Outcome of COVID-19 in Kidney Transplant Recipients Through the SARS-CoV-2 Variants Eras: Role of Anti-SARS-CoV-2 Monoclonal Antibodies.

Kidney transplant recipients (KTR) are at increased risk for COVID-19-associated complications. We aimed to describe the evolving epidemiology and outcome of PCR-documented SARS-CoV-2 infection in KTR followed at our institution from March 2020 to May 2022. The primary endpoint was hospitalization for COVID-19-related symptoms or death within 28 days from diagnosis. Overall, 243 cases were included of which 68 (28%) developed the primary outcome. A significant decrease in the incidence of the primary outcome was observed (p < 0.001, r -0.342) during the study period. Anti-Spike monoclonal antibodies (mAbs) were administered as early treatment (within 5-7 days of onset of symptoms) in 101 patients (14 with casirivimab/imdevimab and 87 with sotrovimab). Among 145 patients who had received at least one vaccination dose before infection, 109 patients were considered as adequately vaccinated. Multivariate analysis revealed that the Charlson Comorbidity Index (P 0.001; OR 1.28, CI 1.11-1.48) was associated with the primary outcome, while early administration of mAbs (P 0.032; OR 0.39, CI 0.16-0.92) was associated with a better outcome, but not infection during the period of the omicron variant predominance or adequate vaccination.

A guide to incubate eggs of Tropidurus lizards under laboratory conditions.

Studies in Evo-Devo benefit from the use of a variety of organisms, as comparative approaches provide a better understanding of Biodiversity and Evolution. Standardized protocols to incubate eggs and manipulate embryo development enable postulation of additional species as suitable biological systems for research in the field. In the past decades, vertebrate lineages such as Squamata (lizards, snakes, and amphisbaenians) emerged as crucial study systems for addressing topics as diverse as phenotypic evolution and climate change. However, protocols for maintaining gravid females and incubating eggs in the lab under experimental conditions are available to only a few squamate species. This resource article presents a simple incubation guide that standardizes conditions to maintain embryos of Tropidurus catalanensis (Squamata: Tropiduridae) under different experimental conditions, manipulating relevant environmental factors like temperature and humidity. We identified associated effects relating the egg incubation condition to developmental stage, incubation time, hatching success, and resulting morphotypes. Temperature and humidity play a key role in development and require attention when establishing the experimental design. Current literature comprises information for Tropidurus lizards that ponders how general in Squamata are the ecomorphs originally described for Anolis. Studies evaluating phenotypic effects of developmental environments suggest plasticity in some of the traits that characterize the ecomorphological associations described for this family. We expect that this incubation guide encourages future studies using Tropidurus lizards to address Evo-Devo questions.

SARS-CoV-2 infection in kidney transplant recipients: Early report of five cases.

From December 2019 to March 2020, China was the epicenter of the SARS-CoV-2 infection pandemic, but from that moment on, Europe surpassed China in the number of new cases and deaths related to this novel viral respiratory infection. The emergence of this world pandemic is particularly important for solid organ transplant recipients, who might have an increased risk of mortality, not only due to their chronic immunosuppression status, but also to the cardiovascular risk that correlates with several years of chronic kidney disease. To the extent that there is still a lack of knowledge about the clinical characteristics, evolution, and prognosis of SARS-CoV-2 infection in kidney transplant recipients, we will report the first 5 cases diagnosed and followed in our transplant unit, as well as share the therapeutic strategies adopted.

Diagnosis of Chediak Higashi disease in a 67-year old woman.

