Fast depressive symptoms improvement in bipolar I disorder after Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT): A two-site feasibility and safety open-label trial.

BACKGROUND: Although there are a few first-line treatment options for bipolar depression, none are rapid-acting. A new rTMS protocol, Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT®), has been shown to have a rapid antidepressant effect in major depressive disorder (MDD). We examined the preliminary safety, tolerability, and efficacy of SAINT for the treatment of depression in a small sample of persons with treatment-resistant bipolar I disorder. METHODS: Participants with treatment-resistant bipolar I disorder currently experiencing moderate to severe depression were treated with open-label SAINT. Resting-state functional MRI (fMRI) was used to generate individualized treatment targets for each participant based on the region of the left dorsolateral prefrontal cortex most anticorrelated with the subgenual anterior cingulate cortex. Participants were treated with 10 iTBS sessions daily, with 50-min intersession intervals, for up to 5 consecutive days. The primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to immediate follow-up after treatment. RESULTS: We treated 10 participants and found a mean reduction of 16.9 in MADRS scores, with a 50 % response rate and 40 % remission rate immediately following treatment. 60 % of participants met remission criteria within the 1-month period following treatment. No serious adverse events, manic episodes, or cognitive side effects were observed. LIMITATIONS: Our study has a limited sample size and larger samples are needed to confirm safety and efficacy. CONCLUSIONS: SAINT has shown preliminary feasibility, safety, tolerability, and efficacy in treating treatment-resistant bipolar I depression. Double-blinded sham-controlled trials with larger samples are needed to confirm safety and efficacy.

Fine-grained knowledge about manipulable objects is well-predicted by contrastive language image pre-training.

Object recognition is an important ability that relies on distinguishing between similar objects (e.g., deciding which utensil(s) to use at different stages of meal preparation). Recent work describes the fine-grained organization of knowledge about manipulable objects via the study of the constituent dimensions that are most relevant to human behavior, for example, vision, manipulation, and function-based properties. A logical extension of this work concerns whether or not these dimensions are uniquely human, or can be approximated by deep learning. Here, we show that behavioral dimensions are generally well-predicted by CLIP-ViT - a multimodal network trained on a large and diverse set of image-text pairs. Moreover, this model outperforms comparison networks pre-trained on smaller, image-only datasets. These results demonstrate the impressive capacity of CLIP-ViT to approximate fine-grained object knowledge. We discuss the possible sources of this benefit relative to other models (e.g., multimodal vs. image-only pre-training, dataset size, architecture).

Effect of the addition of black garlic on the quality parameters of jerked beef meat with pork.

The objective of this work was to evaluate the effects of the replacement of nitrite by natural antioxidants from black garlic (BG) on the quality parameters of jerked beef meat with pork for 60 days. Four formulations were prepared: control, 0.02% of sodium nitrite in brine curing, w/v (CON); 1.5% BG in brine curing, w/v (ASU); 1.5% BG in dry curing, w/w (ASS); and 1.5% of BG in the brine curing, w/v and 1.5% of BG in dry curing, w/w (ASUS). Nutritional composition, pH, water activity, shear force, fatty acid profile, color, and oxidative stability of the formulations were analyzed. The addition of BG did not affect the nutritional composition, pH, water activity, shear force, and fatty acid profile. On the other hand, it resulted in lower weight loss after centrifugation and lower values of L* and a*. TBARS values from the 30th day of storage were lower in the ASUS formulation, while carbonyl compounds at all times were lower than in the CON formulation. Results suggest that BG was an efficient alternative to nitrite in controlling protein oxidation during storage. Thus, the use of pork for the manufacture of jerked beef can be an alternative, and black garlic can be applied as a natural additive to the replacement of nitrite. In addition, black garlic was efficient in improving the oxidative stability of the jerked beef meat with pork.

Even a low comorbidity burden predicts poor outcome in chronic heart failure.

