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Background Drugs are a frequent cause of nephrotoxicity, especially in the context of acute kidney disease (AKD), with a significant number of cases being drug-associated. The WHO's VigiBase is a powerful tool for identifying drugs described and associated with the development of AKD. Methods We retrieved data from the period 1968 to 2022 regarding notifications of adverse drug reactions (ADR). The extracted medications were evaluated for their nephrotoxicity based on the bibliographic score (BS) developed through pre-selected references. The main medications involved were classified as 'non-nephrotoxic', 'potentially nephrotoxic', and 'nephrotoxic'. We utilized the IC025 and reporting odds ratio (ROR) disproportionality indexes to study the relationship between medications and the odds of being included in an AKD notification. Results During the period, a total of 33,932,051 notifications were obtained, revealing 435,677 cases related to drug-associated AKD following MedDRA term filtering, predominantly affecting males aged 45-64. We identified 8,991 active ingredients or suspected combinations associated with AKD development, with the ATC class A - Alimentary Tract and Metabolism being the most frequently described. Among the medications most strongly associated with this phenotype, classes J and N stood out. Among the most notable medications collected, 8.3% were classified as "non-nephrotoxic," 16.7% as "potentially nephrotoxic," and 75% as "known nephrotoxic." Notable active ingredients included cobicistat + elvitegravir + emtricitabine + tenofovir disoproxil (IC025 8.7; ROR 786.96), inotersen (IC025 7.7; ROR 604.57), emtricitabine + tenofovir disoproxil (IC025 7.9; ROR 432.36), esomeprazole (IC025 6.8; ROR 184.23), and pantoprazole (IC025 6.3; ROR 109.86), with proton pump inhibitors dominating the top four positions among the most frequently involved medications. Conclusion AKD is a frequent adverse reaction in VigiBase, with a significantly high reported mortality rate. Evaluation of the notifications revealed medications with a high disproportionality index and a strong association with AKD. We also highlight the potential nephrotoxic role of less suspected medications. This study emphasizes the need to consider AKD as a condition potentially associated with iatrogenic etiology, highlighting various medications and their respective involvement in the various possible manifestations of AKD.
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Traumatic nerve injuries are common lesions that affect several hundred thousand humans, as well as dogs and cats. The assessment of nerve regeneration through animal models may provide information for translational research and future therapeutic options that can be applied mutually in veterinary and human medicine, from a One Health perspective. This review offers a hands-on vision of the non-invasive and conservative approaches to peripheral nerve injury, focusing on the role of neurorehabilitation in nerve repair and regeneration. The peripheral nerve injury may lead to hypersensitivity, allodynia and hyperalgesia, with the possibility of joint contractures, decreasing functionality and impairing the quality of life. The question remains regarding how to improve nerve repair with surgical possibilities, but also considering electrical stimulation modalities by modulating sensory feedback, upregulation of BDNF, GFNF, TrKB and adenosine monophosphate, maintaining muscle mass and modulating fatigue. This could be improved by the positive synergetic effect of exercises and physical activity with locomotor training, and other physical modalities (low-level laser therapy, ultrasounds, pulsed electromagnetic fields, electroacupuncture and others). In addition, the use of cell-based therapies is an innovative treatment tool in this field. These strategies may help avoid situations of permanent monoplegic limbs that could lead to amputation.
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Objective Different factors, such as medication use and shift work, can influence sleep quality. We aimed to determine the association between medication use and sleep quality in shift workers versus daytime workers. Materials and Methods We conducted a quantitative cross-sectional study with a convenience sample of active workers. Online questionnaires were applied to assess sleep quality, sleepiness, medication use, and sociodemographic characteristics. Results A total of 296 participants were included: 124 (41.89%) daytime workers and 172 (58.11%) shift workers. In total, 130 (43.92%) participants worked in the healthcare sector, 116 (39.19%), in industry, and 50 (16.89%), in other sectors. After a bivariate analysis, poor sleep quality was associated with the presence of sleep disorders ( p < 0.001), type of work (shift or day work) ( p < 0.001), and the use of sleeping medication ( p < 0.001). Although shift workers had worse sleep quality, no differences were found regarding the use of medications that act directly on the central nervous system or with proven effects on sleep. No association was found between medication use and sleep quality. When adjusted for the different variables that were individually associated with poor sleep quality, through a logistic regression model, none showed an increased risk of poor sleep quality. Discussion In spite of the need for further research, our results have shown that sleep quality is influenced by many different factors whose impact must be evaluated in combination, and not just in a bivariate manner. There are many factors individually associated with poor sleep quality, but when adjusted to each other, they have shown no increased risk of having poor sleep quality.