Chediak-Higashi disease is a rare disease caused by bi-allelic mutations in the lysosomal trafficking regulator gene, LYST. Individuals typically present in early childhood with partial oculocutaneous albinism, a bleeding diathesis, recurrent infections secondary to immune dysfunction, and risk of developing hemophagocytic lymphohistiocytosis (HLH). Without intervention, mortality is high in the first decade of life. However, some individuals with milder phenotypes have attenuated hematologic and immunologic presentations, and lower risk of HLH. Both classic and milder phenotypes develop progressive neurodegeneration in early adulthood. Here we present a remarkable patient diagnosed with Chediak-Higashi disease at age 67, many decades after the diagnosis is usually established. Diagnosis was suspected by observing the pathognomonic granules within leukocytes, and confirmed by identification of bi-allelic mutations in LYST, reduced LYST mRNA expression, enlarged lysosomes within fibroblasts, and decreased NK cell lytic activity. This case further expands the phenotype of Chediak-Higashi disease and highlights the need for increased awareness. Individuals with milder phenotypes may escape early diagnosis, but identification is important for close monitoring of potential complications, and to further our understanding of the function of LYST.

CRF receptor type 1 (but not type 2) located within the amygdala plays a role in the modulation of anxiety in mice exposed to the elevated plus maze.

The amygdala (Amy) is an important center that processes threatening stimuli. Among the neurotransmitters implicated in the control of emotional states, the corticotrophin releasing factor (CRF) is an important modulator, acting at CRF1 and CRF2 receptors. Few studies have investigated the role of CRF and its receptors in the Amy on anxiety in mice. Here, we investigated the effects of intra-Amy (aimed at the basolateral nucleus) injections of CRF (37.5 and 75pmol/0.1µl), urocortin 3 (UCn3, a selective CRF2 agonist; 4, 8, 16 or 24pmol/0.1µl), CP376395 (a selective CRF1 antagonist; 0.375, 0.75 or 1.5nmol/0.1µl), antisauvagine-30 (ASV-30, a selective CRF2 antagonist; 1 or 3nmol/0.1µl) on the behavior of mice exposed to the elevated plus maze (EPM). Both spatiotemporal (e.g., percentage of open-arm entries and percentage of open-arm time; %OE and %OT) and complementary [e.g., frequency of protected and unprotected stretched attend postures (pSAP and uSAP) and head dips (pHD and uHD); frequency and time spent on open arm end exploration (OAEE)] measures were recorded during a 5-min test in the EPM. While intra-Amy injections of CRF decreased %OE, %OT and OAEE, suggesting an anxiogenic-like action, UCn3 (all doses) did not change any behavior. In contrast, injections of CP376395 (0.75nmol) produced an anxiolytic-like effect, by increasing %OT and OAEE and decreasing pSAP and pHD. Neither spatiotemporal nor complementary measures were changed by intra-Amy ASV-30. These results suggest that CRF plays a marked anxiogenic role at CRF1 receptors in the amygdala of mice exposed to the EPM.

Solid organ transplantation from donors with recent or current SARS-CoV-2 infection: A systematic review.

BACKGROUND: Solid-organ transplantation (SOT) from SARS-CoV-2 positive donors could be a life-saving opportunity worth grasping. We perform a systematic review to evaluate the recipient outcomes of SOT from donors with recent or current SARS-CoV-2 infection. METHODS: Search strategy was performed in PubMed, Cochrane COVID-19 Study Register, and Web of Science databases from the 1st of January 2019 to the 31st of December 2021. SOT adult recipients from a donor with past or current SARS-CoV-2 infection were elegible for inclusion. Outcomes were viral transmission, COVID-19 symptoms, mortality, hospital stay, and complications. PROSPERO Register Number: CRD42022303242 FINDINGS: Sixty-nine recipients received 48 kidneys, 18 livers and 3 hearts from 57 donors. Six additional transplants from positive lungs were identified. IgG+ anti-SARS-CoV-2 titers were detected among 10/16 recipients; only 4% (3/69) recipients were vaccinated. Non-lung transplant recipients received organs from 10/57 (17.5%) donors with persistent COVID-19. In 18/57 donors, SARS-CoV-2 RNA was detected (median 32 Cycle threshold [Ct]) at procurement. Among non-lung transplant recipients, SARS-CoV-2 viral transmission was not documented. Four patients presented delayed graft dysfunction, two patients acute rejection, and two patients died of septic shock. The median (IQR) hospital stay was 18 (11-28) days in recipients from symptomatic donors. Viral transmission occurred from three lung donors to their recipients, who developed COVID-19 symptoms. One of the recipients subsequently died. CONCLUSION: Use of non-lung (kidney, liver and heart) organs from SARS-CoV-2 positive donors seem to be a safe practice, with a low risk of transmission irrespective of the presence of symptoms at the time of procurement. Low viral replication (Ct > 30) was safe among non-lung donors, even if persistently symptomatic at procurement.

