Subacute stroke: new-onset poststroke bladder and bowel dysfunctions and possible associated factors.

PURPOSE: Bladder and bowel poststroke dysfunctions negatively impact patients' health. Stroke-related characteristics associated to these dysfunctions are poorly known. This study aims to estimate the prevalence of new-onset poststroke bladder and bowel dysfunctions, characterize their associated factors, and describe the dysfunctions' clinical approach. MATERIALS AND METHODS: Cross-sectional study including 157 patients admitted to a single hospital's stroke unit with a first-ever stroke, during 3 months. An 18-item questionnaire was applied to assess dysfunctions pre and poststroke. The McNemar test was used to compare pre and poststroke prevalence. A logistic regression was used to estimate associations (OR, 95% CI) between individual characteristics and new-onset dysfunctions. RESULTS: We had 113 (72%) respondents. There was a significant increase in the prevalence of bladder and bowel dysfunctions poststroke (p < 0.001). Higher stroke severity was significantly associated with both new-onset poststroke bladder and bowel dysfunctions (OR = 15.00, 95% CI [4.92,45.76] and OR = 5.87,95%CI [2.14,16.12], respectively). Total anterior circulation strokes, cardioembolic strokes, and lower functionality at discharge were also significantly associated with both dysfunctions. Thirteen patients (11.5%) reported that health professionals addressed these dysfunctions. CONCLUSIONS: Poststroke bladder and bowel dysfunctions are highly prevalent. Being aware of their epidemiology helps draw attention to patients at higher risk of developing these dysfunctions, enhancing the rehabilitation process.IMPLICATIONS FOR REHABILITATIONPoststroke bladder and bowel dysfunctions are highly prevalent and under-recognised consequences of stroke.Being aware of their epidemiology and associated factors may help identify patients at higher risk of developing these dysfunctions.It is necessary to raise clinical awareness to ensure a more efficient diagnostic and therapeutic approach, enhancing patients' rehabilitation process, quality of life and lowering collateral societal burden.

Pain Management Strategies for Botulinum Toxin Type A Injections in Children: A Comprehensive National Survey and Procedural Protocol.

INTRODUCTION: Botulinum toxin type A injections are a first-line treatment for spasticity in children. Our purpose is to delineate the national landscape concerning pain management for botulinum toxin type A injections in pediatric patients and to formulate a protocol grounded in current scientific evidence. METHODS: We conducted a nationwide survey targeting physical medicine and rehabilitation specialists performing botulinum toxin type A injections for focal spasticity in children in Portugal. We conducted a literature review to compare the survey results with clinical guidelines, good practice manuals, and protocols published in the literature. Finally, we developed a procedural protocol for pain management in botulinum toxin procedures. RESULTS: The survey was completed by 17 out of 18 identified specialists. All but one use some form of periprocedural analgesia. Five do not use any type of sedation. The majority do not assess pain during the procedures. From the reviewed articles, we obtained 23 articles, 19 of which provided data for detailed analysis. CONCLUSIONS: A prevailing concern centers around pain management during botulinum toxin procedures in children. Nevertheless, a distinct absence of uniformity persists in appraising and managing procedure-related pain. This notion is further underscored by the marked heterogeneity and paucity of published literature within this realm. The systematic implementation of a procedural protocol thus becomes highly crucial.

Can Failed Back Surgery Syndrome Be Healed by Transverse Myelitis?

Failed back surgery syndrome (FBSS) is a condition characterized by persistent or recurring back pain following spinal surgery. Etiological factors for FBSS are being studied by investigators and clinicians in an attempt to organize them based on their temporal relation to the surgery event. However, many questions regarding the pathophysiology of FBSS remain, which has resulted in a lack of efficacy among its treatment options. In this report, we present a remarkable case of longitudinally extensive transverse myelitis (LETM) in a patient with a medical history of FBSS who was taking multiple pain medications but had persisting pain. The patient, a 56-year-old woman, presented with an incomplete motor injury (American Spinal Injury Association Impairment Scale D) and a neurological level of C4. Investigations revealed an idiopathic LETM that was unresponsive to high doses of corticosteroids. An inpatient rehabilitation program was initiated, resulting in favorable clinical progress. The patient no longer complained of back pain, and her pain medication was gradually discontinued. At the time of discharge, the patient was able to walk with a stick, dress and groom herself independently, and eat with an adapted fork without experiencing pain. As the pain mechanisms underlying FBSS are complex and not yet fully understood, this clinical case aims to contribute to the discussion of possible pathological mechanisms implicated in LETM that may have contributed to the shutdown of pain perception in a patient with a history of FBSS. By doing so, we hope to identify new and effective ways to treat FBSS.

