A New Approach to Vascular Screening: Identification of Impaired Vascular Function Using the FMSF Technique.

Arterial blood pressure monitoring plays an important role in preventive medicine, allowing, in selected cases, the identification of vascular dysfunction. In this review, we propose a new non-invasive approach to assessment of the circulatory system, based on its reaction to hypoxia induced by post-occlusive reactive hyperemia (PORH). Three key parameters can be used for vascular screening: the Reactive Hyperemia Response (RHR), which represents the overall reaction of the macro- and microcirculation to transient hypoxia; Hypoxia Sensitivity (HS), which reflects hypoxia-induced activation of myogenic oscillations of the microcirculation; and Normoxia Oscillatory Index (NOI), which characterizes microcirculatory oscillations under normoxia conditions. A method for assessing these parameters, analogous in simplicity to arterial blood pressure measurement, is provided by the Flow Mediated Skin Fluorescence (FMSF) technique. Reference values are proposed based on numerous test measurements.

Intracoronary electrocardiogram detects coronary microvascular dysfunction and ischemia in patients with no obstructive coronary arteries disease.

BACKGROUND: Coronary microvascular dysfunction (CMD) is the leading cause of ischemia with no obstructive coronary arteries disease (INOCA) disease. Diagnosis of CMD relies on surrogate physiological indices without objective proof of ischemia. OBJECTIVES: Intracoronary electrocardiogram (icECG) derived hyperemic indices may accurately and objectively detect CMD and reversible ischemia in related territory. METHODS: INOCA patients with proven ischemia by myocardial perfusion scan (MPS) and completely normal coronary arteries underwent simultaneous intracoronary electrophysiological (icECG) and physiological (intracoronary Doppler) assessment in all 3 coronary arteries during rest and under adenosine induced hyperemia. RESULTS: Sixty vessels in 21 patients were included in the final analysis. All patients had at least one vessel with abnormal CFR. 41 vessels had CMD (CFR < 2.5), of which 26 had increased microvascular resistance (structural CMD, HMR > 1.9 mmHg.cm-1.s) and 15 vessels had CMD (CFR < 2.5) with normal microvascular resistance (functional CMD, HMR <= 1.9 mmHg.cm-1.s). Only one-third of the patients (n = 7) had impaired CFR < 2.5 in all 3 epicardial arteries. Absolute ST shift between hyperemia and rest (∆ST) has shown the best diagnostic performance for ischemia (cut-off 0.10 mV, sensitivity: 95%, specificity: 72%, accuracy: 80%, AUC: 0.860) outperforming physiological indices (CFR: 0.623 and HMR: 0.653 DeLong's test P = .0002). CONCLUSIONS: In INOCA patients, CMD involves coronary artery territories heterogeneously. icECG can accurately detect CMD causing perfusion abnormalities in patients with INOCA outperforming physiological CMD markers, by demonstrating actual ischemia instead of predicting the likelihood of inducible ischemia based on violated surrogate thresholds of blunted flow reserve or increased minimum microvascular resistance. CONDENSED ABSTRACT: In 21 INOCA patients with coronary microvascular dysfunction (CMD) and myocardial perfusion scan proved ischemia, hyperemic indices of intracoronary electrocardiogram (icECG) have accurately detected vessel-specific CMD and resulting perfusion abnormalities & ischemia, outperforming invasive hemodynamic indices. Absolute ST shift between hyperemia and rest (∆ST) has shown the best classification performance for ischemia in no Obstructive Coronary Arteries (AUC: 0.860) outperforming Doppler derived CMD indices (CFR: 0.623 and HMR: 0.653 DeLong's test P = .0002).icECG can be used to diagnose CMD causing perfusion defects by demonstrating actual reversible ischemia at vessel-level during the initial CAG session, obviating the need for further costly ischemia tests. CLINICALTRIALS: GOV: NCT05471739.

Improvement of objective ocular redness measured with Keratograph 5M in glaucoma patients after instilling brimonidine drops.

