First record of the aquatic plant Echinodorus scaber Rataj (Alismataceae) for the State of Maranhão, Northeastern Brazil.

Echinodorus is the second largest genus of the aquatic plant family Alismataceae, comprising 28 species, of which 24 occur in Brazil. This study represents the first record of Echinodorus scaber Rataj for the State of Maranhão, based on material collected in the Municipality of Brejo, eastern Maranhão. Echinodorus scaber shares morphological similarities with E. macrophyllus (Kunth) Micheli, but it can be distinguished by (I) a highly branched inflorescence, (II) scabrous peduncles and petioles covered by stellate trichomes, and (II) small flowers with reflexed petals. This new record of E. scaber contributes to a better understanding of this genus' diversity and distribution in Maranhão and underscores the necessity to broaden collection efforts for a better comprehension of the state's flooded zones. Comprehensive collection efforts, with a special focus on aquatic plants and in locations far from the state's main urban center, São Luís, may result in a significant knowledge increase of the flora, especially of the genus Echinodorus, which needs a broad taxonomic study. These recommendations may result in new records, range extensions, and species descriptions, contributing to the conservation of the aquatic environments of Maranhão.

Floristic survey of aquatic macrophytes in eastern Maranhão, Brazil: richness, biological forms and three new records.

The aim of this study was to carry out a floristic survey of aquatic macrophytes in the municipality of Chapadinha, eastern Maranhão, and classify their biological forms. The study was done between September 2021 and September 2022. A total of 31 families, 49 genera and 72 species of aquatic macrophytes were catalogued, of which 65 are angiosperms. Among them, Bacopa stricta (Plantaginaceae), Staurogyne diantheroides (Acanthaceae), and Xanthosoma aristeguietae (Araceae) are new records for the flora of Maranhão, with the last two new records for Northeast Brazil. The richest family was Cyperaceae, with 11 species, followed by Plantaginaceae (seven taxa), Fabaceae (five taxa) and Lentibulariaceae (five taxa). Six biological forms were recorded, amphibious (27 taxa) and emergent (26 taxa) being the most common. The aquatic environments of Chapadinha are home to a considerable number of species, families, and life forms of macrophytes. The results show that due to the lack of surveys, evidenced by the new records presented, the state aquatic flora is still underestimated. Further studies in poorly explored areas are suggested, especially in the eastern part of the state, to improve understanding of species richness.

Dupilumab for atopic dermatitis: a real-world Portuguese multicenter retrospective study.

INTRODUCTION: Atopic dermatitis (AD) is a difficult-to-treat inflammatory skin disease with a high impact on patients' quality of life. Dupilumab, an IL-4 and IL-13 inhibitor, was the first monoclonal antibody approved for the treatment of moderate-to-severe AD and is currently approved in patients aged 6 or older. METHODS: This is a nationwide, multicenter, retrospective, 48-week study designed by the Portuguese Group of AD to assess real-world efficacy and safety of dupilumab for the treatment of AD. RESULTS: A total of 169 patients were enrolled, with a mean disease duration of 22.75 (±11.98) years. The percentage of patients achieving an improvement of at least 75% in Eczema Area and Severity Index (EASI) compared to baseline (EASI75 response) at weeks 12 and 48 was 67.6% and 74.1%, respectively. In the same timepoints, 25.0% and 44.1% achieved an EASI90 response. Patient-reported outcome measures also improved throughout the study period. Regarding safety, 32.0% of the patients developed adverse events, with conjunctivitis (26.6%), persistent facial erythema (4.7%), and arthritis/arthralgia (3.6%) as the more frequently reported. CONCLUSION: Data from real-world populations are crucial to guide clinicians in their daily decisions. This study provides data demonstrating that dupilumab is an effective and safe therapeutic option for AD.

[Therapeutic protocol for the empirical treatment of oral and pharyngeal infections]. / Protocolo terapéutico empírico de las infecciones bucales y faríngeas.

INTRODUCTION: Most oral cavity infections are odontogenic, although they can also affect extradental structures (non-odontogenic infections). Pharyngitis is inflammation and/or infection of the pharynx and /or the peri-tonsillar area. TREATMENT: Both infections are highly prevalent in the population, and one of the most common reasons for consultation and the prescription of antibiotics in primary care clinics. Both infections are usually treated empirically, based on clinical diagnosis and the prevalence and antibiotic sensitivity of the most commonly implicated microorganisms.

