Diagnostics

Background: We aimed to measure and correlate inner retinal layer (IRL) thickness and macular sensitivity by optical coherence tomography (OCT) and by microperimetry, respectively, in type 1 diabetes mellitus patients (DM1) without diabetic retinopathy (DR). Methods: Fifty-one DM1 patients and 81 age-matched healthy subjects underwent measurement of the axial length (AL), retinal thickness in the macular ETDRS areas by swept source (SS)-OCT and macular sensitivity by microperimeter. Results: The total retinal and IRL thicknesses were thicker in the DM1 group (p < 0.05) in practically all ETDRS areas, and they had a generalized decrease in sensitivity (p < 0.05) in 9 areas between both groups. There was a significant negative correlation between retinal sensitivity and age in all areas and in visual acuity (VA) in 5 out of the 9 areas for DM1 patients. Only a mild negative correlation was observed between retinal sensitivity in the 5° nasal inner (5NI) area and in IRL thickness in the temporal inner (TI) area (−0.309 with p = 0.029) in the DM1 group. Conclusion: Aging and disease evolution in DM1 patients without DR signs generate a decrease in retinal sensitivity. There was a direct relationship between retinal sensitivity and macular thickness in the DM1 group. Full article

To date, there has been no reliable test to identify unfavorable course of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), especially in aspirin intolerant patients. The research aimed to analyze the expression of transcript variants of PTGS1 and PTGS2 genes in the pathobiology of the disease. The study was performed on 409 adult patients: 206 CRSwNP patients including 44 (21.36%) aspirin intolerant patients and 203 healthy volunteers in the control group. Transcript variants of the PTGS1 and PTGS2 genes named as follows: COX1.1 for NM_000962, COX1.2 for NM_080591, COX1.3 for NM_001271165.1, COX1.4 for NM_001271368.1, COX1.5 for NM_001271166.1, COX2.1 for NM_000963.3, COX2.2 for AY_151286 and COX2.3 for BQ_722004 were confirmed using direct sequencing and quantified using targeted qPCR. The coexistence of all examined transcript variants in the study and the control group and significant differences between both were found. In aspirin sensitive patients, the levels of COX1.2, COX1.3, COX1.4 and COX1.5 isoforms were higher compared to aspirin-tolerant patients. The severity of symptoms was bigger in patients with higher expressions of variants: COX1.1 (R with dCt = −0.134; p = 0.0490), COX1.3 (R = −0.1429; p = 0.0400) and COX1.5 (Rs = −0.1499; p = 0.032). The expression of COX1.1 (Rs = −0.098; p = 0.049) and COX1.5 (Rs = −0.141; p = 0.043) isoforms increased with polyposis advancement in endoscopy. With the CT extent of sinuses opacification, COX1.1 isoform also significantly increased (Rs = −0.163; p = 0.020). The isoforms COX1.3, COX1.4, COX1.5 and COX2.1 may promote milder CRSwNP course. On the contrary, the variants COX1.1, COX1.2 and COX2.2 may be involved in a more aggressive disease. Full article

Gastric cancer preoperative staging is of outmost importance to assure proper management of the disease. Providing a relevant clinical stage relies on different imaging methods such as computed tomography (CT) or endoscopic ultrasound (EUS). We aimed to perform a network meta-analysis for gastric cancer clinical stage diagnostic tests, thus comparing the diagnostic accuracy of EUS vs. multidetector CT (MDCT) and EUS vs. EUS + MDCT. We plotted study estimates of pooled sensitivity and specificity on forest plots and summary receiver operating characteristic space to explore between-study variation in the performance of EUS, MDCT and EUS + MDCT for T1–T4, N0–N3, M0–M1 when data were available. Exploratory analyses were undertaken in RevMan 5. We included twelve studies with 2047 patients. Our results suggest that EUS was superior to MDCT in preoperative T1 and N staging. MDCT is more specific for the M stage but no significant difference in sensitivity was obtained. When comparing EUS vs. EUS + MDCT for T1 both sensitivity and specificity were not relevant. No significant differences were observed in T2–T4 stages. Even though EUS helped differentiate between the presence of invaded nodules, N stages should be carefully assessed by both methods since there is not sufficient data. Full article