BACKGROUND: Patients with heart failure (HF) often have multiple cardiovascular risk factors (CVRF) and comorbidities (CMB). We evaluated the impact of additive CMB and CVRF in HF prognosis. METHODS: We retrospectively analyzed ambulatory patients with systolic dysfunction between January 2012 and May 2018. Follow-up: until January 2021. Endpoint: all-cause death. CVRF analyzed: Arterial hypertension, Diabetes mellitus and smoking. CMB evaluated: coronary artery disease, non-coronary atherosclerotic disease, respiratory disease, dementia, anemia, chronic kidney disease, inflammatory/autoimmune disease, active cancer and atrial fibrillation. Classification according to the number of CVRF and/or CMB: < 2 and ≥ 2. The independent prognostic impact of CVRF/CMB burden was assessed with multivariate Cox-regression. RESULTS: Most patients had ≥ 2 CMB (67.9%). Regarding CVRF, 14.9% presented none, 40.2% had one and 32.1% had two. During a median 49-month follow-up, 419 (49.1%) patients died. Mortality was higher among patients with ≥2 CVRF (56.1 vs 43.4% in those with <2) and in those with ≥2 CMB (57.7 vs 31.0%). While patients with one CMB had similar mortality than those with none. Patients with ≥2 CMB had higher long-term mortality risk: HR=2.47 (95% CI: 1.95-3.14). In patients with ≥2CVRF: HR of dying = 1.39 (1.14- 1.70). When taken together there was a clear survival disadvantage for patients with ≥ 2 CVRF/CMB - adjusted HR: 2.20 (1.45-3.34). CONCLUSION: The presence of only 2 CVRF/CMB more than doubles the patients´ risk of dying. CVRF and CMB should be assessed as part of routine patient management.

Left Ventricular Pseudoaneurysm: A Bursting Threat.

A 55-year-old man submitted to emergency surgery due to cardiac perforation by stabbing. One month later, he presented with chest pain, and a transthoracic echocardiogram revealed moderate-severe mitral regurgitation. After 6 months, a new transthoracic echocardiogram showed a left ventricular pseudoaneurysm, being later submitted to pseudoaneurysm exclusion and mitral valvuloplasty.

Human Herpesvirus-8 (HHV-8)-Positive Human Immunodeficiency Virus (HIV)-Negative Multicentric Castleman Disease With a Fulminant Course.

Multicentric Castleman disease (MCD) is a poorly understood, heterogeneous lymphoproliferative disorder with benign hyperplastic lymph nodes and systemic inflammatory symptoms. Human herpesvirus-8 (HHV-8) may be associated with MCD, whether or not the patient is infected with the human immunodeficiency virus (HIV). A 74-year-old man presented with anaemia, thrombocytopenia and bilateral axillary adenomegaly of unknown origin. The patient was admitted to the hospital two years ago with clinical signs of weight loss, asthenia, anorexia and a maculopapular rash on the trunk and back. Blood analysis showed pancytopenia (haemoglobin 7.7 g/dL, leucocytes 2.55 x 109/L and platelets 41 x 109/L), elevated acute phase reactants (such as C-reactive protein, erythrocyte sedimentation rate, ferritin and fibrinogen), hypoalbuminemia and hypergammaglobulinemia, and HIV serology was negative. Thoracic, abdominal and pelvic axial tomography showed generalised lymphadenopathy. The bone marrow biopsy showed only reactive changes, and the histology of an excisional biopsy of the adenopathy was consistent with the plasmablastic variant of MCD associated with HHV-8. The HHV-8 viral load was 3.8 x 104 copies/mL (4.5 log). He was started on prednisolone 60 mg/day and rituximab. He had a poor response to therapy, despite a reduction in the HHV-8 viral load, with clinical deterioration, transfusion-dependent anaemia and progression to multi-organ dysfunction leading to death three weeks after starting treatment. Our patient had a fulminant course of MCD despite treatment with rituximab. Further studies are needed to validate the different treatment modalities and to better understand the prognosis of this disease.

Reciprocal interactions among parietal and occipito-temporal representations support everyday object-directed actions.

Everyday interactions with common manipulable objects require the integration of conceptual knowledge about objects and actions with real-time sensory information about the position, orientation and volumetric structure of the grasp target. The ability to successfully interact with everyday objects involves analysis of visual form and shape, surface texture, material properties, conceptual attributes such as identity, function and typical context, and visuomotor processing supporting hand transport, grasp form, and object manipulation. Functionally separable brain regions across the dorsal and ventral visual pathways support the processing of these different object properties and, in cohort, are necessary for functional object use. Object-directed grasps display end-state-comfort: they anticipate in form and force the shape and material properties of the grasp target, and how the object will be manipulated after it is grasped. End-state-comfort is the default for everyday interactions with manipulable objects and implies integration of information across the ventral and dorsal visual pathways. We propose a model of how visuomotor and action representations in parietal cortex interact with object representations in ventral and lateral occipito-temporal cortex. One pathway, from the supramarginal gyrus to the middle and inferior temporal gyrus, supports the integration of action-related information, including hand and limb position (supramarginal gyrus) with conceptual attributes and an appreciation of the action goal (middle temporal gyrus). A second pathway, from posterior IPS to the fusiform gyrus and collateral sulcus supports the integration of grasp parameters (IPS) with the surface texture and material properties (e.g., weight distribution) of the grasp target. Reciprocal interactions among these regions are part of a broader network of regions that support everyday functional object interactions.

