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INTRODUCTION/AIMS: Laboratory and clinical data suggest a link between neurologically mediated inflammation and psoriasis, but the risk and features of peripheral neuropathy in psoriasis or psoriatic arthritis remain unknown. The aim of this exploratory study was to evaluate the risk and to describe the features of peripheral neuropathy in patients with psoriasis and psoriatic arthritis. METHODS: One hundred patients with psoriasis and/or psoriatic arthritis and 100 control subjects were consecutively enrolled. Diagnostic confirmation included electrophysiological examination, skin biopsy, and nerve ultrasound for confirmed polyneuropathy. RESULTS: Nine patients were diagnosed with confirmed polyneuropathy, while none of the control subjects had the condition (relative risk [RR] = 19.00, 95% confidence interval [CI] = 1.12-322.11). Specific relative risks for polyneuropathy were 22.09 (95% CI = 1.17-416.43) in psoriasis patients and 18.75 (95% CI = 1.07-327.62) in psoriatic arthritis patients. The observed polyneuropathy in all nine patients was length-dependent, symmetrical, and predominantly sensory, with minimal or no disability. Comorbidities and exposure to therapies known to increase the risk of polyneuropathy were more frequent in psoriasis and/or psoriatic arthritis patients compared to controls (42% vs. 4%, p = .0001). Analyzing data after excluding possible contributory causes, the risk of polyneuropathy in patients with psoriasis and/or psoriatic arthritis was not significant. DISCUSSION: Psoriasis and psoriatic arthritis appear to be associated with an increased risk of polyneuropathy. This increased risk seems to be linked to the higher prevalence of contributing factors for polyneuropathy, rather than a direct increase in neuropathy risk specifically related to psoriasis and psoriatic arthritis.

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BACKGROUND: Emerging data associated subjective cognitive complaints (SCC) with a heightened risk of future cognitive decline in Parkinson´s Disease (PD). OBJECTIVE: To determine whether SCC may predict the development of cognitive impairment in PD patients at baseline. METHODS: Over 4 years, major aspects of motor and non-motor symptoms were assessed. SCC were evaluated by non-motor symptoms scale domain-5 (NMSS5). The predictor value of SCC in cognitive change was assessed with univariate linear regression analyses, with NMSS5 at baseline as predictor. Change in cognition (ΔMoCA) was calculated by subtracting Montreal Cognitive Assessment Scale (MoCA) scores at baseline from scores obtained at reassessment and employed as the outcome. We replicated these analyses by employing alterations in MoCA subdomains as outcomes. RESULTS: 134 patients were evaluated at baseline, of those 73 PD patients were reassessed four years later. In our study, SCC didn´t act as a predictor for future cognitive decline. However, baseline NMSS5 was associated significantly with variation in attention, naming, and orientation domains. CONCLUSION: Our findings did not support that SCC in PD patients acts as a predictor of global cognitive decline. However, our findings enhance comprehension of how SCC correlates with performance in distinct cognitive areas, thereby providing better guidance for patients on their current complaints.

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INTRODUCTION: Cardiology and cardiothoracic surgery are among the specialties that most commonly require neurology inpatient consultations. We aimed to study the neurology referrals by the cardiovascular-specialized hospital included in our tertiary hospital center. METHODS: Retrospective study of consecutive patients referred for neurology inpatient consultation between January 1, 2020, and December 31, 2022. We analyzed referrals, patients' characteristics, and the approach taken. A detailed subanalysis was performed for patients diagnosed with acute ischemic stroke (AIS). RESULTS: 143 patients were observed (mean age 67.3 years, 46 [32.2%] females). Most frequent referral reasons were suspected AIS deficits (39.2%), altered mental status (19.6%), suspected seizures (13.3%), and neuroprognostication (11.9%). Mean referral-to-consult time was 2.7 days, and 117 (81.8%) consults were in-person. Additional investigation, treatment changes, and outpatient clinic referral were proposed, respectively, in 79.7%, 60.1%, and 19.6% of patients. Most common diagnoses were AIS (45.5%), hypoxic-ischemic encephalopathy (18.9%), and delirium (7.0%). Regarding patients with AIS (n = 62), most common stroke causes were post-cardiac procedure (44.6%), infective endocarditis (18.5%), aortic dissection (10.8%), acute myocardial infarction (10.8%), and anticoagulant withdrawal in patients with atrial fibrillation (6.2%). Thirty-four AIS patients were diagnosed less than 24 h since last seen well, of which four (6.2%) were treated (three with thrombolysis and one with mechanical thrombectomy). CONCLUSION: AIS is the most common reason for referral in our cardiovascular hospital. Our results highlight the importance of the availability of a neurologist/neurohospitalist with stroke expertise for consultation of inpatients admitted in a specialized cardiovascular hospital.

