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Mechanical biomarkers distinguish health conditions through quantitative mechanical measurements. The emergence and establishment of nanotechnology in the last decades have provided new tools to obtain mechanical biomarkers at the nanoscale. Mechanical measurements are reproducible, label‐free, start to be applied in vivo can be high throughput, and require small samples. Mechanical protocols in clinical practice at the macro scale like palpation or blood pressure measurement are routinely used by medical doctors. Nanotechnology brought mechanical sensing to the next scale, where cells, tissues, and proteins can be probed and linked to medical conditions. Mechanical changes in cells and tissues may be detected before other markers, such as protein expression, providing an important advantage as biomarkers. In the present review, we explore the biomarker's historical evolution, describe mechanical biomarkers on various diseases and novel discoveries in the nanomechanical field for their characterization. We conclude that mechanical biomarkers are establishing novel hallmarks in diseases, in several cases for early diagnostics of diseases and discovery of drug targets in the proteins involved in the mechanical changes, while advances in instrumentation are bringing commercial products into the clinical practice. Mechanical biomarkers along with clinical testing are establishing an important niche in the market, whose demand is increasing due to the expansion of personalized medicine and unmet needs in the clinics. [ABSTRACT FROM AUTHOR]

Patients with psoriasis have a higher prevalence of cardiovascular risk factors. This study evaluated cardiovascular screening practices and statin prescribing habits among dermatologists, rheumatologists and primary care physicians (PCPs) through an online questionnaire, which was distributed through the Spanish scientific societies of the above-mentioned specialties. A total of 299 physicians (103 dermatologists, 94 rheumatologists and 102 PCPs) responded to the questionnaire. Of these, 74.6% reported screening for smoking, 37.8% for hypertension, 80.3% for dyslipidaemia, and 79.6% for diabetes mellitus. Notably, only 28.4% performed global screening, defined as screening for smoking, hypertension, dyslipidaemia, and diabetes mellitus by the same physician, and 24.4% reported calculating 10-year cardiovascular disease (CVD) risk, probably reflecting a lack of comprehensive cardiovascular risk assessment in these patients. This study also identified unmet needs for awareness of cardiovascular comorbidities in psoriasis and corresponding screening and treatment recommendations among PCPs. Of PCPs, 61.2% reported not being aware of the association between psoriasis and CVD and/or not being aware of its screening recommendations, and 67.6% did not consider psoriasis as a risk-enhancing factor when deciding on statin prescription. Thirteen dermatologists (12.6%) and 35 rheumatologists (37.2%) reported prescribing statins. Among those who do not prescribe, 49.7% would be willing to start their prescription. [ABSTRACT FROM AUTHOR]

Melanoma is considered to be the most serious and aggressive type of skin cancer, and metastasis appears to be the most important factor in its prognosis. Herein, we developed a transfer learning-based biomarker discovery model that could aid in the diagnosis and prognosis of this disease. After applying it to the ensemble machine learning model, results revealed that the genes found were consistent with those found using other methodologies previously applied to the same TCGA (The Cancer Genome Atlas) data set. Further novel biomarkers were also found. Our ensemble model achieved an AUC of 0.9861, an accuracy of 91.05, and an F1 score of 90.60 using an independent validation data set. This study was able to identify potential genes for diagnostic classification (C7 and GRIK5) and diagnostic and prognostic biomarkers (S100A7, S100A7, KRT14, KRT17, KRT6B, KRTDAP, SERPINB4, TSHR, PVRL4, WFDC5, IL20RB) in melanoma. The results show the utility of a transfer learning approach for biomarker discovery in melanoma. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy of oral colistin-neomycin in preventing multidrug-resistant Enterobacterales (MDR-E) infections in solid organ transplant (SOT) recipients. Multicentre, open-label, parallel-group, controlled trial with balanced (1:1) randomization in five transplant units. SOT recipients were screened for MDR-E intestinal colonization (extended-spectrum β-lactamase or carbapenemase producing) before transplantation and +7 and + 14 days after transplantation and assigned 1:1 to receive treatment with colistin sulfate plus neomycin sulfate for 14 days (decolonization treatment (DT) group) or no treatment (no decolonization treatment (NDT) group). The primary outcome was diagnosis of an MDR-E infection. Safety outcomes were appearance of adverse effects, mainly diarrhoea, rash, nausea and vomiting. Patients were monitored weekly until 30 days after treatment. Intention-to-treat analysis was performed. MDR-E rectal colonization was assessed in 768 SOT recipients; 105 colonized patients were included in the clinical trial, 53 receiving DT and 52 NDT. No significant decrease in the risk of infection by MDR-E was observed in the DT group (9.4%, 5/53) compared to the NDT group (13.5%, 7/52) (relative risk 0.70; 95% confidence interval 0.24–2.08; p 0.517). Four patients (5.6%), three (5.6%) in the DT group and one (1.9%) in the NDT group, developed colistin resistance. Twelve patients (22.7%) in the DT group had diarrhoea, eight related to treatment (15.0%); one patient (1.8%) developed skin rash and another (1.8%) nausea and vomiting. Two patients (3.8%) in the NDT group developed diarrhoea. DT does not reduce MDR-E infections in SOT. Colistin resistance and adverse effects such as diarrhoea are a potential issue that must be taken seriously. [ABSTRACT FROM AUTHOR]

