Diagnostic accuracy of the Clear Cell Likelihood Score and selected MRI parameters in the characterization of indeterminate renal masses - a single-institution study.

PURPOSE: We aimed to assess the diagnostic accuracy of the clear cell likelihood score (ccLS) and value of other selected magnetic resonance imaging (MRI) features in the characterization of indeterminate small renal masses (SRMs). METHODS: Fifty patients with indeterminate SRMs discovered on MRI between 2012 and 2023 were included. The ccLS for the characterization of clear cell renal cell carcinoma (ccRCC) was calculated and compared to the final diagnosis (ccRCC vs. 'all other' masses). RESULTS: The ccLS = 5 had a satisfactory accuracy of 64.0% and a very high specificity of 96.3%; however, its sensitivity of 26.1% was relatively low. Receiver operating curve (ROC) analysis revealed that from the selected MRI features, only T1 ratio and arterial to delayed enhancement (ADER) were good discriminators between ccRCC and other types of renal masses (area under curve, AUC = 0.707, p = 0.01; AUC = 0.673, p = 0.03; respectively). The cut-off points determined in ROC analysis using the Youden index were 0.73 (p = 0.01) for T1 ratio and 0.99 for ADER (p = 0.03). The logistic regression model demonstrated that ccLS = 5 and T1 ratio (OR = 15.5 [1.1-218.72], p = 0.04; OR = 0.002 [0.00-0.81], p = 0.04) were significant predictors of ccRCC. CONCLUSIONS: The ccLS algorithm offers an encouraging method for the standardization of imaging protocols to aid in the diagnosis and management of SRMs in daily clinical practice by enhancing detectability of ccRCC and reducing the number of unnecessary invasive procedures for benign or indolent lesions. However, its diagnostic performance needs multi-center large cohort studies to validate it before it can be incorporated as a diagnostic algorithm and will guide future iterations of clinical guidelines. The retrospective nature of our study and small patient population confined to a single clinical center may impact the generalizability of the results; thus, future studies are required to define whether employment of the T1 ratio or ADER parameter may strengthen the diagnostic accuracy of ccRCC diagnosis.

NMR-Based Metabolomics of Blood Serum in Predicting Response to Induction Chemotherapy in Head and Neck Cancer-A Preliminary Approach.

The role of induction chemotherapy (iCHT) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is still to be established due to high toxicity and variable response rates. The aim of this retrospective study is to use NMR-based serum metabolomics to predict the response rates to iCHT from the pretreatment samples. The studied group consisted of 46 LA-HNSCC patients treated with iCHT. The response to the treatment was evaluated by the clinical, fiberoptic, and radiological examinations made before and after iCHT. The proton nuclear magnetic resonance (1H NMR) serum spectra of the samples collected before iCHT were acquired with a 400 MHz spectrometer and were analyzed using multivariate and univariate statistical methods. A significant multivariate model was obtained only for the male patients. The treatment-responsive men with >75% primary tumor regression after iCHT showed pretreatment elevated levels of isoleucine, alanine, glycine, tyrosine, N-acetylcysteine, and the lipid compounds, as well as decreased levels of acetate, glutamate, formate, and ketone bodies compared to those who did not respond (regression of the primary tumor <75%). The results indicate that the nutritional status, capacity of the immune system, and the efficiency of metabolism related to protein synthesis may be prognostic factors for the response to induction chemotherapy in male HNSCC patients. However, larger studies are required that would validate the findings and could contribute to the development of more personalized treatment protocols for HNSCC patients.

Malposition of Central Venous Catheter into Coronary Sinus throughout the Persistent Left Superior Vena Cava and Other Complications Related to Catheterization.