Characterizing the discriminability of visual categorical information in strongly connected voxels.

Functional brain responses are strongly influenced by connectivity. Recently, we demonstrated a major example of this: category discriminability within occipitotemporal cortex (OTC) is enhanced for voxel sets that share strong functional connectivity to distal brain areas, relative to those that share lesser connectivity. That is, within OTC regions, sets of 'most-connected' voxels show improved multivoxel pattern discriminability for tool-, face-, and place stimuli relative to voxels with weaker connectivity to the wider brain. However, understanding whether these effects generalize to other domains (e.g. body perception network), and across different levels of the visual processing streams (e.g. dorsal as well as ventral stream areas) is an important extension of this work. Here, we show that this so-called connectivity-guided decoding (CGD) effect broadly generalizes across a wide range of categories (tools, faces, bodies, hands, places). This effect is robust across dorsal stream areas, but less consistent in earlier ventral stream areas. In the latter regions, category discriminability is generally very high, suggesting that extraction of category-relevant visual properties is less reliant on connectivity to downstream areas. Further, CGD effects are primarily expressed in a category-specific manner: For example, within the network of tool regions, discriminability of tool information is greater than non-tool information. The connectivity-guided decoding approach shown here provides a novel demonstration of the crucial relationship between wider brain connectivity and complex local-level functional responses at different levels of the visual processing streams. Further, this approach generates testable new hypotheses about the relationships between connectivity and local selectivity.

Subacute Neurotoxicity as an Adverse Reaction to Ceftazidime: A Case Report.

Neurotoxicity associated with cephalosporins is an increasingly recognized complication, although among cephalosporins, ceftazidime is rarely reported for such an adverse reaction. Moreover, subacute, rather than acute, presentation of neurotoxicity associated with cephalosporins is rare. A 77-year-old female patient with stage 4 chronic renal disease was admitted due to cellulitis in her right lower limb, multiorgan dysfunction complicated by oliguric acute kidney injury, and a need for hemodialysis via a central venous catheter. On the 13th day after admission, she became febrile, and bacteremia associated with a central venous catheter was identified, which prompted the initiation of empirical antibiotic therapy with vancomycin and ceftazidime. After 13 days of antibiotic therapy with vancomycin and ceftazidime, the patient became confused, with temporal-spatial disorientation and myoclonus, especially in the upper limbs, with worsening renal function. Ceftazidime was discontinued, and the patient's condition improved with complete remission of symptoms on the 8th day after symptom onset. Neurotoxicity associated with ceftazidime is a rare but probably underdiagnosed adverse reaction. It is more frequent in elderly patients with previous neurological dysfunction and end-stage kidney disease and/or acute kidney injury, and it usually manifests soon after starting treatment. Early identification and monitoring of risk factors and symptoms should lead the physician to a rapid withdrawal of the offending drug.

Post-discharge all-cause mortality in COVID-19 recovered patients hospitalized in 2020: the impact of chronic kidney disease.

In Brazil, the COVID-19 burden was substantial, and risk factors associated with higher in-hospital mortality rates have been extensively studied. However, information on short-term all-cause mortality and the factors associated with death in patients who survived the hospitalization period of acute SARS-CoV-2 infection is limited. We analyzed the six-month post-hospitalization mortality rate and possible risk factors of COVID-19 patients in a single center in Brazil. This is a retrospective cohort study focused on a six-month follow-up. The exclusion criteria were death during hospitalization, transference to another hospital, and age under 18. We collected data from the charts of all hospitalized patients from March 2020 to December 2020 with a positive RT-PCR test for SARS-CoV-2, resulting in a sample size of 106 patients. The main outcome was death after hospitalization, whereas comorbidities and demographics were evaluated as risk factors. The crude post-hospitalization death rate was 16%. The first 30 days of follow-up had the highest mortality rate. In a Cox regression model for post-hospitalization mortality, previous chronic kidney disease (HR, 4.06, 95%CI 1.46 - 11.30) and longer hospital stay (HR 1.01, 95%CI 1.00 - 1.02) were the only factors statistically associated with death. In conclusion, a high six-month all-cause mortality was observed. Within the six-month follow-up, a higher risk of death was observed for patients who had prior CKD and longer hospital stay. These findings highlight the importance of more intensive medical surveillance during this period.