Background: The aim of the study was to assess soluble ST2 (sST2) concentration and its dynamic changes in the periprocedural period in patients with chronic thromboembolic pulmonary hypertension (CTEPH) treated with balloon pulmonary angioplasty (BPA). Methods: We prospectively analyzed 57 procedures of BPA performed in 37 patients with CTEPH. Biomarkers, such as N-terminal pro B-type natriuretic peptide (NT-proBNP), troponin T (TnT), and sST2 were assessed at four time points: Before the BPA procedure, 24 h and 48 h after the procedure, and at the discharge from hospital. Each postprocedural period was assessed for complications. Results: Before the BPA procedure, median sST2 concentration was 26.56 ng/mL (IQR: 16.66–40.83 ng/mL). sST2 concentration was significantly higher 24 h and 48 h after the BPA compared to the baseline measurements (33.31 ng/mL (IQR: 20.81–62.56), p = 0.000 and 27.45 ng/mL (IQR: 17.66–54.45), p = 0.028, respectively). sST2 level 24 h after the BPA procedure was significantly higher in the group with complications compared to the group without complications in the postprocedural period (97.66 ng/mL (IQR: 53.07–126.18) vs. 26.86 ng/mL (IQR: 19.10–40.12), p = 0.000). Conclusions: sST2 concentration in patients with CTEPH treated with BPA changes significantly in the postprocedural period and is significantly higher in the group with complications in postprocedural period. Full article

Access to imaging is limited for diagnosing nonalcoholic fatty liver disease (NAFLD) in general populations. This study evaluated the diagnostic performance of noninvasive and nonimaging indexes to predict NAFLD in the general Japanese population. Health checkup examinees without hepatitis virus infection or habitual alcohol drinking were included. Fatty liver was diagnosed by ultrasonography. The hepatic steatosis index (HSI), Zhejiang University (ZJU) index, and fatty liver index (FLI) were determined, and risk of advanced liver fibrosis was evaluated by the fibrosis-4 index. NAFLD was diagnosed in 1935 (28.0%) of the 6927 subjects. The area under the receiver operating characteristic (AUROC) curve of the HSI, ZJU index, and FLI was 0.874, 0.886, and 0.884, respectively. The AUROC of the ZJU index (p < 0.001) and FLI (p = 0.002) was significantly greater than that for the HSI. In subjects with a high risk of advanced fibrosis, the sensitivity of the HSI, ZJU index, and FLI were 88.8%, 94.4%, and 83.3% with a low cut-off value and the specificity was 98.5%, 100%, and 100% with a high cut-off value. In conclusion, all indexes were useful to diagnose NAFLD in the general Japanese population and in subjects with potentially advanced liver fibrosis. Full article

Background and study aim: Transjugular liver biopsy (TJLB) can be used in patients who are ineligible for percutaneous liver biopsy (PLB) with acute and chronic hepatic disease. This study aimed to evaluate the usefulness and safety of TJLB in patients who were not indicated for PLB. Methods: Between July 2014 and February 2019, a total of 134 patients underwent liver biopsies at our institution. Among these, PLB was performed in 110 patients and TJLB in 24 patients. A retrospective comparison of clinical results in these patients was then performed. The primary endpoints of this study were the utility and safety of TJLB in patients who were not indicated for PLB. Results: The procedural success rate was 100% in both groups. The clinical response rate and the effective tissue sampling rate were 100% in the TJLB group and 97% in the PLB group (p = 0.55). There was no difference in the number of portal fields examined retrospectively between the two groups. No serious adverse events were observed in either group. Conclusions: It is suggested that TJLB is useful because it can be safely performed in patients with poor general condition who are not indicated for PLB. Full article