OBJECTIVE: To compare objective ocular redness measured using OCULUS Keratograph 5 M before and after 0.2% brimonidine instillation in glaucoma patients under topical hypotensive treatment. METHODS: 60 eyes from 60 subjects diagnosed with glaucoma or ocular hypertension under hypotensive ocular topical treatment were analyzed. Basal Ophthalmological examination was performed.Outcome variables were OCULUS Keratograph 5 M redness scores (RS) before and after 0.2% brimonidine instillation; overall, bulbar temporal (BT), bulbar nasal (BN), limbar temporal (LT), and limbar nasal (LN); non-invasive average tear film breakup time (Nia-BUT), non-invasive first tear film breakup time (Nif-BUT) and meibography. In addition, the following clinical data were collected: intraocular pressure, type, duration, amount, and preservatives/or not of hypotensive treatment, fluorescein corneal staining score and lower tear meniscus height. RESULTS: All eyes were under topical medication. All redness scores were reduced after brimonidine instillation, mean RS differences were BT 0.82 ± 0.62, BN hyperemia 1.03 ± 0.55, LN hyperemia 0.84 ± 0.49, LT hyperemia 0.71 ± 0.50 and total hyperemia 0.91 ± 0.52 (all p < 0.001). 30 min after brimonidine instillation mean overall RS reduction was 47.97 ± 12.39% (p < 0.001) and after 1 h there was a persistent reduction of overall RS of 45.92 ± 14.27% (p < 0.001). Hyperemia reduction was significant and comparable between preservative and preservative-free group 0.12 ± 0.14 (p > 0.392) and between patient with combination therapy and monotherapy 0.16 ± 0.14 (p > 0.258). CONCLUSION: A significant reduction of conjunctival hyperemia was objectively found in glaucoma patients under topical hypotensive treatment before and after brimonidine instillation. Its fast and long-lasting effect may be useful preoperatively in glaucoma patients to reduce intraoperative bleeding and associated complications.

Clinical features of 26 cases of COVID-19-associated conjunctivitis.

PURPOSE: To explore the clinical features of COVID-19-associated conjunctivitis with the objective of preventing the spread of infection. STUDY DESIGN: Retrospective cohort study. METHODS: From March 2020 to March 2021, we retrospectively reviewed 26 (9.8%) consecutive COVID-19 patients with conjunctivitis among 282 COVID-19 cases admitted to our hospital. Clinical symptoms, onset date of conjunctivitis, time to patient recovery, and eye drop intervention were investigated. In addition, risk factors for developing conjunctivitis were statistically examined among 206 inpatients available for within 5 days of the onset. A multivariate analysis of conjunctivitis risk factors was performed. RESULTS: Among the 282 COVID-19 patients, 4 (1.4%) had conjunctival hyperemia as the primary symptom. The median time of onset was 4 days after the COVID-19 onset. Hyperemia was observed in all cases, but other ocular symptoms were rare. The median duration of hyperemia was 3 days. A multiple logistic regression analysis revealed that a young age (p=0.005) and current smoking habit (p=0.027) were independent risk factors for conjunctivitis after COVID-19. CONCLUSIONS: COVID-19-associated conjunctivitis is rare in the elderly and strongly associated with a history of smoking. It often occurs in the early stages of infection, and while hyperemia is recognized as a clinical symptom, other ocular symptoms are rare or non-existent. Many cases recover within a short time.

Intraobserver Repeatability Assessment of the S390L Firefly WDR Slitlamp in Patients With Dry Eye Disease: Objective, Automated, and Noninvasive Measures.