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Background Asthma represents one of the most common diseases in childhood, with a prevalence ranging between 9% and 13% in Portugal. Therefore, it holds significant importance in pediatric health. While existing studies have shed light on asthma in the Portuguese population, they have predominantly concentrated on urban centers, with the population of Alto Minho remaining underrepresented in the literature. This study aims to understand the main factors of exposure, exacerbation, and the most prevalent allergens in a pediatric sample from the Alto Minho Local Health Unit, Portugal. Methodology A retrospective cohort study was conducted among 239 pediatric asthma patients aged between five and 18 years at the Alto Minho Health Center. Data on demographics, clinical information, family history, environmental exposures, exacerbating factors, and prick test results were analyzed. Results Of the 239 patients, 64.44% were male and 35.56% were female. The majority of the sample exhibited a normal body mass index (82.17%) and a family history of atopy (66.67%). Noteworthy patterns emerged in comorbidities, notably an increased association with allergic rhinitis, the most frequent concomitant atopic pathology (79.50%), followed by atopic dermatitis (27.61%) and food allergy (10.88%). Sensitization to dust mites, particularly Dermatophagoides pteronyssinus, was widespread among the participants. Environmental exposures were marked by significant factors such as proximity to plants and trees, soft toys, and living in rural areas. Exacerbating factors included common triggers such as exercise, seasonal variations, and even laughter. Statistically significant associations were found between atopic comorbidities, exacerbation factors, exposure factors, and prick test results. Conclusions Our findings align with global trends, emphasizing the prevalence of atopic pathologies in pediatric asthma. Sensitization patterns and environmental exposures are indicative of regional influences. Study limitations include sample size and data standardization issues. Despite these limitations, the study significantly contributes to understanding pediatric asthma in Alto Minho, offering valuable insights for prompt diagnosis and targeted treatments.

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Abstract Background: One of the main adverse reactions of adjuvant radiotherapy for breast cancer is radiodermatitis. Objective: To assess the incidence of radiodermatitis in women with breast cancer, identify factors associated with its severity and determine the time at which this event occurs. Methods: Prospective cohort study in 113 women with breast cancer who were evaluated before radiotherapy and at every fifth session until the end of treatment. Logistic regression and Cox proportional regression model were used for the assessment of risk factors; P values < 0.05 were considered significant. Results: The incidence rate of radiodermatitis was 98.2% and it was demonstrated that for each additional point of the Body Mass Index (BMI), the chance of occurrence of grades II to IV radiodermatitis increases by 14% (OR = 1.14 [95% CI 1.04-1.26]; p = 0.004) and statin use increases the risk of more severe skin lesions by four-fold (OR = 4.27 [95% CI 1.11-16.42]; p = 0.035). The exclusive use of hydrogel for skin hydration was an independent factor in delaying the onset of radiodermatitis (HR = 0.55 [95% CI 0.36-0.82]; p = 0.004). Study limitations: The main limitation of this study was its external validity. The identified factors should be considered for services and populations similar to those in this study. Conclusions: There was a high incidence of radiodermatitis and its severity was related to higher BMI, statin use; there was a protective effect of hydrogel use.

