Hospital Universitário Gaffrée e Guinle

Recent investigations in cognitive neuroscience have shown that ordinary human behavior is guided by emotions that are uniquely human in their experiential and interpersonal aspects. These "moral emotions" contribute importantly to human social behavior and derive from the neurobehavioral reorganization of the basic plan of emotions that pervade mammalian life. Disgust is one prototypic emotion with multiple domains that include viscerosomatic reaction patterns and subjective experiences linked to (a) the sensory properties of a class of natural stimuli, (b) a set of aversive experiences and (c) a unique mode of experiencing morality. In the current investigation, we tested the hypotheses that (a) the experience of disgust devoid of moral connotations ("pure disgust") can be subjectively and behaviorally differentiated from the experience of disgust disguised in the moral emotion of "indignation" and that (b) pure disgust and indignation may have partially overlapping neural substrates. Thirteen normal adult volunteers were investigated with functional magnetic resonance imaging as they read a series of statements depicting scenarios of pure disgust, indignation, and neutral emotion. After the scanning procedure, they assigned one basic and one moral emotion to each stimulus from an array of six basic and seven moral emotions. Results indicated that (a) emotional stimuli may evoke pure disgust with or without indignation, (b) these different aspects of the experience of disgust could be elicited by a set of written statements, and (c) pure disgust and indignation recruited both overlapping and distinct brain regions, mainly in the frontal and temporal lobes. This work underscores the importance of the prefrontal and orbitofrontal cortices in moral judgment and in the automatic attribution of morality to social events. Human disgust encompasses a variety of emotional experiences that are ingrained in frontal, temporal, and limbic networks.

Morality has been at the center of informal talks and metaphysical discussions since the beginning of history. Recently, converging lines of evidence from evolutionary biology, neuroscience and experimental psychology have shown that morality is grounded in the brain. This article reviews the main lines of investigation indicating that moral behavior is a product of evolutionary pressures that shaped the neurobehavioral processes related to the selective perception of social cues, the experience of moral emotions and the adaptation of behavioral responses to the social milieu. These processes draw upon specific cortical-subcortical loops that organize social cognition, emotion and motivation into uniquely human forms of experience and behavior. We put forth a model of brain-behavior relationships underlying moral reasoning and emotion that accommodates the impairments of moral behavior observed in neuropsychiatric disorders. This model provides a framework for empirical testing with current methods of neurobehavioral analysis.

The trail making test (TMT) pertains to a family of tests that tap the ability to alternate between cognitive categories. However, the value of the TMT as a localizing instrument remains elusive. Here we report the results of a functional magnetic resonance imaging (fMRI) study of a verbal adaptation of the TMT (vTMT). The vTMT takes advantage of the set-shifting properties of the TMT and, at the same time, minimizes the visuospatial and visuomotor components of the written TMT. Whole brain BOLD fMRI was performed during the alternating execution of vTMTA and vTMTB in seven normal adults with more than 12 years of formal education. Brain activation related to the set-shifting component of vTMTB was investigated by comparing performance on vTMTB with vTMTA, a simple counting task. There was a marked asymmetry of activation in favor of the left hemisphere, most notably in dorsolateral prefrontal cortex (BA 6 lateral, 44 and 46) and supplementary motor area/cingulate sulcus (BA 6 medial and 32). The intraparietal sulcus (BA 7 and 39) was bilaterally activated. These findings are in line with clinico-anatomic and functional neuroimaging data that point to a critical role of the dorsolateral and medial prefrontal cortices as well as the intraparietal sulci in the regulation of cognitive flexibility, intention, and the covert execution of saccades/anti-saccades. Many commonly used neuropsychological paradigms, such as the Stroop, Wisconsin Card Sorting, and go - no go tasks, share some patterns of cerebral activation with the TMT.