Myocardial injury is a common complication of the COVID-19 illness and is associated with a worsened prognosis. Systemic hyperinflammation seen in the advanced stage of COVID-19 likely contributes to myocardial injury. Cardiac magnetic resonance imaging (CMR) is the preferred imaging modality for non-invasive evaluation in acute myocarditis, enabling risk stratification and prognostication. Modified scanning protocols in the pandemic setting reduce risk of exposure while providing critical data regarding cardiac tissue inflammation and fibrosis, chamber remodeling, and contractile function. The growing use of CMR in clinical practice to assess myocardial injury will improve understanding of the acute and chronic sequelae of myocardial inflammation from various pathological etiologies. Full article

An 82-year-old man suffering from prostate cancer that was scheduled for a radioreceptor-ligand therapy (RLT) presented with jaundice to our service. An abdominal ultrasound (US) revealed obstructive extrahepatic cholestasis due to a solid lesion located in the uncinate process of the pancreas. The Prostate Specific Membrane Antigen (PSMA) PET/CT prior to RLT showed multilocular PSMA positive tumor lesions in the lymph nodes, the lung and the pancreas. On request of the cancer board, an Endoscopic Ultrasound (EUS)-guided Fine-Needle Aspiration (FNA) of the pancreatic mass was performed revealing invasive pancreatic ductal adenocarcinoma incompatible with a prostate cancer metastasis leading to the diagnosis of a PSMA positive pancreatic ductal adenocarcinoma. Full article

Information on outcomes of COVID-19 in pulmonary arterial hypertension (PAH) patients is limited to a few case series and surveys. Here, we describe our experience at a large Pulmonary Hypertension Center in New York City at the height of the pandemic. We performed a retrospective chart review of eleven consecutive PAH patients who were diagnosed with SARS-CoV-2 infection. We analyzed demographics, PAH severity, risk factors for COVID-19, and COVID-19 severity and outcomes. We found in our sample that 63.6% of patients required intensive care, and there was a 45.45% overall mortality. Most patients had a known COVID-19 contact and mean duration of symptoms prior to presentation was 12 days. Only 4/11 (36%) patients presented to a center with pulmonary hypertension expertise, all of whom survived. Most patients had at least moderate pulmonary hypertension with an average REVEAL score of 7.81 despite double or triple PAH therapy. Our cases series underscores the gravity of SARS-CoV-2 infection in patients with PAH. It also suggests possible interventions to prevent unfavorable outcomes such as preserving social distancing, PAH management optimization, and early and preferential presentation to a center with specialized expertise in PAH. Full article

Balance problems are one of the most frequent symptoms in patients with Fibromyalgia Syndrome (FMS). However, the extent and nature of this balance disorder are not known. The objective of this work was to determine the best evidence for the alteration of postural balance in patients with FMS and analyze differences with healthy controls. To meet this objective, a systematic review with meta-analysis was performed. A bibliographical search was carried out in PubMed Medline, Scopus, Web of Science, CINAHL and SciELO. Observational studies that assessed postural balance in patients with FMS compared to healthy subjects in baseline conditions, were selected. In a random-effect model, the pooled effect was calculated with the Standardized Mean Difference (SMD) and its 95% confidence interval (CI). Nineteen studies reporting data of 2347 participants (95% female) were included. FMS patients showed poor balance with a large effect on static (SMD = 1.578; 95% CI = 1.164, 1.992), dynamic (SMD = 0.946; 95% CI = 0.598, 1.294), functional balance (SMD = 1.138; 95% CI = 0.689, 1.588) and on balance confidence (SMD = 1.194; 95% CI = 0.914, 1.473). Analysis of the Sensory Organization Test showed large alteration of vestibular (SMD = 1.631; 95% CI = 0.467, 2.795) and visual scores (SMD = 1.317; 95% CI = 0.153, 2.481) compared to healthy controls. Patients with FMS showed worse scores for different measures of postural balance compared to healthy controls. Concretely, FMS patients appear to have poor vestibular and visual scores with a possible somatosensory dependence. Full article