Case report: Disseminated Scedosporium apiospermum infection with invasive right atrial mass in a heart transplant patient.

Scedosporium apiospermum associated endocarditis is extremely rare. We report a case of a disseminated S. apiospermum infection with an invasive right atrial mass in a 52-year-old male, 11 months after heart transplantation, referred to our institution for an endogenous endophthalmitis with a one-month history of diffuse myalgias and fatigue. The patient had been supported two times with extracorporeal membrane oxygenation (ECMO) during the first three postoperative months. The echocardiography on admission revealed a mass in the right atrium attached to a thickened lateral wall. The whole-body [18F]FDG PET/CT revealed systemic dissemination in the lungs, muscles, and subcutaneous tissue. Blood cultures were positive on day three for filamentous fungi later identified as S. apiospermum. The disease was refractory to a 3-week dual antifungal therapy with voriconazole and anidulafungin in addition to reduced immunosuppression, and palliative care was implemented.

Case Report: Anaphylactoid Shock Associated with Snakebite Envenoming in Portugal.

Although rare in Portugal, snakebite envenoming entails severe morbidity and mortality. We present the case of a 65-year-old woman bitten on her leg in a northern coastal region in Portugal, on a walk during the COVID-19 pandemic lockdown. Despite first looking for help at the nearest pharmacy, she developed anaphylactoid shock and was promptly driven to a tertiary hospital, where antivenom was administered in a timely manner under close monitoring. Prophylactic antibiotics were started and maintained based on elevated inflammatory markers and signs of wound inflammation. She evolved favorably, with rapid weaning of vasopressors and resolution of end-organ dysfunction. This case highlights the importance of prompt recognition and describes crucial steps in envenomation management in a country where snakebite is infrequent, but potentially fatal.

Understanding rare infections post-lung transplantation.

Introduction: Lung transplant recipients are at the highest risk of infectious complications among all solid-organ transplant (SOT) recipients. In the current era, many standardized protocols in terms of diagnostic algorithms, prophylaxis, and therapeutic strategies have improved the management of the most common infectious complications. Conversely, diagnosis of rare infections can be particularly challenging and this can delay appropriate treatment.Areas covered: This article will review the epidemiology, clinical presentation, diagnostic and therapeutic management of certain rarely reported viral, fungal, bacterial and parasitic infections in lung transplant recipients.Expert opinion: Once the most frequent infections are excluded, clinical suspicion combined with molecular diagnostic methods such as targeted and broad-spectrum PCRs can allow diagnosis of a rare infection. A multidisciplinary team, including transplant pulmonologists, transplant infectious diseases specialists, microbiologists and pathologists is essential for prompt diagnosis and optimal therapeutic management.

Adult Native Joint Septic Arthritis: A Nine-Year Retrospective Analysis in a Portuguese University Hospital.