The human brain is inherently able to understand the world in moral ways, endowing most of us with an intuitive sense of fairness, concern for others, and observance of cultural norms. We have argued that this moral sensitivity ability depends on a sophisticated integration of cognitive, emotional, and motivational mechanisms, which are modulated by individual experience in different cultural milieus. Different lines of investigation on agency and morality have pointed to overlapping neural systems. Therefore, understanding the relationships between morality and agency may provide key insights into the mechanisms underlying human behavior in several clinical and societal settings. We used functional MRI to investigate the contribution of agency and of specific moral emotions to brain activation using action scripts. Results showed that emotionally neutral agency recruited neural networks previously associated with agency, intentionality and moral cognition, encompassing ventral and subgenual sectors of the medial prefrontal cortex (PFC), insula, anterior temporal cortex and superior temporal sulcus (STS). Compared to emotionally neutral agency, different categories of moral emotions led to distinct activation patterns: (1) prosocial emotions (guilt, embarrassment, compassion) activated the anterior medial PFC and STS, with (2) empathic emotions (guilt and compassion) additionally recruiting the mesolimbic pathway; (3) other-critical emotions (disgust and indignation) were associated with activation of the amygdala-parahippocampal and fusiform areas. These findings indicate that agency related to norm-abiding social behaviors of emotionally neutral scripts share neural substrates both with the "default mode" of brain function and with the moral sensitivity network. Additional activation in specific components of this network is elicited by different classes of moral emotions, in agreement with recent integrative models of moral cognition and emotion.

Dengue is a public health problem, with several gaps in understanding its pathogenesis. Studies based on human fatal cases are extremely important and may clarify some of these gaps. In this work, we analyzed lesions in different organs of four dengue fatal cases, occurred in Brazil. Tissues were prepared for visualization in optical and electron microscopy, with damages quantification. As expected, we observed in all studied organ lesions characteristic of severe dengue, such as hemorrhage and edema, although other injuries were also detected. Cases presented necrotic areas in the liver and diffuse macro and microsteatosis, which were more accentuated in case 1, who also had obesity. The lung was the most affected organ, with hyaline membrane formation associated with mononuclear infiltrates in patients with pre-existing diseases such as diabetes and obesity (cases 1 and 2, respectively). These cases had also extensive acute tubular necrosis in the kidney. Infection induced destruction of cardiac fibers in most cases, with absence of nucleus and loss of striations, suggesting myocarditis. Spleens revealed significant destruction of the germinal centers and atrophy of lymphoid follicles, which may be associated to decrease of T cell number. Circulatory disturbs were reinforced by the presence of megakaryocytes in alveolar spaces, thrombus formation in glomerular capillaries and loss of endothelium in several tissues. Besides histopathological and ultrastructural observations, virus replication were investigated by detection of dengue antigens, especially the non-structural 3 protein (NS3), and confirmed by the presence of virus RNA negative strand (in situ hybridization), with second staining for identification of some cells. Results showed that dengue had broader tropism comparing to what was described before in literature, replicating in hepatocytes, type II pneumocytes and cardiac fibers, as well as in resident and circulating monocytes/macrophages and endothelial cells.

Prenatal exposure to misoprostol has been associated with Moebius and limb defects. Vascular disruption has been proposed as the mechanism for these teratogenic effects. The present study is a multicenter, case-control study that was designed to compare the frequency of prenatal misoprostol use between mothers of Brazilian children diagnosed with vascular disruption defects and matched control mothers of children diagnosed with other types of defects. A total of 93 cases and 279 controls were recruited in eight participating centers. Prenatal exposure was identified in 32 infants diagnosed with vascular disruption defects (34.4%) compared with only 12 (4.3%) in the control group (P<0.0000001). Our data suggest that prenatal exposure to misoprostol is associated to the occurrence of vascular disruption defects in the newborns.