This case concentrates on the persistent left superior vena cava (PLSVC), a rare vascular anomaly which contributes to central venous catheter (CVC) misplacement. A 72-year-old woman with renal insufficiency presented to the hospital with recurrent bleeding from her permanent CVC device placed in the right common jugular vein. An initial attempt to replace the device was unsuccessful, necessitating the placement of a secondary catheter in the left jugular vein. Shortly after the procedure, the patient developed swelling of the face and neck. Further diagnostic imaging, including a chest radiograph and computed tomography (CT), revealed CVC misplacement in the PLSVC and coronary sinus, thrombosis of the common jugular vein, and a posterior mediastinal hematoma. Conservative therapy of the mediastinal hematoma was implemented and proved effective in this case. A temporary CVC was inserted into the left femoral vein. Two months later, the catheter underwent further dysfunction and a decision was made to place a long-term permanent CVC via the right femoral vein. The patient is currently awaiting an arteriovenous fistula for dialysis use. This case emphasizes the importance of radiological techniques for CVC procedural placement, as well as the detection of congenital abnormalities. Providers regularly placing CVCs should have an in-depth knowledge of the possible complications and potential anatomical variations, especially as seen in high-risk patients.

Microvascular angina (Cardiac Syndrome X) from a historical overview, epidemiology, pathophysiology to treatment recommendations - a minireview.

Microvascular angina (MVA) is a condition characterized by the presence of angina-like chest pain, a positive response to exercise stress tests, and no significant stenosis of coronary arteries in coronary angiography, with absence of any other specific cardiac diseases. The etiology of this syndrome is still not known and it is probably multifactorial. Coronary microvascular dysfunction is proposed as the main pathophysiological mechanism in the development of MVA. Altered somatic and visceral pain perception and autonomic imbalance, in addition to myocardial ischemia, has been observed in subjects with MVA, involving dynamic variations in the vasomotor tone of coronary microcirculation with consequent transient ischemic episodes. Other theories suggest that MVA may be a result of a chronic inflammatory state in the body that can negatively influence the endothelium or a local imbalance of factors regulating its function. This article presents the latest information about the epidemiology, diagnostics, etiopathogenesis, prognosis, and treatment of patients with MVA.

Molecular response to induction chemotherapy and its correlation with treatment outcome in head and neck cancer patients by means of NMR-based metabolomics.

BACKGROUND: The aim of this prospective study is to identify the biomarkers associated with the effects of induction chemotherapy (iCHT) in terms of the favorable/weaker response to the treatment in locally advanced head and neck squamous cells carcinomas (LA-HNSCC). METHODS: The studied group consisted of 53 LA-HNSCC patients treated with iCHT. The treatment tolerance was measured by the Common Terminology Criteria for Adverse Events (CTCAE). The response to the treatment was evaluated by the clinical, fiberoptic and radiological examinations made before and after iCHT (the TNM Classification of Malignant Tumors was used for classifying the extent of cancer spread). Proton nuclear magnetic resonance (1H NMR) serum spectra of the samples collected before and after iCHT were acquired with a 400 MHz spectrometer and analyzed using the multivariate and univariate statistical methods. RESULTS: The molecular response to iCHT involves an increase of the serum lipids which is accompanied by the simultaneous decrease of alanine, glucose and N-acetyl-glycoprotein (NAG). Furthermore, in males, the iCHT induced changes in the lipid signals and NAG significantly correlate with the regression of the primary tumor. The OPLS-DA multivariate model identified two subgroups of the patients with a weaker metabolic and clinical response. The first one consisted of the patients with a significantly lower initial nodal stage, the second one showed no differences in the initial clinical and metabolic statuses. CONCLUSIONS: The NMR-based metabolomic study of the serum spectra revealed that iCHT induces the marked changes in the LA-HNSCC patients' metabolic profiles and makes it possible to stratify the patients according to their response to iCHT. These effects are sex dependent. Further studies on a larger scale accounting for sex and the clinical and metabolic factors are warranted.

Anti-cytokine targeted therapies for ANCA-associated vasculitis.