Background: Rare diseases present a wide spectrum of clinical manifestations and severity levels and are often poorly known and underrepresented, making them difficult to classify. Diagnoses are usually coded using the International Classification of Diseases (ICD), with its different versions. In Spain, the ICD-10-ES (stem from the ICD-10-CM-Clinical Modification) is used throughout the National Healthcare System since 2016, indistinctively including rare diseases that often lack a specific code. Orphanet aims to provide high-quality resources on rare diseases. The goal was to interrelate the Orphanet classification with the ICD-10-ES in order to engage a tool to track rare diseases diagnosis and characterize the improvement space for the identification of rare diseases patients in the Spanish Healthcare System.Methods: 5775 disorder level ORPHAcodes were mapped to ICD-10-ES codes by comparing the descriptors associated in both classifications. ORPHAcodes were then clustered based on their assigned ICD-10-ES chapter and the redundancy of each individual ICD-10-ES code was calculated by counting the ORPHAcodes they mapped to. Three groups were established: Group 1 (1 ORPHAcode per ICD-10-ES), Group 2 (between 2-49 ORPHAcodes per ICD-10-ES) and Group 3 (≥ 50 ORPHAcodes per ICD-10-ES).Results: Equivalences to 1700 ICD-10-ES codes were established for 5664 ORPHAcodes. The ORPHAcodes distribution within the ICD-10-ES showed an aggregation in the "Q" (> 40%), "G" (> 14%), and "E" (12%) chapters. The availability of ICD-10-ES codes to map ORPHAcodes reached its lowest at the "G" and "Q" chapters with less than 0.2 ICD-10-ES codes available per ORPHAcode. Global ICD-10-ES codes redundancy analysis revealed that only 1055 of the equivalences pertain to group 1. Group 2 contained 3358 equivalences with 634 ICD-10-ES codes while 1322 equivalences were group 3 (11 ICD-10-ES). Within ICD-10-ES chapters, "G" and "Q" contained over 30% and 45% of their own equivalences in the highest redundancy level (group 3) respectively, but under 10% one to one equivalences each (group 1).Conclusions: ICD-10-ES codes have not enough specificity to identify rare diseases. Direct mapping between ICD and ORPHAcodes or the integration of ORPHAcodes at the healthcare system for diagnoses codification would enable better detection and epidemiological analysis of rare diseases. [ABSTRACT FROM AUTHOR]

In the article, the authors present their multicenter observational retrospective cohort study on the relationship between a schizophrenia spectrum disorder diagnosis and mortality in patients hospitalized for COVID-19. The aim is to determine the need for increased monitoring and targeted interventions of individuals with the said disorder against COVID-19. Also mentioned are the medical risk factors linked with severe COVID-19, including obesity, blood diseases and diabetes mellitus.

This article discusses a case study of a 4-year-old boy with recalcitrant granulomatous rosacea, a skin condition characterized by inflammatory papules and pustules on the face. The boy also experienced recurring oral aphthae, conjunctivitis, viral warts, and oral candidiasis. Genetic testing revealed a gain-of-function mutation in the STAT1 gene, which is associated with immunodeficiency. This case highlights the importance of considering STAT1 mutations in children with immunodeficiency and recalcitrant or extensive rosacea. [Extracted from the article]

Introduction. Renal biopsy is the principal instrument to evaluate the diagnosis and prognosis of children with kidney disease. There are relatively few studies establishing epidemiology of its findings in the pediatric population. Methods. A descriptive study was conducted to describe characteristics of pediatric patients who had undergone a renal biopsy over the last 10 years in a national reference center, trying to accomplish an etiopathogenic approach of biopsy findings. Results. 241 patients were included. Most frequent indications were nephrotic syndrome (34.1%) and systemic disease with renal involvement (30.2%). The most prevalent biopsy diagnosis was glomerulonephritis (44%) and among these patients, glomerulonephritis mediated by immune complexes was the most frequent pathogenic type (90.5%). When the biopsy was indicated for proteinuria plus hematuria and systemic disease with renal involvement, the most frequent biopsy diagnosis was glomerulonephritis (60 and 85%, respectively). For isolated hematuria, the predominant biopsy diagnosis was inherited diseases of the glomerular basement membrane (70%) and for nephrotic syndrome, podocytopathy (82%). Glomerulonephritis was more frequent in patients older than 10 yrs (65%) and the rate of postbiopsy major complications was low (1.2%). Conclusion. Immune complex glomerulonephritis was the most frequent histological finding, differing from previous reports. To our knowledge this is the first description that classifies biopsy findings according to the probable pathogenic mechanism. [ABSTRACT FROM AUTHOR]

Objectives To determine the utility of our transgluteal magnetic resonance imaging ( MRI)-guided prostate biopsy approach. Patients and Methods A total of 960 biopsy series, taken within the period of 1 year, were evaluated, including 301 MRI-guided and 659 transrectal ultrasonography ( TRUS)-guided biopsies. Results The positivity rate and proportion of high grade cancers were significantly higher in MRI-guided than in TRUS-guided biopsies. Of 301 MRI-guided biopsies, 65.4% contained cancer while 57.2% of 659 TRUS biopsies contained cancer ( P = 0.016). Gleason grade 3 + 3 = 6 disease was observed in 16.8% of 197 MRI-guided and in 36.1% of 377 TRUS-guided biopsies ( P < 0.001). There was also a markedly higher quantity of cancer tissue in MRI-guided biopsies. In all cancers, the mean cancer surface area was 64.8 ± 51.6 mm2 in MRI-guided biopsies as compared with 23.0 ± 31.4 mm2 in non- MRI-guided biopsies ( P < 0.001). With respect to the tissue quantity, superiority of MRI-guided biopsy was highest in Gleason grade 3 + 3 = 6 cancers (20.9 ± 27.9 vs 5.1 ± 10.2 mm2; P < 0.001) and in Gleason grade 3 + 4 = 7 cancers (59.7 ± 38.0 vs 17.7 ± 18.4 mm2; P < 0.001). Comparison of biopsy Gleason grades with findings in prostatectomy specimens was possible in 80 patients with MRI-guided and in 170 patients with non- MRI-guided biopsies. This comparison showed a very high but almost identical concordance of TRUS- and MRI-guided biopsies with the prostatectomy specimen findings. With both approaches, undetected high-risk cancers were present in ~10% of patients with low-risk biopsy results. A significant difference was observed, however, in the proportion of patients who had clinically insignificant cancers and who underwent surgery. The proportion of patients with Gleason grade 3 + 3 = 6 carcinoma in their prostatectomy specimen was 11.2% in the post- TRUS biopsy cohort, but only 2.5% in the post- MRI biopsy cohort ( P = 0.021). Conclusion MRI-guided transgluteal prostate biopsy has a high detection rate for high-risk carcinomas, while the risk of detecting clinically insignificant carcinomas appears to be reduced. This may by itself lead to a reduction of unnecessary prostatectomies. Overtreatment may be further avoided by better applicability of molecular testing to MRI-guided biopsies because of the excessive amount of tissue available for analysis, especially in patients with potential low-risk carcinomas. [ABSTRACT FROM AUTHOR]