First clinical symptom as a prognostic factor in systemic sclerosis: results of a retrospective nationwide cohort study.

The objective of the study is to determine the importance of the mode of onset as prognostic factor in systemic sclerosis (SSc). Data were collected from the Spanish Scleroderma Registry (RESCLE), a nationwide retrospective multicenter database created in 2006. As first symptom, we included Raynaud's phenomenon (RP), cutaneous sclerosis, arthralgia/arthritis, puffy hands, interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), and digestive hypomotility. A total of 1625 patients were recruited. One thousand three hundred forty-two patients (83%) presented with RP as first symptom and 283 patients (17%) did not. Survival from first symptom in those patients with RP mode of onset was higher at any time than those with onset as non-Raynaud's phenomenon: 97 vs. 90% at 5 years, 93 vs. 82% at 10 years, 83 vs. 62% at 20 years, and 71 vs. 50% at 30 years (p < 0.001). In multivariate analysis, factors related to mortality were older age at onset, male gender, dcSSc subset, ILD, PAH, scleroderma renal crisis (SRC), heart involvement, and the mode of onset with non-Raynaud's phenomenon, especially in the form of puffy hands or pulmonary involvement. The mode of onset should be considered an independent prognostic factor in systemic sclerosis and, in particular, patients who initially present with non-Raynaud's phenomenon may be considered of poor prognosis.

Parathyroidectomy in Persistent Post-transplantation Hyperparathyroidism - Single-center Experience.

BACKGROUND: Hyperparathyroidism is a common complication in chronic kidney disease and might persist in up to 25% of patients after transplantation. In this setting, vitamin D analogues further aggravate persistent hypercalcemia and cinacalcet has not been approved for these patients, some of whom will require parathyroidectomy to correct post-transplantation hyperparathyroidism. OBJECTIVES: In this single-center, retrospective study we aimed to analyze the long-term effect of parathyroidectomy on calcium, phosphorus, and parathyroid hormone (PTH) levels and its effect on allograft function in kidney transplantation patients submitted to parathyroidectomy. PATIENTS AND METHODS: Fifteen patients underwent parathyroidectomy between January 2005 and January 2015; median age 54 years old; 8 (53.3%) were receiving cinacalcet at the time of surgery. Pre-parathyroidectomy median values of intact PTH, calcium, and phosphorus were, respectively, 262 pg/mL, 10.8 mg/dL, and 2.4 mg/dL. Surgery consisted of uniglandular parathyroidectomy in 5 (33.3%) patients, biglandular in 4 (26.7%), and subtotal in 6 (40%). There was no surgery-related mortality. RESULTS: Compared with baseline, there was a decrease of PTH (262 pg/mL vs. 106 pg/mL, P = .001), calcium, and phosphorus levels (10.8 mg/dL vs. 10.4 mg/dL, P = .3; 2.4 vs. 2.9 mg/dL, P = .05) 1 year after surgery; with normalization of serum calcium at the end of follow-up (10.8 mg/dL vs. 9.4 mg/dL, P = .04). A decrease in estimated glomerular filtration rate occurred 1 month post-surgery (62.7 mL/m vs. 49.7 mL/m, P = .006) but returned to baseline 1 year after surgery (62.7 mL/m vs. 60.8 mL/m, P = .73). CONCLUSION: Parathyroidectomy appears to be a safe procedure and should be considered in kidney transplantation patients with persistent post-transplantation hyperparathyroidism. Although there was an acute estimated glomerular filtration rate decrease, we observed no long-term deterioration in allograft function.

Late Allograft Renal Vein Thrombosis Treated With Anticoagulation Alone: A Case Report.

BACKGROUND: Allograft renal vein thrombosis is a rare complication of kidney transplantation. Most cases occur in the first 2 weeks after transplantation, but there are cases described many years after the transplant surgery. Allograft loss is the usual outcome. METHODS: We present a case of a renal transplant recipient with allograft renal vein thrombosis associated with deep venous thrombosis of a lower limb, 9 years after transplantation. He was successfully treated with anticoagulation alone, with recovery of allograft function. RESULTS: The patient was given unfractioned heparin and elastic compression stockings. Five days later, the patient recovered diuresis and hemodialysis treatment was discontinued. Doppler ultrasound was done and revealed partial re-permeabilization of allograft renal vein, with maximal velocity of 15 cm/s. After 30 months of follow-up, the patient was maintained on oral anticoagulation with warfarin, and no thromboembolic or hemorrhagic events were documented. The patient's serum creatinine was stable, between 1.6 and 1.8 mg/dL. CONCLUSIONS: Our patient demonstrated that anticoagulation alone and dialytic support might be able to promote total recovery of allograft function after renal vein thrombosis.