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BACKGROUND: One of the main adverse reactions of adjuvant radiotherapy for breast cancer is radiodermatitis. OBJECTIVE: To assess the incidence of radiodermatitis in women with breast cancer, identify factors associated with its severity and determine the time at which this event occurs. METHODS: Prospective cohort study in 113 women with breast cancer who were evaluated before radiotherapy and at every fifth session until the end of treatment. Logistic regression and Cox proportional regression model were used for the assessment of risk factors; P values < 0.05 were considered significant. RESULTS: The incidence rate of radiodermatitis was 98.2% and it was demonstrated that for each additional point of the Body Mass Index (BMI), the chance of occurrence of grades II to IV radiodermatitis increases by 14% (OR=1.14 [95% CI 1.04-1.26]; p=0.004) and statin use increases the risk of more severe skin lesions by four-fold (OR=4.27 [95% CI 1.11-16.42]; p=0.035). The exclusive use of hydrogel for skin hydration was an independent factor in delaying the onset of radiodermatitis (HR=0.55 [95% CI 0.36-0.82]; p=0.004). STUDY LIMITATIONS: The main limitation of this study was its external validity. The identified factors should be considered for services and populations similar to those in this study. CONCLUSIONS: There was a high incidence of radiodermatitis and its severity was related to higher BMI, statin use; there was a protective effect of hydrogel use.

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BACKGROUND: The diagnosis of periprosthetic joint infection (PJI) is a major challenge in clinical practice. The role of neutrophils in fighting infection has been increasingly understood, and one mechanism of action of these cells is neutrophil extracellular traps. However, little is known about this process in PJI. QUESTIONS/PURPOSES: (1) Are the biomarkers of neutrophil extracellular trap formation (citrullinated histone H3 [H3Cit], cell-free DNA [cf-DNA], and myeloperoxidase [MPO]) increased in the synovial fluid of patients with PJI? (2) What is the diagnostic accuracy of biomarkers of neutrophil extracellular trap formation for PJI? METHODS: Between May 2020 and March 2021, 43 patients who underwent revision THA or TKA were enrolled in this study. Eleven patients were excluded and 32 patients were categorized into the PJI group (n = 16) or non-PJI group (n = 16) according to the 2018 Second International Consensus Meeting on Musculoskeletal Infection criteria. There were 15 men and 17 women in this study, with a median (range) age of 70 years (60 to 80 years). Twenty-seven patients had TKA and five had THA. We measured cf-DNA, MPO, and H3Cit in synovial fluid. The sensitivity, specificity, and receiver operating characteristic curve were calculated for each biomarker using the Musculoskeletal Infection Society criteria as the gold standard for diagnosis and considering a clinical surveillance of 2 years for patients in the non-PJI group. RESULTS: Patients with PJI had higher levels of synovial fluid cf-DNA (median [range] 130 ng/µL [18 to 179] versus 2 ng/µL [0 to 6]; p < 0.001), MPO (1436 ng/µL [55 to 3996] versus 0 ng/µL [0 to 393]; p < 0.001), and H3Cit (2115 ng/µL [5 to 2885] versus 3 ng/µL [0 to 87]; p < 0.001) than those in the non-PJI group. In receiver operating characteristic curve analyses, we observed near-perfect performance for all biomarkers evaluated, with an area under the curve of 1 (95% CI 0.9 to 1), 0.98 (95% CI 0.9 to 1), and 0.94 (95% CI 0.8 to 0.99) for cf-DNA, MPO, and H3Cit, respectively. The sensitivity for detecting PJI using synovial fluid was 100% for cf-DNA, 94% for MPO, and 88% for H3Cit. The specificity was 100% for cf-DNA and MPO, and 88% for H3Cit. CONCLUSION: Our results show that neutrophils in the periprosthetic microenvironment release neutrophil extracellular traps as part of the bactericidal arsenal to fight infection. These results allow a better understanding of the cellular and molecular processes that occur in this microenvironment, enabling the design of more assertive strategies for identifying new biomarkers and improving the available ones. Novel studies are needed to define whether and how neutrophil extracellular trap-related biomarkers can be useful for diagnosing PJI. LEVEL OF EVIDENCE: Level II, diagnostic study.