Estudo de variações genômicas para a identificação de biomarcadores personalizados e novos alvos terapêuticos em tumores colorretais / Study of genomic variation to identify biomarkers and novel therapeutic targets in colorectal tumors

O câncer colorretal é um dos tipos de tumores mais frequentes no mundo. A atual dificuldade na avaliação correta da resposta ao tratamento torna necessário o desenvolvimento de novas abordagens de detecção tumoral. Atualmente, o sequenciamento genômico em larga escala permite um estudo mais compreensivo das alterações estruturais e de sequência presentes no tumor. A aplicação destas abordagens de maneira personalizada permite o desenvolvimento de biomarcadores tumor específicos que podem facilitar a avaliação de resposta ao tratamento e a presença de doença residual, bem como revelar alterações de sequência em genes capazes de servir de novos alvos terapêuticos. Neste estudo foi desenvolvida uma metodologia eficiente para a identificação de biomarcadores baseados na existência de variações estruturais em genomas de tumores de reto, eliminando a necessidade de sequenciamento do genoma normal do mesmo paciente e diminuindo portanto o custo da abordagem. Os biomarcadores encontrados para cada um dos seis pacientes foram utilizados para avaliar a presença de doença residual após o tratamento através da detecção de DNA tumoral circulante nas amostras de plasma coletadas em momentos diferentes do tratamento. O sequenciamento em baixa cobertura personalizado é portanto uma alternativa viável e promissora para avaliar a resposta ao tratamento em pacientes com tumores de reto. Na segunda parte do estudo, a análise de linhagens celulares de tumores colorretais revelou uma grande quantidade de mutações pontuais somáticas (SNVs e InDels) em genes codificadores para proteínas de superfície celular (surfaceoma). Estas alterações no surfaceoma indicam potenciais novos alvos para drogas e vias regulatórias alteradas neste tipo de tumor. Além disso, estas mutações pontuais também são responsáveis pela geração de epítopos com potencial imunogênico e estes novos epítopos podem ser aplicados como vacinas antitumorais personalizadas e já haviam sido propostos como uma alternativa terapêutica. A presença de novos epítopos, principalmente nas linhagens com elevadas taxas de mutação (resultante da instabilidade de microssatélites e mutações em genes de reparo de DNA tipo mismatch ou POLE), sugerem também um potencial uso de drogas moduladoras do sistema imune em pacientes com tumores que apresentam estas mesmas características. Portanto, o estudo de alterações genômicas em tumores primários e linhagens de câncer colorretal permitiu a detecção de variações estruturais que foram utilizadas como biomarcadores personalizados em pacientes com tumores de reto assim como a identificação de genes contendo mutações pontuais em linhagens celulares de câncer colorretal, que revelam potenciais novos alvos terapêuticos a serem explorados na clínica

Colorectal cancer is one of the more frequent tumor types in the world. To select the appropriate treatment course, it is necessary to develop more precise diagnostic approaches. The current availability of high throughput genome sequencing methods allows for a comprehensive characterization of the structural and sequence alterations present in each tumor. The use of tumor genome sequencing in a personalized setting can result in tumor specific biomarkers that help evaluate response to treatment and the presence of residual disease, improving the clinical management of these patients, and also reveal sequence alterations in genes capable of serving as new therapeutic targets. In this study we developed an efficient bioinformatics pipeline to identify biomarkers based on the existing structural alterations in rectal tumor genomes, eliminating the need to sequence the matched normal genome and therefore reducing the cost for this approach. The biomarkers found for each of the six patients were used to evaluate the presence of residual disease after treatment through the detection of circulating tumor DNA in plasma samples collected at different points during the treatment. Sequencing tumor genomes with low coverage is therefore a viable and promising alternative to follow up rectal cancer patient's response to treatment. In the second part of this study, the analysis of colorectal cancer cell lines revealed a large quantity of point mutations (SNVs and InDels) in genes coding for proteins located in the cell surface (surfaceome). These alterations in the surfaceome indicate potential new drug targets and altered pathways in this type of tumor. Furthermore, these point mutations are also responsible for the generation of new epitopes with immunogenic potential and these new epitopes can be applied as personalized tumor vaccines and had previously been proposed as a therapeutic alternative. The presence of new epitopes, especially in the cell lines with elevated mutation rates (resulting from MSI and mutations in DNA mismatch-repair genes or POLE), suggests a potential use of immune checkpoint target drugs in patients with tumors that share these genetic characteristics. With a large-scale bioinformatics approach, we detected new tumor epitopes resulting from point mutations, present in most of the cell lines used. The analysis of gene expression data puts into perspective both the somatic mutations found and which targets are promising as well as the development of therapies based on vaccines derived from tumor epitopes. In conclusion, the study of genomic alterations in primary tumors and colorectal cancer cell lines allowed the detection of structural variations that were used as personalized biomarkers in patients with rectal tumors as well as the identification of genes containing point mutations in colorectal cancer cell lines, that reveal potential new therapeutic targets to be explored in the clinical setting