Role of arterial blood glucose and interstitial fluid glucose difference in evaluating microcirculation and clinical prognosis of patients with septic shock: a prospective observational study.

BACKGROUND: Microcirculation abnormality in septic shock is closely associated with organ dysfunction and mortality rate. It was hypothesized that the arterial blood glucose and interstitial fluid (ISF) glucose difference (GA-I) as a marker for assessing the microcirculation status can effectively evaluate the severity of microcirculation disturbance in patients with septic shock. METHODS: The present observational study enrolled patients with septic shock admitted to and treated in the intensive care unit (ICU) of a tertiary teaching hospital. The parameters reflecting organ and tissue perfusion, including lactic acid (Lac), skin mottling score, capillary refill time (CRT), venous-to-arterial carbon dioxide difference (Pv-aCO2), urine volume, central venous oxygen saturation (ScvO2) and GA-I of each enrolled patient were recorded at the time of enrollment (H0), H2, H4, H6, and H8. With ICU mortality as the primary outcome measure, the ICU mortality rate at any GA-I interval was analyzed. RESULTS: A total of 43 septic shock patients were included, with median sequential organ failure assessment (SOFA) scores of 10.5 (6-16), and median Acute Physiology and Chronic Health Evaluation (APACHAE) II scores of 25.7 (9-40), of whom 18 died during ICU stay. The GA-I levels were negative correlation with CRT (r = 0.369, P < 0.001), Lac (r = -0.269, P < 0.001), skin mottling score (r=-0.223, P < 0.001), and were positively associated with urine volume (r = 0.135, P < 0.05). The ICU mortality rate of patients with septic shock presenting GA-I ≤ 0.30 mmol/L and ≥ 2.14 mmol/L was significantly higher than that of patients with GA-I at 0.30-2.14 mmol/L [65.2% vs. 15.0%, odds ratio (OR) = 10.625, 95% confidence interval (CI): 2.355-47.503]. CONCLUSION: GA-I was correlated with microcirculation parameters, and with differences in survival. Future studies are needed to further explore the potential impact of GA-I on microcirculation and clinical prognosis of septic shock, and the bedside monitoring of GA-I may be beneficial for clinicians to identify high-risk patients.

Endovascular Treatment of Complicated Popliteal Aneurysms Using the Novel "Trap and Fix" Technique.

Herein, we present 2 patients with lower limb ischemia caused by complicated popliteal aneurysms with thrombosis and distal embolization, compromising blood flow to the foot. In both cases, covered stents were first implanted guided by intravascular ultrasound and computed tomography angiography, respectively. After "trapping" the thrombi, mechanical thrombectomy or further stent implantations were performed, "fixing" the remaining lesions and preventing embolization. (Level of Difficulty: Intermediate.).

Microcirculation in Hypertension: A Therapeutic Target to Prevent Cardiovascular Disease?

Arterial hypertension is a common condition worldwide and an important risk factor for cardio- and cerebrovascular events, renal diseases, as well as microvascular eye diseases. Established hypertension leads to the chronic vasoconstriction of small arteries as well as to a decreased lumen diameter and the thickening of the arterial media or wall with a consequent increased media-to-lumen ratio (MLR) or wall-to-lumen ratio (WLR). This process, defined as vascular remodeling, was firstly demonstrated in small resistance arteries isolated from subcutaneous biopsies and measured by micromyography, and this is still considered the gold-standard method for the assessment of structural alterations in small resistance arteries; however, microvascular remodeling seems to represent a generalized phenomenon. An increased MLR may impair the organ flow reserve, playing a crucial role in the maintenance and, probably, also in the progressive worsening of hypertensive disease, as well as in the development of hypertension-mediated organ damage and related cardiovascular events, thus possessing a relevant prognostic relevance. New non-invasive techniques, such as scanning laser Doppler flowmetry or adaptive optics, are presently under development, focusing mainly on the evaluation of WLR in retinal arterioles; recently, also retinal microvascular WLR was demonstrated to have a prognostic impact in terms of cardio- and cerebrovascular events. A rarefaction of the capillary network has also been reported in hypertension, which may contribute to flow reduction in and impairment of oxygen delivery to different tissues. These microvascular alterations seem to represent an early step in hypertension-mediated organ damage since they might contribute to microvascular angina, stroke, and renal dysfunction. In addition, they can be markers useful in monitoring the beneficial effects of antihypertensive treatment. Additionally, conductance arteries may be affected by a remodeling process in hypertension, and an interrelationship is present in the structural changes in small and large conductance arteries. The review addresses the possible relations between structural microvascular alterations and hypertension-mediated organ damage, and their potential improvement with antihypertensive treatment.