Background & AimsSeveral studies have reported that low doses of interferon can delay the development of hepatocellular carcinoma (HCC) and progression of chronic hepatitis C. We investigated the incidence of clinical events among participants of the Evaluation of PegIntron in Control of Hepatitis C Cirrhosis (EPIC)3 program.MethodsData were analyzed from an open-label randomized study of patients with chronic hepatitis C who had failed to respond to interferon alfa plus ribavirin. All patients had compensated cirrhosis with no evidence of HCC. Patients received peginterferon alfa-2b (0.5 μg/kg/week; n = 311) or no treatment (controls, n = 315) for a maximum period of 5 years or until 98 patients had a clinical event (hepatic decompensation, HCC, death, or liver transplantation). The primary measure of efficacy was time until the first clinical event.ResultsThere was no significant difference in time to first clinical event among patients who received peginterferon alfa-2b compared with controls (hazard ratio [HR], 1.452; 95% confidence interval [CI]: 0.880–2.396). There was no decrease in the development of HCC with therapy. The time to disease progression (clinical events or new or enlarged varices) was significantly longer for patients who received peginterferon alfa-2b compared with controls (HR, 1.564; 95% CI: 1.130–2.166). In a prospectively defined subanalysis of patients with baseline portal hypertension, peginterferon alfa-2b significantly increased the time to first clinical event compared with controls (P = .016). There were no new safety observations.ConclusionsMaintenance therapy with peginterferon alfa-2b is not warranted in all patients and does not prevent HCC. However, there is a potential clinical benefit of long-term suppressive therapy in patients with preexisting portal hypertension. Several studies have reported that low doses of interferon can delay the development of hepatocellular carcinoma (HCC) and progression of chronic hepatitis C. We investigated the incidence of clinical events among participants of the Evaluation of PegIntron in Control of Hepatitis C Cirrhosis (EPIC)3 program. Data were analyzed from an open-label randomized study of patients with chronic hepatitis C who had failed to respond to interferon alfa plus ribavirin. All patients had compensated cirrhosis with no evidence of HCC. Patients received peginterferon alfa-2b (0.5 μg/kg/week; n = 311) or no treatment (controls, n = 315) for a maximum period of 5 years or until 98 patients had a clinical event (hepatic decompensation, HCC, death, or liver transplantation). The primary measure of efficacy was time until the first clinical event. There was no significant difference in time to first clinical event among patients who received peginterferon alfa-2b compared with controls (hazard ratio [HR], 1.452; 95% confidence interval [CI]: 0.880–2.396). There was no decrease in the development of HCC with therapy. The time to disease progression (clinical events or new or enlarged varices) was significantly longer for patients who received peginterferon alfa-2b compared with controls (HR, 1.564; 95% CI: 1.130–2.166). In a prospectively defined subanalysis of patients with baseline portal hypertension, peginterferon alfa-2b significantly increased the time to first clinical event compared with controls (P = .016). There were no new safety observations. Maintenance therapy with peginterferon alfa-2b is not warranted in all patients and does not prevent HCC. However, there is a potential clinical benefit of long-term suppressive therapy in patients with preexisting portal hypertension.

CONTEXT AND OBJECTIVES: The appropriate use of antibiotic prophylaxis in the perioperative period may reduce the rate of infection in the surgical site. The purpose of this review was to evaluate adherence to guidelines for surgical antibiotic prophylaxis. METHODS: The present systematic review was performed according to the Cochrane Collaboration methodology. The databases selected for this review were: Medline (via PubMed), Scopus and Portal (BVS) with selection of articles published in the 2004-2014 period from the Lilacs and Cochrane databases. RESULTS: The search recovered 859 articles at the databases, with a total of 18 studies selected for synthesis. The outcomes of interest analyzed in the articles were as follows: appropriate indication of antibiotic prophylaxis (ranging from 70.3% to 95%), inappropriate indication (ranging from 2.3% to 100%), administration of antibiotic at the correct time (ranging from 12.73% to 100%), correct antibiotic choice (ranging from 22% to 95%), adequate discontinuation of antibiotic (ranging from 5.8% to 91.4%), and adequate antibiotic prophylaxis (ranging from 0.3% to 84.5%). CONCLUSIONS: Significant variations were observed in all the outcomes assessed, and all the studies indicated a need for greater adherence to guidelines for surgical antibiotic prophylaxis.