Neurogenic thoracic outlet syndrome (NTOS) is the most frequent form of TOS. It may affect both sides, but specific complementary exams are lacking. We aimed to evaluate duplex scanning results in a group of patients with unilateral or bilateral NTOS and no clinical vascular signs, referred for rehabilitation. We performed a retrospective observational study in patients with unilateral or bilateral NTOS and no vascular symptoms. Subclavian vessels were assessed by duplex scanning. Compressions were considered in case of >50% of increased or decreased blood flow. A total of 101 patients met NTOS criteria; mean age was 40 +/− 10.2; 79.2% women. Seventy patients had a unilateral NTOS and 31 a bilateral form. Duplex scanning showed that 56.4% of the patients had vessels compression, 55.7% in the unilateral group and 58.1% in the bilateral (p = 0.81). In unilateral NTOS, 21 (30%) patients had bilateral vascular compression, 17 (24.3%) had ipsilateral compression and 1 (1.4%) had contralateral compression. In bilateral NTOS, 15 (48.4%) had bilateral compression and 3 (9.7%) compression on only one side. We found a significant difference of the rate of vascular compressions between symptomatic and non-symptomatic upper-limbs, 54.5% vs. 32.9%, respectively, (p = 0.002) and a significant association between symptomatic upper-limbs and vascular compression (OR = 2.45 [95%IC: 1.33–4.49]; p = 0.002). The sensitivity and the specificity of the duplex scanning were 54.5% and 67%, respectively. The ROC curve area was of 0.608 [95%IC: 0.527–0.690]. Despite a highly significant association between symptomatic upper-limbs and vascular compression, duplex scanning did not help make the diagnosis of NTOS. Full article

Kirsten rat sarcoma viral oncogene (KRAS) is the isoform most frequently mutated in human tumors. Testing for activating KRAS mutations has important implications for diagnosis and the personalized medicine of cancers. The current techniques for detecting KRAS mutations have moderate sensitivity. The emerging clustered regularly interspaced short palindromic repeats (CRISPR) system shows great promise in the detection of nucleic acids and is revolutionizing medical diagnostics. This study aimed to develop CRISPR–Cas12a as a sensitive test to detect KRAS mutations. Serially diluted DNA samples containing KRAS mutations are subjected to CRISPR–Cas12a and polymerase chain reaction (PCR). CRISPR–Cas12a and PCR can specifically detect 0.01% and 0.1% mutant KRAS DNA in the presence of wild-type KRAS DNA, respectively. Twenty pairs of lung tumor and noncancerous lung tissues are tested by CRISPR–Cas12a, PCR, and direct sequencing. CRISPR–Cas12a could identify the G12C mutation in five of 20 tumor tissues, while both PCR and direct sequencing discovered the KRAS mutation in three of the five tumor tissues. Furthermore, the results of CRISPR–Cas12a for testing the mutation could be directly and immediately visualized by a UV light illuminator. Altogether, CRISPR–Cas12a has a higher sensitivity for the detection of KRAS mutations compared with PCR and sequencing analysis, and thus has diagnostic and therapeutic implications. Nevertheless, the technique needs to be validated for its clinical significance in a large and prospective study. Full article

The new coronavirus that was first identified in December 2019 in Wuhan China, now called SARS-CoV-2, which causes the disease called COVID-19, has spread from China to the entire world in a few months. Due to its contagious potential (R0: 5.7) and because there is still no effective treatment to stop the infection, and a vaccine for prevention it is not yet available to the general population, COVID-19 is currently considered a global health problem. The need to implement sensitive methods for the identification of individuals with COVID-19 has led to the development of different molecular and immunological tests. The importance of a timely and accurate diagnosis is essential to determine the course of the pandemic. The interpretation of the results obtained by each test as well as the factors that affect these results have not been fully described. In this review, we describe and analyze the different SARS-CoV-2 detection methods that have been performed in Mexico and are available worldwide, outlining their strengths and weaknesses. Further, a broader perspective of the correct use and interpretation of the results obtained with these diagnostic tools is proposed to improve the containment strategy and identify the true impact of the pandemic. Full article