Post-discharge all-cause mortality in COVID-19 recovered patients hospitalized in 2020: the impact of chronic kidney disease

ABSTRACT In Brazil, the COVID-19 burden was substantial, and risk factors associated with higher in-hospital mortality rates have been extensively studied. However, information on short-term all-cause mortality and the factors associated with death in patients who survived the hospitalization period of acute SARS-CoV-2 infection is limited. We analyzed the six-month post-hospitalization mortality rate and possible risk factors of COVID-19 patients in a single center in Brazil. This is a retrospective cohort study focused on a six-month follow-up. The exclusion criteria were death during hospitalization, transference to another hospital, and age under 18. We collected data from the charts of all hospitalized patients from March 2020 to December 2020 with a positive RT-PCR test for SARS-CoV-2, resulting in a sample size of 106 patients. The main outcome was death after hospitalization, whereas comorbidities and demographics were evaluated as risk factors. The crude post-hospitalization death rate was 16%. The first 30 days of follow-up had the highest mortality rate. In a Cox regression model for post-hospitalization mortality, previous chronic kidney disease (HR, 4.06, 95%CI 1.46 - 11.30) and longer hospital stay (HR 1.01, 95%CI 1.00 - 1.02) were the only factors statistically associated with death. In conclusion, a high six-month all-cause mortality was observed. Within the six-month follow-up, a higher risk of death was observed for patients who had prior CKD and longer hospital stay. These findings highlight the importance of more intensive medical surveillance during this period.

Effects of transcranial direct current stimulation on neural activity and functional connectivity during fear extinction

Background/Objective: Anxiety disorders are highly prevalent and negatively impact daily functioning and quality of life. Transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex (dlPFC), especially in the right hemisphere impacts extinction learning; however, the underlying neural mechanisms are elusive. Therefore, we aimed to investigate the effects of cathodal tDCS stimulation to the right dlPFC on neural activity and connectivity patterns during delayed fear extinction in healthy participants. Methods: We conducted a two-day fear conditioning and extinction procedure. On the first day, we collected fear-related self-reports, clinical questionnaires, and skin conductance responses during fear acquisition. On the second day, participants in the tDCS group (n = 16) received 20-min offline tDCS before fMRI and then completed the fear extinction session during fMRI. Participants in the control group (n = 18) skipped tDCS and directly underwent fMRI to complete the fear extinction procedure. Whole-brain searchlight classification and resting-state functional connectivity analyses were performed. Results: Whole-brain searchlight classification during fear extinction showed higher classification accuracy of threat and safe cues in the left anterior dorsal and ventral insulae and hippocampus in the tDCS group than in the control group. Functional connectivity derived from the insula with the dlPFC, ventromedial prefrontal cortex, and inferior parietal lobule was increased after tDCS. Conclusion: tDCS over the right dlPFC may function as a primer for information exchange among distally connected areas, thereby increasing stimulus discrimination. The current study did not include a sham group, and one participant of the control group was not randomized. Therefore, to address potential allocation bias, findings should be confirmed in the future with a fully randomized and sham controlled study. (AU)

A Straining Heart: Transthyretin Amyloidosis as a Cause of Heart Failure.

Cardiac amyloidosis is a disease caused by the deposition of amyloid fibrils in the extracellular space of the heart, most often by immunoglobulin light chains or by transthyretin. It is often underdiagnosed because the signs and symptoms are nonspecific or due to the false perception that the diagnosis always requires an endomyocardial biopsy. Transthyretin amyloidosis is being increasingly recognized as a cause of heart failure, particularly in patients with heart failure with preserved ejection fraction (HFpEF). We present the clinical case of an 86-year-old man whose diagnosis was based on signs and symptoms compatible with cardiac amyloidosis and in which imaging performed a preponderant role. This case reminds clinicians to consider the diagnosis in older patients with HFpEF, left ventricular hypertrophy and rhythm disturbances. It highlights the importance of evaluating global longitudinal strain (GLS) in a standard echocardiographic evaluation.

Kimura's Disease: A Literature Review Based on a Clinical Case.