OBJECTIVE Neuroplasticity is analyzed in this article as the capacity of the CNS to adapt to external and internal stimuli. It is being increasingly recognized as an important factor for the successful outcome of nerve transfers. Better-known factors are the number of axons that cross the coaptation site, the time interval between trauma and repair, and age. Neuroplasticity is mediated initially by synaptic and neurotransmitter changes. Over time, the activation of previously existing but lowly active connections in the brain cortex contributes further. Dendritic sprouting and axonal elongation might also take place but are less likely to be prominent. METHODS The authors reviewed different factors that play roles in neuroplasticity and functional regeneration after specific nerve transfers. RESULTS The authors found that these different factors include, among others, the distance between cortical areas of the donor and receptor neurons, the presence versus absence of preexisting lowly active interneuronal connections, gross versus fine movement restoration, rehabilitation, brain trauma, and age. CONCLUSIONS The potential for plasticity should be taken into consideration by surgeons when planning surgical strategy and postoperative rehabilitation, because its influence on results cannot be denied.

Comparative studies have established that a number of structures within the rostromedial basal forebrain are critical for affiliative behaviors and social attachment. Lesion and neuroimaging studies concur with the importance of these regions for attachment and the experience of affiliation in humans as well. Yet it remains obscure whether the neural bases of affiliative experiences can be differentiated from the emotional valence with which they are inextricably associated at the experiential level. Here we show, using functional MRI, that kinship-related social scenarios evocative of affiliative emotion induce septal-preoptic-anterior hypothalamic activity that cannot be explained by positive or negative emotional valence alone. Our findings suggest that a phylogenetically conserved ensemble of basal forebrain structures, especially the septohypothalamic area, may play a key role in enabling human affiliative emotion. Our finding of a neural signature of human affiliative experience bears direct implications for the neurobiological mechanisms underpinning impaired affiliative experiences and behaviors in neuropsychiatric conditions.

Dengue hemorrhagic fever (DHF) is a severe febrile disease, characterized by abnormalities in hemostasis and increased vascular permeability, which in some cases results in hypovolemic shock syndrome and in dengue shock syndrome. The clinical features of DHF include plasma leakage, bleeding tendency and liver involvement. We studied the histopathological features of a fatal case of dengue-3 virus infection. The patient, a 63-year old male, presented with an acute onset of severe headache, myalgia and maculopapular rash. Tissue fragments (liver, spleen, lung, heart, kidney and lymph nodes) were collected for light microscopy studies and stained by standard methods. Histopathology revealed severe tissue damage, caused by intense hemorrhage, interstitial edema and inflammation. Some tissue sections were also processed with the immunoperoxidase reaction, which revealed the dengue viral antigen. Dengue-3 virus was isolated and identified with electron microscopy in a C6/36 cell culture inoculated with the patient's serum. Viral particles were detected in the infected cell culture.

Dengue infection is a leading cause of illness and death in tropical and subtropical regions of the world. Forty percent of the world's population currently lives in these areas. The clinical picture resulting from dengue infection can range from relatively minor to catastrophic hemorrhagic fever. Recently, reports have increased of neurological manifestations. Neuropathogenesis seems to be related to direct nervous system viral invasion, autoimmune reaction, metabolic and hemorrhagic disturbance. Neurological manifestations include encephalitis, encephalopathy, meningitis, Guillain-Barré syndrome, myelitis, acute disseminated encephalomyelitis, polyneuropathy, mononeuropathy, and cerebromeningeal hemorrhage. The development of neurological symptoms in patients with positive Immunoglobulin M (IgM) dengue serology suggests a means of diagnosing the neurological complications associated with dengue. Viral antigens, specific IgM antibodies, and the intrathecal synthesis of dengue antibodies have been successfully detected in cerebrospinal fluid. However, despite diagnostic advancements, the treatment of neurological dengue is problematic. The launch of a dengue vaccine is expected to be beneficial.

