DXA-based appendicular composition measures in healthy aging Caucasian Greek women: a cross-sectional study.

As the global population of older persons increases, age-related medical conditions will have a greater impact on public health. DXA-derived bone and soft tissue metrics are associated with adverse clinical events in aging persons. This study aims to investigate the regional body composition of the appendices by whole-body DXA scans, and the age-related relationships between measures of bone and soft tissue in healthy Caucasian females of a Greek origin residing in the Mediterranean area. Body composition of the legs and the arms was analyzed, and lean mass (LM) and fat mass (FM) metrics were calculated in 330 women aged 20-85 years, using DXA. Peak bone mineral density (BMD) of the legs and arms was achieved between ages 20-30 and 41-50 years, respectively. The overall BMD reduction with age was for the legs 43% and the arms 32.2% (p < 0.001). Peak %LM of the legs and the arms was achieved between ages 20-30. The overall reduction of %LM with age was for the legs 22.5% (p < 0.001) and arms 6.6% (p < 0.05). Peak %FM of the legs and arms was attained between ages 31-40 and 61-70, respectively. The overall %FM reduction with age was for the legs and arms 7.5% and 1.9% (p > 0.05). In appendicular sites, Greek women reach peak values of bone mass in the legs first, in early adulthood. Bone loss predominates in the legs as women age. Also, with advancing age Greek women show preferential significant decreases of %LM and %FM in the legs as opposed to the arms. Although variation in appendicular bone and soft tissue metrics is present, the implications of variable biological crosstalks among the tissue components as women age may ultimately lay the foundation for future clinical trials aimed at healthy aging.

Age-related variations in trunk composition and patterns of regional bone and soft tissue changes in adult Caucasian women by DXA.

We explored the regional variations in body composition with advancing age in healthy Caucasian females living in the Mediterranean area. The objectives of this study were to establish body composition values for the trunk in healthy women of a Greek origin and to evaluate the effects of aging on the distribution of truncal bone mass, fat mass (FM) and lean mass (LM). Body composition of the trunk and detailed analysis of its anatomical components-the ribs, the thoracic spine, the lumbar spine and the pelvis, and FM and LM ratios--were calculated in 330 women aged 20-85 years, using DXA. Peak bone mineral density (BMD) of the trunk was attained between ages 30 and 33. The overall truncal BMD reduction with age was 20.7% (p < 0.001). Peak %LM of the trunk was achieved at age 20. The overall reduction of %LM with age for the trunk was 9.8% (p < 0.001). Peak %FM of the trunk was attained between ages 68 and 73, and the overall %FM reduction with age was 2.8% (p > 0.05). Multiple comparative analyses showed that the 51-60 years age group was the landmark age for significant changes of truncal bone mass measures across all age groups (p = 0). For truncal LM and FM metrics, multigroup comparative analysis showed the turning point of significant changes in soft tissue was the 41-50 age bracket (p = 0 and p = 0, respectively). In Greek women, truncal %LM exceeded by far %FM across all ages (p = 0). Our results suggest that aging affects body composition of the trunk in ambulatory healthy women of a Greek origin differently, leading to menopausal loss of bone mass, senior adulthood loss of lean mass, and middle-age storage of fat mass. In adult women, these age-related associations between bone and soft tissue metrics on DXA exams carry implications for the attainment of optimal peak values and shifts in body composition overtime, impacting lifelong skeletal health.

Silent severe myocardial ischemia in a past illicit drug user imaged with myocardial perfusion scintigraphy.

Patients with illicit drug use may have deleterious acute and chronic cardiac effects. We present a case of a 42-year-old man, former alcohol and various illicit drugs user, who was admitted to the psychiatric unit for management of psychosis. Because of his previous drug and alcohol history, a cardiological evaluation was performed which revealed silent severe myocardial ischemia detected by myocardial perfusion imaging (MPI). The myocardial ischemia was attributed to coronary microvascular dysfunction, occurring several years after quitting the illicit drugs. This study highlights the potential myocardial ischemia that may occur in patients with previous alcohol and illicit drug use, and the role of MPI, a non-invasive test that can provide important information regarding the myocardial status of such patients, even without obvious cardiac symptoms or findings.

Conversion of Propranolol to Carvedilol Improves Renal Perfusion and Outcome in Patients With Cirrhosis and Ascites.