A single dose of oral nattokinase accelerates skin temperature recovery after cold water immersion: A double-blind, placebo-controlled crossover study.

Nattokinase (NK) intake may improve blood flow; however, its effects on skin temperature, which is predominantly controlled by skin surface blood flow, are unknown. The purpose of this study was to determine the effects of a single dose of NK on changes in skin temperature after cold water immersion. A double-blinded, placebo-controlled, crossover intervention study was performed on nine healthy men. The participants were randomised to receive either a single dose of 2,000 fibrinolytic units (FU) of NK or a placebo with subsequent crossover. Two hours after supplementation, the participants immersed both hands in a water bath maintained at 10 °C for 1 min. Skin temperature, perceived coldness, cardiac output, and sympathetic nervous activity were measured before, during, and after water immersion. Two-way analysis of variance showed a significant effect of treatment interaction on the skin temperature of the middle finger, palm, and back of the right hand (p < 0.05). These findings represented that the skin temperatures of the middle finger, palm, and back of the right hand immersed in the cold water were significantly dropped due to the cold water immersion, and then recovered more quickly by NK intake than by placebo intake. The results of the current study highlight the potential implications of NK for the prevention of excessive vasoconstriction. It may be more significant for those with cold-sensitive constitution, such as women and elderly. In contrast, the acute administration of 2,000 FU of NK did not affect changes in heart rate, cardiac output, sympathetic nervous activity compared with a placebo in healthy men.

Successful Conservative Treatment of Mobile Aortic Thrombus Causing Acute Limb Ischemia.

In this clinical vignette, we present the case of an 83-year-old female patient with acute limb ischemia, resulting from a large (1.8 × 2.8 cm) mobile thrombus in the descending aorta. The peripheral obstruction was treated with mechanical thrombectomy, whereas the intra-aortic thrombus was treated conservatively with clopidogrel and fondaparinux. (Level of Difficulty: Beginner.).

Modeling Reactive Hyperemia to Better Understand and Assess Microvascular Function: A Review of Techniques.

Reactive hyperemia is a well-established technique for the non-invasive evaluation of the peripheral microcirculatory function, measured as the magnitude of limb re-perfusion after a brief period of ischemia. Despite widespread adoption by researchers and clinicians alike, many uncertainties remain surrounding interpretation, compounded by patient-specific confounding factors (such as blood pressure or the metabolic rate of the ischemic limb). Mathematical modeling can accelerate our understanding of the physiology underlying the reactive hyperemia response and guide in the estimation of quantities which are difficult to measure experimentally. In this work, we aim to provide a comprehensive guide for mathematical modeling techniques that can be used for describing the key phenomena involved in the reactive hyperemia response, alongside their limitations and advantages. The reported methodologies can be used for investigating specific reactive hyperemia aspects alone, or can be combined into a computational framework to be used in (pre-)clinical settings.

State of the Art Review: Vascular Remodeling in Hypertension.

Although the gold-standard method for the assessment of structural alteration in small resistance arteries is the evaluation of the MLR by micromyography in bioptic tissues, new, noninvasive techniques are presently under development, focusing mainly on the evaluation of WLR in retinal arterioles. These approaches represent a promising and interesting future perspective. Appropriate antihypertensive treatment is able to prevent the development of microvascular alterations or to induce their regression. Also, conductance arteries may be affected by a remodeling process in hypertension, and a cross-talk may exist between structural changes in the small and large arteries. In conclusion, the evaluation of microvascular structure is ready for clinical prime time, and it could, in the future, represent an evaluation to be performed in the majority of hypertensive patients, to better stratify cardiovascular risk and better evaluate the effects of antihypertensive therapy. However, for this purpose, we need a clear demonstration of the prognostic relevance of noninvasive measures of microvascular structure, in basal conditions and during treatment. Vascular remodeling may be frequently observed in hypertension, as well as in obesity and diabetes mellitus. An increased media to lumen ratio (MLR) or wall to lumen ratio (WLR) in microvessels is the hallmark of hypertension, and may impair organ flow reserve, being relevant in the maintenance and, probably, also in the progressive worsening of hypertensive disease, as well as in the development of hypertension-mediated organ damage/cardiovascular events. The molecular mechanisms underlying the development of vascular remodeling are only partly understood.

The Impact of Controlled Physical Training with Hydrotherapy on Changes in Swelling and Claudication Distance in Patients with Atherosclerotic Ischemia of the Lower Limbs.

BACKGROUND: Patients with peripheral artery disease (PAD) often experience intermittent claudication. It is manifested by pain typically seen in the distal part of the legs during walking, which impairs the ability to walk, limits physical activity and results in lower health-related quality of life. It often leads to chronic ischemic pain, ulceration and even amputation. The aim of the study was to evaluate the effect of controlled physical training and whirlpool massage on changes in circuits, range of motion and distance of claudication in people with atherosclerotic ischemia of the lower limbs. MATERIAL AND METHODS: The study included 100 patients, males and females aged 39 to 79 years, with peripheral circulation disorders of the lower limbs. The subjects were randomly divided into two groups. Group I (G) was treated with a series of 10 lower-limb whirling massages and took part in individually planned training, including breathing, relaxation and active free lower-limb exercises. Group II-control group (GC) took part only in individually planned training. Prior to the treatment procedures and after their completion, the ranges of movement of the ankle joint and the circumference of the lower limbs were measured and the corridor test (6MWT, six-minute walk test) was performed. RESULTS: Statistically significant reduction in the circumference of the foot, ankle, calf and thigh in the G group was noticed. Both, in G and in GC group, a statistically significant increase in the range of dorsiflexion of the foot was found in comparison to the period before the procedures (p = 0.010; p = 0.006, respectively). There was also a statistically significant increase in the range of motion of the plantar flexion of the foot after the procedures in G (p = 0.007) and in GC (p = 0.048). Differences in the circumference of the lower limbs and the range of ankle joint movements between the study group and the control group before and after the therapy were not statistically significant. However, there was a statistically significant difference between these groups after the procedures in the 6-min walk test-significantly higher values of 6MWT were recorded in group G (p = 0.003). CONCLUSIONS: Individually planned training, supplemented with hydrotherapy as thermal therapy, has a beneficial effect on reducing swelling of the lower limbs, increasing the range of foot movements and extending the distance in the 6-min walk test.

First-in-Man Robotic-Assisted Renal Denervation.

To the best of our knowledge, this is the first report of robotic-assisted renal denervation. Robotic-assisted renal denervation represents a new frontier in robotic-assisted percutaneous interventions. Robotic assistance provides increased procedural and technical accuracy while minimizing radiation exposure for both the operators and the patients. (Level of Difficulty: Advanced.).

Effects of half-body and foot baths on peripheral circulation in healthy adult males: a pilot study.

[Purpose] This study aimed to clarify the optimal conditions of warm-water bathing required to improve peripheral circulation. [Participants and Methods] Ten healthy males experienced three warm-water bathing depths (half-body, low-leg, and foot) on different days. Peripheral circulation (earlobe blood flow), tympanic temperature, pulse rate, and blood pressure were measured during each session and compared among the bathing conditions. [Results] In half-body bathing, the relative blood flow of participants increased steeply to a level 2.7-fold higher than the baseline during bathing and rapidly decreased after that. Conversely, the relative blood flow gradually and continuously increased to a level 1.7-fold higher than that at the baseline during low-leg bathing and maintained a similar level after that. The blood flow did not markedly change throughout the experiment in foot bathing. The pulse rate during foot bathing and that during low-leg bathing did not change throughout the observation period, but that of half-body bathing increased considerably. [Conclusion] Rapid changes in pulse rate or blood pressure associated with bathing are considered risky. We suggest that low-leg bathing, rather than the usually adopted half-body bathing, is appropriate for improving peripheral circulation in terms of effectiveness and safety.

Autologous free tissue transfer in paediatric patient with a univentricular heart.

We report on the case of a 30-month-old boy who developed severe deep cervical necrosis after bypass surgery for total cavopulmonary connection, followed by low-cardiac output and extracorporeal life support. As several bedside debridements failed to result in sufficient wound healing, a 2-stage necrectomy followed by autologous reconstruction with a free anterolateral thigh-flap was required. Due to impaired circulation, postoperative flap monitoring was extremely difficult. To ensure flap perfusion, mean arterial pressure had to be raised by catecholamines over 7 days.

Peripheral circulation disturbances in two consecutive children with spinal muscular atrophy and literature review.

Spinal muscular atrophy is a progressive and severe hereditary (autosomal recessive) neuromuscular disease characterized by lower motor neuron degeneration in the spinal cord and brainstem causing a clinical picture of progressive muscle atrophy and weakness of skeletal and respiratory muscles. There is an ongoing discussion on the extent to which other tissues might be affected in patients with SMA. Several animal models and some case reports or small case series report involvement of other organ systems, such as peripheral nerve, brain, muscle, heart, vascular system, and pancreas. Recent literature reviews identified a number of cases with vascular abnormalities. We present two consecutive cases of patients diagnosed with SMA who developed peripheral circulation disturbances and combine the findings with a thorough review the literature.

Persistent Changes of Peripheral Blood Lymphocyte Subsets in Patients with Oral Squamous Cell Carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a common cancer with high morbidity and mortality. Alterations of antitumor immune responses are involved in the development of this malignancy, and investigation of immune changes in the peripheral blood of OSCC patients has aroused the interest of researchers. METHODS: In our study, we assessed the proportions of CD3+ total T lymphocytes, CD3+CD4+ helper T lymphocytes, CD3+CD8+ suppressor/cytotoxic T lymphocytes, CD3-CD19+ total B lymphocytes, and CD3-CD16+CD56+ NK cells in the peripheral blood of OSCC patients. RESULTS: The data obtained both pre- and post-therapy showed a similar level of total CD3+ T lymphocytes in OSCC patients and control subjects, pinpointing the stability of this immune parameter. On the other hand, pre-therapeutic data showed a lower proportion of helper T lymphocytes (CD4+), a significantly higher level of cytotoxic/suppressive T lymphocytes (CD8+), and a much lower CD4+ T lymphocyte/CD8+ T lymphocyte ratio compared to control subjects. Conversely, evaluation of circulating NK (CD16+) cells showed a markedly higher pre-therapeutic level compared to the control group. CONCLUSIONS: Our results related to immune changes in the peripheral blood add new information to this complex universe of connections between immuno-inflammatory processes and carcinogenesis.

Skin Mottling as Clinical Manifestation of Cardiogenic Shock.

A 59 years old male came to the emergency department with chief complain of dyspnea. Dyspnea has worsened since 3 days before admission accompanied with dyspnea on effort, orthopnea and paroxysmal nocturnal dyspnea. In the emergency department, patient experienced cardiac arrest after defecating, leading to cardiopulmonary resuscitation for 45 minutes. Administration of vasoactive drugs were done and the patient was intubated.Post resucitaiton physical examination showed that the patient was sedated, with blood pressure of 72/40 (on dobutamine support). Peripheral circulation examination showed cold and clammy extremities, skin mottling of the lower extremity with mottling score of 2. CRT is more than 2 seconds. Blood gas analysis showed severe metabolic acidosis with blood lactate of 8.1.Angiographic examination were previously done on the patient during the previous admission with the results of three vessels disease with a chronic total occlusion in the left anterior descending artery. However, patient had refused further intervention regarding the coronary problems. Patient also has longtsanding atrial fibrillation.Patient was admitted into the intensive care unit for further management. Patient was stabilized during admisison in the intensive care with inotropes, however despite the hemodynamic stablilization the skin remain mottled-regardless. Patient had complicating factors in the form of pneumonia and sepsis. Patient had difficulty in weaning the ventilator and died because of arrythmia complication.

The Impact of Physical Exercise on the Circulating Levels of BDNF and NT 4/5: A Review.

(1) Background: One mechanism through which physical activity (PA) provides benefits is by triggering activity at a molecular level, where neurotrophins (NTs) are known to play an important role. However, the expression of the circulating levels of neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4/5), in response to exercise, is not fully understood. Therefore, the aim was to provide an updated overview on the neurotrophin (NT) variation levels of BDNF and NT-4/5 as a consequence of a long-term aerobic exercise intervention, and to understand and describe whether the upregulation of circulating NT levels is a result of neurotrophic factors produced and released from the brain, and/or from neurotrophic secreting peripheral organs. (2) Methods: The articles were collected from PubMed, SPORTDiscus, Web of Science, MEDLINE, and Embase. Data were analyzed through a narrative synthesis. (3) Results: 30 articles studied humans who performed training protocols that ranged from 4 to 48 weeks; 22 articles studied rodents with an intervention period that ranged from 4 to 64 weeks. (4) Conclusions: There is no unanimity between the upregulation of BDNF in humans; conversely, concerning both BDNF and NT-4/5 in animal models, the results are heterogeneous. Whilst BDNF upregulation appears to be in relative agreement, NT-4/5 seems to display contradictory and inconsistent conclusions.

Entrapped Crown of Orbital Atherectomy Device by Intimal Tissue Entanglement During Peripheral Intervention.

Orbital atherectomy is a commonly used procedure for peripheral arterial disease. Crown entrapment is a rare but potentially dangerous complication of orbital atherectomy. We describe a case of crown entrapment by markedly excessive atheromatous intimal tissue attachment to the device and an innovative retrieval technique that may minimize vascular injury. (Level of Difficulty: Beginner.).

Assessment of ocular blood flow in continuous-flow ventricular assist device by laser speckle flowgraphy.

Although the influence of continuous-flow left ventricular assist device (CF-LVAD) support on peripheral circulation has been widely discussed, its monitoring modalities are limited. The aim of this study was to assess the peripheral circulation using the laser speckle flowgraph (LSFG) which can quantitatively measure the ocular blood flow. We implanted a centrifugal CF-LVAD (EVAHEART®; Sun Medical Technology Research Corporation, Nagano, Japan) in five adult goats (body weight 44.5 ± 2.9 kg) under general anesthesia. The waveform of the central retinal artery using the mean blur rate (MBR) for ocular blood velocity and fluctuations as a parameter of pulsatility were obtained before LVAD implantation and after LVAD full-bypass support. The MBR waveform and LSFG fluctuation data were compared with the waveform and pulsatility index of the external carotid artery using an ultrasonic flow meter to evaluate circulatory patterns at different levels. The MBR waveform pattern of the central retinal artery was pulsatile before LVAD implantation and less pulsatile under LVAD full bypass. The fluctuation was 14.7 ± 1.86 before LVAD implantation and 3.85 ± 0.61 under LVAD full bypass (p < 0.01), respectively. The fluctuations of LSFG showed a strong correlation with the pulsatility index of the external carotid artery meaning that similar changes in circulatory pattern were observed at two different levels. Measuring the ocular blood flow using LSFG has potential utility for the assessment of the status of the peripheral circulation and its pulsatility during CF-LVAD.

Heart Rate Variability (HRV) and Pulse Rate Variability (PRV) for the Assessment of Autonomic Responses.

Introduction: Heart Rate Variability (HRV) and Pulse Rate Variability (PRV), are non-invasive techniques for monitoring changes in the cardiac cycle. Both techniques have been used for assessing the autonomic activity. Although highly correlated in healthy subjects, differences in HRV and PRV have been observed under various physiological conditions. The reasons for their disparities in assessing the degree of autonomic activity remains unknown. Methods: To investigate the differences between HRV and PRV, a whole-body cold exposure (CE) study was conducted on 20 healthy volunteers (11 male and 9 female, 30.3 ± 10.4 years old), where PRV indices were measured from red photoplethysmography signals acquired from central (ear canal, ear lobe) and peripheral sites (finger and toe), and HRV indices from the ECG signal. PRV and HRV indices were used to assess the effects of CE upon the autonomic control in peripheral and core vasculature, and on the relationship between HRV and PRV. The hypotheses underlying the experiment were that PRV from central vasculature is less affected by CE than PRV from the peripheries, and that PRV from peripheral and central vasculature differ with HRV to a different extent, especially during CE. Results: Most of the PRV time-domain and Poincaré plot indices increased during cold exposure. Frequency-domain parameters also showed differences except for relative-power frequency-domain parameters, which remained unchanged. HRV-derived parameters showed a similar behavior but were less affected than PRV. When PRV and HRV parameters were compared, time-domain, absolute-power frequency-domain, and non-linear indices showed differences among stages from most of the locations. Bland-Altman analysis showed that the relationship between HRV and PRV was affected by CE, and that it recovered faster in the core vasculature after CE. Conclusion: PRV responds to cold exposure differently to HRV, especially in peripheral sites such as the finger and the toe, and may have different information not available in HRV due to its non-localized nature. Hence, multi-site PRV shows promise for assessing the autonomic activity on different body locations and under different circumstances, which could allow for further understanding of the localized responses of the autonomic nervous system.

Optimization of extracorporeal membrane oxygenation therapy using near-infrared spectroscopy to assess changes in peripheral circulation: A pilot study.

Near-infrared spectroscopy (NIRS) has been proposed as a noninvasive modality for detecting complications in patients undergoing extracorporeal membrane oxygenation (ECMO), and it can simultaneously reveal the global circulatory status of these patients. We optimized ECMO therapy on the basis of real-time peripheral NIRS probing. Three patients underwent venoarterial (VA) ECMO and one patient underwent venovenous (VV) ECMO. All patients received peripheral ECMO cannulation with routine distal perfusion catheter placement. We designed an experimental protocol to adjust ECMO blood flow over 1 hour. Hemodynamic responses were measured using NIRS devices attached to the calf at approximately 60% of the distance from the ankle to the knee. HbO2 levels change substantially with adjustments in ECMO flow, and they are more sensitive than HHb levels and the tissue saturation index (TSI) are. NIRS for optimizing ECMO therapy may be reliable for monitoring global circulatory status.