The article offers information on the study of analyzing the oncological treatment of nonagenarian metastatic colorectal cancer (mCRC) patients. It mentions the aim of the study was to investigate the cancer characteristics, treatments administered and outcomes for nonagenarians and centenarians diagnosed with mCRC using our state-wide population-based mCRC registry to understand the current patterns of care and outcomes in this age subgroup of patients.

In human congenital toxoplasmosis the effects of parasite burden and pregnancy time at infection on clinical outcome are well known, but there is controversy regarding the role of Toxoplasma gondii type. Through a systematic review of the literature, we aimed to discern if T. gondii type has a role on clinical outcome in human congenital toxoplasmosis. We built up a database of congenital toxoplasmosis from reports of cases, case series and screening-based cohorts, which had information about parasite type, gestation time at maternal infection and/or clinical outcome in the product. Then, we obtained frequencies for loci used to genotype geographical origin of cases and types found. Also, odds ratios were calculated for association between time of maternal infection or parasite type on outcome. Type II parasites were the most common in Europe, Asia and Africa, while in America there were mainly atypical strains. More newborns with clinical problems were born from mothers infected during the first half of gestation than from those acquiring the parasite after week 24, regardless of parasite genotype (92.9 vs. 16.1 %, OR = 67.9, CI 25.4-181.6). Type I and atypical parasites were associated with clinical problems as opposed to types II and III, regardless of pregnancy period at infection (86.9 vs. 72.9 %, OR = 2.47, CI 1.1-5.4). A significant and remarkable tendency of type I parasites to be present during early pregnancy was also observed (94.4 vs. 5.6 %, P < 0.009). In addition to parasite burden and period of gestation, T. gondii genotype seems involved in CT clinical outcome. [ABSTRACT FROM AUTHOR]

Objective. To estimate rates of cases of respiratory symptomatic subjects and the incidence rate of pulmonary tuberculosis in two border areas of Ecuador, and contrast them with official figures. Materials and methods. Cross-sectional survey in the southeastern (SEBA), and the Andean southern Ecuadorian border areas (ASBA), which were conducted, respectively, in 1 598 and 2 419 persons aged over 15 years recruited over periods of three weeks. In identified respiratory symptomatic cases, a sputum sample was taken for smear testing. The results (odds ratios and their respective 95% confidence intervals), were compared with local and national official figures using maximum likelihood contrasts. Results. The rates of respiratory symptomatic subjects (7.7% and 5.9% in the SEBA, and ASBA, respectively) and of pulmonary tuberculosis (cumulative incidence rates of 125 and 140 per 100 000 inhabitants, in the same order) were significantly greater than the official figures (of 0.98 and 0.99% for respiratory symptomatic subjects in the SEBA and ASBA, respectively; and of 38.23 per 100 000 inhabitants for pulmonary tuberculosis in Ecuador as a whole) (p<0.001). Conclusion. It is necessary to reinforce both active case finding for respiratory symptomatic subject cases, and epidemiological surveillance of pulmonary tuberculosis in Ecuadorian border regions. [ABSTRACT FROM AUTHOR]

Objectives: As longer times from the first symptom to diagnosis and treatment of oral cancers have been linked to poorer outcomes, this study investigates the contribution of the specialist to this time (STI). Subjects and Methods: A series of 228 oral/oropharyngeal squamous cell carcinoma patients were retrospectively studied to determine the STI and its related factors. Results: Patients were mostly males (n = 170; 74.5%), (50.7% stages I‐II), mean age = 61.4 ± 12.5 years. The STI median was 6 days (X±SD:6.8 ± 5.6 days). Time first symptom to diagnosis was 64 days (X±SD:91.0 ± 84.6 days). Univariate regression unveiled a significant association between STI and TNM stage, which was confirmed by multivariate regression. Conclusions: Specialist time interval is a short time interval in oral cancer diagnosis, imposing a limited time burden in the context of the whole interval until diagnosis. However, there seems to be room for improvement and a possible target for future interventions to shorten STI particularly for patients at early stages after their disease has been disclosed. [ABSTRACT FROM AUTHOR]