INTRODUCTION: Septic arthritis of a native joint represents a medical emergency. Drainage and effective antibiotic treatment are critical to avoid joint destruction and long-term impairment. The aim of this study was to evaluate epidemiological and clinical characteristics of patients with the diagnosis of septic arthritis to help establish local guidelines for empirical antibiotic treatment. MATERIAL AND METHODS: Retrospective analysis of adult patients admitted at Centro Hospitalar Universitário do Porto from 2009 to 2017 with suspected native joint septic arthritis. Relevant demographics, microbiology findings and respective antibiotic susceptibilities were analysed. RESULTS: Ninety-seven patients, predominantly males (59.8%) with a median age of 61 years old were included. The most commonly reported comorbidity associated with septic arthritis was diabetes mellitus (20.6%). The knee was the most commonly affected joint (71.1%). Arthrocentesis was performed in all patients, but only 50.5% had positive microbial growth in the synovial fluid. Staphylococcus aureus was the most frequently identified microorganism, 86% of which were methicillin susceptible. Gram-negative bacteria were the causative agent in 15% of cases. A wide range of empirical antibiotic regimens were prescribed with a combination of vancomycin/carbapenem being the most common (30.9%). Analysis of antibiotic susceptibility profiles revealed that amoxicillin/clavulanate would have been appropriate as the initial regimen in 89% of cases. DISCUSSION: The main causative pathogen was Staphylococcus aureus, with methicillin resistant Staphylococcus aureus remaining rare. The proportion of Gram-negative bacteria implies that these agents should be covered by empirical treatment, although no case of Pseudomonas infection has been identified. Therefore, antipseudomonal coverage is not necessary in empirical regimens. CONCLUSION: Routine coverage of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa is not warranted but must be considered when specific risk factors are found. Amoxicillin/clavulanate can provide adequate antibiotic coverage as an empirical treatment for adult native joint septic arthritis. Its use may allow a reduction in use of broader spectrum antibiotics.

Introdução: A artrite séptica representa uma patologia grave que pode levar à destruição articular e diminuição funcional a longo prazo. Adicionalmente à drenagem articular, uma antibioterapia efetiva é crucial. O objetivo deste estudo consistiu em avaliar as características epidemiológicas e clínicas dos doentes admitidos com diagnóstico de artrite séptica e analisar a terapêutica antimicrobiana, estabelecendo orientações locais de tratamento antibiótico empírico. Material e Métodos: Análise retrospetiva de doentes adultos admitidos no Centro Hospitalar Universitário do Porto com artrite séptica de articulação nativa de 2009 a 2017. Foram revistos os resultados microbiológicos, os perfis de suscetibilidade aos antimicrobianos e os registos médicos. Resultados: Dos 97 doentes incluídos, 59,8% eram do género masculino, com uma idade média de 61 anos. A comorbilidade mais comum foi a diabetes mellitus (20,6%). O joelho foi a articulação mais afetada (71,1%). Realizou-se artrocentese em todos os doentes, com isolamento microbiano em 50,5% dos produtos. O Staphylococcus aureus foi o microrganismo mais frequente, sendo sensível à meticilina, em 86% dos casos. As bactérias Gram-negativo foram o agente causal em 15% das infeções. A associação do carbapenemo e vancomicina foi a antibioterapia empírica mais comummente iniciada (30,9%), embora em 89% dos casos a amoxicilina/clavulanato teria sido apropriada como regime inicial. Discussão: O principal agente etiológico foi o Staphylococcus aureus, continuando o Staphylococcus aureus resistente à meticilina a ser um agente raro. A percentagem de bactérias Gram-negativo implica a sua cobertura como terapêutica empírica, embora não tenha havido casos de infeção por Pseudomonas. Por isso, a utilização empírica de um antibiótico com atividade antipseudomónica não é necessária. Conclusão: A cobertura antibiótica de Staphylococcus aureus resistente à meticilina e Pseudomonas não é obrigatória, mas pode ser considerada na presença de alguns fatores de risco específicos. A amoxicilina/ clavulanato é uma antibioterapia empírica adequada para a artrite séptica de articulação nativa, permitindo reduzir a utilização inadequada de antibióticos de espectro mais alargado.

Donor-derived fatal hyperinfection strongyloidiasis in renal transplant recipient.

Strongyloides stercoralis is a nematode, endemic in tropical and subtropical areas. Strongyloidiasis has been reported in recipients of hematopoietic stem cells, kidney, liver, heart, intestine, and pancreas, eventually presenting as disseminated strongyloidiasis and hyperinfection syndrome (SHS) which is associated with high mortality. We report one case of a recent renal transplant recipient, who presented with gastrointestinal and respiratory symptoms, evolving into shock. The identification of Strongyloides stercoralis in the bronchoalveolar lavage (BAL) lead us to the diagnosis of SHS. Treatment with subcutaneous ivermectin was started, however the patient did not survive. Retrospective serum donor analysis allowed us to identify the donor as the source of infection.