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Foot ulceration and infection is associated with a substantial increase in morbidity and mortality in patients with diabetes. We present a clinical case of recurrent diabetic foot infection with an atypical clinical evolution. A 58-year-old male patient with type 1 diabetes and a history of bilateral Charcot foot neuroarthropathy was followed at our Diabetic Foot Clinic for an unhealed plantar foot ulcer for >1.5 years with recurrent episodes of infection. He was admitted to hospital due to foot ulcer reinfection with sepsis and ipsilateral lower limb cellulitis. The foot infection was found to be associated with an underlying abscess in the anterior compartment of the leg, with a cutaneous fistulous course with extensive alterations of an inflammatory nature. Exudate from the lesion was drained and tissue biopsied, revealing Serratia marcescens and Klebsiella oxytoca with dystrophic calcification (DC). Surgical excision of dystrophic tissue with debridement of the fistulous tracts was performed. The excised material corroborated the presence of fibroadipose connective tissue with marked DC, as well as areas of mixed inflammation compatible with a chronic infectious aetiology. Targeted long-term antibiotic therapy was implemented, for a total of six weeks, with a favourable clinical evolution and complete closure of the lesion at the final follow-up. DC results from calcium deposition in degenerated tissues without evidence of systemic mineral imbalance and is a potential cause of non-healing ulcers. Few cases of DC have been reported in diabetic foot patients and its treatment remains challenging and controversial. A longer follow-up period is necessary to verify the effectiveness of our approach.
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Calcinose , Diabetes Mellitus , Pé Diabético , Sepse , Dermatopatias , Masculino , Humanos , Pessoa de Meia-Idade , Pé Diabético/complicações , Perna (Membro) , Abscesso , Calcinose/complicaçõesRESUMO
INTRODUCTION: Malignant triton tumor (MTT) is a rare and aggressive subtype of malignant peripheral nerve sheath tumor consisting of a neurogenic tumor with rhabdomyoblastic differentiation. Only 170 cases have been reported to date, two-thirds occurring in young patients with neurofibromatosis type 1 and the remaining third presenting as a sporadic tumor. CASE PRESENTATION: We present the case of a 49-year-old man with a sporadic grade 2 MTT of the lower limb which had had a previous tibial fracture. The patient underwent an above-knee amputation. Five months post-operatively metastases were present in the liver and vertebral column causing compression of the spinal cord, so decompressive radiotherapy and palliative chemotherapy were initiated. CONCLUSION: Due to the precocious spread of the disease, we would suggest that adjuvant chemotherapy be considered for the eradication of micrometastases. To our knowledge, this is only the second reported case of an MTT arising in a site with a history of previous severe trauma.
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Neurofibrossarcoma , Neoplasias Cutâneas , Masculino , Humanos , Pessoa de Meia-Idade , Extremidade Inferior , Fígado , Micrometástase de NeoplasiaRESUMO
This prospective observational cohort pilot study included 22 cats diagnosed with partial traumatic brachial plexus injury (PTBPI), aiming to explore responses to an early intensive neurorehabilitation protocol in a clinical setting. This protocol included functional electrical stimulation (FES), locomotor treadmill training and kinesiotherapy exercises, starting at the time with highest probability of nerve repair. The synergetic benefits of this multimodal approach were based on the potential structural and protective role of proteins and the release of neurotrophic factors. Furthermore, FES was parametrized according to the presence or absence of deep pain. Following treatment, 72.6% of the cats achieved ambulation: 9 cats within 15 days, 2 cats within 30 days and 5 cats within 60 days. During the four-year follow-up, there was evidence of improvement in both muscle mass and muscle weakness, in addition to the disappearance of neuropathic pain. Notably, after the 60 days of neurorehabilitation, 3 cats showed improved ambulation after arthrodesis of the carpus. Thus, early rehabilitation, with FES applied in the first weeks after injury and accurate parametrization according to the presence or absence of deep pain, may help in functional recovery and ambulation, reducing the probability of amputation.