Introduction: Currently, a new subclassification of the Pi-RADS 3 lesions and subgroups is being used: 3a (indolent or low-risk lesions with volume <0.5 ml) and 3b (significant or high-risk lesions with volume ≥0.5 ml). The prostate-specific antigen density (PSAd) has been identified as a diagnostic tool that helps to predict clinically significant prostate cancer (csCaP). The aim of this study is to evaluate the association of the volume of the Pi-RADS 3 lesions and the PSAd in the diagnosis of csCaP.Material and Methods: We conducted a retrospective study that included prostate biopsies performed using a transperineal approach and guided by ultrasound between 2015 and 2020. csCaP was defined as Gleason score ≥3 + 4. The population was divided into groups according to the Pi-RADS 3 subclassification and the PSAd value. We calculated sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of 3b lesions for the detection of high-grade prostate cancer, alone and combined with PSAD groups.Results: In total, 99 patients with Pi-RADS 3 lesions were included. Forty-three patients were in group 3a and 56, in 3b. Mean PSA was 7.28 ± 2.6 ng/ml. Pi-RADS 3a lesion did not present csCaP but 17.8% of Pi-RADS 3b lesion did. In group 3b with PSAd > 0.15, 62.5% presented csCaP. In those Pi-RADS 3b with PSAd ≤ 0.15, all biopsies were insignificant prostate cancer (isCaP) and 40 biopsies could have been avoided. Considering 3b as positive for csCaP detection, sensitivity was 100%, specificity 48.3%, NPV 17.8%, and PPV 100%. When adding PSAd to group 3b, sensitivity was 100%, specificity was 86.9%, NPV was 62.5%, PPV was 100%. In total, only the subgroup 3b with PSAd > 0.15 presented csCaP and 83.8% biopsies could be avoided.Conclusions: In this series, the association of the volume of PIRADS 3 lesion and the PSAd improves specificity and PPV contributing to improve the management of csCaP. [ABSTRACT FROM AUTHOR]

Lung cancer (LC) is the leading cause of cancer-related death worldwide. Although the diagnosis and treatment of non-small cell lung cancer (NSCLC), which accounts for approximately 80% of LC cases, have greatly improved in the past decade, there is still an urgent need to find more sensitive and specific screening methods. Recently, new molecular biomarkers are emerging as potential non-invasive diagnostic agents to screen NSCLC, including multiple microRNAs (miRNAs) that show an unusual expression profile. Moreover, peripheral blood mononuclear cells' (PBMCs) miRNA profile could be linked with NSCLC and used for diagnosis. We developed a molecular beacon (MB)-based miRNA detection strategy for NSCLC. Following PBMCs isolation and screening of the expression profile of a panel of miRNA by RT-qPCR, we designed a MB targeting of up-regulated miR-21-5p. This MB 21-5p was characterized by FRET-melting, CD, NMR and native PAGE, allowing the optimization of an in-situ approach involving miR-21-5p detection in PBMCs via MB. Data show the developed MB approach potential for miR-21-5p detection in PBMCs from clinical samples towards NSCLC. [ABSTRACT FROM AUTHOR]

Coxsackie eruptions concentrated in areas of atopic dermatitis, a phenomenon termed 'eczema coxsackium,' has been well described in the literature but, to our knowledge, the concentration of coxsackie viral lesions to areas of ichthyosis has not been reported. This case describes a rare presentation of coxsackie viral lesions concentrated in areas of epidermolytic ichthyosis in a 3-year-old boy. [ABSTRACT FROM AUTHOR]

The article presents a case study of 78-year old woman with atrial fibrillation. It states that the woman had multiple duodenal diverticula with bleeding inside the diverticulum based on the diagnosis. Also mentioned that Hemospray medication has been aplied to the woman to stop the gastrointestinal bleeding after the failure of several medication such as epinephrine and fibrin glue injections.

Background: Research regarding the feasibility and effects of dancing and exercise with musical support programmes on the physical fitness of adults with intellectual disability (ID) is scarce. The purpose of this study was to provide scientific evidence regarding the feasibility of a training programme consisting of dancing and exercise with music designed for adults with ID, as well as to assess its impact on their body composition and cardiovascular and muscular fitness. Methods: A total of 30 adults (mean age 36.37 ± 11.24 years) with mild (n = 13), moderate (n = 16) or severe (n = 1) ID took part in a 10‐week dancing and exercise with music programme. Recruitment and completion rate, adherence to the programme, participation and adverse effects were registered as measures of feasibility. The body mass index, cardiovascular endurance (6‐min walk test) and muscular strength (standing long jump test) of the participants were assessed in order to determine the effects of the programme on their fitness level. Results: A 92.5% recruitment rate and a 90% completion rate were achieved. Adherence to the programme stood at 76.6%, and no adverse effects were registered. The comparison between the values obtained in the initial and final evaluations indicated the existence of positive changes in all the fitness dimensions measured. Conclusion: A training programme combining dancing and exercise with music proved to be feasible when performed by adults with ID. These kind of programmes can have a positive effect on the fitness level of this specific group. [ABSTRACT FROM AUTHOR]

Early diagnosis, monitoring and treatment selection of cancer represent major challenges in medicine. The definition of the complex clinical and molecular landscape of cancer requires the combination of multiple techniques and the investigation of multiple targets. As a result, diagnosis is normally lengthy, expensive and, in many cases, cannot be performed recursively. In recent years, optical biosensors, especially those based on the unique properties of plasmonic nanostructures, have emerged as one of the most exciting tools in nanomedicine, capable of overcoming key limitations of classical techniques. In this review, we specifically focus our attention on the latest advances in optical biosensors exploiting surface-enhanced Raman scattering encoded particles for the characterization of tumor single cells (molecular biology) and tissues (immunohistochemistry and guided surgery), as well as their application in guided surgery or even in bioimaging of living organisms. [ABSTRACT FROM AUTHOR]

Changes in protein expression levels and protein structure may indicate genomic mutations and may be related to some diseases. Therefore, the precise quantification and characterization of proteins can be used for disease diagnosis. Compared with several other alternative methods, surface-enhanced Raman scattering (SERS) spectroscopy is regarded as an excellent choice for the quantification and structural characterization of proteins. Herein, we review the main advance of using plasmonic nanostructures as SERS sensing platform for this purpose. Three design approaches, including direct SERS, indirect SERS, and SERS-encoded nanoparticles, are discussed in the direction of developing new precise approaches of quantification and characterization of proteins. While this Review is focused on proteins, in order to highlight concepts of SERS-based sensors also detection of other biomolecules will be discussed [ABSTRACT FROM AUTHOR]