OBJECTIVES: To assess the intraobserver repeatability of automated, objective, and noninvasive measures obtained with the S390L Firefly WDR slitlamp. METHODS: This cross-sectional study included 50 eyes of patients with dry eye disease with a mean age of 55.06±12.96 years. Three consecutively repeated measures of the following variables were obtained: first noninvasive break-up time (F-NIBUT), average noninvasive break-up time (A-NIBUT), tear meniscus height, tear meniscus area (TMA), nasal ciliary hyperemia (NCIH), temporal ciliary hyperemia (TCIH), nasal conjunctival hyperemia (NCOH), temporal conjunctival hyperemia (TCOH), upper loss area meibomian gland (U-LAMG), lower loss area meibomian gland (L-LAMG), upper meibomian gland dysfunction grade (U-MGD grade), and lower meibomian gland dysfunction grade (L-MGD grade). Intraobserver repeatability was estimated with coefficient of variation (CoV), intrasubject standard deviation (SD) (S w ), and Bland-Altman plots. RESULTS: All variables showed no statistically significant differences in the repeated-measures analysis except for L-MGD grade ( P =0.045). F-NIBUT and A-NIBUT obtained the highest CoV with an average value of 0.48±0.41 [0.02-1.00] and 0.34±0.25 [0.02-1.00], respectively. The remaining variables showed CoVs between 0.04±0.11 [0.00-0.43] and 0.18±0.16 [0.00-0.75]. A-NIBUT, TMA, NCOH, and L-LAMG obtained an S w of 2.78s, 0.21 mm 2 , <0.001, and 4.11%, respectively. Bland-Altman plots showed a high level of agreement between pairs of repeated measures. CONCLUSION: The S390L Firefly WDR slitlamp has moderate intraobserver repeatability for F-NIBUT and A-NIBUT, which suggests that F-NIBUT and A-NIBUT are tests with high variability. The remaining variables show satisfactory intraobserver repeatability.

Prognostic Value of the Severity of Clinical Congestion in Patients Hospitalized for Decompensated Heart Failure: Findings From the Japanese KCHF Registry.

BACKGROUND: Congestion is a leading cause of hospitalization and a major therapeutic target in patients with heart failure (HF). Clinical practice in Japan is characterized by a long hospital stay, which facilitates more extensive decongestion during hospitalization. We herein examined the time course and prognostic impact of clinical congestion in a large contemporary Japanese cohort of HF. METHODS AND RESULTS: Peripheral edema, jugular venous pressure, and orthopnea were graded on a standardized 4-point scale (0-3) in 3787 hospitalized patients in a Japanese cohort of HF. Composite Congestion Scores (CCS) on admission and at discharge were calculated by summing individual scores. The primary outcome was a composite of all-cause death or HF hospitalization. The median admission CCS was 4 (interquartile range, 3-6). Overall, 255 patients died during the median hospitalization length of 16 days, and 1395 died or were hospitalized for HF over a median postdischarge follow-up of 396 days. The cumulative 1-year incidence of the primary outcome increased at higher tertiles of congestion on admission (32.5%, 39.3%, and 41.0% in the mild [CCS ≤3], moderate [CCS = 4 or 5], and severe [CCS ≥6] congestion groups, respectively, log-rank P < .001). The adjusted hazard ratios of moderate and severe congestion relative to mild congestion were 1.205 (95% confidence interval [CI], 1.065-1.365; P = .003) and 1.247 (95% CI, 1.103-1.410; P < .001), respectively. Among 3445 patients discharged alive, 85% had CCS of 0 (complete decongestion) and 15% had a CCS of 1 or more (residual congestion) at discharge. Although residual congestion predicted a risk of postdischarge death or HF hospitalization (adjusted hazard ratio, 1.314 [1.145-1.509]; P < .001), the admission CCS correlated with the risk of postdischarge death or HF hospitalization, even in the complete decongestion group. No correlation was observed for postdischarge death or HF hospitalization between residual congestion at discharge and admission CCS (P for the interaction = .316). CONCLUSIONS: In total, 85% of patients were discharged with complete decongestion in Japanese clinical practice. Clinical congestion, on admission and at discharge, was of prognostic value. The severity of congestion on admission was predictive of adverse outcomes, even in the absence of residual congestion. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02334891 (NCT02334891) https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017241 (UMIN000015238).

Meibomian gland secretion quality association with ocular parameters in university students during COVID- 19 restrictions.