The COVID-19 outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global major concern. In this review, we addressed a theoretical model on immunopathogenesis associated with severe COVID-19, based on the current literature of SARS-CoV-2 and other epidemic pathogenic coronaviruses, such as SARS and MERS. Several studies have suggested that immune dysregulation and hyperinflammatory response induced by SARS-CoV-2 are more involved in disease severity than the virus itself.Immune dysregulation due to COVID-19 is characterized by delayed and impaired interferon response, lymphocyte exhaustion and cytokine storm that ultimately lead to diffuse lung tissue damage and posterior thrombotic phenomena.Considering there is a lack of clinical evidence provided by randomized clinical trials, the knowledge about SARS-CoV-2 disease pathogenesis and immune response is a cornerstone to develop rationale-based clinical therapeutic strategies. In this narrative review, the authors aimed to describe the immunopathogenesis of severe forms of COVID-19.

BACKGROUND: Urinary tract infections (UTIs) in elderly patients can be a complex problem in terms of approach to diagnosis, treatment, and prevention, because the patients often present nonspecific symptoms. The epidemiological and clinical characteristics of UTI in elderly women were studied, in order to make early diagnosis and prevent serious clinical complications secondary to UTI. METHODS: This was a prospective population-based study, with elderly women, during their first medical office visit. Medical records were obtained by clinical history and physical examination in order to detect signs and symptoms of UTI and the presence of co-morbidities. Clean-catch midstream urine specimens for urinary dipstick test, sediment, and culture were collected; cervical samples for conventional Pap smears were also collected. RESULTS: UTI was found in 16.55% of elderly women. The most frequent urinary symptom was foul smelling urine, in 60.6%. E. coli was responsible for 98 (76.56%) cases of significant bacteriuria; 34 (34.69%) were resistant to trimethoprim-sulfamethoxazole, and 21 (21.42%) to fluoroquinolones. Asymptomatic bacteriuria (AB) was not treated. The presence of predisposing factors demonstrated that the history of previous UTI (p < 0.001), vaginitis (p < 0.001), and diabetes (p = 0.042) increased the risk for UTI. CONCLUSION: This study confirmed the high prevalence of UTI among elderly women and its unusual clinical presentation. Diabetes, history of previous UTI, and vaginitis were shown to be predisposing factors for UTI; it is not necessary to treat AB in elderly women, even among diabetics.

BACKGROUND: Lamivudine is an oral nucleoside analogue widely used for the treatment of chronic hepatitis B. The main limitation of lamivudine use is the selection of resistant mutations that increases with time of utilization. Hepatitis B virus (HBV) isolates have been classified into eight genotypes (A to H) with distinct geographical distributions. HBV genotypes may also influence pathogenic properties and therapeutic features. Here, we analyzed the HBV genotype distribution and the nature and frequency of lamivudine resistant mutations among 36 patients submitted to lamivudine treatment for 12 to 84 months. RESULTS: Half of the patients were homosexual men. Only 4/36 (11%) patients were HBV DNA negative. As expected for a Brazilian group, genotypes A (24/32 positive individuals, 75%), D (3/32, 9.3%) and F (1/32, 3%) were present. One sample was from genotype C, which is a genotype rarely found in Brazil. Three samples were from genotype G, which had not been previously detected in Brazil. Lamivudine resistance mutations were identified in 20/32 (62%) HBV DNA positive samples. Mean HBV loads of patients with and without lamivudine resistance mutations were not very different (2.7 x 107 and 6.9 x 107 copies/mL, respectively). Fifteen patients showed the L180M/M204V lamivudine resistant double mutation. The triple mutant rt173V/180M/204V, which acts as a vaccine escape mutant, was found in two individuals. The three isolates of genotype G were entirely sequenced. All three showed the double mutation L180M/M204V and displayed a large genetic divergence when compared with other full-length genotype G isolates. CONCLUSION: A high (55%) proportion of patients submitted to long term lamivudine therapy displayed resistant mutations, with elevated viral load. The potential of transmission of such HBV mutants should be monitored. The identification of genotypes C and G, rarely detected in South America, seems to indicate a genotype distribution different to that observed in non treated patients. Disparities in routes of transmission (genotype G seems to be linked to homosexual behavior) and in pathogenic properties (genotype C is very aggressive) among HBV genotypes may explain the presence of rare genotypes in the present work.