Early diagnosis of genetic rare diseases is an unmet need in Brazil, where an estimated 10–13 million people live with these conditions. Increased use of chromosome microarray assays, exome sequencing, and whole genome sequencing as first-tier testing techniques in suitable indications can shorten the diagnostic odyssey, eliminate unnecessary tests, procedures, and treatments, and lower healthcare expenditures. A selected panel of Brazilian experts in fields related to rare diseases was provided with a series of relevant questions to address before a multi-day conference. Within this conference, each narrative was discussed and edited through numerous rounds of discussion until agreement was achieved. The widespread adoption of exome sequencing and whole genome sequencing in Brazil is limited by various factors: cost and lack of funding, reimbursement, awareness and education, specialist shortages, and policy issues. To reduce the burden of rare diseases and increase early diagnosis, the Brazilian healthcare authorities/government must address the barriers to equitable access to early diagnostic methods for these conditions. Recommendations are provided, including broadening approved testing indications, increasing awareness and education efforts, increasing specialist training opportunities, and ensuring sufficient funding for genetic testing. [ABSTRACT FROM AUTHOR]

Background and Overview. Dens invaginatus (DI) is defined as a rare dental malformation. The inherent structural variants of this anatomic disorder make it difficult to perform conventional endodontic treatment procedures by means of a conservative access cavity. In this clinical case report, the authors describe the treatment of a type II DI by means of guided splints for cavity access. Case Description. This is a clinical report of a case of type II DI in a maxillary lateral incisor. The authors established the diagnosis by means of cone-beam computed tomography (CBCT). The authors manufactured 3 splint guides from a Digital Imaging and Communications in Medicine file and a stereolithography file obtained from a plaster model of the patient by using software for guided implant placement, for access opening, and for locating the root canals. Conclusions. CBCT is an effective method for obtaining information about the root canal system in teeth with DI. In addition, guided implant surgery software is effective for manufacturing splint guides for endodontic treatment with conservative pulp chamber access. Practical Implications. Information obtained from CBCT allows the clinician to fabricate splint guides for minimally invasive access opening in this type of case, thus reducing the loss of dental tissue. [ABSTRACT FROM AUTHOR]

Background: Lung neuroendocrine tumors account for approximately 15% of all lung cancer cases. LNET are subdivided into typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small-cell lung cancer (SCLC). The Ki-67 index has been used for decades to evaluate mitotic counts however, the role of Ki-67 as a biomarker for assessing prognosis and guiding therapy in metastatic LNET still lacks feasible clinical validation. Recent clinical trials have indicated that inhibition of CD47 with anti-CD47 antibodies exerts a promising antitumor effect against several human malignancies, including NSCLC, melanoma, and hematologic malignancies. However, the clinical relevance of CD47 expression in LNET has remained unclear.Methods: We performed a retrospective study in which we analyzed tumor biopsies from 51 patients with a confirmed diagnosis of LNET that received treatment at our hospital. Then, we analyzed if there was any correlation between CD47 expression with any clinical or pathological characteristic. We also analyzed the prognostic significance of CD47, assessed as progression-free survival and overall survival.Results: A total of 51 patients with LNET were enrolled in our study. The mean age at diagnosis was 57.6 (±11.6) years; 30 patients were women (59%). 27.5% of patients were positive for CD47 expression, and 72.5% of patients showed a CD47 expression of less than 1% and were considered as negatives. In patients with high-grade tumors (this time defined as Ki-67 > 40%), the positive expression of CD47 was strongly associated with an increased PFS. Albeit, these differences did not reach statistical significance when analyzing OS.Conclusion: Contrary to what happens in a wide range of hematologic and solid tumors, a higher expression of CD47 in patients with LNET is associated with a better progression-free survival, especially in patients with a Ki-67 ≥ 40%. This "paradox" remains to be confirmed and explained by larger studies. [ABSTRACT FROM AUTHOR]

We report a fatal case of coxsackievirus B4 chronic infection in a 30-year-old woman with a diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disorder controlled by rituximab monotherapy for 3 years. Initially presenting as self-limited meningitis, the infection remained silent for 8 months before the sudden onset of fulminant myocarditis. Analysis of the complete genome showed that the same virus was responsible for both episodes. [ABSTRACT FROM AUTHOR]

Introduction: Flow cytometry (FC) is a helpful tool for the diagnosis of myelodysplastic syndrome (MDS). Different FC score systems have been developed. The "Ogata score" is a simple diagnostic score that has been validated having a sensitivity of 69% and a specificity of 92% in low‐risk MDS. We aimed to study the feasibility and the utility of the "Ogata score" for the diagnosis of MDS among Latin America (LA) Laboratories. Methods: This is a case and control study conducted in LA institutions members of Grupo Latinoamericano de Mielodisplasia (GLAM). A total of 146 MDS patients and 57 control patients were included. "Ogata score" was calculated. Results: The sensitivity of "Ogata score" was 75.6% (95% CI, 66.8‐81.3), specificity was 91.2% (95% CI, 79.7‐96.7), PPV was 95.6% (95% CI, 88.5‐98.3), and NPV was 65.4% (95% CI, 49.1‐71.9). In low/intermediate‐1 IPSS patients group, the sensitivity was 70.1% (95% CI, 60.2‐78.2), specificity was 91.2% (CI‐95%, 79.7‐96.7), PPV was 94.2% (95% CI, 86.4‐97.8), and NPV was 62.1% (95% CI, 53.0‐78.7). In the group of patients "without MDS specific markers" (patients without ring sideroblasts, blast excess, or chromosomal abnormalities), the sensitivity was 66.7% (CI‐95%, 55.8‐76.0), specificity was 91.2% (95% CI, 79.7‐96.7), PPV was 92.3% (95% CI, 82.2‐97.1), and NPV was 63.5% (95% CI, 51.9‐73.5). Conclusions: The diagnostic power found in this study was similar to the reported by Della‐Porta et al. Also in LA, the analysis was made in modern equipment with acquisition of at least 100 000 events which permits a good reproducibility of the results. [ABSTRACT FROM AUTHOR]