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Aim: Peripheral nerve injury regeneration studies using animal models are crucial to different pre-clinical therapeutic approaches efficacy evaluation whatever the surgical technique explored. Materials & methods: A 944 articles systematic review on 'peripheral nerve injury in animal models' over the last 9 years was carried out. Results: It was found that 91% used rodents, and only 9% employed large animals. Different nerves are studied, with generated gaps (10,78 mm) and methods applied for regeneration evaluation uniformed. Sciatic nerve was the most used (88%), followed by median and facial nerves (2.6%), significantly different. Conclusion: There has not been a significant scale-up of the in vivo testing to large animal models (anatomically/physiologically closer to humans), allowing an improvement in translational medicine for clinical cases.
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Traumatismos dos Nervos Periféricos , Humanos , Animais , Nervo Isquiático , Modelos Animais , Regeneração Nervosa/fisiologia , Avaliação de Resultados em Cuidados de Saúde , Modelos Animais de DoençasRESUMO
BACKGROUND: Delirium is a potentially severe form of acute encephalopathy. Minocycline has neuroprotective effects in animal models of neurologic diseases; however, data from human studies remain scarce. RESEARCH QUESTION: Does the neuroprotective effect of minocycline prevent delirium occurrence in critical ill patients? STUDY DESIGN AND METHODS: This study was a randomized, placebo-controlled, double-blind trial conducted in four ICUs. Patients aged 18 years or older were eligible and randomized to receive minocycline (100 mg, twice daily) or placebo. The primary outcome was delirium incidence within 28 days or before ICU discharge. Secondary outcomes included days in delirium during ICU stay, delirium/coma-free days, length of mechanical ventilation, ICU length of stay, ICU mortality, and hospital mortality. The kinetics of various inflammatory (IL-1ß, IL-6, IL-10, and C-reactive protein) and brain-related biomarkers (brain-derived neurotrophic factor and S100B) were used as exploratory outcomes. RESULTS: A total of 160 patients were randomized, but one patient in the placebo group died before treatment; thus the data from 159 patients were analyzed (minocycline, n = 84; placebo, n = 75). After the COVID-19 pandemic it was decided to stop patient inclusion early. There was a small but significant decrease in delirium incidence: 17 patients (20%) in the minocycline arm compared with 26 patients (35%) in the placebo arm (P = .043). No other delirium-related outcomes were modified by minocycline treatment. Unexpectedly, there was a significant decrease in hospital mortality (39% vs. 23%; P = .029). Among all analyzed biomarkers, only plasma levels of C-reactive protein decreased significantly after minocycline treatment (F = 0.75, P = .78, within time; F = 4.09, P = .045, group × time). INTERPRETATION: Our findings in this rather small study signal a possible positive effect of minocycline on delirium incidence. Further studies are needed to confirm the benefits of this drug as a preventive measure in critically ill patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04219735; URL: www. CLINICALTRIALS: gov.
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Introduction: Noncommunicable diseases and obesity are between the major health threat due to consumption of unhealthy foods and limited time spent on physical activities, a situation of particular concern among children. Since children spend most of their time at school, this study intends to investigate the effect of a school intervention program, which combines recreational football and nutrition education, on body composition, physical fitness, physical activity, blood pressure and heart rate, eating behaviours, nutritional knowledge, and psychological status in elementary school children. Methods: A total of 67 children, between 7 and 10 years old, were allocated into three groups: the Football Group (FG) which held 2 weekly sessions of 60â min of recreational football, the Nutrition and Football Group (NFG) which held 2 sessions per week of 60â min of recreational football plus 60â min of nutritional education and the Control Group (CG) which maintained its usual curriculum. The intervention lasted 12 weeks. All measurements were collected before and after the intervention. Results: Intervention groups significantly (p < 0.05) improved BMI Z-score, rest heart rate, horizontal jump and shuttle test, physical activity level, and psychosocial health. The NFG group significantly decreased (p < 0.05) waist-to-height ratio and blood pressure, and significantly increased (p < 0.05) nutritional knowledge, fruit, and fish consumption. While FG significantly decreased (p < 0.05) the percentage of fat mass and significantly increased (p < 0.05) muscle mass and performance in the 20â m sprint. Discussion: The results have shown to improve nutritional status, explosive strength, aerobic and neuromuscular fitness, as well as increase the level of physical activity. The nutritional education sessions contributed to increase nutritional knowledge and to improve the consumption of healthy food groups in a ludic-educational way. The "Football and Nutrition for Health" program was able to induce short-term improvements in several health markers, highlighting the role of the school curriculum in children's health.
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Peripheral nerve injury (PNI) remains a medical challenge with no easy resolution. Over the last few decades, significant advances have been achieved in promoting peripheral nerve regeneration, and new assessment tools have been developed, both functional and imaging, to quantify the proportion and quality of nerve recovery. The exploration of new animal models, larger, more complex, and with more similarities to humans, has made it possible to reduce the gap between the results obtained in classic animal models, such as rodents, and the application of new therapies in humans and animals of clinical interest. Ultrasonography is an imaging technique recurrently used in clinical practice to assess the peripheral nerves, allowing for its anatomical and topographic characterization, aiding in the administration of anesthesia, and in the performance of nerve blocks. The use of this technique in animal models is scarce, but it could be a useful tool in monitoring the progression of nerve regeneration after the induction of controlled experimental lesions. In this work, sheep, a promising animal model in the area of peripheral nerve regeneration, were subjected to an ultrasonographic study of three peripheral nerves of the hind limb, the common peroneal, and tibial and sciatic nerves. The main aim was to establish values of dimensions and ultrasound appearance in healthy nerves and landmarks for their identification, as well as to perform an ultrasound evaluation of the cranial tibial muscle, an effector muscle of the common peroneal nerve, and to establish normal values for its ultrasound appearance and dimensions. The results obtained will allow the use of these data as control values in future work exploring new therapeutic options for nerve regeneration after induction of common peroneal nerve injuries in sheep.
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In this work, the fan assisted extraction approach is originally exploited to determine volatile compounds in liquid samples based on the full evaporation technique. The feasibility of this strategy was firstly evaluated using model solutions containing different volatile carbonyl compounds. Different media, volumes of sample, temperatures of extraction, and times of extraction were tested. Linear regressions presenting r > 0.999, intermediate precision values < 6%, and recoveries within 76-95% were attained using a period of extraction of 10 min, a volume of sample solution of 5 µL, and a temperature of extraction of 50 °C. Analyses of brewed coffees were performed. The slopes of the calibration curves obtained using aqueous model solutions and brewed coffee samples were not significantly different. These results revealed no matrix effect under the selected experimental conditions, enabling the use of the external calibration method for quantification purposes. Twenty-four volatile carbonyl compounds were identified in brewed coffee, which elucidates the sensitivity of this approach.
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The recognition that the gut microbiota of obese children differs from lean children has grown, and some studies suggest that physical activity positively influences the gut microbiota. This systematic review explores the changes in the gut microbiota composition of obese and non-obese children and adolescents and provides an understanding of the effects of physical activity interventions in modulating their microbiota. The PRISMA protocol was used across PubMed, Scopus, and Web of Science. Overall, twenty-four research papers were included in accordance with the chosen inclusion and exclusion criteria, eighteen studies compared the gut microbiota of obese and normal-weight children and adolescents, and six studies explored the effect of physical activity interventions on the gut microbiota. The analysis indicated that obese gut microbiota is reduced in Bacteroidetes, Bifidobacterium and alpha diversity but enriched in Proteobacteria and Lactobacillus. Interventions with physical activity seem to improve the alpha diversity and beneficial bacteria linked to body weight loss in children and adolescents. The gut microbiota of obese children exhibited a remarkably individual variation. More interventions are needed to clearly and accurately explore the relationships between child obesity, gut microbiota, and physical activity and to develop approaches to decrease the incidence of paediatric obesity.
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Exosomes have shown promising potential as a therapeutic approach for wound healing. Nevertheless, the translation from experimental studies to commercially available treatments is still lacking. To assess the current state of research in this field, a systematic review was performed involving studies conducted and published over the past five years. A PubMed search was performed for English-language, full-text available papers published from 2018 to June 2023, focusing on exosomes derived from mammalian sources and their application in wound healing, particularly those involving in vivo assays. Out of 531 results, 148 papers were selected for analysis. The findings revealed that exosome-based treatments improve wound healing by increasing angiogenesis, reepithelization, collagen deposition, and decreasing scar formation. Furthermore, there was significant variability in terms of cell sources and types, biomaterials, and administration routes under investigation, indicating the need for further research in this field. Additionally, a comparative examination encompassing diverse cellular origins, types, administration pathways, or biomaterials is imperative. Furthermore, the predominance of rodent-based animal models raises concerns, as there have been limited advancements towards more complex in vivo models and scale-up assays. These constraints underscore the substantial efforts that remain necessary before attaining commercially viable and extensively applicable therapeutic approaches using exosomes.
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BACKGROUND: Hidradenocarcinoma is a rare malignant sweat gland tumour, characterized by a slow but aggressive course, with high rates of local recurrence and metastasis. Due to its rarity, histological criteria and therapeutic guidelines are poorly defined, posing a major challenge for clinicians and pathologists. OBJECTIVES: To present two new cases of metastatic hidradenocarcinoma as well as a review of the literature. MATERIALS & METHODS: We describe two case studies and a review of the literature based on a search using the MEDLINE (PubMed) electronic database. RESULTS: The first patient was a 61-year-old woman with a perimamillary hidradenocarcinoma that arose from the malignant transformation of a benign childhood lesion and developed regional lymph node metastases after wide excision and adjuvant radiotherapy. The second patient was a 63-year-old man who developed cutaneous and renal metastases several years after the complete excision of a lumbar hidradenocarcinoma. As far as we can ascertain, kidney metastasis from hidradenocarcinoma has not previously been described. CONCLUSION: Most authors recommend wide excision as the treatment of choice for hidradenocarcinoma, however, optimal adjuvant therapy remains to be determined. Our cases add to the limited knowledge available, but high-quality studies to find new effective treatments are needed.
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Carcinoma de Apêndice Cutâneo , Neoplasias Renais , Neoplasias Cutâneas , Neoplasias das Glândulas Sudoríparas , Masculino , Feminino , Humanos , Criança , Pessoa de Meia-Idade , Neoplasias das Glândulas Sudoríparas/cirurgia , Terapia Combinada , Bases de Dados FactuaisRESUMO
Childhood obesity continues to represent a growing challenge, and it has been associated with gut microbiota dysbiosis. This study examines the gut microbiota composition in overweight and obese school children and assesses whether a 12-week multidisciplinary intervention can induce changes in the gut microbiota. The intervention, which combined recreational football and nutritional education, was implemented among 15 school children, aged 7-10 years, with a Body Mass Index ≥ 85th percentile. The children were assigned into two groups: Football Group (n = 9) and Nutrition and Football Group (n = 6). Faecal samples were collected at the beginning and end of the program and analysed by sequencing the 16S rRNA gene. Over the intervention, a significant decrease was found collectively for Bifidobacterium genera (p = 0.011) and for Roseburia genera in the Football Group (p = 0.021). The relative abundance of Roseburia (p = 0.002) and Roseburia faecis (p = 0.009) was negatively correlated with moderate to vigorous physical activity (MVPA), while Prevotella copri was positively correlated with MVPA (p = 0.010) and with the daily intake of protein (p = 0.008). Our findings suggest that a multidisciplinary intervention was capable of inducing limited but significant positive changes in the gut microbiota composition in overweight and obese school children.