PURPOSE: To determine if the Meibomian Gland (MG) secretion quality is associated with symptoms of ocular discomfort, hours of Video Display Terminals (VDT) use, eyelid margin abnormalities, conjunctival hyperemia, and Meibomian Gland Loss Area (MGLA) in a sample of university students. METHODS: An online survey that included an Ocular Surface Disease Index (OSDI) questionnaire and an extra question about hours of VDT use recruited an initial sample of 183 participants. Only 120 participants that fulfilled the inclusion criteria were scheduled for a battery of ocular surface and MG specific exam. The tests include: 1) meibometry, 2) slit lamp exploration of eyelid margin abnormalities (irregularity, hyperemia and MG orifices plugging), MG secretion quality and conjunctival hyperemia, and 3) Meibography. RESULTS: Significant positive correlations between the MG secretion quality and eyelid margin hyperemia, MG orifices plugging, MGLA, nasal conjunctival hyperemia, and temporal conjunctival hyperemia (Spearman Rho; all r>0.186, p<0.042) were found. Multivariate regression found association between OSDI with hours of VDT use (B=0.316, p=0.007), and eyelid hyperemia (B=0.434, p≤ 0.001). A statistical association between MG secretion quality and eyelid margin hyperemia, MG orifices plugging, MGLA and conjunctival hyperemia (Fisher's exact; all p<0.039) were found. Multivariate regression found association between MG secretion quality with MG orifices plugging (B=0.295, p=0.004) and meibometry (B=-0.001, p=0.029). CONCLUSION: Participants with higher values in MG secretion quality have higher values in eyelid margin hyperemia, MG plugging, MGLA, and conjunctival hyperemia. No direct relationship between MG secretion quality and hours of VDT use or OSDI were found.

Analysis of the Differences in Ocular Surface Damage and Inflammatory Signs between Healthy and Evaporative Dry Eye Participants.

OBJECTIVE: Distinguish between EDE severity levels by analysing the MGLA, conjunctival hyperemia and corneal staining. METHODS: One hundred participants were recruited based on OSDI, TO, TFBUT, TMH, and LLP to be categorised as healthy (Group 1) or EDE (Group 2). Group 2 was divided into Group 2A (mild symptoms), 2B (moderate), and 2C (severe). MGLA, conjunctival hyperemia, and corneal staining were measured. RESULTS:  Positive correlation between MGLA, conjunctival hyperemia, and corneal staining were found (all r ≥ 0.221, p ≤ 0.027). Significant differences were found: MGLA between Group 1 vs. 2C and 2C vs. 2A or 2B; conjunctival hyperemia between Group 1 vs. 2A, 2B or 2C; corneal staining between Group 1 vs. 2B or 2C and 2A vs. 2B or 2C (all p ≤ 0.049). CONCLUSION: Severe EDE participants have higher MGLA, conjunctival hyperemia, and corneal staining values than healthy, mild, or moderate EDE participants.

Contrast-enhanced cine MR sequences in the assessment of myocardial hyperemia in acute myocarditis: can they help? A feasibility study.

The study was designed to assess the accuracy of contrast-enhanced balanced steady-state free precession (cine-SSFP) CMR imaging sequences to exhibit myocardial hyperemia in acute myocarditis, which has for a long time been investigated in some centers using early gadolinium enhancement (EGE) sequence. Contrast-enhanced cine-SSFP (CESSFP) sequences were compared to precontrast cine-SSFP sequences to calculate the early cine-contrast enhancement in 36 consecutive patients with acute myocarditis and 36 controls matched for age and gender. Four-chamber views images were obtained in each subject before and after gadolinium injection. Absolute and relative left ventricular myocardial enhancement of the overall myocardium, then separately of the lateral wall and interventricular septum was analyzed in telediastole. Myocarditis patients displayed higher cine-SSFP absolute enhancement than controls (overall left ventricular myocardium 2.38 ± 0.33 vs 1.84 ± 0.31; lateral wall 2.45 ± 0.35 vs 1.83 ± 0.32; and septum 2.26 ± 0.29 vs 1.82 ± 0.29, p < 0.0001 for all). Less significant differences were observed for the relative enhancement (p < 0.05 for all). Using ROC curves, the optimal threshold value of absolute enhancement to diagnose acute myocarditis was 2.05 (sensitivity: 86%; specificity: 81%). Given the simplicity of use, contrast-enhanced cine-SSFP sequences should be used as an additional diagnostic tool to detect hyperemia in acute myocarditis patients.

Combined use of hyperemic and non-hyperemic pressure ratios for revascularization decision-making: From the ILIAS registry.