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The treatment of severe musculoskeletal injuries, such as loss of bone tissue and consolidation disorders, requires bone transplantation, and the success of this bone reconstruction depends on the grafts transplant's osteogenic, osteoconductive, and osteoinductive properties. Although the gold standard is autograft, it is limited by availability, morbidity, and infection risk. Despite their low capacity for osteoinduction and osteogenesis, decellularized bone allografts have been used in the search for alternative therapeutic strategies to improve bone regeneration. Considering that bone marrow stromal cells (BMSCs) are responsible for the maintenance of bone turnover throughout life, we believe that associating BMSCs with allograft could produce a material that is biologically similar to autologous bone graft. For this reason, this study evaluated the osteogenic potential of bone allograft cellularized with BMSCs. First, BMSC was characterized and allograft decellularization was confirmed by histology, scanning electron microscopy, and DNA quantification. Subsequently, the BMSCs and allografts were associated and evaluated for adhesion, proliferation, and in vitro and in vivo osteogenic potential. We demonstrated that, after 2 hours, BMSCs had already adhered to the surface of allografts and remained viable for 14 days. In vitro osteogenic assays indicated increased osteogenic potential of allografts compared with beta-tricalcium phosphate (ß-TCP). In vivo transplantation assays in immunodeficient mice confirmed the allograft's potential to induce bone formation, with significantly better results than ß-TCP. Finally, our results indicate that allograft can provide structural support for BMSC adhesion, offering a favorable microenvironment for cell survival and differentiation and inducing new bone formation. Taken together, our data indicate that this rapid methodology for cellularization of allograft with BMSCs might be a new therapeutic alternative in regenerative medicine and bone bioengineering.

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Communication between Deaf and hearing individuals remains a persistent challenge requiring attention to foster inclusivity. Despite notable efforts in the development of digital solutions for sign language recognition (SLR), several issues persist, such as cross-platform interoperability and strategies for tokenizing signs to enable continuous conversations and coherent sentence construction. To address such issues, this paper proposes a non-invasive Portuguese Sign Language (Língua Gestual Portuguesa or LGP) interpretation system-as-a-service, leveraging skeletal posture sequence inference powered by long-short term memory (LSTM) architectures. To address the scarcity of examples during machine learning (ML) model training, dataset augmentation strategies are explored. Additionally, a buffer-based interaction technique is introduced to facilitate LGP terms tokenization. This technique provides real-time feedback to users, allowing them to gauge the time remaining to complete a sign, which aids in the construction of grammatically coherent sentences based on inferred terms/words. To support human-like conditioning rules for interpretation, a large language model (LLM) service is integrated. Experiments reveal that LSTM-based neural networks, trained with 50 LGP terms and subjected to data augmentation, achieved accuracy levels ranging from 80% to 95.6%. Users unanimously reported a high level of intuition when using the buffer-based interaction strategy for terms/words tokenization. Furthermore, tests with an LLM-specifically ChatGPT-demonstrated promising semantic correlation rates in generated sentences, comparable to expected sentences.

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Background Blood biomarkers are a potential tool for early stroke diagnosis. We aimed to perform a pilot and exploratory study on untargeted blood biomarkers in patients with suspected stroke by using mass spectrometry analysis. Methods and Results This was a prospective observational study of consecutive patients with suspected stroke admitted within 6 hours of last being seen well. Blood samples were collected at admission. Patients were divided into 3 groups: ischemic stroke (IS), intracerebral hemorrhage (ICH), and stroke mimics. Quantitative analysis from mass spectrometry data was performed using a supervised approach. Biomarker-based prediction models were developed to differentiate IS from ICH and ICH+stroke mimics. Models were built aiming to minimize misidentification of patients with ICH as having IS. We included 90 patients, one-third within each subgroup. The median age was 71 years (interquartile range, 57-81 years), and 49 participants (54.4%) were women. In quantitative analysis, C3 (complement component 3), ICAM-2 (intercellular adhesion molecule 2), PLGLA (plasminogen like A), STXBP5 (syntaxin-binding protein 5), and IGHV3-64 (immunoglobulin heavy variable 3-64) were the 5 most significantly dysregulated proteins for both comparisons. Biomarker-based models showed 88% sensitivity and 89% negative predictive value for differentiating IS from ICH, and 75% sensitivity and 95% negative predictive value for differentiating IS from ICH+stroke mimics. ICAM-2, STXBP5, PLGLA, C3, and IGHV3-64 displayed the highest importance score in our models, being the most informative for identifying patients with stroke. Conclusions In this proof-of-concept and exploratory study, our biomarker-based prediction models, including ICAM-2, STXBP5, PLGLA, C3, and IGHV3-64, showed 75% to 88% sensitivity for identifying patients with IS, while aiming to minimize misclassification of ICH. Although our methodology provided an internal validation, these results still need validation in other cohorts and with different measurement techniques.