BACKGROUND: In recent years, concerns have been raised on the potential adverse effects of nonselective beta-blockers, and particularly carvedilol, on renal perfusion and survival in decompensated cirrhosis with ascites. We investigated the long-term impact of converting propranolol to carvedilol on systemic hemodynamics and renal function, and on the outcome of patients with stable cirrhosis and grade II/III nonrefractory ascites. PATIENTS AND METHODS: Ninety-six patients treated with propranolol for esophageal varices' bleeding prophylaxis were prospectively evaluated. These patients were randomized in a 2:1 ratio to switch to carvedilol at 12.5 mg/d (CARVE group; n=64) or continue propranolol (PROPRA group; n=32). Systemic vascular resistance, vasoactive factors, glomerular filtration rate, and renal blood flow were evaluated at baseline before switching to carvedilol and after 6 and 12 months. Further decompensation and survival were evaluated at 2 years. RESULTS: During a 12-month follow-up, carvedilol induced an ongoing improvement of systemic vascular resistance (1372±34 vs. 1254±33 dynes/c/cm5; P=0.02) along with significant decreases in plasma renin activity (4.05±0.66 vs. 6.57±0.98 ng/mL/h; P=0.01) and serum noradrenaline (76.7±8.2 vs. 101.9±10.5 pg/mL; P=0.03) and significant improvement of glomerular filtration rate (87.3±2.7 vs. 78.7±2.3 mL/min; P=0.03) and renal blood flow (703±17 vs. 631±12 mL/min; P=0.03); no significant effects were noted in the PROPRA group. The 2-year occurrence of further decompensation was significantly lower in the CARVE group than in the PROPRA group (10.5% vs. 35.9%; P=0.003); survival at 2 years was significantly higher in the CARVE group (86% vs. 64.1%; P=0.01, respectively). CONCLUSION: Carvedilol at the dose of 12.5 mg/d should be the nonselective beta-blocker treatment of choice in patients with cirrhosis and nonrefractory ascites, as it improves renal perfusion and outcome.

Vitamin D Deficiency as a Risk Factor for Myocardial Ischemia.

Background and Objectives: Vitamin D (Vit D) deficiency has been implicated in various conditions, including cardiovascular disease. The purpose of this retrospective study was to investigate the incidence of patients with myocardial ischemia in relation to their serum levels of vitamin D. Materials and Methods: A 64-month search (January 2016 to April 2021) in our database of the Nuclear Medicine Laboratory revealed 113 patients who had both myocardial perfusion imaging with single photon emission computed tomography (MPI SPECT) and Vit D measurements. MPI SPECT obtained myocardial images during both stress (summed stress score, SSS) and rest (summed rest score, SRS). Abnormal MPI SPECT was when the SSS was ≥4. Vit D was determined by radioimmunoassay (RIA). Patients with Vit D values <10 ng/mL, 10-29 ng/mL and ≥30 ng/mL were defined as having a deficiency, insufficiency and sufficiency, respectively. Results: Among patients, 46/113 (40.7%) were male and 67/113 (59.3%) were female. Abnormal MPI was found in 58/113 (51.3%) patients. Vit D deficiency was noted in 20/113 (17.7%) patients, insufficiency in 86/113 (76.1%) patients, and normal Vit D was noted in only 7/113 (6.2%) patients. Sixteen of the 20 patients (80%) with Vit D deficiency, and 38/86 (44.2%) with insufficiency had an abnormal MPI SPECT. In contrast, only 1/7 (14.3%) patients with sufficient Vit D levels had an abnormal MPI SPECT. The Mann-Whitney U-test showed that ischemia reduced the values of Vit D. Correlation analysis showed a negative association of Vit D levels with SSS (rho = -0.232, p = 0.014) and SRS (rho = -0.250, p = 0.008). Further evaluation with a Vit D cut off 20 ng/mL retrieved no statistical significance. Finally, Vit D and gender were independently associated with myocardial ischemia. Conclusions: Low Vit D levels may represent a risk factor for myocardial ischemia.

Myocardial perfusion SPECT as a potential mediator on circulating chromogranin A in patients with old myocardial infarction.