OBJECTIVE: To evaluate the impact of a preliminary positive blood culture result, subsequently confirmed to be a false positive blood culture result on rate of hospitalization, antibiotic therapy and use of microbiologic tests. DESIGN: Retrospective chart review. PATIENTS AND METHODS: Children between 1 month and 18 years old on whom a blood culture was performed were eligible, excluding those with an underlying condition for whom a false positive blood culture may be difficult to assess. During the 1-year study period 9959 blood cultures were performed of which 778 (7.8%) produced growth. Charts of 81 patients with a false positive blood culture were reviewed and compared with those of 162 patients with a true negative blood culture. Patients already hospitalized when blood culture was drawn (n = 24) were analyzed separately from those who were not (n = 219). Among these, patients were divided into those who were followed as outpatients (n = 104) and hospitalized (n = 115). RESULTS: Both groups (false positive vs. true negative) were comparable for age, sex, temperature at consultation, white blood cell count and illness severity. Twenty-six percent of patients followed as outpatients who had a false positive blood culture were hospitalized because of a preliminary positive blood culture result. Among patients hospitalized at the initial assessment, the frequency of antibiotic therapy (91% vs. 71%, P < 0.01), the frequency of use of intravenous antibiotics (80% vs. 58%, P < 0.01) and the percentage of unwarranted antibiotic prescription (13% vs. 0%, P < 0.01) were significantly greater in the false positive group than in the true negative group. The same results were found for each of these outcomes among the group of patients followed as outpatients (61% vs. 28%, P < 0.01, 17% vs. 0%, P < 0.01 and 39% vs. 0%, P < 0.01) for false positive vs. true negative, respectively. Patients with false positive blood cultures had more blood cultures drawn subsequently (P < 0.01). Children already hospitalized when the blood culture was obtained did not show significant differences in main outcomes. CONCLUSIONS: False positive blood culture results generate unnecessary hospitalizations, antibiotic therapy and use of microbiologic tests.

In Ridley Scott's film "Blade Runner", empathy-detection devices are employed to measure affiliative emotions. Despite recent neurocomputational advances, it is unknown whether brain signatures of affiliative emotions, such as tenderness/affection, can be decoded and voluntarily modulated. Here, we employed multivariate voxel pattern analysis and real-time fMRI to address this question. We found that participants were able to use visual feedback based on decoded fMRI patterns as a neurofeedback signal to increase brain activation characteristic of tenderness/affection relative to pride, an equally complex control emotion. Such improvement was not observed in a control group performing the same fMRI task without neurofeedback. Furthermore, the neurofeedback-driven enhancement of tenderness/affection-related distributed patterns was associated with local fMRI responses in the septohypothalamic area and frontopolar cortex, regions previously implicated in affiliative emotion. This demonstrates that humans can voluntarily enhance brain signatures of tenderness/affection, unlocking new possibilities for promoting prosocial emotions and countering antisocial behavior.