Background: Those infected by human immunodeficiency virus (HIV) have a higher risk of opportunistic infections. The risk is related to the level of immunosuppression. We report a case of a young male with the unusual scenario of three opportunistic infections occurring simultaneously: Cryptococcosis, Histoplasmosis and Cryptosporidiosis. Histoplasmosis and cryptococcosis are major causes of morbimortality in immunocompromised patients due to HIV infection.Case Presentation: We report the case of a patient with HIV infection with a CD4 T lymphocyte cell (CD4) count of 2 cells/mm3, who presented with 6 months of diarrhea, non-productive dry cough, nocturnal diaphoresis, fever, weight loss, and a maculopapular rash. He had a concurrent infection with three opportunistic microorganisms: fungemia by cryptococcosis, disseminated histoplasmosis confirmed by detection of the antigen in urine and chronic diarrhea by cryptosporidiosis confirmed by direct observation in feces by modified Ziehl-Neelsen stain. The patient received antifungal treatment with a satisfactory outcome.Conclusions: There are still regions where HIV detection programs are deficient thus facilitating occurrence of HIV infection cases in advanced stages of immunosuppression. A high level of suspicion of systemic mycoses and concurrent infection by several opportunistic pathogens is required in severely immunocompromised patients. [ABSTRACT FROM AUTHOR]

Abstract Background Myeloid differentiation factor-2 (MD-2) has been shown to be an important modulator of the innate immune system, but its role in cardiac diseases is unknown. We investigated whether MD-2 plays a role as risk predictor and contributor in dilated cardiomyopathy (DCM). Methods and results We included 174 patients with reduced left ventricular (LV) ejection fraction (LVEF <45%) due to DCM. Coronary artery disease and severe valvular diseases were excluded in all patients by angiography or echocardiography. Cardiac inflammation, viral infection and MD-2 expression were analyzed from right ventricular endomyocardial biopsies. MD-2 was quantified by ELISA in serum upon first hospital admission. Myocyte contractility and inflammatory response after stimulation with recombinant MD-2 protein were analyzed in isolated rat cardiomyocytes. Median follow-up of the patients was 3.51 years (2.73; 4.48) with 34 deaths. Absolute mortality risk increases in patients displaying a MD-2 serum concentration greater than the median (302 ng/ml) was 23% (P < 0.0001). Age- and sex-adjusted Cox regression analyses demonstrated that mortality risk was highly related to MD-2 concentrations (P < 0.001), but not to age or sex. An increase of 100 ng/ml in the MD-2 level was associated with an absolute mortality risk increase of 50.4%. Receiver operating characteristic (ROC) analyses showed no difference between MD-2 and nterminal-pro brain natriuretic peptide (NT-pro-BNP), while the combination of both MD-2 and NT-pro-BNP resulted in a significantly increased capability of risk prediction when compared to NT-pro-BNP alone (P = 0.014). In-vitro, recombinant MD-2 decreases cell shortening and modulates cytokine activation in isolated cardiomyocytes. Conclusion MD-2 predicts long-term outcome in DCM patients and improves mortality risk prediction capability compared to NT-pro-BNP alone. In addition, MD-2 exerts direct negative inotropic effects on isolated cardiomyocytes in-vitro. Further randomized trials should confirm MD-2 as a diagnostic and therapeutic target. Highlights • Dilated cardiomyopathy (DCM) is the most common cause of heart transplantation. • Significant proportion of DCM affected subjects shows increased mortality. • For the first time a relation between MD-2 and clinical outcome in DCM is shown. • MD-2 as a biomarker in addition to NT-pro BNP significantly increases the prediction of mortality in DCM. • Based on MD-2, clinical trials should focus on high risk patients without cardiac recovery. [ABSTRACT FROM AUTHOR]

