The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response. In addition, surveillance for recurrence is similarly important for these patients, as early detection of recurrence allows salvage resections and adjuvant interventions. We report the use of liquid biopsies and personalized biomarkers for monitoring treatment response to nCRT and detecting residual disease and recurrence in patients with rectal cancer. We sequenced the whole-genome of four rectal tumors to identify patient-specific chromosomal rearrangements that were used to monitor circulating tumor DNA (ctDNA) in liquid biopsies collected at diagnosis and during nCRT and follow-up. We compared ctDNA levels to clinical, radiological and pathological response to nCRT. Our results indicate that personalized biomarkers and liquid biopsies may not be sensitive for the detection of microscopic residual disease. However, it can be efficiently used to monitor treatment response to nCRT and detect disease recurrence, preceding increases in CEA levels and radiological diagnosis. Similar good results were observed when assessing tumor response to systemic therapy and disease progression. Our study supports the use of personalized biomarkers and liquid biopsies to tailor the management of rectal cancer patients, however, replication in a larger cohort is necessary to introduce this strategy into clinical practice.     

Follicular fluid lipid peroxidation levels in women with endometriosis during controlled ovarian hyperstimulation

This observational study aimed to establishing a relationship between lipid peroxidation and endometriosis in women undergoing controlled ovarian hyperstimulation. A total of 79 women were divided into two groups: (i) controls (tubal or male factor); and (ii) endometriosis (stages III/IV). The endometriosis diagnosis was confirmed by videolaparoscopy and the controlled ovarian stimulation protocol was similar to all patients. Follicular fluid (FF) lipid peroxidation levels were determined through the quantification of malondialdehyde. Statistical analysis was performed using parametric and non-parametric tests, logistic regression was performed to estimate the chance of achieving a pregnancy in each group and a moving average was calculated for the endometriosis group. Peroxidation levels in the endometriosis group were significantly higher when compared to controls. The moving average showed a decrease of MDA levels in the endometriosis group with increasing female age. Moreover, women with endometriosis who were under 33 years of age were 4.3 times more likely to achieve a pregnancy than women above that age. In conclusion, endometriosis is associated with increased FF oxidative stress (OS) in patients undergoing in vitro fertilization (IVF). Also, increasing age is associated with a decrease in severity of the oxidative status, but a decreased chance of pregnancy.     

Late-onset epilepsy and occult cerebrovascular disease

The interface between cerebrovascular disease (CVD) and epilepsy is complex and multifaceted. Late-onset epilepsy (LOE) is increasingly common and is often attributed to CVD, and is indeed associated with an increased risk of stroke. This relationship is easily recognizable where there is a history of stroke, particularly involving the cerebral cortex. However, the relationship with otherwise occult, subcortical CVD is currently less well established yet causality is often invoked. In this review, we consider the diagnosis of LOE in clinical practice—including its behaviour as a potential mimic of acute ischemic stroke and transient ischemic attack; evidence for an association between occult CVD and LOE; and potential mechanisms of epileptogenesis in occult CVD, including potential interrelationships between disordered cerebral metabolism and perfusion, disrupted neurovascular unit integrity, blood–brain barrier dysfunction, and inflammation. We also discuss recently recognized issues concerning antiepileptic drug treatment and vascular risk and consider a variety of less common CVD entities associated with seizures.     

Accuracy of direct examination and culture as compared to the anatomopathological examination for the diagnosis of chromoblastomycosis: a systematic review

BackgroundChromoblastomycosis is a skin infection caused by dematiaceous fungi that take the form of muriform cells in the tissue. It mainly manifests as verrucous plaques on the lower limbs of rural workers in tropical countries.ObjectivesThe primary objective of this review is to evaluate the accuracy of diagnostic methods for the identification of chromoblastomycosis, considering the histopathological examination as the reference test.MethodsMEDLINE, LILACS and Scielo databases were consulted using the terms “chromoblastomycosis” AND “diagnosis”. The eligibility criteria were: studies that evaluated the accuracy of tests for the diagnosis of chromoblastomycosis. Eleven studies were selected. Statistical analysis included the calculation of sensitivity and specificity of the diagnostic methods.ResultsConsidering the histopathological examination as the reference test, the culture showed a sensitivity (S) of 37.5% - 90.9% and a specificity (Sp) of 100%; while direct mycological examination showed S = 50% - 91.6% and Sp of 100% . Considering the culture as the reference test, the serology (precipitation techniques) showed S of 36% - 99%; and Sp of 80% - 100%; while the intradermal test showed S of 83.3% - 100% and Sp of 99.4% - 100%.Study limitationsThe small number of studies and very discrepant sensitivity results among them do not allow the calculation of summary measures through a meta-analysis.ConclusionsDirect mycological examination, culture, intradermal test and serology show sensitivity and specificity values ??for the diagnosis of chromoblastomycosis with no significant difference between the studies.