Solitary pulmonary nodule malignancy predictive models applicable to routine clinical practice: a systematic review

Background Solitary pulmonary nodule (SPN) is a common finding in routine clinical practice when performing chest imaging tests. The vast majority of these nodules are benign, and only a small proportion are malignant. The application of predictive models of nodule malignancy in routine clinical practice would help to achieve better diagnostic management of SPN. The present systematic review was carried out with the purpose of critically assessing studies aimed at developing predictive models of solitary pulmonary nodule (SPN) malignancy from SPN incidentally detected in routine clinical practice. Methods We performed a search of available scientific literature until October 2020 in Pubmed, SCOPUS and Cochrane Central databases. The inclusion criteria were observational studies carried out in low-risk population from 35 years old onwards aimed at constructing predictive models of malignancy of pulmonary solitary nodule detected incidentally in routine clinical practice. Studies had to be published in peer-reviewed journals, either in Spanish, Portuguese or English. Exclusion criteria were non-human studies, or predictive models based in high-risk populations, or models based on computational approaches. Exclusion criteria were non-human studies, or predictive models based in high-risk populations, or models based on computational approaches (such as radiomics). We used The Transparent Reporting of a multivariable Prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement, to describe the type of predictive model included in each study, and The Prediction model Risk Of Bias ASsessment Tool (PROBAST) to evaluate the quality of the selected articles. Results A total of 186 references were retrieved, and after applying the exclusion/inclusion criteria, 15 articles remained for the final review. All studies analysed clinical and radiological variables. The most frequent independent predictors of SPN malignancy were, in order of frequency, age, diameter, spiculated edge, calcification and smoking history. Variables such as race, SPN growth rate, emphysema, fibrosis, apical scarring and exposure to asbestos, uranium and radon were not analysed by the majority of the studies. All studies were classified as high risk of bias due to inadequate study designs, selection bias, insufficient population follow-up and lack of external validation, compromising their applicability for clinical practice. Conclusions The studies included have been shown to have methodological weaknesses compromising the clinical applicability of the evaluated SPN malignancy predictive models and their potential influence on clinical decision-making for the SPN diagnostic management. Systematic review registration PROSPERO CRD42020161559

Communication between cells: exosomes as a delivery system in prostate cancer

Despite the considerable efforts in screening and diagnostic protocols, prostate cancer still represents the second leading cause of cancer-related death in men. Many patients with localized disease and low risk of recurrence have a favourable outcome. In a substantial proportion of patients, however, the disease progresses and becomes aggressive. The mechanisms that promote prostate cancer progression remain still debated. Many findings point to the role of cross-communication between prostate tumor cells and their surrounding microenvironment during the disease progression. Such a connection fosters survival, proliferation, angiogenesis, metastatic spreading and drug-resistance of prostate cancer. Recent years have seen a profound interest in understanding the way by which prostate cancer cells communicate with the surrounding cells in the microenvironment. In this regard, direct cell-to-cell contacts and soluble factors have been identified. Increasing evidence indicates that PC cells communicate with the surrounding cells through the release of extracellular vesicles, mainly the exosomes. By directly acting in stromal or prostate cancer epithelial cells, exosomes represent a critical intercellular communication system. By querying the public database (https://pubmed.ncbi.nlm.nih.gov) for the past 10 years, we have found more than four hundred papers. Among them, we have extrapolated the most relevant about the role of exosomes in prostate cancer malignancy and progression. Emerging data concerning the use of these vesicles in diagnostic management and therapeutic guidance of PC patients are also presented. Graphical Abstract

The Role of Bronchoscopy in the Diagnosis and Management of Patients with SARS-Cov-2 Infection

Bronchoscopy has several major diagnostic and therapeutic indications in pulmonology. However, it is an aerosol-generating procedure that places healthcare providers at an increased risk of infection. Now more than ever, during the spread of the coronavirus disease 2019 (COVID-19) pandemic, the infectious risk during bronchoscopy is significantly raised, and for this reason its role in diagnostic management is debated. In this review, we summarized current evidence regarding the indications for bronchoscopy and the measures that should be applied to decrease risk exposure. Indeed, seeing the long-lasting period of the pandemic, resuming standard of care for all patients is required.