OBJECTIVE: The aim of this study is to evaluate the diagnostic and prognostic value of non-hyperaemic Pd/Pa and to determine its additional value when combined with the gold standard hyperaemic pressure ratio (FFR) to guide revascularization. METHODS: In a large, multi-center, retrospective registry, we included a total of 2141 patients with a clinical indication for coronary angiography providing physiological data in 2726 vessels. A classification was made based on the FFR (cut-off value: 0.80) and non-hyperaemic Pd/Pa (cut-off value: 0.92) values and the primary outcome was target-vessel failure (TVF) at 5-year follow-up. RESULTS: Mean age was 63 ± 10.0 and 75% of the study population were men. Regression analysis showed an overall good correlation between FFR and non-hyperaemic Pd/Pa (r = 0.73, p < 0.005) and discordance was present in 17% of the vessels. Resting Pd/Pa was independently associated with TVF at 5-year follow-up (HR 0.08, 95%CI: 0.02-0.27; p < 0.005). The risk for TVF was the lowest in vessles with concordant normal pressure ratio's, with the highest risk in vessels with any abnormal pressure ratio in which revascularization was deferred. In these vessels, there was no difference in risk for TVF between the discordant and concordant abnormal values. CONCLUSION: Abnormal pressure ratios in both non-hyperemic and hyperemic conditions portend important prognostic value. Combined application of FFR and non-hyperemic Pd/Pa efficiently identifies those vessels with concordant normal resting and hyperemic pressure ratios of which long-term clinical outcomes are excellent. These data lead to hypothesize that the decision to defer revascularization should potentially be based on combined non-hyperemic and hyperemic pressure ratios. CLINICAL TRIAL REGISTRATION: Inclusive Invasive Physiological Assessment in Angina Syndromes Registry (ILIAS Registry), NCT04485234.

Understanding the Basis for Hyperemic and Nonhyperemic Coronary Pressure Assessment.

Despite the now routine integration of invasive physiologic systems into coronary catheter laboratories worldwide, it remains critical that all operators maintain a sound understanding of the fundamental physiologic basis for coronary pressure assessment. More specifically, performing operators should be well informed regarding the basis for hyperemic (ie, fractional flow reserve) and nonhyperemic (ie, instantaneous wave-free ratio and other nonhyperemic pressure ratio) coronary pressure assessment. In this article, we provide readers a comprehensive history charting the inception, development, and validation of hyperemic and nonhyperemic coronary pressure assessment.

Noninvasive Investigation of the Presence and Extent of Coronary Artery Disease by the Evaluation of Fingertip-Reactive Hyperemia.

OBJECTIVE: Fingertip-reactive hyperemia-peripheral artery tonometry (RH-PAT) is an emerging novel noninvasive method for evaluating endothelial function. We aimed to evaluate endothelial function with fingertip-reactive hyperemia by RH-PAT in symptomatic patients undergoing elective coronary angiography and to assess the relationship between the degree of endothelial dysfunction (ED) and the presence and the severity of coronary artery disease (CAD). SUBJECTS AND METHODS: We assessed 92 patients. Before coronary angiography, endothelial function was measured by RH-PAT and reactive hyperemia index (RHI) was obtained. For each patient, the Gensini score was calculated according to the coronary angiographic findings to evaluate the severity of CAD. RESULTS: In CAD (+) group, RHI (1.35 ± 0.57 vs. 1.74 ± 0.46, p = 0.001) mean values were lower than CAD (-) group. In multivariate logistic regression analysis, age, high-density lipoprotein, and RHI were found to be independent parameters predicting the presence of CAD. In multivariate linear regression analysis, RHI was found to be an independent predictor associated with the severity of CAD. In receiver operating characteristic curve analysis, RHI achieved an area under the curve of 0.763 (95% confidence interval 0.663-0.846, p = 0.001) for the ability to predict the presence of CAD. A cut-off value of 1.49 for an RHI predicted the presence of CAD with a sensitivity of 75% and a specificity of 72.9%. CONCLUSION: RH-PAT is an objective and highly reproducible test with superior diagnostic accuracy for the evaluation of ED. We found significant correlations between ED and the presence and the severity of CAD.

Using blood glucose and lactate levels for early detection of venous congestion following a free flap procedure for lower extremity open fractures.