[Human Psittacosis: A Case Report]. / Psitacose: A Propósito de Um Caso Clínico.

Psittacosis is a rare disease caused by Chlamydophila psittaci, an intracellular bacteria transmitted by contaminated birds. The clinical and radiological presentations are nonspecific. We describe a case of a 42-year-old woman, with known exposure to birds, who presented to the emergency department with one-week evolution of myalgia, polyarthritis, and respiratory symptoms. At admission, she had fever, respiratory failure, raised inflammatory markers and bilateral interstitial infiltrates at chest radiography. Considering the clinical findings and epidemiological background, we raised the hypothesis of a Chlamydophila psittaci atypical pneumonia that was serologically confirmed. Tetracyclines are the mainstay of treatment and the macrolides are an effective alternative. We highlight the importance of the epidemiological context in the early diagnosis and treatment of this infection.

A psitacose é uma entidade rara provocada pela Chlamydophila psittaci, uma bactéria intracelular obrigatória que se transmite através do contacto com aves contaminadas. A apresentação clínica e imagiológica é inespecífica. Reporta-se o caso clínico de uma mulher de 42 anos, com história de exposição a pássaros, que se apresenta no Serviço de Urgência com um quadro de mialgias, poliartralgias e clínica de infeção respiratória, com uma semana de evolução. À admissão, encontrava-se febril, com insuficiência respiratória do tipo 1, elevação dos parâmetros inflamatórios e infiltrados intersticiais difusos bilaterais na radiografia de tórax. Considerando o quadro clínico e o contexto epidemiológico de risco, colocou-se a hipótese de pneumonia atípica por Chlamydophila psittaci, confirmada serologicamente. As tetraciclinas são o esteio do tratamento, sendo os macrólidos uma alternativa eficaz. Realça-se a importância do contexto epidemiológico, para uma abordagem diagnóstica e terapêutica apropriadas.

[Late Neuroborreliosis in an Erasmus Programme Student]. / Neuroborreliose Tardia num Estudante em Programa Erasmus.

Lyme disease is an endemic zoonosis, the most prevalent tick-transmitted infection in temperate areas of Europe, North America and Asia. It is a multisystemic disease with cutaneous, musculoskeletal, neurologic and cardiac manifestations, according to the stage of the disease. We describe a case of late neuroborreliosis in an Erasmus programme student living in Porto. We discuss the importance of the epidemiological suspicion, the clinical approach, the diagnostic criteria and the most adequate treatment.

A doença de Lyme é uma zoonose endémica nos Estados Unidos da América (EUA), na Ásia e no continente europeu, nomeadamente nos países do centro da Europa. Trata-se de uma doença multissistémica, com manifestações cutâneas, articulares, neurológicas e cardíacas, que variam de acordo com a fase da doença. Apresentamos o caso de uma neuroborreliose tardia num jovem estudante belga a residir temporariamente no Porto. Discutimos a importância da suspeita epidemiológica, a investigação etiológica, os critérios de diagnóstico e o tratamento mais adequado.

Single aggressive and non-aggressive social interactions elicit distinct behavioral patterns to the context in mice.