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INTRODUCTION: Chronic atrophic gastritis may contribute to gastric polyps (GP) phenotype in familial adenomatous polyposis (FAP). Considering the high prevalence of Helicobacter-pylori (HP) infection in Portugal, we aim to characterise GP in a series of Portuguese patients. METHODS: In a retrospectively-selected series of 53 FAP patients, clinical data and histopathological features of GP and background gastric mucosa were studied. SPSS (27.0) was used for statistical analysis. RESULTS: Thirteen patients (24.5%) developed fundic gland polyps (FGP), seven (13.2%) gastric adenomas (GA) and ten (18.9%) both FGP and GA. Out of 100 GP, four were hyperplastic polyps, 58 FGP (24 with dysplasia), 35 intestinal-type GA (intGA) and three foveolar-type GA (fovGA). IntGA were larger (60% >7mm, p=0.03), occurred predominantly in the distal stomach (66.7%, p=0.024), in patients harbouring gastric intestinal metaplasia (IM) (86.7%, p<0.001) and duodenal adenomas (86.7%, p<0.001) Conclusion: This is the first Western series showing high prevalence of intGA in FAP patients, comparable to Asian cohorts. HP infection and chronic atrophic gastritis/intestinal metaplasia are likely responsible for this difference, with risk of neoplastic transformation and management implications. Biopsy/excision of GP >7mm, in the distal stomach, and in patients harbouring gastric intestinal metaplasia/duodenal adenomas should be considered.

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Background and Objectives: The RFC1 spectrum has become considerably expanded as multisystemic features beyond the triad of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) have started to be unveiled, although many still require clinical replication. Here, we aimed to clinically characterize a cohort of RFC1-positive patients by addressing both classic and multisystemic features. In a second part of this study, we prospectively assessed small nerve fibers (SNF) and autonomic function in a subset of these RFC1-related patients. Methods: We retrospectively enrolled 67 RFC1-positive patients from multiple neurologic centers in Portugal. All patients underwent full neurologic and vestibular evaluation, as well as neuroimaging and neurophysiologic studies. For SNF and autonomic testing (n = 15), we performed skin biopsies, quantitative sensory testing, sudoscan, sympathetic skin response, heart rate deep breathing, and tilt test. Results: Multisystemic features beyond CANVAS were present in 82% of the patients, mainly chronic cough (66%) and dysautonomia (43%). Other features included motor neuron (MN) affection and motor neuropathy (18%), hyperkinetic movement disorders (16%), sleep apnea (6%), REM and non-REM sleep disorders (5%), and cranial neuropathy (5%). Ten patients reported an inverse association between cough and ataxia severity. A very severe epidermal denervation was found in skin biopsies of all patients. Autonomic dysfunction comprised cardiovascular (67%), cardiovagal (54%), and/or sudomotor (50%) systems. Discussion: The presence of MN involvement, motor neuropathy, small fiber neuropathy, or extrapyramidal signs should not preclude RFC1 testing in cases of sensory neuronopathy. Indeed, the RFC1 spectrum can overlap not only with multiple system atrophy but also with hereditary motor and sensory neuropathy, hereditary sensory and autonomic neuropathy, and feeding dystonia phenotypes. Some clinical-paraclinical dissociations can pose diagnostic challenges, namely large and small fiber neuropathy and sudomotor dysfunction which are usually subclinical.