OBJECTIVE: Chromogranin A (CgA) is a soluble polypeptide stored within and released from secretory granules of endocrine and other cell types (including cardiomyocytes); CgA appears to be a marker of the overall neuroendocrine activity. Increased levels of serum CgA have been found not only in patients with neuroendocrine neoplasms but also with other malignancies, hypertension, myocardial infarction, heart, or renal failure. SUBJECTS AND METHODS: A population of 307 patients (202 males, 105 females) was enrolled. The study group consisted of 118 individuals (38.4%) with myocardial infarction more than one year old (MI group); the remaining 189 (61.6%) had no known heart disease (control group). All patients underwent myocardial perfusion scintigraphy (MPS) after blood withdrawal for serum CgA measurement. To test whether a possible effect of old infarction on serum CgA is mediated by MPS findings, we employed analysis of covariance for three distinct categories of left ventricular (LV) perfusion deficits as dichotomous predictors: (1) any-type deficits (abnormal MPS); (2) reversible deficits (ischemia); and (3) fixed deficits (scar). RESULTS: In all three MPS conditions, the effect of age, gender, and LV ejection fraction (EFLV) on serum CgA was statistically significant: women exhibited higher CgA levels than men (P=0.008-0.023), whereas increasing age and decreasing EFLV were associated with increasing CgA (all P<0.001). Conversely, no statistically significant differences in mean CgA levels were found between MI patients and normal controls with either abnormal MPS, scar, or ischemia, or their degree and extent. CONCLUSION: Although serum CgA is significantly associated with age, gender, and EFLV in patients with an old MI, no association was found between CgA levels and either old MI history or MPS findings. The verified involvement of circulating CgA in the acute/subacute phase of infarction appears to be blunted in infarctions older than a year.

Diagnosis and treatment of limbic encephalitis in the cancer patient.

Limbic encephalitis is an inflammatory process involving the limbic structures of the brain, manifested with short-term memory deficits, confusion, depression and seizures. It is usually a paraneoplastic condition but it may also appear as a nonparaneoplastic syndrome. Patients with this condition may exhibit a variety of antibodies in their serum or/and cerebrospinal fluid targeting basement membrane components that bind to a variety of neurotransmitter receptors such as α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and GABA B and proteins associated to the ion channels such as LGI1, Caspr2 or intracellular components. Flurodeoxyglucose PET/computed tomography usually demonstrates increased uptake in the limbic structures, and it may reveal the site of the primary tumor. Treatment consists of tumor removal if possible. Symptomatic treatment includes steroids, gamma immune globulin, plasma exchange, immunosuppressive therapies and anti-epileptic drugs. Prognosis is better when it is associated with antibodies against basement membrane rather than intracellular antibodies.

Principles and current trends in the correlative evaluation of glioma with advanced MRI techniques and PET

Cerebral gliomas comprise a heterogeneous group of primary neoplasms of the central nervous system, representing a signifcant cause of cancer morbidity and mortality. Contrast-enhanced magnetic resonance imaging (MRI) is paramount for identifying structural brain abnormalities related to the development of gliomas. Although morphological MRI remains the current standard of care for initial diagnostic workup, surgical planning, monitoring therapy response and surveillance during follow-up, it is rather diffcult to define tumor grade and boundaries and to assess response to radiochemotherapy solely by contrast-enhancement, due to a variety of factors influencing blood-brain barrier (BBB) permeability and contrast agent distribution. The nature of a lesion lies beyond often misleading gross structural patterns, down to the cellular and molecular level, hence the imaging techniques of advanced multimodal MRI and positron emission tomography (PET) have emerged to provide critical non-invasive insight into the underlying biology of primary brain cancer. Out of the various PET radiotracers, labeled amino acids are of particular significance due to their non-dependency on BBB disruption to reach glioma cells and their excellent tumor-to-background contrast. After discussing the basic imaging principles of MR perfusion, diffusion, spectroscopy and PET in glioma, this review focuses on the correlative imaging with amino acid PET and advanced MRI techniques in tumor grading and staging, in guiding stereotactic biopsy and surgical excision and in assessing therapy response, post-therapy surveillance and prognosis. Lastly, a reference is made on the expanding availability of integrated PET/MRI systems and the resulting benefits of simultaneous image acquisition.

Novel molecular and metabolic aspects in osteosarcoma.