Endometriosis (EM) is an infrequent cause of peripheral neuropathy, most commonly sciatic. Perineural spread has recently been introduced as an alternate explanation for cases of lumbosacral or sciatic nerve EM. We performed a literature review to collect all reported cases of peripheral and central nervous system EM in search of anatomic patterns of involvement; potentially to support the perineural spread theory. If available, intraneural invasion and presence of peritoneal EM were recorded. The search revealed 83 articles describing 365 cases of somatic peripheral nervous EM and 13 cases of central nervous EM. The most frequently involved site was the sacral plexus (57%, n = 211), followed by the sciatic nerve (39%, n = 140). Other nerves were reported in significantly smaller numbers. Ninety seven percent (97%, n = 355) of peripheral nerve cases presented with pain, 20% ( n = 72) reported weakness and 31% ( n = 114), numbness. Thirty four percent (34%, n = 38) had solely intraneural EM of which 89% ( n = 33) had no peritoneal EM (percentage based on available information). In the central nervous system, the conus medullaris and/or cauda equina constituted the majority of cases with 54% ( n = 7). Apart from perineural spread, other discussed mechanisms include retrograde menstruation with peritoneal seeding, hematogenous and lymphogenous spread, stem cell implantation either hematogenously or via retrograde menstruation with subsequent EM differentiation, and coelomic or Müllerian duct metaplasia. We believe this literature review supports perineural spread as an alternate mechanism for EM of nerve, particularly the subgroup with intraneural EM and without peritoneal disease. Clin. Anat. 28:1029–1038, 2015. © 2015 Wiley Periodicals, Inc.

Purpose: To review the role of corneal biomechanics for the clinical evaluation of patients with ectatic corneal diseases. Methods: A total of 1295 eyes were included for analysis in this study. The normal healthy group (group N) included one eye randomly selected from 736 patients with healthy corneas, the keratoconus group (group KC) included one eye randomly selected from 321 patients with keratoconus. The 113 nonoperated ectatic eyes from 125 patients with very asymmetric ectasia (group VAE-E), whose fellow eyes presented relatively normal topography (group VAE-NT), were also included. The parameters from corneal tomography and biomechanics were obtained using the Pentacam HR and Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany). The accuracies of the tested variables for distinguishing all cases (KC, VAE-E, and VAE-NT), for detecting clinical ectasia (KC + VAE-E) and for identifying abnormalities among the VAE-NT, were investigated. A comparison was performed considering the areas under the receiver operating characteristic curve (AUC; DeLong’s method). Results: Considering all cases (KC, VAE-E, and VAE-NT), the AUC of the tomographic-biomechanical parameter (TBI) was 0.992, which was statistically higher than all individual parameters (DeLong’s; p &lt; 0.05): PRFI- Pentacam Random Forest Index (0.982), BAD-D- Belin -Ambrosio D value (0.959), CBI -corneal biomechanical index (0.91), and IS Abs- Inferior-superior value (0.91). The AUC of the TBI for detecting clinical ectasia (KC + VAE-E) was 0.999, and this was again statistically higher than all parameters (DeLong’s; p &lt; 0.05): PRFI (0.996), BAD-D (0.995), CBI (0.949), and IS Abs (0.977). Considering the VAE-NT group, the AUC of the TBI was 0.966, which was also statistically higher than all parameters (DeLong’s; p &lt; 0.05): PRFI (0.934), BAD- D (0.834), CBI (0.774), and IS Abs (0.677). Conclusions: Corneal biomechanical data enhances the evaluation of patients with corneal ectasia and meaningfully adds to the multimodal diagnostic armamentarium. The integration of biomechanical data and corneal tomography with artificial intelligence data augments the sensitivity and specificity for screening and enhancing early diagnosis. Besides, corneal biomechanics may be relevant for determining the prognosis and staging the disease.