Depression is apparently the most common psychiatric disease among the mood disorders affecting about 10% of the adult population. The etiology and pathogenesis of depression are still poorly understood. Hence, as for most human diseases, animal models can help us understand the pathogenesis of depression and, more importantly, may facilitate the search for therapy. In this review we first describe the more common tests used for the evaluation of depressive-like symptoms in rodents. Then we describe different models of depression and discuss their strengths and weaknesses. These models can be divided into several categories: genetic models, models induced by mental acute and chronic stressful situations caused by environmental manipulations (i.e., learned helplessness in rats/mice), models induced by changes in brain neuro-transmitters or by specific brain injuries and models induced by pharmacological tools. In spite of the fact that none of the models completely resembles human depression, most animal models are relevant since they mimic many of the features observed in the human situation and may serve as a powerful tool for the study of the etiology, pathogenesis and treatment of depression, especially since only few patients respond to acute treatment. Relevance increases by the fact that human depression also has different facets and many possible etiologies and therapies. Full article

Liver tumors are common and may be unamenable to surgery or ablative treatments. Consequently, other treatments have been devised. To assess the safety and efficacy of transarterial radioembolization (TARE) with Yttrium-90 for hepatocellular carcinoma (HCC), liver-dominant hepatic colorectal cancer metastases (mCRC), and cholangiocarcinoma (CCA), performed according to current recommendations, we conducted a single-center retrospective study in 70 patients treated with TARE (HCC, n = 44; mCRC, n = 20; CCA, n = 6). Safety and toxicity were assessed using the National Cancer Institute Common Terminology Criteria. Treatment response was evaluated every 3 months on imaging studies using Response Evaluation Criteria in Solid Tumors (RECIST) or mRECIST criteria. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. The median delivered dose was 1.6 GBq, with SIR-Spheres^® or TheraSphere^® microspheres. TARE-related grade 3 adverse events affected 17.1% of patients. Median follow-up was 32.1 months. Median progression-free survival was 5.6 months and median overall time from TARE to death was 16.1 months and was significantly shorter in men. Progression-free survival was significantly longer in women (HR, 0.49; 95%CI, 0.26–0.90; p = 0.031). Risk of death or progression increased with the number of systemic chemotherapy lines. TARE can be safe and effective in patients with intermediate- or advanced-stage HCC, CCA, or mCRC refractory or intolerant to appropriate treatments. Full article

Chronothanatology has always been a challenge in forensic sciences. Therefore, the importance of a multidisciplinary approach for the characterization of matrices (organs, tissues, or fluids) that respond linearly to the postmortem interval (PMI) is emerging increasingly. The vitreous humor is particularly suitable for studies aimed at assessing time-related modifications because it is topographically isolated and well-protected. In this work, a novel approach based on thermogravimetry and chemometrics was used to estimate the time since death in the vitreous humor and to collect a databank of samples derived from postmortem examinations after medico–legal evaluation. In this study, contaminated and uncontaminated specimens with tissue fragments were included in order to develop a classification model to predict time of death based on partial least squares discriminant analysis (PLS-DA) that was as robust as possible. Results demonstrate the possibility to correctly predict the PMI even in contaminated samples, with an accuracy not lower than 70%. In addition, the correlation coefficient of the measured versus predicted outcomes was found to be 0.9978, confirming the ability of the model to extend its feasibility even to such situations involving contaminated vitreous humor. Full article