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Importance: Metabolomics reflect the net effect of genetic and environmental influences and thus provide a comprehensive approach to evaluating the pathogenesis of complex diseases, such as depression. Objective: To identify the metabolic signatures of major depressive disorder (MDD), elucidate the direction of associations using mendelian randomization, and evaluate the interplay of the human gut microbiome and metabolome in the development of MDD. Design, Setting and Participants: This cohort study used data from participants in the UK Biobank cohort (n = 500 000; aged 37 to 73 years; recruited from 2006 to 2010) whose blood was profiled for metabolomics. Replication was sought in the PREDICT and BBMRI-NL studies. Publicly available summary statistics from a 2019 genome-wide association study of depression were used for the mendelian randomization (individuals with MDD = 59 851; control individuals = 113 154). Summary statistics for the metabolites were obtained from OpenGWAS in MRbase (n = 118 000). To evaluate the interplay of the metabolome and the gut microbiome in the pathogenesis of depression, metabolic signatures of the gut microbiome were obtained from a 2019 study performed in Dutch cohorts. Data were analyzed from March to December 2021. Main Outcomes and Measures: Outcomes were lifetime and recurrent MDD, with 249 metabolites profiled with nuclear magnetic resonance spectroscopy with the Nightingale platform. Results: The study included 6811 individuals with lifetime MDD compared with 51 446 control individuals and 4370 individuals with recurrent MDD compared with 62 508 control individuals. Individuals with lifetime MDD were younger (median [IQR] age, 56 [49-62] years vs 58 [51-64] years) and more often female (4447 [65%] vs 2364 [35%]) than control individuals. Metabolic signatures of MDD consisted of 124 metabolites spanning the energy and lipid metabolism pathways. Novel findings included 49 metabolites, including those involved in the tricarboxylic acid cycle (ie, citrate and pyruvate). Citrate was significantly decreased (ß [SE], -0.07 [0.02]; FDR = 4 × 10-04) and pyruvate was significantly increased (ß [SE], 0.04 [0.02]; FDR = 0.02) in individuals with MDD. Changes observed in these metabolites, particularly lipoproteins, were consistent with the differential composition of gut microbiota belonging to the order Clostridiales and the phyla Proteobacteria/Pseudomonadota and Bacteroidetes/Bacteroidota. Mendelian randomization suggested that fatty acids and intermediate and very large density lipoproteins changed in association with the disease process but high-density lipoproteins and the metabolites in the tricarboxylic acid cycle did not. Conclusions and Relevance: The study findings showed that energy metabolism was disturbed in individuals with MDD and that the interplay of the gut microbiome and blood metabolome may play a role in lipid metabolism in individuals with MDD.

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Metamizole is a drug with analgesic and antipyretic properties widely available in Portugal. Its use is highly controversial because of the risk of agranulocytosis, a rare but serious adverse event. A 70-year-old female patient with a recent history of treatment with metamizole for post-surgery fever and pain presented to the ED with sustained fever, diarrhea, and painful mouth ulcers. Laboratory tests revealed agranulocytosis. The patient was placed under protective isolation and started treatment with granulocyte-colony stimulating factor (G-CSF) and empiric antibiotic therapy with piperacillin/tazobactam and vancomycin for neutropenic fever. After an extensive workup, no source of infection was identified. During hospitalization, infectious and neoplastic causes of agranulocytosis were investigated, but the results were negative. Metamizole-induced agranulocytosis was suspected. The patient completed a total of three days of G-CSF and eight days of empiric antibiotic therapy with sustained clinical improvement. She was discharged completely asymptomatic and remained clinically stable during follow-up without a resurgence of agranulocytosis. This case report is intended to increase awareness of metamizole-induced agranulocytosis. While this is a well-known side effect, it is also often overlooked. It is paramount that both physicians and patients know how to correctly manage metamizole to prevent and promptly treat agranulocytosis.

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BACKGROUND AND PURPOSE: The aim was to evaluate the risk of relapse after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, and its safety and tolerability, in patients with chronic inflammatory neuropathies. METHODS: In this multicenter, cohort and case-crossover study, the risk of relapse associated with SARS-CoV-2 vaccination was assessed by comparing the frequency of relapse in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) patients who underwent or did not undergo vaccination. Frequency of relapse in the 3 months prior to and after vaccination, and safety and tolerability of SARS-CoV-2 vaccination, were also assessed. RESULTS: In all, 336 patients were included (278 CIDP, 58 MMN). Three hundred and seven (91%) patients underwent SARS-CoV-2 vaccination. Twenty-nine patients (9%) did not undergo vaccination. Mild and transient relapses were observed in 16 (5%) patients (13 CIDP, 3 MMN) after SARS-CoV-2 vaccination and in none of the patients who did not undergo vaccination (relative risk [RR] 3.21, 95% confidence interval [CI] 0.19-52.25). There was no increase in the specific risk of relapse associated with type of vaccine or diagnosis. Comparison with the 3-month control period preceding vaccination revealed an increased risk of relapse after vaccination (RR 4.00, 95% CI 1.35-11.82), which was restricted to CIDP patients (RR 3.25, 95% CI 1.07-9.84). The safety profile of SARS-CoV-2 vaccination was characterized by short-term, mild-to-moderate local and systemic adverse events. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in CIDP and MMN patients does not seem to be associated with an increased risk of relapse at the primary end-point, although a slightly increased risk in CIDP patients was found compared to the 3 months before vaccination.