Kimura's disease (KD) was first described in 1937. It is a rare, benign, and chronic immune-mediated inflammatory disorder affecting the subcutaneous tissue, salivary glands, and lymph nodes. The disease is more common in the second to third decades of life in middle-aged Southeast Asian countries. The cause of Kimura's disease remains unknown; some authors believe it is related to an autoimmune or delayed-type hypersensitivity reaction. It commonly presents as a solitary painless lymph node in the head and neck or generalized lymphadenopathy (67%-100%) associated with peripheral eosinophilia and elevated IgE levels. Renal involvement may occur in some patients. Diagnosis is made by histology. A 21-year-old Caucasian man with no relevant medical history presented with a non-tender swelling of the left hemiface without other associated symptoms. Laboratory investigations revealed a leukocyte count with eosinophilia (2.29×10^9/L- 26.5%) and elevated total IgE and IgG4. He had no renal dysfunction. He underwent surgical resection of the lesion in the jugal, infraorbital, and left nasolabial regions, and the anatomopathological examination revealed the characteristics of Kimura's disease. Three months after surgery, an MRI showed an increase in the size of the mass, and he was started on corticosteroids. Six months after surgery, he presented with a slight increase in the size of the mass and was started on Ciclosporin, which allowed a progressive reduction in the dose of corticosteroid with evidence of a progressive reduction in swelling. Ciclosporin was stopped due to toxic serum levels, and he was started on mycophenolate mofetil. The dose was increased because of the increase in facial mass; on mycophenolate mofetil 2500mg/day, the patient remains stable. KD is a chronic disorder of unknown etiology that mainly affects young people in Southeast Asia and is rare in Western countries, as in the case of this young man. Studies have shown no significant differences in region or race, complications, multiplicity, laterality, anatomical distribution, maximum size, eosinophil count, or IgE levels between age groups. There is no consensus on the optimal treatment for KD; several treatments have been used, including surgery, systemic corticosteroids, immunosuppressants, and radiation. Due to the tendency to relapse and the rarity of the disease, there is no consensus on treatment options for relapse.

Hematological and coagulation parameters as predictors of death by Coronavirus disease in hospitalized patients: a Brazilian follow-up study

Abstract This study aimed to evaluate the hematological and coagulation parameters according to the clinical outcomes of coronavirus disease (COVID-19). We analyzed the hematological and coagulation parameters of hospitalized patients with COVID-19 at admission, and two and three weeks during hospitalization. To assess the performance of these parameters in predicting poor outcomes, receiver operating characteristic (ROC) curves were created. We studied 128 patients with COVID-19 (59.2±17.7 years, 56% male). Non-survivors (n=54, 42%) presented significant alterations in hematological and coagulation parameters at admission, such as increased in white blood cells (WBC), neutrophil, and band cell counts, as well as elevated prothrombin time (PT), activated partial thromboplastin time, and D-dimer levels. During follow-up, the same group presented a gradual increase in D-dimer and PT levels, accompanied by a reduction in PT activity, hemoglobin, and red blood cell count (RBC). ROC curves showed that WBC, neutrophil, and band cell counts presented the best area under the curve (AUC) values with sensitivity and specificity of >70%; however, a logistic regression model combining all the parameters, except for RBC, presented an AUC of 0.89, sensitivity of 84.84%, and specificity of 77.41%. Our study shows that significant alterations in hematological and coagulation tests at admission could be useful predictors of disease severity and mortality in COVID-19.

Evaluation of herpesvirus members on hospital admission in patients with systemic lupus erythematous shows higher frequency of Epstein-Barr virus and its associated renal dysfunction / Avaliação de membros da família Herpesviridae na admissão hospitalar de pacientes com lúpus eritematoso sistêmico mostra maior frequência do vírus Epstein-Barr e sua disfunção renal associada

Abstract Introduction: Members of the Herpesviridae family have been described in patients with systemic lupus erythematous (SLE), but the clinical impact on renal function is not well known. Methods: HSV1, HSV2, VZV, EBV, CMV, HHV-6, HHV-7, and HHV-8 were evaluated by molecular biology on admission in blood samples from 40 consecutive SLE patients hospitalized for lupus activity. Results: Patients were 90.0% female, 77.5% non-white, with average age of 32.7 ± 13.6 years. We found positivity for EBV (65.0%), CMV (30.0%), HSV-1 (30.0%), HHV-6 (12.5%), and HHV-7 (7.5%). For all viruses, age, SLEDAI, hematological tests, ferritin, LDH, C-reactive protein, and erythrocyte sedimentation rate (ESR) were not significant. However, EBV positivity was a significant factor for higher serum creatinine (3.0 ± 2.8 vs. 0.9 ± 0.8; P = 0.001) and urea (86 ± 51 vs. 50 ± 46; P = 0.03). Moreover, positive cases for EBV only or with combined co-infections (66.7%-CMV; 58.3%-HSV-1) or negative for EBV only were evaluated by Kruskal-Wallis test again showed statistical significance for serum creatinine and urea (both P ≤ 0.01), with posttest also showing statistical differences for renal dysfunction and EBV presence (alone or in combined co-infections). The presence of EBV viral load was also significant for nephrotic-range proteinuria, renal flare, and the need for hemodialysis. Conclusion: Members of the Herpeviridae family (mainly EBV, HSV-1 and CMV) are common on hospital admission of SLE patients, reaching 65% for EBV, which seems to be associated with renal dysfunction and could reflect a previous association or overlapping disease, which is not well understood.