BACKGROUND: Anti-neutrophilic cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) are a group of rare auto-inflammatory diseases that affects mainly small vessels. AAV includes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Anti-cytokine targeted therapy uses biological agents capable of specifically targeting and neutralising cytokine mediators of the inflammatory response. OBJECTIVES: To assess the benefits and harms of anti-cytokine targeted therapy for adults with AAV. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (2019, Issue 7), MEDLINE and Embase up to 16 August 2019. We also examined reference lists of articles, clinical trial registries, websites of regulatory agencies and contacted manufacturers. SELECTION CRITERIA: Randomised controlled trials (RCTs) or controlled clinical trials of targeted anti-cytokine therapy in adults (18 years or older) with AAV compared with placebo, standard therapy or another modality and anti-cytokine therapy of different type or dose. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included four RCTs with a total of 440 participants (mean age 48 to 56 years). We analysed the studies in three groups: 1) mepolizumab (300 mg; three separate injections every four weeks for 52 weeks) versus placebo in participants with relapsing or refractory EGPA; 2) belimumab (10 mg/kg on days 0, 14, 28 and every 28 days thereafter until 12 months after the last participant was randomised) or etanercept (25 mg twice a week) with standard therapy (median 25 months) versus placebo with standard therapy (median 19 months) in participants with GPA/MPA; and 3) infliximab (3 mg/kg on days 1 and 14, before the response assessment on day 42) versus rituximab (0.375g/m2 on days 1, 8, 15 and 22) in participants with refractory GPA for up to 12 months. None of the studies were assessed as low risk of bias in all domains: one study did not report randomisation or blinding methods clearly. Three studies were at high risk and one study was at unclear risk of bias for selective outcome reporting. One trial with 136 participants with relapsing or refractory EGPA compared mepolizumab with placebo during 52 weeks of follow-up and observed one death in the mepolizumab group (1/68, 1.5%) and none in the placebo group (0/68, 0%) (Peto odds ratio (OR) 7.39, 95% confidence interval (CI) 0.15 to 372.38; low-certainty evidence). Low-certainty evidence suggests that more participants in the mepolizumab group had ≥ 24 weeks of accrued remission over 52 weeks compared to placebo (27.9% versus 2.9%; risk ratio (RR) 9.5, 95% CI 2.30 to 39.21), and durable remission within the first 24 weeks sustained until week 52 (19.1% mepolizumab versus 1.5% placebo; RR 13.0, 95% CI 1.75 to 96.63; number needed to treat for an additional beneficial outcome (NNTB) 6, 95% Cl 4 to 13). Mepolizumab probably decreases risk of relapse (55.8% versus 82.4%; RR 0.68, 95% CI 0.53 to 0.86; NNTB 4, 95% CI 3 to 9; moderate-certainty evidence). There was low-certainty evidence regarding similar frequency of adverse events (AEs): total AEs (96.9% versus 94.1%; RR 1.03, 95% CI 0.96 to 1.11), serious AEs (17.7% versus 26.5%; RR 0.67, 95% CI 0.35 to 1.28) and withdrawals due to AEs (2.9% versus 1.5%; RR 2.00, 95% CI 0.19 to 21.54). Disease flares were not measured. Based on two trials with different follow-up periods (mean of 27 months for etanercept study; up to four years for belimumab study) including people with GPA (n = 263) and a small group of participants with MPA (n = 22) analysed together, we found low-certainty evidence suggesting that adding an active drug (etanercept or belimumab) to standard therapy does not increase or reduce mortality (3.4% versus 1.4%; Peto OR 2.45, 95% CI 0.55 to 10.97). Etanercept may have little or no effect on remission (92.3% versus 89.5%; RR 0.97, 95% CI 0.89 to 1.07), durable remission (70% versus 75.3%; RR 0.93, 95% CI 0.77 to 1.11; low-certainty evidence) and disease flares (56% versus 57.1%; RR 0.98, 95% CI 0.76 to 1.27; moderate-certainty evidence). Low-certainty evidence suggests that belimumab does not increase or reduce major relapse (1.9% versus 0%; RR 2.94, 95% CI 0.12 to 70.67) or any AE (92.5% versus 82.7%; RR 1.12, 95% CI 0.97 to 1.29). Low-certainty evidence suggests a similar frequency of serious or severe AEs (47.6% versus 47.6%; RR 1.00, 95% CI 0.80 to 1.27), but more frequent withdrawals due to AEs in the active drug group (11.2%) compared to the placebo group (4.2%), RR 2.66, 95% CI 1.07 to 6.59). One trial involving 17 participants with refractory GPA compared infliximab versus rituximab added to steroids and cytotoxic agents for 12 months. One participant died in each group (Peto OR 0.88, 95% CI, 0.05 to 15.51; 11% versus 12.5%). We have very low-certainty evidence for remission (22% versus 50%, RR 0.44, 95% Cl 0.11 to 1.81) and durable remission (11% versus 50%, RR 0.22, 95% CI 0.03 to 1.60), any severe AE (22.3% versus 12.5%; RR 1.78, 95% CI 0.2 to 16.1) and withdrawals due to AEs (0% versus 0%; RR 2.70, 95% CI 0.13 to 58.24). Disease flare/relapse and the frequency of any AE were not reported. AUTHORS' CONCLUSIONS: We found four studies but concerns about risk of bias and small sample sizes preclude firm conclusions. We found moderate-certainty evidence that in patients with relapsing or refractory EGPA, mepolizumab compared to placebo probably decreases disease relapse and low-certainty evidence that mepolizumab may increase the probability of accruing at least 24 weeks of disease remission. There were similar frequencies of total and serious AEs in both groups, but the study was too small to reliably assess these outcomes. Mepolizumab may result in little to no difference in mortality. However, there were very few events. In participants with GPA (and a small subgroup of participants with MPA), etanercept or belimumab may increase the probability of withdrawal due to AEs and may have little to no impact on serious AEs. Etanercept may have little or no impact on durable remission and probably does not reduce disease flare.