PURPOSE: Gustilo-Anderson type IIIB and IIIC open fractures of the lower extremities require reconstruction of extensively injured soft tissues using a free flap; however, impaired blood flow through the flap is an early postoperative complication. To detect flap congestion due to venous thrombosis, blood glucose and lactate level measurements within the flap are taken to determine variations in these levels. We aimed to detect early-stage venous congestion and to perform salvage operations. METHODS: We included 22 limbs with lower leg and foot open fractures, with fracture sites covered using a free flap. A pinprick test was used to measure blood glucose and lactate levels. RESULTS: Of 7 and 15 congested and non-congested limbs, respectively, the 7 congested limbs had a mean flap blood glucose level immediately before salvage surgery of 3.8 ± 2.0 (7.4-1.8) mmol/L. The ratio to blood glucose levels in healthy fingertips was 0.6 ± 0.2 (0.8-0.3). Lactate levels increased to 13.3 ± 5.1 (9.4-22.8) mmol/L. The ratio of blood glucose levels in congested flaps and in healthy fingertips was significantly lower than that in non-congested flaps and in healthy fingertips (p = 0.0016). Lactate levels were significantly higher in patients with congestion (p = 0.0013). Salvage surgery was performed, thrombi were removed, and six limb flaps were viable. CONCLUSION: Flap blood glucose and lactate levels provide a quantitative method of evaluating blood flow and detecting flow abnormalities postoperatively, and are useful in detecting early congestion due to venous thrombosis.

A comparison of subjective and objective conjunctival hyperaemia grading with AOS® Anterior software.

CLINICAL RELEVANCE: This study evaluates a commercially available conjunctival hyperaemia grading system, providing validation of an important tool for ocular surface research and clinical trials. BACKGROUND: Bulbar conjunctival hyperaemia is a sign of ocular surface inflammation, and proper measurement is essential to clinical care and trials. The aim of this study was to assess the validity and repeatability of an objective grading system in comparison with subjective grading. METHODS: This study was a retrospective, randomised analysis of 300 bulbar conjunctival images that were collected at an academic institution. The images used were de-identified and collected from the Keratograph K5 and Haag-Streit slitlamp. Six investigators graded the images with either a 0.1 or 0.5 unit scaling using a 0-4 Efron grading scale. Three of the investigators also imported the images into the AOS ® Anterior software and graded them objectively. All measurement techniques were assessed for repeatability and comparability to each other. RESULTS: Mean hyperaemia with the objective system (1.1 ± 0.7) was significantly less than the subjective grading (2.0 ± 0.8) (P < 0.001). Both inter- and intra-subject repeatability of the objective system (0.15) was better than the subjective methods (1.70). CONCLUSION: The results showed excellent repeatability of the AOS ® Anterior objective conjunctival hyperaemia grading software, although they were not found to be interchangeable with subjective scores. This system has value in monitoring levels of hyperaemia in contact lens wearers and patients in clinical care and research trials.

Energetic Basis for Exercise-Induced Pulmonary Congestion in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Transient pulmonary congestion during exercise is emerging as an important determinant of reduced exercise capacity in heart failure with preserved ejection fraction (HFpEF). We sought to determine whether an abnormal cardiac energetic state underpins this process. METHODS: We recruited patients across the spectrum of diastolic dysfunction and HFpEF (controls, n=11; type 2 diabetes, n=9; HFpEF, n=14; and severe diastolic dysfunction attributable to cardiac amyloidosis, n=9). Cardiac energetics were measured using phosphorus spectroscopy to define the myocardial phosphocreatine to ATP ratio. Cardiac function was assessed by cardiovascular magnetic resonance cine imaging and echocardiography and lung water using magnetic resonance proton density mapping. Studies were performed at rest and during submaximal exercise using a magnetic resonance imaging ergometer. RESULTS: Paralleling the stepwise decline in diastolic function across the groups (E/e' ratio; P<0.001) was an increase in NT-proBNP (N-terminal pro-brain natriuretic peptide; P<0.001) and a reduction in phosphocreatine/ATP ratio (control, 2.15 [2.09, 2.29]; type 2 diabetes, 1.71 [1.61, 1.91]; HFpEF, 1.66 [1.44, 1.89]; cardiac amyloidosis, 1.30 [1.16, 1.53]; P<0.001). During 20-W exercise, lower left ventricular diastolic filling rates (r=0.58; P<0.001), lower left ventricular diastolic reserve (r=0.55; P<0.001), left atrial dilatation (r=-0.52; P<0.001), lower right ventricular contractile reserve (right ventricular ejection fraction change, r=0.57; P<0.001), and right atrial dilation (r=-0.71; P<0.001) were all linked to lower phosphocreatine/ATP ratio. Along with these changes, pulmonary proton density mapping revealed transient pulmonary congestion in patients with HFpEF (+4.4% [0.5, 6.4]; P=0.002) and cardiac amyloidosis (+6.4% [3.3, 10.0]; P=0.004), which was not seen in healthy controls (-0.1% [-1.9, 2.1]; P=0.89) or type 2 diabetes without HFpEF (+0.8% [-1.7, 1.9]; P=0.82). The development of exercise-induced pulmonary congestion was associated with lower phosphocreatine/ATP ratio (r=-0.43; P=0.004). CONCLUSIONS: A gradient of myocardial energetic deficit exists across the spectrum of HFpEF. Even at low workload, this energetic deficit is related to markedly abnormal exercise responses in all 4 cardiac chambers, which is associated with detectable pulmonary congestion. The findings support an energetic basis for transient pulmonary congestion in HFpEF.