Resumo Introdução: Membros da família Herpesviridae tem sido descritos em pacientes com lúpus eritematoso sistêmico (LES), mas o impacto clínico na função renal não é bem conhecido. Métodos: Avaliou-se HSV1, HSV2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8 por biologia molecular na admissão em amostras sanguíneas de 40 pacientes com LES consecutivos hospitalizados por atividade lúpica. Resultados: Pacientes 90,0% mulheres, 77,5% não brancos, idade média 32,7 ± 13,6 anos. Encontramos positividade para EBV (65,0%), CMV (30,0%), HSV-1 (30,0%), HHV-6 (12,5%), HHV-7 (7,5%). Para todos os vírus, idade, SLEDAI, exames hematológicos, ferritina, LDH, proteína C reativa, velocidade de hemossedimentação não foram significativos. Entretanto, positividade para EBV foi estatisticamente significativo para creatinina (3,0 ± 2,8 vs. 0,9 ± 0,8; P = 0,001) e ureia (86 ± 51 vs. 50 ± 46; P = 0,03) séricas mais elevadas. Ademais, casos positivos para EBV isolado ou com coinfecções combinadas (66,7%-CMV; 58,3%-HSV-1) ou negativos apenas para EBV foram avaliados pelo teste Kruskal-Wallis e novamente mostraram significância estatística para creatinina e ureia séricas (ambas P ≤ 0,01), com pós-teste mostrando também diferenças estatísticas para disfunção renal e presença de EBV (sozinho ou em coinfecções combinadas). A presença de carga viral do EBV também foi significativa para proteinúria de faixa nefrótica, inflamação aguda, necessidade de hemodiálise. Conclusão: Membros da família Herpeviridae (principalmente EBV, HSV-1, CMV) são comuns na admissão de pacientes com LES, chegando a 65% para EBV, que parece associar-se à disfunção renal podendo refletir associação prévia ou doença sobreposta, o que não é bem compreendido.

"Flattening the curve": effective measures from Niterói city (Rio de Janeiro, Brazil) for COVID-19 control / "Achatando a curva": medidas eficazes da cidade de Niterói (RJ, Brasil) para o controle da COVID-19

Abstract Background In Brazil, some local city government's adopted several measures, which probably had a positive impact on COVID-19 control. Objective To report the distribution of COVID-19 cases in Brazil, Rio de Janeiro state and Niterói city. In parallel, we aimed to demonstrate the preventive strategies adopted by Niterói city. Method Data provided by the Brazilian Ministry of Health and Municipal Health Foundation of Niterói were used to report COVID-19 cases and deaths. For some analysis, data were grouped by week and normalized for 100,000 inhabitants. Results By July 18th, 2020, Brazil reported 2,074,860 cases and 78,772 deaths and Rio de Janeiro state registered 135,230 cases and 11,919 deaths; both still presenting ascendant curves for COVID-19 deaths. In contrast, the rate of new deaths per 100,000 inhabitants is consistently lower in Niterói city. Importantly, we estimated that 712 deaths were prevented by the measures adopted by Niterói city, in comparison to which was observed in Rio de Janeiro. Conclusion The early preventive measures adopted in Niterói city were effective in reducing both the viral spread and rate of deaths. In this regard, this discussion could be relevant for making future decisions during the COVID-19 outbreak in Brazil.