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Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect almost every organ. Lupus protein-losing enteropathy (PLE) is one of the rarest manifestations of gastrointestinal involvement. Lupus flare as initial presentation is rare and the disease can act as a trigger to other pathologic immune syndromes like Hemophagocytic Lymphohistiocytosis (HLH), although this association is rare. We report the case of a previously healthy African 39-year-old female patient, with a recent history of cesarean section. Admitted to the Emergency Department (ED) with diffuse abdominal pain and fever, having completed a cycle of antibiotic therapy for initially suspected endometritis. The clinical picture progressed with sustained high fever, new-onset lymphadenopathies, systemic rash, acute pulmonary edema and seizures. Laboratory findings included hyperferritinemia, hypertriglyceridemia, proteinuria and hypoalbuminemia. The auto-immune panel was positive for antinuclear antibodies (ANA), anti-dsDNA, anti-SSA and anti-SSB, anti-PL7, anti-RNP, anti-U1-SnRNP, and anti-Pm-Scl75. She also presented hypocomplementemia. An inaugural flare of SLE with multisystemic involvement and concomitant secondary Hemophagocytic Syndrome was considered and therapy with methylprednisolone pulses, Anakinra and Cyclophosphamide was started. By the end of the first cycle of cyclophosphamide, the patient presented clinical worsening with abdominal pain recrudescence and profuse diarrhea. After the exclusion of an infectious process, a Lupus PLE was assumed and Cyclophosphamide protocol was resumed, with sustained clinical improvement after the induction protocol. Despite initially suspected gynecological infection, the clinical progression with multisystemic involvement together with the auto-immune panel made the diagnosis of SLE possible, with other laboratory findings raising the suspicion of HLH. This case represents a rare report of severe SLE with multiple organ involvement accompanied by HLH. Gastrointestinal involvement with PLE added rarity and morbidity to the clinical picture. The case reinforces the idea that when organ dysfunction is due to a severe autoimmune response, supportive treatment can be lifesaving until immunosuppressive drugs reach their full effect.

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Glyphosate-based herbicides can be harmful to the environment and human health. Especially in developing countries, these herbicides are often used indiscriminately in agricultural and urban areas. Here, we optimized a simple and efficient flow injection-based spectrophotometric method to monitor environmentally relevant glyphosate concentrations in surface waters. The method was then used to assess the environmental mobility of glyphosate in Southeast Brazil by monitoring surface runoff from experimental agricultural soil plots that received glyphosate applications in 2015. Further, water samples from low-order streams were collected in five agricultural, urban, and natural areas, as well as from the 5th-order Rio das Mortes during the rainy season. Finally, 20 drinking water sources were sampled in urban, rural, and agricultural areas. Runoff from reference plots without glyphosate application showed concentrations below the method's detection limit of 0.49 mg.L-1, whereas runoff from plots with standard glyphosate application had concentrations between 1.24 and 6.1 mg.L-1. Similarly, concentrations in natural stream water were below the detection limit, whereas agricultural streams had concentrations of up to 3.7 mg.L-1 (average: 0.97 mg.L-1). In an agricultural stream monitored weekly, concentration peaks were observed after glyphosate applications by farmers, and concentrations were correlated to stream discharge. Urban streams had concentrations of up to 5.8 mg.L-1 (average: 2.6 mg.L-1), but samples from the catchment's major river were mostly below detection limits, illustrating the dilution of urban and agricultural runoff in high-order rivers. In the sampled drinking water resources, glyphosate pollution occurred mainly in the rainy season, with detectable concentrations between 0.5 and 8.7 mg.L-1 in 80% of the sampled drinking water sources. In conclusion, our results suggest considerable environmental mobility of glyphosate in the studied Southeast Brazilian catchment. Substantial pollution, well above national and international limits, was detected in surface runoff, stream water, and drinking water resources.

