18FDG-PET/CT in traumatic brain injury patients: the relative hypermetabolism of vermis cerebelli as a medium and long term predictor of outcome.

PURPOSE: Both, the constant presence of apparent hypermetabolism of the vermis cerebelli compared to the cerebellar hemispheres in traumatic brain injury, and the presence of a good relationship between the intensity of this sign and the severity of the clinical conditions have been addressed in previous studies. Aim of the present paper is to evaluate the possible correlation between the intensity of the finding and the medium and long term outcome in a group of patients. MATERIALS AND METHODS: A group of 105 patients consecutively admitted to the Brain Injury Rehabilitation Center of our Hospital between 2005 and 2012 was studied with a 18FDG-PET/CT study of the brain after head trauma; the metabolic activity of the cerebellar vermis was semiquantitatively assessed (vermis/cerebellum ratio, V/C). After that, all patients received systematic monitoring of their performance status via the timely administration of commonly used tests (DRS, LCF and GOS) during one whole year after the head trauma. The V/C parameter was compared with the evolution of performance abilities, as shown by the rating scales. RESULTS: Statistical analysis showed a significant direct association between the V/C ratio and the DRS score at each time point (3 months: P<0.001; 6 months: P<0.001; 12 months: P<0.001) and significant inverse association with the LCF score (3 months: P<0.001; 6 months: P<0.001; 12 months: P<0.001) and the GOS score (3 months: P<0.001; 6 months: P<0.001; 12 months: P<0.001) at each time point. Moreover, patients with a V/C ratio ≥ 1 have a significantly greater probability to achieve a good functional outcome as defined by a DRS score ≥ 3 points, a LCF score ≥ 7 points and and a GOS score =5 points. CONCLUSIONS: In our group of patients, the V/C parameter has demonstrated to be a predictor of outcome. If validated by more extensive experiences, this approach could offer the possibility of performing a reliable prognostic evaluation in a notoriously "difficult" class of patients with an acceptable technique and economical effort.

Relative hypermetabolism of vermis cerebelli in traumatic brain injured patients studied with 18FDG PET: a descriptor of brain damage and a possible predictor of outcome.

PURPOSE: The almost constant presence of apparent metabolic hypermetabolism of cerebellar vermis seen on 18FDG PET in a population of injured brains has been reported in a previous paper. Aim of this paper is to determine a) whether there is a correlation between the entity of this sign, semi quantitatively determined, and the severity of the trauma at its onset, and b) whether the entity of the relative enhancement correlates with the medium and long term clinical outcome. METHODS: A group of 45 consecutive patients admitted to the Acquired Brain Injury Unit of our Hospital for recent, major head trauma, underwent a basal 18FDG PET/CT scan of the brain; the presence of relative hypermetabolism of the vermis cerebelli was visually assessed and semi quantitatively determined (vermis/cerebellum ratio: V/C); the median V/C value was used as a divide between low V/C ratios (group A) and high V/C ratios (group B). During one year after trauma, every patient from both groups received an extensive testing to evaluate cognitive and behavioral performances and evolution: Disability Rating Scale (DRS) and Levels of Cognitive Function (LCF) were administered monthly from month 1 to month 6, and at 12 months from the trauma; Glasgow Outcome Scale (GOS) was administered at 3, 6 and 12 months from the head trauma. Numerical scores from each of these performance-testing protocols were cross-matched with values derived from the V/C 18FDG PET/CT determinations. A relative risk estimate via Chi-square testing was performed on the results of both groups for LCF and DRS scales at 1, 6 and 12 months from trauma. RESULTS: At one month after trauma, overall LCF (LCF1) values ranged from 2 to 8, avg. 3.77, SD ± 2.10; the average value in group A was 5.21, SD ± 2.09, in B group 2.47, SD ± 0.98 (F=17.5, P = 0). At this time, overall average DRS (DRS1) was 6.7, SD ± 2.05, ranging from 2 to 9; the average value was 5.52, SD ± 0.47 in group A, and 7.72, SD ± 0.30 in group B (F = 6.3, P = 0.01). Relative risk estimates for patients with higher V/C ratios for poor performance in DRS scale were: 2.46 at 1 month (confidence boundaries 1.66 - 3.64), 3.75 (c.b. 1.64 - 8.64) at 6 months, 5.17 (c.b. 1.76 - 15.16) at one year. Relative risk estimates for LCF scale were: 3.20 (c.b. 1.74 - 5.90) at 1 month, 6.909 (c.b. 1.03 - 46.15) at 6 months, 4.22 (c.b. 0.65 - 27.10) at 12 months. CONCLUSIONS: A) there is a strong correlation between the semi quantitatively determined values of vermian relative hypermetabolism and the severity of trauma as determined by standard cognitive and performance testings; the V/C ratio may therefore be considered a reliable, although non-specific, index of brain suffering. B) there is a good statistical correlation between the semi quantitative vermian/cerebellar ratio determined shortly after the trauma, and the clinical outcome of the patients, evaluated by standard clinical performance tests and relative risk estimates.

Biomarkers in kidney and heart disease.

There is much symptomatic similarity between acute kidney disease and acute heart disease. Both may present with shortness of breath and chest discomfort, and thus it is not surprising that biomarkers of acute myocardial and renal disease often coexist in many physicians' diagnostic work-up schedules. In this review we explore the similarities and differences between current and future tests of myocardial and renal injury and function, with particular emphasis on the diagnostic utility of currently available biomarkers to assist with the diagnosis of cardiorenal syndromes. Imaging studies have not traditionally been viewed as clinical biomarkers, but as tests of structure and function; they contribute to the diagnostic process, and we believe that they should be considered alongside more traditional biomarkers such as blood and urine measurements of circulating proteins and metabolites. We discuss the place of natriuretic peptides, novel tests of kidney damage as well as kidney function and conclude with a discussion of their place in guiding future research studies whose goals must include better characterization of the degree of dysfunction imposed on one organ system by failure of the other.

Heart-kidney biomarkers in patients undergoing cardiac stress testing.

We examined association of inducible myocardial perfusion defects with cardiorenal biomarkers, and of diminished left ventricular ejection fraction (LVEF) with kidney injury marker plasma neutrophil gelatinase-associated lipocalin (NGAL). Patients undergoing nuclear myocardial perfusion stress imaging were divided into 2 groups. Biomarkers were analyzed pre- and poststress testing. Compared to the patients in the low ischemia group (n = 16), the patients in the high ischemia group (n = 18) demonstrated a significantly greater rise in cardiac biomarkers plasma BNP, NT-proBNP and cTnI. Subjects were also categorized based on pre- or poststress test detectable plasma NGAL. With stress, the group with no detectable NGAL had a segmental defect score 4.2 compared to 8.2 (P = .06) in the detectable NGAL group, and 0.9 vs. 3.8 (P = .03) at rest. BNP rose with stress to a greater degree in patients with detectable NGAL (10.2 vs. 3.5 pg/mL, P = .03). LVEF at rest and with stress was significantly lower in the detectable NGAL group; 55.8 versus 65.0 (P = .03) and 55.1 vs. 63.8 (P = .04), respectively. Myocardial perfusion defects associate with biomarkers of cardiac stress, and detectable plasma NGAL with significantly lower LVEF, suggesting a specific heart-kidney link.

Cardiorenal syndromes: an executive summary from the consensus conference of the Acute Dialysis Quality Initiative (ADQI).

The cardiorenal syndrome (CRS) is a disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The general definition has been expanded into five subtypes reflecting the primacy of organ dysfunction and the time-frame of the syndrome: CRS type 1 = acute worsening of heart function leading to kidney injury and/or dysfunction; CRS type 2 = chronic abnormalities in heart function leading to kidney injury or dysfunction; CRS type 3 = acute worsening of kidney function leading to heart injury and/or dysfunction; CRS type 4 = chronic kidney disease leading to heart injury, disease and/or dysfunction, and CRS type 5 = systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. Different pathophysiological mechanisms are involved in the combined dysfunction of heart and kidney in these five types of the syndrome.

Cardio-renal syndromes: report from the consensus conference of the acute dialysis quality initiative.

A consensus conference on cardio-renal syndromes (CRS) was held in Venice Italy, in September 2008 under the auspices of the Acute Dialysis Quality Initiative (ADQI). The following topics were matter of discussion after a systematic literature review and the appraisal of the best available evidence: definition/classification system; epidemiology; diagnostic criteria and biomarkers; prevention/protection strategies; management and therapy. The umbrella term CRS was used to identify a disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ. Different syndromes were identified and classified into five subtypes. Acute CRS (type 1): acute worsening of heart function (AHF-ACS) leading to kidney injury and/or dysfunction. Chronic cardio-renal syndrome (type 2): chronic abnormalities in heart function (CHF-CHD) leading to kidney injury and/or dysfunction. Acute reno-cardiac syndrome (type 3): acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. Chronic reno-cardiac syndrome (type 4): chronic kidney disease leading to heart injury, disease, and/or dysfunction. Secondary CRS (type 5): systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. Consensus statements concerning epidemiology, diagnosis, prevention, and management strategies are discussed in the paper for each of the syndromes.

Image-guided robotic stereotactic radiosurgery for unresectable liver metastases: preliminary results.

The aim of this study was to evaluate the usefulness of image-guided robotic stereotactic radiosurgery for the local control of unresectable liver metastases from colorectal and non-colorectal cancer. Twenty-seven consecutive patients (median age 62 years, range 47-80 years) with liver metastases considered unsuitable for surgery were enrolled in the study. The diagnosis was colorectal cancer liver metastasis in 11 (41%) and other secondary malignancies in 16 (59%) patients. The patients were treated with 25 to 60 Gy (median 36 Gy) delivered in 3 consecutive fractions, and the isodose value covering the planning target volume was 80% of the prescribed dose. Overall, the mean tumour volume was 81.6+/-35.9 ml. Inhibition of growth or a reduction in size was obtained in 20 (74.1%) patients: 7 with complete response and 13 with partial response. There was a local complete response with other single lesions appearing in 3 (11.1%) patients and progressive disease in 4 (14.8%). The median post-treatment volume of the tumour was 24 ml (range 0-54 ml) among the responders. Mild or moderate transient hepatic dysfunction was evident in 9 patients and minor complications in five. Two patients with progressive disease died of liver failure. In conclusion, in patients with liver metastases unsuitable for surgery, stereotactic radiosurgery achieves high rates of local disease control, representing an acceptable alternative therapy, but should be further studied in larger series.

The effect of 18F-FDG-PET/CT respiratory gating on detected metabolic activity in lung lesions.

OBJECTIVE: Respiratory gated PET/CT (positron emission tomography/computed tomography) of the lung is expected to increase the accuracy of quantitative determinations in lesional activities, regardless of the gating method used; reasonably, respiratory gating should increase standard uptake value (SUV; and possibly decrease lesional size), on the basis of the reduction of the "smearing effect." However, literature data are very limited, particularly for in vivo studies. The objective of this article is to test the SUV variations in a large group of lung lesion studies. METHODS: A group of 26 consecutive positive studies (21 men, 5 women, age 36-84, mean 68), performed on patients referred to our institution for known or suspected lung cancer, are examined. All studies were performed both with conventional PET/CT total body scan and with Real-Time Position Management (RPM) triggered selective gated study of the thorax. Four studies were considered technically unsatisfactory and were discarded; the remaining 22 studies are the object of this work. Max lesional SUVs were evaluated in both settings by semi-automated algorithms; for the gated studies, both values of the bin that showed more relevant variations from the clinical routinary study ("best bin") and an average value that was calculated over all bins were determined. Results were compared on a one-to-one basis. RESULTS: In conventional, SUV showed a mean +/- standard deviation (SD) value of 9.2 +/- 6.9 (range 0.9-26). In the averaged gated studies, the mean +/- SD value was 13.4 +/- 11.7 (range 1.4-47); in the "best bin" dataset the mean +/- SD was 14.9 +/- 12.9, ranging from 1.6 to 53.1. In general, the use of respiratory trigger induced rather variable but overall consistent increases in SUV. If the percentage variations in the average trigger dataset are considered, there is an average increase of +60%, SD +/- 97 (P < 0.05). Similar results are found in the "best bin" dataset, the average percentage increase in SUV values being +77.2% (SD +/- 04.6). CONCLUSIONS: In lung cancer, triggering procedures increase the signal to noise ratio. The increase in SUV determined by gating is very variable, but generally relevant. This could lead to an SUV values cut-off revision, and may have an impact on smaller lesions detection.

Pre-therapy hyperfunctioning follicular thyroid carcinoma evaluation with I-131 whole-body scan and with F-18 FDG PET/CT.

We describe a patient with persistent hyperthyroidism after total thyroidectomy for toxic multinodular goiter and without therapy with levothyroxine evaluated with I-131 whole-body scan and with F-18 FDG PET/CT scan. Scintigraphy performed 48 hours after radiopharmaceutical administration showed many areas of focal radioiodine uptake. A week later we performed a PET/CT scan to better localize the anatomic site of the iodine-positive lesions. Both scans, performed after methimazole withdrawal, visualized the same lesions, and these results were used as a guide for biopsy. Histologic examination was consistent with metastatic follicular thyroid carcinoma.

Competitive sport after coronary angioplasty: suggested eligibility criteria for moderate-high intensity sport.

Physical activity is encouraged following coronary revascularization to reduce restenosis and progression of coronary disease. Some patients may even opt to take on or resume competitive sport. Therefore, sport physicians have to face a decision whether patients are eligible or not to do so. The most recent Italian cardiology protocols regarding eligibility for competitive sport suggest that after examination on a case-by-case basis, subjects with isolated stenosis of a coronary vessel may be deemed eligible even for sports involving high-cardiovascular demand. This is possible if the subject is at low risk, has successfully undergone coronary angioplasty at least 1 year earlier, and undergoes obligatory 6-monthly follow-up examinations. In our view, in addition to fulfilling the criteria drawn up by the cardiology protocols, patients should also have completed a period of cardiologic rehabilitation, should not display perfusion defects on exercise myocardial scintigraphy (carried out annually), and should be free from cardiovascular risk factors, for which we propose restrictive threshold values. If an individual has not completed an adequate period of rehabilitation or presents cardiovascular risk factors, a further assessment should be made after at least 8 weeks of cardiac rehabilitation and after the risk factors have been corrected.

Volume overload modulates effects of cardiac resynchronization therapy independently of myocardial reperfusion: results of the RESYNC study.

OBJECTIVES: Cardiac resynchronization therapy (CRT) may induce significant changes in regional wall motion and perfusion. However, the link between these variables in patients with heart failure has not been investigated. METHODS: Thirty-six patients with idiopathic (n = 22) or ischemic (n = 14) cardiomyopathy (mean age 70 +/- 8 years, 24 male) were studied by echocardiography and gated single-photon emission computed tomography (SPECT) before and within 2 months after CRT. RESULTS: New York Heart Association class improved in all but four patients. The perfusion analysis indicated that, in all but three patients, there was a significant improvement of tracer uptake. Baseline end-diastolic volume index obtained by gated SPECT modulated increase of ejection fraction (P < 0.001), reduction of end-systolic volume index (P < 0.01) and improvement of motion (P < 0.001), as well as of left ventricular wall thickening (P < 0.002). Finally, despite CRT inducing significant reperfusion independently of volume overload (P < 0.05), extension of perfusion defect correlated with global improvement in the follow-up (P < 0.05). CONCLUSIONS: Volume overload may identify responders to resynchronization therapy. CRT induced a significant 'reperfusion' both in ischemic and idiopathic cardiomyopathies, even if this is not sufficient to improve left ventricular function in patients with more severe volume overload. Finally, simultaneous evaluation of volume overload and perfusion defects may result useful in identifying CRT responders.

Cerebellar vermis relative hypermetabolism: an almost constant PET finding in an injured brain.

Cortical alterations of brain metabolism, as seen in PET, obviously depend on the nature of the damage (either mechanical, toxic, anoxic, or other). However, some subcortical abnormalities seem to occur rather frequently regardless of the extension, position and cause of the damage. In particular, relative cerebellar vermis activation seems to be frequently encountered. The aim of this work was to determine the incidence of this pattern in a heterogeneous population of brain trauma, and to compare it on a quantitative basis with a group of age-sex matched controls. The case records of this study consist of 58 consecutive patients, 44 males, 14 females, age 14-69 (median 34) 44 traumatic, 8 anoxic, 4 vascular and 2 toxic injuries. In the trauma group, the visualization of the cerebellar vermis was readily appreciable as a consistent majority of cases. In particular, the mean vermis/cerebellum ratio (calculated by appropriate ROI positioning) was 1.26 +/- 0.17 SD (range 0.92-1.82); in the control group the same parameters showed much less dispersion: average 0.92 +/- 0.06, range 0.80-1.10 (P < 0.005). If, on the basis of the normal group data, a cut-off value of 1 is accepted for the v/c ratio, it is noted that 54/57 trauma patients (95%) showed a ratio above this value. In conclusion, a hypermetabolic cerebellar vermis is a common finding in a damaged brain, regardless of the nature of the trauma (probably due to the relative preservation compared with other structures of alternative metabolic pathways), and seems to be the hallmark of the injured brain.

Direct intramyocardial percutaneous delivery of autologous bone marrow in patients with refractory myocardial angina.

BACKGROUND: Intramyocardial injection of autologous bone marrow (ABM) may induce angiogenesis. We tested the safety and feasibility of catheter-based direct percutaneous intramyocardial delivery of ABM in patients with refractory angina pectoris. METHODS: Ten patients (9 men, 67 +/- 8 years) with refractory angina (Canadian Cardiovascular Society class III-IV) and documented myocardial ischemia were enrolled. After left ventricular electromechanical mapping, freshly aspirated and filtered ABM was percutaneously injected into target myocardial ischemic areas. Clinical symptoms (as assessed according to the Canadian Cardiovascular Society class), quality of life, and myocardial perfusion were evaluated before the procedure and through the follow-up. RESULTS: In all patients, ABM was successfully injected into the target regions. No periprocedural complications occurred. At 12 months, no major cardiac events (death, acute myocardial infarction, stroke, and malignant ventricular arrhythmias) occurred. Severity of angina improved of > or = 2 classes in 3 patients. Quality of life showed a significant improvement in all patients. Myocardial perfusion in the target regions improved in 4 of 8 patients. CONCLUSIONS: Direct percutaneous intramyocardial delivery of ABM appears feasible and safe. Further evaluation is warranted to test its clinical efficacy.

The extent of perfusion-F18-fluorodeoxyglucose positron emission tomography mismatch determines mortality in medically treated patients with chronic ischemic left ventricular dysfunction.

OBJECTIVES: The purpose of this study was to assess the determinants of mortality in a large group of patients with ischemic cardiomyopathy who are treated medically and the impact of the extent of viable tissue on prognosis. BACKGROUND: Whether the presence of viability drives mortality in patients with ischemic cardiomyopathy who are treated medically and whether the extent of viability is important are issues that are currently unclear. METHODS: Two hundred sixty-one patients with ischemic cardiomyopathy underwent positron emission tomography (PET) for assessment of viability. Prospective follow-up was obtained. RESULTS: Ninety-four patients were revascularized and 167 were not. The cardiac death rate was significantly less in the revascularized patients as compared with medically treated patients (13% vs. 24%, p < 0.05). In the revascularized patients, there was a trend toward better survival in patients with viable myocardium as compared with nonviable myocardium (3.5-year survival, 85% and 75% respectively, p = NS). In the medically treated group, age (hazard ratio [HR] 2.1, 95% confidence interval [CI] 1.2 to 3.7), presence of left bundle branch block (HR 3.4, 95% CI 1.6 to 7.2) and extent of perfusion-metabolism mismatch on PET (HR 1.36, 95% CI 1.1 to 1.6) predicted cardiac death during a median follow-up period of 2.1 years. The risk of cardiac death was not significantly increased when the extent of mismatch was < or =20% (HR 0.97, 95% CI 0.46 to 2.05) but was significantly increased when the extent of mismatch was >20% (HR 3.21, 95% CI 1.38 to 7.49). CONCLUSIONS: Medically treated patients with ischemic cardiomyopathy and large areas of viable myocardium on PET are at high risk for cardiac death.

Evidence of reverse mismatch with positron emission tomography imaging in a patient with reversible myocardial dysfunction.

We describe the case of a patient who came to our attention because of a reversible depression of myocardial contractility, probably due to myocarditis. A positron emission tomography study showed, in correspondence to the malfunctioning segments, a decreased F18-2-fluoro-2-deoxyglucose (F18-FDG) uptake in the presence of a normal perfusion as assessed by means of N13-labeled ammonia uptake. This phenomenon, called "reverse mismatch", shows that viability is not always dependent on FDG uptake and that it could be associated with the recovery of myocardial contractility. Some interpretations of the association between a reversible dysfunction and a reduced myocardial glucose metabolism are presented. The central role of nitric oxide and of cyclic guanosine monophosphate is hypothesized to explain both the mechanical and metabolic abnormalities.