Hyponatremia and Renal Venous Congestion in Heart Failure Patients.

OBJECTIVE: The interrelationship between the heart and kidneys has a great importance in the homeostasis of the cardiovascular system. Heart failure patients present intrarenal arterial hypoperfusion and intrarenal venous congestion due to reduced left ventricle ejection fraction, which triggers numerous neurohormonal factors. The aim of this study was to investigate intrarenal vascularization (arterial and venous), as well as the links between it and systemic congestion and, on the other side, with the mortality in patients with heart failure. Material and Methods. This cross-sectional study was performed on a group of 44 patients with heart failure in different stages of evolution and 44 healthy subjects, matched for age and gender, as controls. Serum natremia, NT-proBNP, and creatinine analyses were performed in all patients and controls. Renal and cardiac ultrasonography was done in all patients and controls, recording intrarenal arterial resistive index (RRI), intrarenal venous flow (IRVF) pattern, renal venous stasis index (RVSI), and left ventricular ejection fraction (LVEF). Data are recorded and presented as mean ± standard deviation. Statistical analyses were performed using the Student t-test, ANOVA test, and the Pearson correlation. Differences were considered statistically significant at the value of p < 0.05. RESULTS: Hyponatremia was identified in 47.72% of the HF patients. This study revealed correlations between serum natremia and LVEF, NT-proBNP, serum creatinine, interlobar venous RVSI (p < 0.00001), and interlobar artery RRI (p ≤ 0.002). Hyponatremia and renal venous congestion represent negative prognostic factors in HF patients. CONCLUSION: In HF patients, hyponatremia was correlated with cardiac dysfunction and intrarenal venous congestion. Hyponatremia and renal venous congestion represented negative prognostic factors in HF patients.

Are there Clinical Ways to Assess Inflammation in Dry Eye Disease?

In the diagnostic process of dry eye disease, the detection of inflammatory activity is critical in order to evaluate the risk of progression and immunologic shift of the disease, to predict patient response to treatment, and to design an efficient therapeutic strategy, including artificial tear replacement, punctal occlusion or anti-inflammatory therapy.Even if it is difficult to quantify, some indicators of the presence of inflammation are collectible during the examination of the ocular surface in a first-line clinical setting. This review presents and critically discusses the assessment of inflammation in dry eye disease in clinical practice.

Bilateral Traumatic Carotid-Cavernous Fistula in a Child: Corkscrew Eyelid Vessels as an Indicator of Severe Congestion.

An 11-year-old girl presented with bilateral traumatic caroticocavernous fistula associated with corkscrew eyelid vessels, which were considered indicators of severe congestive disease in this case. Coil embolization was performed; similar to other congestive findings such as proptosis, orbital bruit, increased intraocular pressure, congested scleral and retinal vessels, engorged eyelid vessels resolved immediately after coil embolization. This pediatric case is unique given the caroticocavernous fistula was bilateral and was associated with prominent dilatation of the eyelid vessels, named for the first time as corkscrew eyelid vessels.