Cryptococcosis in Renal Transplant Recipients: A Single-Center Experience.

BACKGROUND: In solid organ transplant patients, 8% of invasive fungal infections are attributed to Cryptococcus. The aim of this study was to determine the frequency, risk factors, clinical characteristics, and outcome of kidney transplant recipients (TR) infected with Cryptococcus. CASE SERIES: Between 2007 and 2014, a total of 500 kidney transplantations were performed at São João Hospital, in Porto, Portugal. Six infections by C. neoformans were reported, an incidence of 1.2% (3 disseminated, 2 meningeal, and 1 cutaneous). Patients were 65-72 years of age and 4 of 6 were male, compared with all kidney TR, among whom the mean age was 51.1 years and 60% were male. Three cases of crytococcosis occurred within the first 6 months after transplantation; 3 patients had cytomegalovirus infection and leukopenia, and 2 patients' immunosuppression had been increased in the last 6 months. Meningitis presented with headache, fever, and acute mental confusion; pulmonary involvement presented with respiratory insufficiency and infiltrative or nodular lung lesions; and cutaneous infections presented as cellulitis or skin abscess. Blood cultures for C. neoformans were positive in 3 cases; all of these patients had positive cryptococcal antigen of 1:128 to 1:8192. Five patients received liposomal amphotericin B for 9-21 days, followed by fluconazole. Four patients lost their grafts, and one patients died after a persistent vegetative state due to cryptococcal meningitis. CONCLUSIONS: This small case series led to suspicion of an association between cryptococcosis and older age, renal dysfunction, cytomegalovirus infection, and intensification of immunosuppression after rejection episodes. In our series, cryptococcosis was associated with poor graft outcome.

The Role of the Gut Microbiome on Chronic Kidney Disease.

Chronic kidney disease (CKD) is estimated to affect nearly 500 million people worldwide and cardiovascular (CV) disease is a major cause of death in this population. However, therapeutic interventions targeting traditional CV risks are not effective at lowering the incidence of CV events or at delaying the progression of the disease in CKD patients. In recent years, disturbances of normal gut microbiome were recognized in the pathogenesis of diverse chronic diseases. Gut dysbiosis is being unraveled in CKD and pointed as a nontraditional risk factor for CV risk and CKD progression. The most often reported changes in gut microbiome in CKD are related to the lower levels of Bifidobacteriaceae and Lactobacillaceae and to higher levels of Enterobacteriaceae. Although metagenomics brought us an amplified vision on the microbial world that inhabits the human host, it still lacks the sensitivity to characterize the microbiome up to species level, not revealing alterations that occur within specific genus. Here, we review the current state-of-the-art concerning gut dysbiosis in CKD and its role in pathophysiological mechanisms in CKD, particularly in relation with CV risk. Also, the strategies towards prevention and treatment of gut dysbiosis in CKD progression will be discussed.

Post-transplant Lymphoproliferative Disorder: A Single-Center Experience.

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is the second most common neoplasia after adult kidney transplantation (KT). METHODS: We retrospectively analyzed 8 adult patients who underwent KT in our center, diagnosed with PTLD between 2001 and 2014. RESULTS: Six patients were men. The median age at presentation was 43 years and the median time since transplantation was 7.3 years. Three patients had previously received anti-thymocyte globulin/OKT3, and all were taking calcineurin inhibitors (CNI) at diagnosis. The monomorphic type was the most common, with diffuse large B-cell lymphoma as the origin. The most frequent presentation was fever. Four in five patients had Epstein-Barr-related PTLD. All patients received various regimens of immunosuppression reduction (IR), with 4 converting CNI to mTOR inhibitor (imTOR). Subsequent treatment (when needed) was chemotherapy, radiotherapy, and surgery. The maximum follow-up time was 6.7 years, with a 50% mortality rate that occurred at a median time of 3.5 months (2 died with functioning kidney). All 4 patients who were in remission at the end of follow-up had CNI conversion to imTOR, and none lost the allograft. CONCLUSIONS: Despite the small number of cases, our results confirm the high PTLD impact in overall and allograft survival. Our PTLD type distribution is in accord with the literature. First-line PTLD treatment is IR, but the best method is still unknown; our results may suggest a beneficial effect of CNI conversion to imTOR.