Background: Compression ultrasonography is the most effective diagnostic tool in the emergency department (ED) for the diagnosis of deep vein thrombosis (DVT). It has been demonstrated to be highly accurate and cost-effective.Objective: The objective of this study was to determine the accuracy of emergency physicians who performed three-point compression ultrasound (US) for suspected above-knee DVT within the context of using Wells score and D-dimer.Method: This was a prospective diagnostic test assessment of three-point ultrasound conducted in a district general hospital of patients who presented to the ED with suspected DVT of the lower limb. The accuracy of three-point ultrasound carried out by the emergency physicians was assessed by comparison of the Doppler ultrasound carried out by the Radiology Department as reference standard. The study incorporated ultrasound alongside the Wells score and D-dimer.Results: A total of 109 patients (66.1%) had a three-point compression point-of-care ultrasound in the ED and a second ultrasound performed by the Radiology Department. Bedside three-point compression ultrasound of the lower extremity performed by physicians in the ED had a sensitivity of 93.2% (95% confidence interval [CI] 83.8-97.3%) and a specificity of 90.0% (95% CI 78.6-95.7%), with an accuracy of 91.7% (95% CI 85-95.6%).Conclusions: Emergency physicians can obtain a level of competence equivalent to that of radiologists, but it requires substantial training and practice to achieve and maintain this performance. Providers should be aware of their limitations and maintain regular training with ultrasound applications. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: Minimal hepatic encephalopathy (MHE) predicts poor prognosis and could reflect an advanced liver disease. We aimed to assess whether MHE could be a surrogate marker of a further liver disease. Methods: Prospective multicenter study including 320 cirrhotic patients, followed for up to 5 years, which were classified at baseline in compensated cirrhosis without (stage 1) and with varices (stage 2), one decompensating event (stage 3), and any second decompensating event (stage 4). Cirrhosis progression was defined by a transition towards a different stage (competing events: liver transplant due to hepatocellular carcinoma and non‐liver‐related death). MHE was detected by critical flicker frequency and psychometric tests. Results: Minimal hepatic encephalopathy was diagnosed in 18.2% (57/314) of patients. Cirrhosis progression occurred in 38.1% (122/320) of patients, while liver transplant was required in 10.9% (35/320), and 19.1% (61/320) died. In competing risk regression, MHE was associated with disease progression: model 1 {subhazard ratio [sHR] 2.34 [95%confidence interval (CI) 1.58–3.46]; P = 0.0001}; model 2 [sHR 2.18 (95%CI 1.43–3.33); P = 0.0001]; model 3 [sHR 2.48 (95%CI 1.63–3.76); P = 0.0001]. The annual incidence rate of progression was higher in MHE patients: stage 1 (19.4 vs 5.6 cases per 100 person‐years); stage 2 (26.8 vs 15.6); stage 3 (45.7 vs 16.5); and stage 4 (40.7 vs 12.8). MHE showed a higher cumulative incidence of disease progression from the first year in decompensated and the third year in compensated cirrhosis. Conclusion: Minimal hepatic encephalopathy was associated with cirrhosis progression and showed a higher cumulative and annual incidence rate of disease progression. MHE could be a surrogate marker of disease progression, irrespective of cirrhosis status, identifying patients at risk of suffering a more aggressive cirrhosis form. [ABSTRACT FROM AUTHOR]

A newly proposed classification by the European Laryngological Society (ELS) of glottic lesions by narrow-band imaging (NBI) divides their vascular patterns into longitudinal and perpendicular ones. The latter are further subdivided into the wide and narrow patterns. The longitudinal, wide, and narrow patterns are characteristic of benign disease, papilloma, and malignancy, respectively. The aim of the study was to investigate the diagnostic effectiveness of the classification. Forty patients with glottic lesions underwent microlaryngoscopy. The vascular patterns of all vocal cords were defined with NBI. The affected vocal cords were histologically analysed and comprised the arm (A). Unaffected vocal cords were not histologically analysed but followed-up and comprised the arm (B) and were regarded as true negatives if no suspicious changes appeared during the follow-up. The vocal cords from the arm A were categorised into the benign and malignant group according to the histologic result. The ratio of vascular patterns was determined and the groups were statistically compared using the Chi-square test and Fisher's exact test. Perpendicular changes were observed in 36.6% (9/26) of benign diseases and in 100% (23/23) of cancer conditions ( p < 0.001). Wide perpendicular changes appeared only in papillomas (6/6) while narrow ones mostly in malignancies (23/26) and also in benign conditions (3/26) ( p < 0.001). The sensitivity, specificity, positive and negative predictive values, and accuracy were 100, 95, 88, 100 and 96%, respectively. The new ELS classification can be used effectively and safely to differentiate malignant from benign disease. [ABSTRACT FROM AUTHOR]

Early diagnosis, monitoring and treatment selection of cancer represent major challenges in medicine. The definition of the complex clinical and molecular landscape of cancer requires the combination of multiple techniques and the investigation of multiple targets. As a result, diagnosis is normally lengthy, expensive and, in many cases, cannot be performed recursively. In recent years, optical biosensors, especially those based on the unique properties of plasmonic nanostructures, have emerged as one of the most exciting tools in nanomedicine, capable of overcoming key limitations of classical techniques. In this review, we specifically focus our attention on the latest advances in optical biosensors exploiting surface-enhanced Raman scattering encoded particles for the characterization of tumor single cells (molecular biology) and tissues (immunohistochemistry and guided surgery), as well as their application in guided surgery or even in bioimaging of living organisms. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between body fat mass distribution measured by bioelectrical impedanciometry (BEI) and high-grade prostate cancer (HGPC). Methods: We prospectively analyze 323 patients who underwent prostate biopsy. BEI was performed prior to biopsy. Prostate cancer (PC) was stratified according to D'Amico classification. For univariate analysis, Student t test was done. For multivariate analysis, bivariate logistic regression was performed using PSA, body mass index (BMI), percentage central body fat, percentage total body fat, and visceral fat as explicative variables for the diagnosis of HGPC. Results: PC was found in 134 patients. Thirty seven (27.2%) were HGPC. This group had higher age, PSA, and percentage central body fat (p = 0.001, p = 0.001, p = 0.04). BMI showed no association with HRPC. Age, PSA, and percentage central body fat (OR 1,123, 95% CI 1,022-1,233, p = 0.001) were independent risk factors. Conclusions: Central body fat measured by BEI could explain the association between obesity and HGPC better than BMI suggesting the use of this technique to study body fat distribution. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the diagnostic performance of gray scale transrectal ultrasound-B-mode US (BMUS), power Doppler (PDUS), and sonographic contrast (CEUS) in early imaging-based diagnosis of localized prostate cancer (PCa) and to compare the diagnostic profitability of randomized biopsy (RB), US-targeted prostate biopsy by means of PDUS and CEUS.Material and Methods: A single-center, prospective, transversal, epidemiological study was conducted from January 2010 to January 2014. We consecutively included patients who an imaging study of the prostate with BMUS, PDUS, and CEUS was performed, followed by prostate biopsy due to clinical suspicion of prostate cancer (PSA 4-20ng/mL and/or rectal exam suggestive of malignancy). The diagnostic performance of BMUS, PDUS, and CEUS was determined by calculating the Sensitivity (S), Specificity (Sp), Predictive values (PV), and diagnostic odds ratio (OR) of the diagnosis tests and, for these variables, in the population general and based on their clinical stage according to rectal exam (cT1 and cT2). PCa detection rates determined by means of a randomized 10-core biopsy scheme were compared with detection rates of CEUS-targeted (SonoVue) 2-core biopsies.Results: Of the initial 984 patients, US contrast SonoVue was administered to 179 (18.2%). The PCa detection rate by organ of BMUS/PDUS in the global population was 38% versus 43% in the subpopulation with CEUS. The mean age of the patients was 64.3±7.01years (95% CI, 63.75-64.70); mean total PSA was 8.9±3.61ng/mL (95% CI, 8.67-9.13) and the mean prostate volume was 56.2±29cc (95% CI, 54.2-58.1). The detection rate by organ of targeted biopsy with BMUS, PDUS, and CEUS were as follows: Global population (10.6, 8.2, 24.5%), stage cT1 (5.6, 4.2, 16.4%), and stage cT2 (32.4, 22.3, 43.5%). Comparing the detection rates of the CEUS-targeted biopsy and randomized biopsy, the following results were obtained: Global population (24.5% vs. 41.8%), stage cT1 (16% vs. 35%), and stage cT2 (43.5% vs. 66.6%), with a p value<0.05. Following the "core-by-core" analysis, the detection rates by core of CEUS-targeted biopsy versus randomized biopsy were: Global population (16% vs. 13%), stage cT1 (30.3% vs. 28%), and stage cT2 (48% vs. 37%), with a p value>0.05. The NNT for CEUS-targeted biopsy was 83.3.Conclusions: The low sensitivity, specificity, positive predictive and negative predictive values of gray scale-B-mode, PDUS and CEUS represent scant diagnostic performance of these variables in prostate cancer detection. Prostate cancer detection rates yielded by randomized biopsy were superior than the detection rate of targeted biopsy using B-mode, PDUS and CEUS; as a result, randomized biopsy versus CEUS-targeted biopsies cannot be excluded from biopsy strategy plans for the diagnosis of prostate cancer. [ABSTRACT FROM AUTHOR]