Electronic tools in clinical laboratory diagnostics: key examples, limitations, and value in laboratory medicine

Electronic tools in clinical laboratory diagnostics can assist laboratory professionals, clinicians, and patients in medical diagnostic management and laboratory test interpretation. With increasing implementation of electronic health records (EHRs) and laboratory information systems worldwide, there is increasing demand for well-designed and evidence-based electronic resources. Both complex data-driven and simple interpretative electronic healthcare tools are currently available to improve the integration of clinical and laboratory information towards a more patient-centered approach to medicine. Several studies have reported positive clinical impact of electronic healthcare tool implementation in clinical laboratory diagnostics, including in the management of neonatal bilirubinemia, cardiac disease, and nutritional status. As patients have increasing access to their medical laboratory data, it is essential that accessible electronic healthcare tools are evidence-based and user-friendly for individuals of varying digital and medical literacy. Indeed, studies suggest electronic healthcare tool development processes significantly lack the involvement of relevant healthcare professionals and often present misinformation, including erroneous calculation algorithms or inappropriate interpretative recommendations. The current review provides an overview of the utility of available electronic healthcare tools in clinical laboratory diagnostics and critically reviews potential limitations and benefits of their clinical implementation. The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) online database is also detailed as an example of a pediatric diagnostic tool with widespread global impact.

Study of serum Micro-RNA 221 Expression in Patients with Thyroid Nodules and Its Relation to Outcome

A major dilemma in the diagnostic management of thyroid nodules is to determine whether it is a benign or malignant lesion and hence to determine decision for surgery. The majority of individuals with thyroid nodules are asymptomatic. The current first line of evaluation of thyroid nodules encompasses thyroid hormone laboratory tests, and ultrasonography of the thyroid gland, fine-needle aspiration (FNA) biopsy is often used to rule out cancer in thyroid nodules, in 20–30% of cases, however, FNAB yields indeterminate cytological results and suspicious for malignancy. Surgery was classically recommended for such indeterminate nodules for their risk of malignancy, which, overall, is about 25% when confirmed histopathologically upon thyroidectomy. As a result, about 75% of patients with cytologically indeterminate thyroid nodules would undergo unnecessary thyroid surgeries for nodules that prove to be benign only after surgery. Recent advances in research on thyroid carcinogenesis have yielded applications of diagnostic molecular biomarkers and profiling panels in the management of thyroid nodules. Among these markers are MicroRNAs (miRs) are small RNA sequences (19–25 nucleotides) that function to regulate the expression of genes. In this paper we aim to detect a possible of Micro-RNA 221 expression in sera of Patients With thyroid nodules and its relation to outcome after surgery.

Advances in Functional Imaging of Differentiated Thyroid Cancer

The present review provides a description of recent advances in the field of functional imaging that takes advantage of the functional characteristics of thyroid neoplastic cells (such as radioiodine uptake and FDG uptake) and theragnostic approach of differentiated thyroid cancer (DTC). Physical and biological characteristics of available radiopharmaceuticals and their use with state-of-the-art technologies for diagnosis, treatment, and follow-up of DTC patients are depicted. Radioactive iodine is used mostly with a therapeutic intent, while PET/CT with 18F-FDG emerges as a useful tool in the diagnostic management and complements the use of radioactive iodine. Beyond 18F-FDG PET/CT, other tracers including 124I, 18F-TFB and 68Ga-PSMA, and new methods such as PET/MR, might offer new opportunities in selecting patients with DTC for specific imaging modalities or treatments.

Seizure Forecasting Using a Novel Sub-Scalp Ultra-Long Term EEG Monitoring System

Accurate identification of seizure activity, both clinical and subclinical, has important implications in the management of epilepsy. Accurate recognition of seizure activity is essential for diagnostic, management and forecasting purposes, but patient-reported seizures have been shown to be unreliable. Earlier work has revealed accurate capture of electrographic seizures and forecasting is possible with an implantable intracranial device, but less invasive electroencephalography (EEG) recording systems would be optimal. Here, we present preliminary results of seizure detection and forecasting with a minimally invasive sub-scalp device that continuously records EEG. Five participants with refractory epilepsy who experience at least two clinically identifiable seizures monthly have been implanted with sub-scalp devices (Minder®), providing two channels of data from both hemispheres of the brain. Data is continuously captured via a behind-the-ear system, which also powers the device, and transferred wirelessly to a mobile phone, from where it is accessible remotely via cloud storage. EEG recordings from the sub-scalp device were compared to data recorded from a conventional system during a 1-week ambulatory video-EEG monitoring session. Suspect epileptiform activity (EA) was detected using machine learning algorithms and reviewed by trained neurophysiologists. Seizure forecasting was demonstrated retrospectively by utilizing cycles in EA and previous seizure times. The procedures and devices were well-tolerated and no significant complications have been reported. Seizures were accurately identified on the sub-scalp system, as visually confirmed by periods of concurrent conventional scalp EEG recordings. The data acquired also allowed seizure forecasting to be successfully undertaken. The area under the receiver operating characteristic curve (AUC score) achieved (0.88), which is comparable to the best score in recent, state-of-the-art forecasting work using intracranial EEG.