Combined C4d and CD3 immunostaining predicts immunoglobulin (Ig)A nephropathy progression.

A number of molecules have been shown recently to be involved in the pathogenesis and progression of immunoglobulin (Ig)A nephropathy (IgAN). Among these, we have selected C4d (complement lectin pathway involvement), CD3 (T cell marker, traducing interstitial inflammation), transglutaminase 2 (TGase-2, involved in tissue fibrosis development) and p-extracelluar-regulated kinase (ERK)1/2 (protein kinase intracellular signaling molecule) to perform a panel of immunohistological biomarkers and assess its predictive value for disease progression. Immunohistochemical staining of these biomarkers was performed in paraffin sections from 74 renal biopsy cases with the clinical diagnosis of IgAN. Association between score analysis of these parameters and disease course was assessed through univariate and multivariate analysis, including baseline clinical and histological data. Univariate analysis showed that glomerular C4d, tubulointerstitial TGase2 and CD3 scores were associated with baseline proteinuria and disease progression. Multivariate analysis showed that only baseline estimated glomerular filtration rate (eGFR), C4d and CD3 were associated independently with progressive kidney disease (decline of at least 50% in the eGFR or progression to end-stage renal disease (ESRD) during the follow-up period). Establishing an accurate prediction model for IgAN progression is still a matter of research in clinical nephrology. The complement system, particularly lectin pathway activation, and T cell activation, have been shown previously to be potential modifiers of the disease course. Here we show that the combination of two histological biomarkers (C4d and CD3) can be a powerful predictor of IgAN progression and a potential useful tool for the clinical approach of this disease.

Collagen type IV-related nephropathies in Portugal: pathogenic COL4A3 and COL4A4 mutations and clinical characterization of 25 families.

Pathogenic mutations in genes COL4A3/COL4A4 are responsible for autosomal Alport syndrome (AS) and thin basement membrane nephropathy (TBMN). We used Sanger sequencing to analyze all exons and splice site regions of COL4A3/COL4A4, in 40 unrelated Portuguese probands with clinical suspicion of AS/TBMN. To assess genotype-phenotype correlations, we compared clinically relevant phenotypes/outcomes between homozygous/compound heterozygous and apparently heterozygous patients. Seventeen novel and four reportedly pathogenic COL4A3/COL4A4 mutations were identified in 62.5% (25/40) of the probands. Regardless of the mutated gene, all patients with ARAS manifested chronic renal failure (CRF) and hearing loss, whereas a minority of the apparently heterozygous patients had CRF or extrarenal symptoms. CRF was diagnosed at a significantly younger age in patients with ARAS. In our families, the occurrence of COL4A3/COL4A4 mutations was higher, while the prevalence of XLAS was lower than expected. Overall, a pathogenic COL4A3/COL4A4/COL4A5 mutation was identified in >50% of patients with fewer than three of the standard diagnostic criteria of AS. With such a population background, simultaneous next-generation sequencing of all three genes may be recommended as the most expedite approach to diagnose collagen IV-related glomerular basement membrane nephropathies.

Collagen type IV-related nephropathies in Portugal: pathogenic COL4A5 mutations and clinical characterization of 22 families.

Alport syndrome (AS) is caused by pathogenic mutations in the genes encoding α3, α4 or α5 chains of collagen IV (COL4A3/COL4A4/COL4A5), resulting in hematuria, chronic renal failure (CRF), sensorineural hearing loss (SNHL) and ocular abnormalities. Mutations in the X-linked COL4A5 gene have been identified in 85% of the families (XLAS). In this study, 22 of 60 probands (37%) of unrelated Portuguese families, with clinical diagnosis of AS and no evidence of autosomal inheritance, had pathogenic COL4A5 mutations detected by Sanger sequencing and/or multiplex-ligation probe amplification, of which 12 (57%) are novel. Males had more severe and earlier renal and extrarenal complications, but microscopic hematuria was a constant finding irrespective of gender. Nonsense and splice site mutations, as well as small and large deletions, were associated with younger age of onset of SNHL in males, and with higher risk of CRF and SNHL in females. Pathogenic COL4A3 or COL4A4 mutations were subsequently identified in more than half of the families without a pathogenic mutation in COL4A5. The lower than expected prevalence of XLAS in Portuguese families warrants the use of next-generation sequencing for simultaneous COL4A3/COL4A4/COL4A5 analysis, as first-tier approach to the genetic diagnosis of collagen type IV-related nephropathies.