Complete removal of malignant skin lesions with minimal impact on the aesthetic and functional aspects is the ideal of every dermatologic surgeon. Incomplete surgical excisions and tumor recurrences of basal cell carcinomas (BCC) commonly occur due to the subclinical extension of tumor lateral margins. Presently, the lateral excision margins for BCC cannot be objectively assessed preoperatively, dermoscopy proving to be relatively inefficient in this respect. The question is whether BCC lateral excision margins can be precisely determined preoperatively through the use of complementary non-invasive imaging techniques such as dermoscopy and reflectance confocal microscopy (RCM), thus permitting the complete removal of the lesion in a single stage, estimation of the post-excisional defect, and planning an appropriate reconstruction, especially in medical centers where Mohs micrographic surgery is not available. We present the results of a prospective, histopathologically controlled study designed to determine the feasibility of preoperative, non-invasive, in vivo evaluation of the lateral excision margins for primary basal cell carcinoma, through dermoscopy and RCM. Full article

Introduction: F18-FDG PET/CT is the most important hybrid imaging used in the diagnostic, staging, follow-up, and treatment evaluation response in cancer patients. However, it is well-known that in breast cancer the use of F18-FDG is not included in the first line protocol of initial diagnostic, both in female and male breast cancer patients. F18-FDG PET/CT is a valuable tool to provide information on extra-axillary lymph node involvement, distant metastases, and other occult primary cancers. This study assesses F18-FDG PET/CT systemic staging in male patients with diagnosed breast cancer and determines detection rates for unsuspected distant metastases and synchronous malignancies. Methods: We analyzed a number of 170 male patients with breast cancer, seen between 2000–2020, in a tertiary center. From this group, between 2013–2020 a number of 23 patients underwent F18-FDG PET/CT. Rates of upstaging were determined for each case and the detection of other primary malignancies was analyzed. Results: Median age of male breast cancer group was 61.3 y (range, 34–85 y), most had intraductal carcinoma (82.4%) and unsuspected distant metastases, which increased patient stage to IV, observed in 27%. In 4 out 23 patients (17.4%), F18-FDG PET/CT identified synchronous cancers (2 prostate cancers, 1 thyroid and 1 colon cancer). Conclusion: F18-FDG PET/CT is a valuable tool to provide information on extra-axillary lymph node involvement, distant metastases, and other occult primary cancers. Baseline F18-FDG PET/CT has a substantial impact on the initial staging and on clinical management in male breast patients and should be considered for use in newly diagnosed patients. Full article

To evaluate the effect of radiation dose reduction on image quality and diagnostic confidence in contrast-enhanced whole-body computed tomography (WBCT) staging. We randomly selected March 2016 for retrospective inclusion of 18 consecutive patients (14 female, 60 ± 15 years) with clinically indicated WBCT staging on the same 3rd generation dual-source CT. Using low-dose simulations, we created data sets with 100, 80, 60, 40, and 20% of the original radiation dose. Each set was reconstructed using filtered back projection (FBP) and Advanced Modeled Iterative Reconstruction (ADMIRE^®, Siemens Healthineers, Forchheim, Germany) strength 1–5, resulting in 540 datasets total. ADMIRE 2 was the reference standard for intraindividual comparison. The effective radiation dose was calculated using commercially available software. For comparison of objective image quality, noise assessments of subcutaneous adipose tissue regions were performed automatically using the software. Three radiologists blinded to the study evaluated image quality and diagnostic confidence independently on an equidistant 5-point Likert scale (1 = poor to 5 = excellent). At 100%, the effective radiation dose in our population was 13.3 ± 9.1 mSv. At 20% radiation dose, it was possible to obtain comparably low noise levels when using ADMIRE 5 (p = 1.000, r = 0.29). We identified ADMIRE 3 at 40% radiation dose (5.3 ± 3.6 mSv) as the lowest achievable radiation dose with image quality and diagnostic confidence equal to our reference standard (p = 1.000, r > 0.4). The inter-rater agreement for this result was almost perfect (ICC ≥ 0.958, 95% CI 0.909–0.983). On a 3rd generation scanner, it is feasible to maintain good subjective image quality, diagnostic confidence, and image noise in single-energy WBCT staging at dose levels as low as 40% of the original dose (5.3 ± 3.6 mSv), when using ADMIRE 3. Full article