The coronavirus disease 2019 (COVID-19) pandemic began in December 2019 in Wuhan, China. Since then, it has rapidly spread across the globe and impacted several countries. Brazil has more than 5.5 million COVID-19 confirmed cases, almost 160,000 deaths and is the leader in numbers of health care professionals infected. Most recent studies suggest that immunity can be developed after an episode of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection. This brings a false sense of safety for professionals who have already been infected and have recovered from the disease. They return to the battlefields exposed to high viral load, often without adequate protection. A 36-year-old female medical doctor, without comorbidities, presented on 20th March 2020 with rhinorrhea and sore throat followed by low fever, diarrhea, asthenia, and mild headache until the seventh day of symptoms when reverse transcription polymerase chain reaction (RT-PCR) was obtained by nasal swab. The RT-PCR collected on 27th March 2020 was positive for SARS-CoV2 with a log of 513 copies (detection limit of RT-PCR less than 100 copies). After 11 days of initial clinical symptoms, she presented with erythematous vesicles on her right calf, along with severe musculoskeletal pain of the lower limbs with hyperesthesia. The first serological test was performed using enzyme-linked immunosorbent assay (ELISA), 23 days after the onset of symptoms, with 0.477 immunoglobulin G (IgG) titers (negative: less than 1.00 S/CO). There was complete resolution of the symptoms 24 days after onset (Figure 1). The patient returned to medical work at COVID-intensive care unit in two hospitals. After returning to work she was tested twice for COVID by chemiluminescence method serologies. The results were both negative for IgM and IgG detection, 33 days and 67 days after the acute presentation of symptoms. Approximately 12 weeks after the first episode of COVID-19, she presented a new clinical symptomes with nasal obstruction and hyaline rhinorrhea, sudden and complete anosmia and ageusia, frontal headache, and asthenia. On the tenth day of this new clinical episode, there was worsening of prostration with persistent anosmia and ageusia. She sought emergency care on the 11th day of symptoms, where she underwent a computed tomography (CT) scan that revealed a pattern of acute viral pneumonia typical of COVID-19 (Figure 2A). The ELISA serology on the 13th day of symptoms revealed positive immunoglobulin A for COVID-19 with 4240 titers (negative: less than 1.00 S/CO). Nasal swab RT-PCR on the 11th and 13th days of symptoms were negative. d-Dimer increased to 761 ng/ml and DHL to 290 U/L, however, serum values normalized after 48 h. The neutralizing IgG titration performed by the ELISA method on the 20th day of symptoms was positive in 1173, and after 45 days was 7473 (immunity: titer greater than 1.00 S/CO). The pulmonary pathological changes identified on the chest CT practically disappeared on the twenty-fourth day after the onset of symptoms (Figure 2B). About 11 months after the first cases of COVID-19, there is still no consensus in literature of reinfection by SARS-CoV-2, although some reports around the world show strong evidence that it is happening. The strongest evidence of reinfection requires documentation of a new infection by a molecularly distinct form of the same virus after the elimination of the previous infection.1-3 Human reinfection by SARS-CoV-2 was confirmed for the first time in August 2020 in Hong Kong, through genetic sequencing of two samples collected by nasal swab from the same patient with a time difference of 142 days. There was evidence that the viral genomes belong to different lineages, one of which was more incident between March and April 2020, while the other is close to strains found today.4 As genetic difference between strains increases over time, cross-immunity between those lineages may become more difficult and different clinical pictures may occur.4 However, it is unknown how intense the second clinical episode will be. We raise the discussion whether the presence of a new mutation, such as D614G, which replicates faster in the upper airway, could be more related to pneumonia and anosmia, to the detriment of other symptoms, such as gastrointestinal manifestations.5 Despite evidence of an effective acquired immune response after COVID-19, some studies have shown that patients with mild symptoms have developed a weaker and less lasting immune response to the virus, with a decrease in the level of antibodies after 2–3 months of infection.6, 7 As the patient maintained intense exposure to COVID-19 in those 3 months between clinical episodes, had different symptoms and antibody detection only recently, this suggests reinfection by different lineages of SARS-CoV-2. Therefore, the hypothesis of herd immunity and duration of protection afforded by vaccines, is questioned. The authors declare that there are no conflict of interests. Danielle de Araujo Torres: Conceived the presented idea and elaborated the manuscript. Luciana do Carmo Bueno Ribeiro: Provided the clinical data and exams, and elaborated the manuscript. Anna Patrícia de Freitas Linhares Riello, Dafne Dain Gandelman Horovitz, Luis Felipe Ribeiro Pinto, and Julio Croda: revised the manuscript, provided critical feedback and proposed format adjustments.