Human respiratory syncytial virus (HRSV) is a major cause of acute lower respiratory tract infections in infants and children worldwide. We performed molecular analysis of HRSV among infants and children with clinical diagnosis of severe pneumonia in four study sites in the Philippines, including Biliran, Leyte, Palawan, and Metro Manila from June 2012 to July 2013. Nasopharyngeal swabs were collected and screened for HRSV using real-time polymerase chain reaction (PCR). Positive samples were tested by conventional PCR and sequenced for the second hypervariable region (2nd HVR) of the G gene. Among a total of 1,505 samples, 423 samples were positive for HRSV (28.1%), of which 305 (72.1%) and 118 (27.9%) were identified as HRSV-A and HRSV-B, respectively. Two genotypes of HRSV-A, NA1 and ON1, were identified during the study period. The novel ON1 genotype with a 72-nucleotide duplication in 2nd HVR of the G gene increased rapidly and finally became the predominant genotype in 2013 with an evolutionary rate higher than the NA1 genotype. Moreover, in the ON1 genotype, we found positive selection at amino acid position 274 (p<0.05) and massive O- and N-glycosylation in the 2nd HVR of the G gene. Among HRSV-B, BA9 was the predominant genotype circulating in the Philippines. However, two sporadic cases of GB2 genotype were found, which might share a common ancestor with other Asian strains. These findings suggest that HRSV is an important cause of severe acute respiratory infection among children in the Philippines and revealed the emergence and subsequent predominance of the ON1 genotype and the sporadic detection of the GB2 genotype. Both genotypes were detected for the first time in the Philippines. [ABSTRACT FROM AUTHOR]

Unexpected acute respiratory failure after anesthesia is a diagnostic challenge: residual neuromuscular blockade, bronchial hyperresponsiveness, laryngospasm, atelectasis, aspiration pneumonitis, and other more uncommon causes should be taken into account at diagnosis. Lung ultrasound and echocardiography are diagnostic tools that would provide the differential diagnosis. We report a suspected case of a transfusion related acute lung injury (TRALI) following administration of platelets. The usefulness of lung and cardiac ultrasound is discussed to facilitate the challenging diagnosis of the acute early postoperative respiratory failure. [ABSTRACT FROM AUTHOR]

Since its 2013 emergence in the Americas, Chikungunya virus (CHIKV) has posed a serious threat to public health. Early and accurate diagnosis of the disease, though currently lacking in clinics, is integral to enable timely care and epidemiological response. We developed a dual detection system: a CHIKV antigen E1/E2-based enzyme-linked immunosorbent assay (ELISA) and a lateral flow test using high-affinity anti-CHIKV antibodies. The ELISA was validated with 100 PCR-tested acute Chikungunya fever samples from Honduras. The assay had an overall sensitivity and specificity of 51% and 96.67%, respectively, with accuracy reaching 95.45% sensitivity and 92.03% specificity at a cycle threshold (Ct) cutoff of 22. As the Ct value decreased from 35 to 22, the ELISA sensitivity increased. We then developed and validated two lateral flow tests using independent antibody pairs. The sensitivity and specificity reached 100% for both lateral flow tests using 39 samples from Colombia and Honduras at Ct cutoffs of 20 and 27, respectively. For both lateral flow tests, sensitivity decreased as the Ct increased after 27. Because CHIKV E1/E2 are exposed in the virion surfaces in serum during the acute infection phase, these sensitive and specific assays demonstrate opportunities for early detection of this emerging human pathogen. [ABSTRACT FROM AUTHOR]