Resumo Introdução No Brasil, algumas cidades adotaram várias medidas que provavelmente tiveram um impacto positivo no controle da Covid-19. Objetivo Relatar a distribuição dos casos de Covid-19 no Brasil, no estado do Rio de Janeiro e na cidade de Niterói. Paralelamente, buscamos demonstrar as estratégias preventivas adotadas pela cidade de Niterói para o controle da Covid-19. Método Dados fornecidos pelo Ministério da Saúde e Fundação Municipal de Saúde de Niterói foram usados ​​para relatar o número de casos e óbitos causados pela Covid-19. Para algumas análises, os dados foram agrupados por semana e normalizados para 100.000 habitantes. Resultados Até 18 de julho de 2020, o Brasil registrou 2.074.860 casos e 78.772 mortes e o estado do Rio de Janeiro registrou 135.230 casos e 11.919 mortes; ambos ainda apresentando curvas ascendentes para mortes por Covid-19. Em contrapartida, a taxa de novos óbitos/100.000 habitantes é consistentemente menor na cidade de Niterói. Estimamos que 712 mortes foram evitadas pelas medidas adotadas pela cidade de Niterói, em comparação com o que foi observado no Rio de Janeiro. Conclusão As medidas preventivas adotadas pela cidade de Niterói foram eficazes na redução tanto da disseminação do vírus quanto da taxa de óbitos. Portanto, esta discussão se mostra relevante para a tomada de decisões futuras durante o surto de Covid-19 no Brasil.

Serum ferritin at admission in hospitalized COVID-19 patients as a predictor of mortality

ABSTRACT Introduction: Some COVID-19 patients have higher mortality and the responsible factors for this unfavorable outcome is still not well understood. Objective: To study the association between ferritin levels at admission, representing an inflammatory state, and hospital mortality in COVID-19 patients. Methods: From May through July 2020, SARS-CoV-2 positive patients with moderate to severe clinical symptoms were evaluated at admission, regarding clinical and laboratory data on renal and hepatic function, hematologic parameters, cytomegalovirus co-infection, and acute phase proteins. Results: A total of 97 patients were included; mean age = 59.9 ± 16.3 years, 58.8% male, 57.7% non-white, in-hospital mortality = 45.4%. Age, ferritin, C-reactive protein, serum albumin and creatinine were significantly associated with mortality. Ferritin showed area under the curve (AUC) of 0.79 (p < 0.001) for the cut-off of 1873.0 ng/mL, sensitivity of 68.4% and specificity of 79.3% in predicting in-hospital mortality. Age ≥60 years had an odds ratio (OR) of 10.5 (95% CI = 1.8-59.5; p = 0.008) and ferritin ≥1873.0 ng/mL had an OR of 6.0 (95% CI = 1.4-26.2; p = 0.016), both independently associated with mortality based on logistic regression analysis. Conclusion: The magnitude of inflammation present at admission of COVID-19 patients, represented by high ferritin levels, is independently predictive of in-hospital mortality.

Timeline analysis of IgA and IgG levels in Covid-19 hospitalized patients according to the clinical outcome / Análise temporal das concentrações de IgA e IgG em pacientes hospitalizados com Covid-19 de acordo com o desfecho clínico

ABSTRACT Introduction: Studies suggest the association between antibody production and the severity of coronavirus disease 2019 (Covid-19). Objectives: To evaluate the concentrations of immunoglobulins class A (IgA) and class G (IgG) during the hospitalization period of Covid-19 patients according to the outcome (survival vs death). Materials and methods: Patients with severe acute respiratory syndrome of coronavirus 2 (Sars-CoV-2) infection confirmed by reverse transcriptase reaction followed by polymerase chain reaction (RT-PCR) were included in this prospective study. Samples were obtained weekly during the follow-up of individuals, considering symptom onset. Titers of anti-Sars-CoV-2 IgA and IgG were measured using a commercial immunoassay. Correlations between IgA/IgG and cycle threshold (Ct) values for N1 and N2 target genes were also assessed. Results: We studied 55 Covid-19 patients (59.7±16.2 years, 63.6% male), of which 28 (50.9%) died. We observed IgA and IgG positivity (IgA+ and IgG+) in 90.9% and 80% of patients, respectively. The highest IgA+ frequency was observed at weeks 2 and 3 and the highest IgG+ at weeks 3 and 4. It is important to note that patients who died presented lower IgA titers in the first two weeks (p < 0.05); however, a significant increase in IgA levels was observed in the subsequent weeks. Lastly, we identified that significant correlations between Ct values and immunoglobulins levels, both IgA and IgG were correlated with Ct N2 in patients who died. Conclusion: Our results suggest that lower IgA titers in early Covid-19, which is associated with lower Ct values, may indicate patients at higher risk for death.

