresses and increased pectin content in recently formed internodes under –N compared to the control. Using CW-epitope specific monoclonal antibodies (mAbs), lower amounts of extensins incorporated in the wall were also observed under –N and –P conditions. Conversely, increased pectins with a low degree of methyl-esterification and richer in long linear 1,5-arabinan rhamnogalacturonan-I (RG-I) side chains were observed under –N and –P in mature internodes which, in the former condition, were able to form dimeric association through calcium ions. –N was the only condition in which 1,5-arabinan branched RG- content was not altered, as –P and –S older internodes showed, respectively, lower and higher amounts of this polymer. Higher xyloglucan content in older internodes was also observed under –N. The results suggest that impairments of specific CW components led to changes in the deposition of other polymers to promote stiffening of the CW. The unchanged extensin amount observed under –S may contribute to attenuating the effects on the CW integrity caused by this stress. Our work showed that, in organized V. vinifera tissues, modifications in a given CW component can be compensated by synthesis of different polymers and/or alternative linking between polymers. The results also pinpoint different strategies at the CW level to overcome mineral stress depending on how essential they are to cell growth and plant development

Assessment of patients with lower urinary tract symptoms where an undiagnosed neurological disease is suspected: A report from an International Continence Society consensus working group

Aim Lower urinary tract symptoms (LUTS) are a common urological referral, which sometimes can have a neurological basis in a patient with no formally diagnosed neurological disease (“occult neurology”). Early identification and specialist input is needed to avoid bad LUTS outcomes, and to initiate suitable neurological management. Methods The International Continence Society established a neurological working group to consider: Which neurological conditions may include LUTS as an early feature? What diagnostic evaluations should be undertaken in the LUTS clinic? A shortlist of conditions was drawn up by expert consensus and discussed at the annual congress of the International Neurourology Society. A multidisciplinary working group then generated recommendations for identifying clinical features and management. Results The relevant conditions are multiple sclerosis, multiple system atrophy, normal pressure hydrocephalus, early dementia, Parkinsonian syndromes (including early Parkinson's Disease and Multiple System Atrophy) and spinal cord disorders (including spina bifida occulta with tethered cord, and spinal stenosis). In LUTS clinics, the need is to identify additional atypical features; new onset severe LUTS (excluding infection), unusual aspects (eg, enuresis without chronic retention) or “suspicious” symptoms (eg, numbness, weakness, speech disturbance, gait disturbance, memory loss/cognitive impairment, and autonomic symptoms). Where occult neurology is suspected, healthcare professionals need to undertake early appropriate referral; central nervous system imaging booked from LUTS clinic is not recommended. Conclusions Occult neurology is an uncommon underlying cause of LUTS, but it is essential to intervene promptly if suspected, and to establish suitable management pathways

Performance of the minimally invasive autopsy tool for cause of death determination in adult deaths from the Brazilian Amazon: an observational study

The uncertainty about the real burden of causes of death (CoD) is increasingly recognized by the international health community as a critical limitation for prioritizing effective public health measures. The minimally invasive autopsy (MIA) has shown to be a satisfactory substitute of the complete diagnostic autopsy (CDA), the gold standard for CoD determination in low- and middle-income countries. However, more studies are needed to confirm its adequate performance in settings with different epidemiology. In this observational study, the CoD obtained with the MIA were compared with the clinical diagnosis and the results of the CDA in 61 deaths that occurred in an infectious diseases referral hospital in Manaus, Brazilian Amazon. Concordance between the categories of diseases obtained by the three methods was evaluated by the Kappa statistic. Additionally, we evaluated discrepancies between clinical and complete diagnostic autopsy diagnoses. The MIA showed a substantial concordance with the CDA (Kappa\xE2\x80\x89=\xE2\x80\x890.777, 95% CI 0.608-0.946), and a perfect or almost perfect coincidence in specific diagnosis (ICD-10 code) between MIA and CDA was observed in 85% of the cases. In contrast, the clinical diagnosis showed a fair concordance with the CDA (Kappa\xE2\x80\x89=\xE2\x80\x890.311, 95% CI 0.071-0.552). Major clinico-pathological discrepancies were identified in 49% of cases. In conclusion, the MIA showed a substantial performance for CoD identification. Clinico-pathological discrepancies remain high and justify the need for post-mortem studies, even in referral hospitals. The MIA is a robust substitute of the CDA for CoD surveillance and quality improvement of clinical practice in low- and middle-income settings

The Beaker phenomenon and the genomic transformation of northwest Europe

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain’s gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries