Reconstrução escrotal após gangrena de Fournier / Scrotal reconstruction after Fournier's gangrene

Introdução: Gangrena de Fournier é uma infecção polibacteriana, geralmente causada por bactérias anaeróbias e aeróbias, sendo caracterizada por fasciite necrosante escrotal e perineal. Seu tratamento é embasado em intervenção cirúrgica com excisão da área necrótica e antibioticoterapia precoces. Diversas são as estratégias de reconstrução do defeito resultante do desbridamento, devendo ser salientado que perdas teciduais maiores do que 50% costumam ser reconstruídas com retalhos. Métodos: Análise retrospectiva da série de casos de reconstrução escrotal após gangrena de Fournier procedidos pelos autores ao longo de 2020, totalizando oito pacientes. Resultados: O retalho mais utilizado foi o fasciocutâneo de coxa, que apresentou taxa de necrose parcial de 14,29%, sem necrose total. Em um dos casos foi possível reconstruir uma uretra esponjosa com músculo grácil sem fistulização, evitando que o paciente fosse submetido a uma uretrostomia definitiva. Quanto às complicações, foi comum a ocorrência de intercorrências menores que necessitaram de procedimentos revisionais simples. Destaca-se a prevalência de 75% de diabetes mellitus em nossa casuística, o que pode ter interferido negativamente no processo cicatricial. Conclusão: A reconstrução escrotal com retalhos é importante para acelerar a cicatrização da ferida proveniente do desbridamento de gangrena de Fournier e para manter o aspecto de bolsa necessário para a termorregulação do testículo. Nossa opção primária foi o retalho fasciocutâneo de coxa, que se mostrou seguro. Pequenas intercorrências foram frequentes nesta série, sem comprometimento do resultado final.

Introduction: Fournier's gangrene is a polybacterial infection, usually caused by anaerobic and aerobic bacteria, characterized by scrotal and perineal necrotizing fasciitis. Its treatment is based on surgical intervention by excision of the necrotic area and early antibiotic therapy. There are several strategies to reconstruct the defect resulting from debridement, and it should be noted that tissue losses greater than 50% are usually reconstructed with flaps. Methods: Retrospective analysis of the series of cases of scrotal reconstruction after Fournier's gangrene performed by the authors throughout 2020, totaling eight patients. Results: The most used flap was thigh fasciocutaneous flap, which presented a partial necrosis rate of 14.29%, without total necrosis. In one of the cases, it was possible to reconstruct a spongy urethra with gracilis muscle without fistulization, preventing the patient from undergoing a definitive urethrostomy. As for complications, the occurrence of minor complications that required simple revision procedures was common. The prevalence of 75% of diabetes mellitus in our series is highlighted, which may have negatively interfered with the healing process. Conclusion: Scrotal reconstruction with flaps is important to accelerate wound healing from Fournier gangrene debridement and to maintain the pouch aspect necessary for testicular thermoregulation. Our primary option was thigh fasciocutaneous flap, which proved to be safe. And minor complications were frequent in this series, without compromising the final result.

Effects of antiepileptic drugs on sleep architecture parameters in adults.

Objectives: Physiological and restorative sleep is fundamental for physical and mental well-being. Polysomnography parameters are objective methods to access sleep structure. Antiepileptic drugs (AEDs) are a group of drugs whose interference in the sleep structure is still not well known, especially in what concern the new ones. We did a systematic review of the literature to compare the effect of classic and newer AEDs on sleep architecture. Material and Methods: A search was performed in PubMed and Scopus, using keywords "sleep" and "antiepileptics", and each AED combined with "sleep". Only studies concerning objective measures were selected. Results: 63 articles were included, only 21 were randomized, controlled and double-blinded. Studies not only in epilepsy, but also in restless leg syndrome, bruxism, insomnia, fibromyalgia and obstructive sleep apnea were found. Among classic AEDs, carbamazepine has a negative effect on sleep while phenobarbitone has a slightly dose-dependent interference and is also the only one to reduce N3 stage. Valproic acid has little to no effect while clobazam and clonazepam have a positive effect. No conclusion can be drawn about phenytoin. All of them reduce REM stage. In the newer AEDs group gabapentine, lamotrigine, perampanel, pregabaline and tiagabine increase N3 sleep in best evidence. Lacosamide and zonisamide appear to be innocent while levetiracetam reduces REM sleep. Conclusion: Studies found used different methodologies not always addressing the analysis on the same parameters. In spite of these, newer AEDs have less effects on sleep structure when compared with classic AEDs but furthermore robust evidence is needed.

Long term outcome of functional hemispherectomy for refractory epilepsy: Experience from a single center.

BACKGROUND: Hemispherectomy has an established role as a treatment of last resort in patients with unilateral hemispheric lesions suffering from refractory epilepsy. METHODS: Seven patients were evaluated at our Epilepsy Unit. We compared the seizure outcome at 6 months, 1, 2, 5 years post-surgery, as well as at end follow-up (mean 7.1 years) using Engel classification. Reduction of antiepileptic drugs (AEDs) was also assessed utilizing equal time frames. RESULTS: The mean age of seizure onset was 5.4 years. Engel I was achieved in 5 patients at 6 months (71.4%). Engel at 1 year was predicted by the Engel at 6 months (p=0.013) with a similar number of patients being classified as Engel I outcome. Engel at 2 years was also predicted by Engel at 6 months and at 1 year (p=0.030). At end follow-up only 3 patients (42.9%) remained categorized as Engel I outcome. There was a trend toward a stability in Engel classification. All patients with developmental causes for their epilepsy experienced some deterioration of the surgical outcomes. Conversely, all patients with acquired causes were stable throughout follow-up. Seizure outcome at 6 months was worse in the patients who had post-op complications (p=0.044). Adult and pediatric populations did not differ significantly in any tested variable. CONCLUSIONS: Hemispherectomy is a valuable resource for seizure control in properly selected patients. Engel patient's evolution could be predicted at 6 months interval. Hemispherectomy could be considered a useful attitude in difficult cases.

Epilepsy progression is associated with cumulative DNA methylation changes in inflammatory genes.

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is the most common focal epilepsy in adults. It is characterized by alarming rates of pharmacoresistance. Epileptogenesis is associated with the occurrence of epigenetic alterations, and the few epigenetic studies carried out in MTLE-HS have mainly focused on the hippocampus. In this study, we obtained the DNA methylation profiles from both the hippocampus and anterior temporal neocortex of MTLE-HS patients subjected to resective epilepsy surgery and autopsied non-epileptic controls. We assessed the progressive nature of DNA methylation changes in relation to epilepsy duration. We identified significantly altered hippocampal DNA methylation patterns encompassing multiple pathways known to be involved in epileptogenesis. DNA methylation changes were even more striking in the neocortex, wherein pathogenic pathways and genes were common to both tissues. Most importantly, DNA methylation changes at many genomic sites varied significantly with epilepsy duration. Such progressive changes were associated with inflammation-related genes in the hippocampus. Our results suggest that the neocortex, relatively spared of extensive histopathological damage, may also be involved in epilepsy development. These results also open the possibility that the observed neocortical impairment could represent a preliminary stage of epileptogenesis before the establishment of chronic lesions or a consequence of prolonged seizure exposure. Our two-tissue multi-level characterization of the MTLE-HS DNA methylome suggests the occurrence of a self-propagating inflammatory wave of epigenetic dysregulation.

Cardiovascular Risk Factors, Functionality, and Quality of Life in Climacteric Women

Abstract Background: Cardiovascular disease (CVD) comprises a group of cardiac and circulatory diseases. Despite the high incidence in males, women after menopause have an exponential increase in the risk of CVD. Objective: To identify the leading risk factors for CVD and describe quality of life and functionality in women hospitalized for cardiac causes during the climacteric period. Materials and methods: Observational descriptive study. Quality of life was assessed through the SF-36 questionnaire, and functionality through the Functional Independence Measurement (FIM) scale. Records were used to identify the main risk factors associated with CVD in climacteric women. Results: We included 30 patients (mean age, 55 ± 6 years). The mean FIM score was 118 ± 3, and the mean SF-36 score, 20 ± 10. Hypertension and sedentary lifestyle were the most prevalent cardiovascular risk factors in these women. Conclusion: Hypertension and sedentary lifestyle were the most prevalent cardiovascular risk factors in this sample of climacteric women hospitalized for cardiac causes. Quality of life was strongly affected, with social, emotional, and mental health domains showing the most impact.

Long term outcome of functional hemispherectomy for refractory epilepsy: Experience from a single center.

BACKGROUND: Hemispherectomy has an established role as a treatment of last resort in patients with unilateral hemispheric lesions suffering from refractory epilepsy. METHODS: Seven patients were evaluated at our Epilepsy Unit. We compared the seizure outcome at 6 months, 1, 2, 5 years post-surgery, as well as at end follow-up (mean 7.1 years) using Engel classification. Reduction of antiepileptic drugs (AEDs) was also assessed utilizing equal time frames. RESULTS: The mean age of seizure onset was 5.4 years. Engel I was achieved in 5 patients at 6 months (71.4%). Engel at 1 year was predicted by the Engel at 6 months (p=0.013) with a similar number of patients being classified as Engel I outcome. Engel at 2 years was also predicted by Engel at 6 months and at 1 year (p=0.030). At end follow-up only 3 patients (42.9%) remained categorized as Engel I outcome. There was a trend toward a stability in Engel classification. All patients with developmental causes for their epilepsy experienced some deterioration of the surgical outcomes. Conversely, all patients with acquired causes were stable throughout follow-up. Seizure outcome at 6 months was worse in the patients who had post-op complications (p=0.044). Adult and pediatric populations did not differ significantly in any tested variable. CONCLUSIONS: Hemispherectomy is a valuable resource for seizure control in properly selected patients. Engel patient's evolution could be predicted at 6 months interval. Hemispherectomy could be considered a useful attitude in difficult cases.

Mandibular-related bone metabolism in orchiectomized rats treated with sex hormones.

OBJECTIVE: This study aimed to compare the impact of testosterone and estrogen replacement therapy on mandibular bone density and bone-related markers. DESIGN: Forty male adult rats were randomly allocated to 4 experimental groups (n = 10/group): Sham (Control); Orchiectomy; Orchiectomy plus testosterone replacement; and orchiectomy plus estradiol replacement. Twenty-four days after orchiectomy, the hemi-mandibles were collected and processed for analysis of microhardness in cortical and trabecular bone, radiographic bone density and histomorphometric evaluation. Serum was collected for the analysis of calcium, phosphorus, alkaline phosphatase and magnesium. RESULTS: The orchiectomy group had the lowest mandibular bone density (p < 0.01) and also their serum levels of alkaline phosphatase were higher than all other experimental groups (p < 0.001). Estradiol replacement significantly reduced microhardness when compared to orchiectomy in cortical bone (p < 0.05). Both testosterone and estrogen replacement reverted orchiectomy impact on this parameter (p < 0.01); and decreased alkaline phosphatase to levels comparable to the Sham-Control group. The effect of estrogen was more pronounced than testosterone, and a statistically significant difference was observed between Sham-Control and testosterone replacement (p < 0.05) but not between Sham-Control and estradiol replacement groups. CONCLUSION: Our findings demonstrated that both estradiol and testosterone replacement therapies play a role in mandibular bone metabolism, but suggest different pathways.

Correction of a Splicing Mutation Affecting an Unverricht-Lundborg Disease Patient by Antisense Therapy.

Unverricht-Lundborg disease (ULD) is a common form of progressive myoclonic epilepsy caused by mutations in the cystatin B gene (CSTB) that encodes an inhibitor of several lysosomal cathepsins. Presently, only pharmacological treatment and psychosocial support are available for ULD patients. To overcome the pathogenic effect of the ULD splicing mutation c.66G>A (exon 1), we investigated whether an antisense oligonucleotide therapeutic strategy could correct the defect in patient cells. A specific locked nucleic acid (LNA) antisense oligonucleotide was designed to block a cryptic 5'ss in intron 1. Overall, this approach allowed the restoration of the normal splicing pattern. Furthermore, the recovery was both sequence and dose-specific. In general, this work provides a proof of principle on the correction of a CSTB gene defect causing ULD through a mutation-specific antisense therapy. It adds evidence to the feasibility of this approach, joining the many studies that are paving the way for translating antisense technology into the clinical practice. The insights detailed herein make mutation-based therapy a clear candidate for personalized treatment of ULD patients, encouraging similar investigations into other genetic diseases.

Immunogenetic predisposing factors for mesial temporal lobe epilepsy with hippocampal sclerosis.

PURPOSE: Neuroinflammation appears as an important epileptogenic mechanism. Experimental and clinical studies have demonstrated an upregulation of pro-inflammatory cytokines such as IL-1ß and TNF-α, in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). Expression of these cytokines can be modulated by polymorphisms such as rs16944 and rs1800629, respectively, both of which have been associated with febrile seizures (FS) and MTLE-HS development. The human leukocyte antigen (HLA) system has also been implicated in diverse epileptic entities, suggesting a variable role of this system in epilepsy. Our aim was to analyse the association between immunogenetic factors and MTLE-HS development. For that rs16944 (-511 T>C, IL-1ß), rs1800629 (-308 G>A, TNF-α) polymorphisms and HLA-DRB1 locus were genotyped in a Portuguese Population. METHODS: We studied 196 MTLE-HS patients (108 females, 88 males, 44.7 ± 12.0 years, age of onset = 13.6 ± 10.3 years, 104 with FS antecedents) and 282 healthy controls in a case-control study. RESULTS: The frequency of rs16944 TT genotype was higher in MTLE-HS patients compared to controls (14.9% in MTLE-HS vs. 7.7% in controls, p = 0.021, OR [95% CI] = 2.20 [1.13-4.30]). This association was independent of FS antecedents. No association was observed between rs1800629 genotypes or HLA-DRB1 alleles and MTLE-HS susceptibility. Also, no correlation was observed between the studied polymorphisms and disease age of onset. CONCLUSION: The rs16944 TT genotype is associated with MTLE-HS development what may be explained by the higher IL-1ß levels produced by this genotype. High IL-1ß levels may have neurotoxic effects or imbalance neurotransmission leading to seizures.