Cardiovascular response to different types of acute stress stimulations.

INTRODUCTION: Stress is an ubiquitous phenomenon in the modern world and one of the major risk factors for cardiovascular disease. e aim of our study was to evaluate the effect of various acute stress stimuli on autonomic nervous system (ANS) activity, assessed on the basis of heart rate (HRV) and blood pressure (BPV) variability analysis. MATERIALS AND METHODS: the study included 15 healthy volunteers: 9 women, 6 men aged 20-30 years (23.3 ± 1.8). ANS activity was assessed by HRV and BPV measurement using Task Force Monitor 3040 (CNSystems, Austria). ECG registration and Blood Pressure (BP) measurement was done 10 minutes at rest, 10 minutes a er the stress stimulus (sound signal, acoustic startle, frequency 1100 Hz, duration 0.5 sec, at the intensity 95 dB) and 10 minutes after the cold pressor test. The cold pressor test (CPT) was done by placing the person's hand by wrist in ice water (0-4°C) for 120 s. RESULTS: Every kind of stress stimulation (acoustic startle; the CPT) caused changes of HRV indicator values. The time domain HRV analysis parameters (pNN50, RMSSD) decreased after acoustic stress and the CPT, but were significantly lower after the CPT. In frequency domain HRV analysis, significant differences were observed only after the CPT: (LF-RRI 921.23 ms2 vs. 700.09 ms2; p = 0.009 and HF-RRI 820.75 ms2 vs. 659.52 ms2; p = 0.002). The decrease of LF-RRI and HF-RRI value after the CPT was significantly higher than after the acoustic startle (LF-RRI 34% vs. 0.4%, p = 0.022; HF-RRI 19.7% vs. 7% ms2, p = 0.011). The decreased value of the LF and HF components of HRV analysis are indicative of sympathetic activation. Nonlinear analysis of HRV indicated a significant decrease in the Poincare plot SD1 (p = 0.039) and an increase of DFAα2 (p = 0.001) in response to the CPT stress stimulation. The systolic BPV parameter LF/HF-sBP increased significantly after the CPT (2.84 vs. 3.31; p = 0.019) and was higher than after the acoustic startle (3.31 vs. 3.06; p = 0.035). Significantly higher values of diastolic BP (67.17 ± 8.10 vs. 69.65 ± 9.94 mmHg, p = 0.038) and median BP (83.39 ± 8.65 vs. 85.30 ± 10.20 mmHg, p = 0.039) were observed in the CPT group than in the acoustic startle group. CONCLUSIONS: the Cold Pressor Test has a greater stimulatory effect on the sympathetic autonomic system in comparison to the unexpected acoustic startle stress. Regardless of whether the stimulation originates from the central nervous system (acoustic startle) or the peripheral nervous system (CPT), the final response is demonstrated by an increase in the low frequency components of blood pressure variability and a decrease in the low and high frequency components of heart rate variability.