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Aspergillus is a ubiquitous fungus whose clinical manifestations and prognosis after infection depend on the host's immune status. The disease can have an insidious course, making it a challenging diagnosis that should be considered in patients with risk factors. We report the case of a 78-year-old man with a known history of asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome and idiopathic pulmonary fibrosis on long-term therapy with high-dose oral corticosteroids, hypertension, dyslipidemia, type 2 diabetes, and hypo coagulated atrial fibrillation. He was admitted to the Emergency Department (ED) for dyspnea, productive cough, and wasting syndrome. Recent hospitalization due to pneumonia of the left upper lobe (LUE) with no agent isolation is worth mentioning, treated with levofloxacin. Due to slow improvement, he underwent bronchoscopy (BFC), which revealed friable bronchial mucosa, with isolation of Candida albicans in bronchial secretions (BS) but without evidence of neoplastic cells in the pathological anatomy (PA). He completed 14 days of itraconazole. He was discharged after partial clinical improvement. One week later, he was again admitted to a medical ward because of worsening respiratory symptoms and wasting syndrome. Laboratory findings included an elevated C-reactive protein (CRP) and sedimentation rate, hypoosmolar hyponatremia, hypoproteinemia, and hypoalbuminemia. The study of hyponatremia revealed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), and the persistence of respiratory symptoms led us to perform a chest computed tomography (CT), which revealed a subsegmental LUE atelectasis. Due to suspicion of neoplasia, he repeated BFC with isolation of Aspergillus on the bronchoalveolar lavage (BAL) and PA. Subacute invasive pulmonary aspergillosis (IPA) was assumed and voriconazole was started. However, he had an unfavorable evolution with marked cachexia and hemorrhagic shock due to lower gastrointestinal bleeding as a complication of hypocoagulation resulting in death. Chronic exposure to corticosteroids and structural lung disease are recognized risk factors for Aspergillus infection. The presentation as a wasting syndrome associated with respiratory symptoms and SIADH raised suspicion for neoplasia, which was excluded. The PA was fundamental for the definitive diagnosis of IPA. The fatal outcome, probably attributable to late diagnosis, reinforces the importance of high clinical suspicion for Aspergillus infection in patients with risk factors.

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Clusterin (CLU) is one of the most significant genetic risk factors for late onset Alzheimer's disease (AD). However, the mechanisms by which CLU contributes to AD development and pathogenesis remain unclear. Studies have demonstrated that the trafficking and localisation of glycosylated CLU proteins is altered by CLU-AD mutations and amyloid-ß (Aß), which may contribute to AD pathogenesis. However, the roles of non-glycosylated and glycosylated CLU proteins in mediating Aß toxicity have not been studied in human neurons. iPSCs with altered CLU trafficking were generated following the removal of CLU exon 2 by CRISPR/Cas9 gene editing. Neurons were generated from control (CTR) and exon 2 -/- edited iPSCs and were incubated with aggregated Aß peptides. Aß induced changes in cell death and neurite length were quantified to determine if altered CLU protein trafficking influenced neuronal sensitivity to Aß. Finally, RNA-Seq analysis was performed to identify key transcriptomic differences between CLU exon 2 -/- and CTR neurons. The removal of CLU exon 2, and the endoplasmic reticulum (ER)-signal peptide located within, abolished the presence of glycosylated CLU and increased the abundance of intracellular, non-glycosylated CLU. While non-glycosylated CLU levels were unaltered by Aß25-35 treatment, the trafficking of glycosylated CLU was altered in control but not exon 2 -/- neurons. The latter also displayed partial protection against Aß-induced cell death and neurite retraction. Transcriptome analysis identified downregulation of multiple extracellular matrix (ECM) related genes in exon 2 -/- neurons, potentially contributing to their reduced sensitivity to Aß toxicity. This study identifies a crucial role of glycosylated CLU in facilitating Aß toxicity in human neurons. The loss of these proteins reduced both, cell death and neurite damage, two key consequences of Aß toxicity identified in the AD brain. Strikingly, transcriptomic differences between exon 2 -/- and control neurons were small, but a significant and consistent downregulation of ECM genes and pathways was identified in exon 2 -/- neurons. This may contribute to the reduced sensitivity of these neurons to Aß, providing new mechanistic insights into Aß pathologies and therapeutic targets for AD.

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