Aggressive interactions between conspecific animals have been used as a social stressor with ethological characteristics to study how social interactions can modulate animal's behavior. Here, a new protocol based on aggressive and non-aggressive interactions was developed to study how different social interactions can alter the behavioral profile of animals re-exposed to the context in which the interaction occurred. We used factor analysis to trace the behavioral profile of socially defeated and non-defeated mice when they were re-exposed to the apparatus [three interconnected chambers: home chamber, tunnel and surface area]; we also compared the behavior presented before (habituation) and 24 h after (re-exposure) the non-aggressive or aggressive interactions. A final factor analysis from defeated animals yielded 4 factors that represented 72.09% of total variance; whereas non-defeated animal's analysis was loaded with 5 factors that represented 85.46% of total variance. A 5-min non-aggressive interaction reduced the frequency of stretched attend behavior in the tunnel, whereas a single social defeat reduced time in the tunnel and increased time spent performing self-grooming in the home chamber without conditioning any other spatio-temporal and complementary measures. Together, these results suggest that different social interactions may modulate distinct behavioral profiles in animals when re-exposed to the context.

Cytomegalovirus acute infection with pulmonary involvement in an immunocompetent patient.

Introduction: Cytomegalovirus (CMV) infection in healthy adults is usually asymptomatic or causes a mild mononucleosis syndrome, while severe infections are rare in immunocompetent patients and poorly documented. When described, gastrointestinal tract and the central nervous systems are the most frequent sites of severe CMV infection. Lung disease can occur, but it's rare. Clinical case: A 29 years old man presenting with a 2-weeks history of fever, headache, malaise, dry non-productive cough and thoracic pleuritic pain, without improvement after one-week therapy with levofloxacin. Blood exams showed lymphocytosis of almost 50%, nine percent of atypical lymphocytes and elevated transaminases. Thoracic CT-scan showed bilateral infiltrate with internal air bronchogram. Blood serology showed positivity for CMV IgG and IgM, with low CMV IgG avidity. Serum and bronchoalveolar detection of CMV by polymerase chain reaction (PCR) technique was also positive. Cultures were all negative. The patient became increasingly hypoxemic and the liver transaminases worsening, the reason for which ganciclovir was started. He made a full recovery and was discharged seven days later with oral valganciclovir, completing a 3 weeks antiviral course at home. Discussion: CMV pneumonia is a rare condition, however it's one of the three most common cause of severe viral community acquired pneumonia (CAP), along with influenza and adenovirus. CMV pneumonia should be considered in patients with atypical lymphocytes and mildly elevated serum transaminases. Conclusion: In immunocompetent hosts, even with severe CMV-CAP, the prognosis is good. However, antiviral treatment should be considered in the rare occasion of severe CMV infection. Nevertheless, more studies are needed to clarify the clinical benefit of antiviral treatment.

Amygdaloid involvement in the defensive behavior of mice exposed to the open elevated plus-maze.

Previous studies have shown that the exposure to an open elevated plus maze (oEPM, an EPM with all four open arms) elicits fear/anxiety-related responses in laboratory rodents. However, very little is known about the underlying neural substrates of these defensive behaviors. Accordingly, the present study investigated the effects of chemical inactivation of the amygdala [through local injection of cobalt chloride (CoCl2: a nonspecific synaptic blocker)] on the behavior of oEPM-exposed mice. In a second experiment, the pattern of activation of the basolateral (BLA) and central (CeA) nuclei of the amygdala was assessed through quantification of Fos protein expression in mice subjected to one of several behavioral manipulations. To avoid the confound of acute handling stress, 4 independent groups of mice were habituated daily for 10days to an enclosed EPM (eEPM) and, on day 11 prior to immunohistochemistry, were either taken directly from their home cage (control) or individually exposed for 10min to a new clean holding cage (novelty), an eEPM, or the oEPM. An additional group of mice (maze-naïve) was not subjected to either the habituation or exposure phase but were simply chosen at random from their home cages to undergo an identical immunohistochemistry procedure. Results showed that amygdala inactivation produced an anxiolytic-like profile comprising reductions in time spent in the proximal portions of the open arms and total stretched attend postures (SAP) as well as increases in time spent in the distal portions of the open arms and total head-dipping. Moreover, Fos-positive labeled cells were bilaterally increased in the amygdaloid complex, particularly in the BLA, of oEPM-exposed animals compared to all other groups. These results suggest that the amygdala (in particular, its BLA nucleus) plays a key role in the modulation of defensive behaviors in oEPM-exposed mice.