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Introduction: Degenerative myelopathy (DM) is a neurodegenerative spinal cord disease with upper motor neurons, with progressive and chronic clinical signs, similar to amyotrophic lateral sclerosis (ALS). DM has a complex etiology mainly associated with SOD1 gene mutation and its toxic role, with no specific treatment. Daily intensive rehabilitation showed survival time near 8 months but most animals are euthanized 6-12 months after clinical signs onset. Methods: This prospective controlled blinded cohort clinical study aims to evaluate the neural regeneration response ability of DM dogs subjected to an intensive neurorehabilitation protocol with mesenchymal stem cells (MSCs) transplantation. In total, 13 non-ambulatory (OFS 6 or 8) dogs with homozygous genotype DM/DM and diagnosed by exclusion were included. All were allocated to the intensive neurorehabilitation with MSCs protocol (INSCP) group (n = 8) or to the ambulatory rehabilitation protocol (ARP) group (n = 5), which differ in regard to training intensity, modalities frequency, and MSCs transplantation. The INSCP group was hospitalized for 1 month (T0 to T1), followed by MSCs transplantation (T1) and a second month (T2), whereas the ARP group was under ambulatory treatment for the same 2 months. Results: Survival mean time of total population was 375 days, with 438 days for the INSCP group and 274 for the ARP group, with a marked difference on the Kaplan-Meier survival analysis. When comparing the literature's results, there was also a clear difference in the one-sample t-test (p = 0.013) with an increase in time of approximately 70%. OFS classifications between groups at each time point were significantly different (p = 0.008) by the one-way ANOVA and the independent sample t-test. Discussion: This INSCP showed to be safe, feasible, and a possibility for a long progression of DM dogs with quality of life and functional improvement. This study should be continued.
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Objetivo: identificar a incidência, fatores de risco e desfechos associados ao infarto agudo do miocárdio sem obstrução de artérias coronárias (myocardial infarction with nonobstructive coronary arteries MINOCA). Método: estudo de coorte prospectivo em prontuários clínicos num hospital terciário do extremo Sul catarinense. Foram incluídos pacientes diagnosticados com infarto agudo do miocárdico (IAM) submetidos a estudo hemodinâmico nos anos de 2017 e 2018. Resultados: ao analisar 445 prontuários, observou-se a ocorrência de MINOCA em 28 pacientes (6,3%). Comparando o grupo MINOCA com o grupo IAM obstrutivo, os pacientes do grupo MINOCA eram mais jovens, com média de 54 anos (DP ± 14; p=0,007), tinham menor incidência de tabagismo (2 versus 156, p<0,001), hipertensão arterial (10 versus 242; p=0,002), menor tempo médio (dias) de internação hospitalar (5,79 ± 3,05 versus 7,49 ± 5,20; p= 0,02) e menos admissões em unidade de tratamento intensivo (5 versus 212; p=0,002). Conclusão: a incidência de MINOCA estimada dentre o total de IAM no Sul de Santa Catarina foi de 6,3% [IC 95]. Os pacientes do grupo MINOCA tiveram menor prevalência de comorbidades, melhor evolução intra-hospitalar e melhor desfecho.
Objective: to identify the incidence, risk factors and outcomes associated with myocardial infarction with nonobstructive coronary arteries (MINOCA). Method: it is a with prospective cohort study data collection from medical records data. Patients with acute myocardial infarction (AMI) that went through hemodynamic study in 2017 and 2018 were included. Results: when analyzing 445 medical records, the occurrence of MINOCA was observed in 28 patients (6.3%). Comparing the MINOCA group with the obstructive AMI group, patients in the MINOCA group were younger, with a mean age of 54 years (SD ± 14; p=0.007), had a lower incidence of smoking (2 versus 156, p<0.001), hypertension (10 versus 242; p=0.002), shorter mean length of hospital stay (days) (5.79 ± 3.05 versus 7.49 ± 5.20; p= 0.02) and fewer admissions to intensive care unit (5 versus 212; p=0.002). Conclusion: the estimated incidence of MINOCA among the total number of AMI in southern Santa Catarina was 6.3% [CI 95]. Patients in the MINOCA group had a lower prevalence of comorbidities, better in-hospital evolution and better outcome.
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Doenças Cardiovasculares , Oclusão Coronária , Placa Aterosclerótica , Fatores de Risco de Doenças Cardíacas , Infarto do MiocárdioRESUMO
CARD14-associated papulosquamous eruption (CAPE) is a rare inflammatory skin eruption that can have features of psoriasis, pityriasis rubra pilaris, and erythroderma. This skin condition is known for its resistance to topical or conventional systemic therapies. Successful treatment of CAPE with anti-IL-12/IL-23 and IL-17 inhibitors has been reported. We present a case of a 2-year-old girl with CAPE who was successfully treated with ustekinumab.