RESUMEN Introducción: Los estudios sugieren una asociación entre la producción de anticuerpos y la gravedad de la enfermedad por coronavirus 2019 (Covid-19). Objetivos: Evaluar las concentraciones de inmunoglobulinas clase A (IgA) y clase G (IgG) durante la hospitalización de pacientes con Covid-19 según el desenlace (supervivencia vs muerte). Materiales y métodos: Se incluyeron en este estudio prospectivo pacientes con síndrome respiratorio agudo severo de infección por coronavirus 2 (Sars-CoV-2) confirmado por la reacción en cadena de la polimerasa con transcriptasa inversa (RT-PCR). Las muestras se obtuvieron semanalmente durante el seguimiento de los individuos, considerando la aparición de los síntomas. Los títulos de IgA e IgG anti-Sars-CoV-2 se midieron usando un inmunoensayo comercial. También se evaluaron las correlaciones entre IgA/IgG y los valores de los umbrales de ciclo [cycle threshold (Ct)] para los genes N1 y N2. Resultados: Se estudiaron 55 pacientes Covid-19 (59,7 ± 16,2 años, 63,6% varones), de los cuales 28 (50,9%) fallecieron. Observamos positividad de IgA e IgG (IgA+ e IgG+) en el 90,9% y el 80% de los pacientes, respectivamente. La frecuencia más alta de IgA+ se observó en las semanas dos y tres y la IgG + más alta en las semanas tres y cuatro. Es importante señalar que los pacientes que fallecieron presentaron títulos de IgA más bajos en las dos primeras semanas (p < 0,05); sin embargo, se observó un aumento significativo en los niveles de IgA en las semanas siguientes. Conclusión: Identificamos correlaciones significativas entre los valores de Ct y los niveles de Ig, tanto IgA como IgG se correlacionaron con Ct N2 en los pacientes que fallecieron. Nuestros resultados sugieren que los títulos de IgA más bajos en Covid-19 temprano, que se asocia con valores de Ct más bajos, pueden indicar que los pacientes tienen un mayor riesgo de muerte.

RESUMO Introdução: Estudos sugerem a associação entre a produção de anticorpos e a gravidade da coronavirus disease 2019 (Covid-19). Objetivos: Avaliar as concentrações de imunoglobulinas da classe A (IgA) e da classe G (IgG) durante a internação de pacientes com Covid-19 de acordo com o desfecho (sobrevida vs óbito). Materiais e métodos: Pacientes com infecção pela síndrome respiratória aguda grave do coronavírus 2 (Sars-CoV-2) confirmada por reação da transcriptase reversa seguida de reação em cadeia da polimerase (RT-PCR) foram incluídos neste estudo prospectivo. As amostras foram obtidas semanalmente durante o acompanhamento dos indivíduos, considerando o início dos sintomas. Os títulos de IgA e IgG anti-Sars-CoV-2 foram mensurados por meio de um imunoensaio comercial. Correlações entre IgA/IgG e valores de limiar de detecção [cycle thresholds (Ct)] para os genes alvos N1 e N2 também foram avaliadas. Resultados: Estudamos 55 pacientes com Covid-19 (59,7 ± 6,2 anos; 63,6% do sexo masculino); destes, 28 (50,9%) morreram. Observamos positividade para IgA e IgG (IgA+/IgG+) em 90,9% e 80% dos pacientes, respectivamente. A maior frequência de IgA+ foi verificada nas semanas 2 e 3, e a maior frequência de IgG+, nas semanas 3 e 4. É importante observar que os pacientes que morreram apresentaram títulos de IgA mais baixos nas primeiras duas semanas (p < 0,05); no entanto, um aumento significativo na concentração de IgA foi observado nas semanas subsequentes. Por fim, identificamos correlações significativas entre os valores de Ct e imunoglobulinas; tanto IgA quanto IgG foram correlacionadas com Ct N2 em pacientes que morreram. Conclusão: Nossos resultados sugerem que títulos mais baixos de IgA no início da Covid-19 - que estão associados a valores mais baixos de Ct - podem indicar pacientes com risco elevado de evoluir para óbito.

Disseminated gonococcal infection and the inaugural diagnosis of latent autoimmune diabetes in a young adult

Disseminated gonococcal infection (DGI) is a rare and emerging disease that should be considered in individuals who present with acute polyarthralgias, skin lesions and/or tenosynovitis, even in the absence of genitourinary symptoms.We describe a 29 years old man presenting with fever, arthralgias, skin lesions and signs of tenosynovitis. The diagnostic approach identified a disseminated gonococcal infection and an unrecognized and latent autoimmune diabetes.We emphasize not only the particularities of diagnostic and treatment approach currently required by this emergent infection, but also the importance of investigation of rare risk factors associated with an underlying immunosuppression. In latent autoimmune diabetes of adults a timely recognition and individualized treatment are fundamental for prognostic

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