Characterization of a rare Unverricht-Lundborg disease mutation.

Cystatin B (CSTB) gene mutations cause Unverricht-Lundborg disease (ULD), a rare form of myoclonic epilepsy. The previous identification of a Portuguese patient, homozygous for a unique splicing defect (c.66G > A; p.Q22Q), provided awareness regarding the existence of variant forms of ULD. In this work we aimed at the characterization of this mutation at the population level and at the cellular level. The cellular fractionation studies here carried out showed mislocalization of the protein and add to the knowledge on this disease.

Effects of doxycycline on depressive-like behavior in mice after lipopolysaccharide (LPS) administration.

Current evidences support inflammation, oxidative and nitrogen stress, as well as brain-derived neurotrophic factor (BDNF) signaling mechanisms as important in depression pathophysiology. Tetracycline antibiotics have anti-inflammatory and antioxidant properties. Preliminary evidence indicates that minocycline has antidepressant properties. Doxycycline (DOXY) has favorable pharmacokinetic and safety profiles when compared to other tetracycline congeners. The antidepressant activity of DOXY has not been adequately investigated. This study evaluated the effects of DOXY (25 and 50 mg/kg, i.p.) on LPS-induced (0.5 mg/kg, i.p.) depressive-like behavior. Doxycycline was administered 30 min before LPS (pre-LPS) or 1.5 and 23.5 h following LPS (post-LPS) administration in mice. LPS-treated animals presented an increase in immobility time in the forced swimming test (FST) when compared to controls 24 h after endotoxin administration. Similarly to imipramine (IMI-10 mg/kg, i.p.), DOXY at both doses prevented and reversed LPS-induced alterations in the FST. IL-1ß content was increased 24 h after LPS administration in striatum, hippocampus and prefrontal cortex. IMI and DOXY prevented and reversed LPS-induced increase in IL-1ß. IMI and DOXY also prevented and reversed LPS-induced alterations in nitrite content and oxidative stress parameters (lipid peroxidation and reduced glutathione levels). Both DOXY and IMI prevented LPS-induced decrease in hippocampal BDNF levels. Taken together, our results demonstrate that DOXY is comparable to IMI in effectively ameliorate LPS-induced depressive-like behavior, providing a rationale for testing DOXY's antidepressant efficacy in humans.

Unverricht-Lundborg disease: homozygosity for a new splicing mutation in the cystatin B gene.

Unverricht-Lundborg disease is the most common form of progressive myoclonic epilepsy (PME). It is due to cystatin B gene (CSTB) mutations. Several mutations in CSTB gene have been published, but few in homozygosity. We describe a patient with a new splicing alteration. Mutation Gln22Gln leads to abnormal splicing and partial inclusion of intronic sequence. This is one of the few cases of homozygosity for a non-classic mutation and adds to mutational heterogeneity of CSTB.

In vivo growth inhibition of sarcoma 180 by piperlonguminine, an alkaloid amide from the Piper species.

Many authors have already emphasized that phytochemicals from spices have biological applications. Piperlonguminine is a known alkaloid amide from peppers, including Piper divaricatum. The aim of this study was to investigate the in vitro and in vivo antitumor effects of piperlonguminine in experimental models. In order to evaluate the toxicological aspects related to piperlonguminine treatment, hematological, biochemical, histopathological and morphological analyses of treated animals were performed. Piperlonguminine did not show any significant in vitro cytotoxic effect at experimental exposure levels, but showed an in vivo antitumor effect. After 7 days of treatment, the inhibition rates were 38.71% and 40.68% at doses of 25 mg kg(-1) and 50 mg kg(-1), respectively. The histopathological analysis suggests that the liver and kidney were only weakly affected by piperlonguminine treatment. Neither the enzymatic activity of transaminases (AST and ALT) nor the urea levels were significantly altered. In the hematological analysis, all parameters analysed remained constant after piperlonguminine treatment. In conclusion, these data reinforce the anticancer potential of spice components.