Inherited Retinal Diseases Due to RPE65 Variants: From Genetic Diagnostic Management to Therapy

Inherited retinal diseases (IRDs) are a heterogeneous group of conditions that include retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) and early-onset severe retinal dystrophy (EO[S]RD), which differ in severity and age of onset. IRDs are caused by mutations in >250 genes. Variants in the RPE65 gene account for 0.6–6% of RP and 3–16% of LCA/EORD cases. Voretigene neparvovec is a gene therapy approved for the treatment of patients with an autosomal recessive retinal dystrophy due to confirmed biallelic RPE65 variants (RPE65-IRDs). Therefore, the accurate molecular diagnosis of RPE65-IRDs is crucial to identify ‘actionable’ genotypes—i.e., genotypes that may benefit from the treatment—and is an integral part of patient management. To date, hundreds of RPE65 variants have been identified, some of which are classified as pathogenic or likely pathogenic, while the significance of others is yet to be established. In this review, we provide an overview of the genetic diagnostic workup needed to select patients that could be eligible for voretigene neparvovec treatment. Careful clinical characterization of patients by multidisciplinary teams of experts, combined with the availability of next-generation sequencing approaches, can accelerate patients’ access to available therapeutic options.

Grisel’s syndrome – case report

Introduction: By definition from the literature, Grisel’s syndrome is described as non-traumatic rotational atlantoaxial instability between C1 and C2 vertebrae. It can occur during an infection of a soft tissue in the cervicocranial region or after an operation in the ENT region. Because of the frequent occurrence after operations, we inclined to the definition which includes a traumatic subluxation as a cause of origin, and it’s not defined as non-traumatic only. The instability manifests itself with abnormal head posture that is called torticollis. Increased incidence in adolescence is more common because of a greater ligamentous laxity of the joint capsules, increased perfusion of antlantoaxial regions and longer alar ligaments. In this article, the case of a child with Grisel’s syndrome after adenotomy is described. The pathophysiology, symptomatology, diagnostic management and treatment are discussed. Keywords: Grisel’s syndrome – torticollis – atlantoaxial instability – adenotomy

Seizure Forecasting Using a Novel Sub-Scalp Ultra-Long Term EEG Monitoring System

Accurate identification of seizure activity, both clinical and subclinical, has important implications in the management of epilepsy. Accurate recognition of seizure activity is essential for diagnostic, management and forecasting purposes, but patient-reported seizures have been shown to be unreliable. Earlier work has revealed accurate capture of electrographic seizures and forecasting is possible with an implantable intracranial device, but less invasive electroencephalography (EEG) recording systems would be optimal. Here, we present preliminary results of seizure detection and forecasting with a minimally invasive sub-scalp device that continuously records EEG. Five participants with refractory epilepsy who experience at least two clinically identifiable seizures monthly have been implanted with sub-scalp devices (Minder TM), providing two channels of data from both hemispheres of the brain. Data is continuously captured via a behind-the-ear system, which also powers the device, and transferred wirelessly to a mobile phone, from where it is accessible remotely via cloud storage. EEG recordings from the sub-scalp device were compared to data recorded from a conventional system during a 1-week ambulatory video-EEG monitoring session. Suspect epileptiform activity (EA) was detected using machine learning algorithms and reviewed by trained neurophysiologists. Seizure forecasting was demonstrated retrospectively by utilising cycles in EA and previous seizure times. The procedures and devices were well tolerated and no significant complications have been reported. Seizures were accurately identified on the sub-scalp system, as confirmed by periods of concurrent conventional scalp EEG recordings. The data acquired also allowed seizure forecasting to be successfully undertaken. The area under the receiver operating characteristic curve (AUC score) achieved (0.88) is comparable to the best score in recent, state-of-the-art forecasting work using intracranial EEG.