Osteosarcoma (OS) is the most frequent bone-forming malignancy in children and adolescents. Concerning its molecular landscape, there is no a direct relationship with a specific gene, but a combination of genetic events. A broad spectrum of activated oncogenes and downregulated suppressor genes has been already explored and considered crucial for its progressive pathogenesis. Mechanisms of gene deregulation include amplifications, point mutations, allelic losses and also epigenetic abnormalities such as aberrant promoter methylation. Although a significant progress in understanding the molecular nature of the OS has been achieved, its aggressive phenotype - characterized by high metastatic potential - remains unexplored. Novel targeted therapeutic strategies include monoclonal antibodies (mABs) and also tyrosine-kinase inhibitors (TKIs). Additionally, sophisticated and innovative diagnostic techniques, such as 18 fluorodeoxyglucose positron emission tomography plus CT (18F-FDG/PET/CT), provide critical data regarding its biological behavior. In the current paper, we present novel molecular and metabolic advances by analyzing OS genetic profile and biochemical microenvironment.

The diagnostic role of (18)F fluorodeoxyglucose positron emission tomography in patients with fever of unknown origin.

BACKGROUND: Identification of aetiology for fever of unknown origin (FUO) is challenging, due to the high rates of undiagnosed cases. The current diagnostic approach includes initially first-line procedures such as general examination and various laboratory tests and basic imaging techniques followed by second-line tests such as more advanced imaging techniques including (18)F fluorodeoxyglucose positron emission tomography (FDG PET) and tissue biopsies. If no diagnosis is obtained, more invasive measures may be in order such as liver biopsy and exploratory laparotomy. MATERIALS AND METHODS: This review article is based on the relative published material found on MEDLINE and PubMed up to August 2014. We looked for the terms 'fever of unknown origin, FDG PET' in combination with 'cancer, infection and autoimmune disease'. RESULTS: Several clinical studies have investigated the utility of the FDG PET during the diagnostic approach of FUO. Recent evidence suggests that FDG PET has the advantage of total body imaging and may depict all common causes of FUO such as infections, noninfectious inflammatory causes and tumours because they all exhibit glucose hypermetabolism. Depiction of an abnormal lesion on FDG PET could guide clinicians to the next diagnostic procedure (another imaging method, culture, biopsy or surgery) to establish the diagnosis. CONCLUSIONS: Emerging evidence suggests that FDG PET, when available, may provide critical diagnostic information early during evaluation of FUO.

Relationships between body composition analysis measures in Greek women and US white women.

We investigated the regional changes in body composition relative to age, in healthy Caucasian women living in the Mediterranean area. Body composition of total and subtotal body was measured, and fat mass (FM) ratios along with FM and lean mass (LM) indices were calculated in 330 women aged 20-85 years, using DXA. Data were compared with the NHANES reference database. Peak bone mineral density and bone mineral content of total body were 1.149 g/cm(2) and 2,209 g and were achieved between ages 41 and 50. Peak %FM of total body, FM index (FMI; FM/height(2)), FM of trunk to legs, and FM of trunk to limbs were 41.5%, 13.69 kg/m(2), 1.623, and 1.14, respectively. Peak %FM and FMI were achieved between 61 and 70 years. Unlike US counterparts, in our series, both FM ratios showed a propensity for women to accrue fat in the trunk following the android pattern of fat distribution. Peak LM index for total body (LMI; LM/height(2)) and limbs (ASMMI; appendicular skeletal muscle mass/height(2)) was 18.08 kg/m(2) and 7.33 kg/m(2), respectively, and was achieved between 61 and 70 years. For Greeks, the ASMMI was greater from 55 years onwards. Greek women have increasing bone mass in early adulthood followed by significant decline during fifties and onwards. Compared with US white women, Greek women have significantly greater truncal fat for all ages, implying a greater risk of obesity-associated diseases. Middle-aged and older Greek women have greater appendicular skeletal muscle mass, which may eliminate the overall risk of sarcopenic obesity.

Imaging of cardiac amyloidosis by (99m)Tc-PYP scintigraphy.

OBJECTIVE: Cardiac amyloidosis (CA) is an underestimated and underdiagnosed cause of cardiac insufficiency. Despite being often considered as a solitary entity attributable to extracellular deposition of fibrillary proteins, there exist at least two different pathophysiologic backgrounds, with different clinical course and treatment. a) In light-chain cardiac amyloidosis (immunoglobulin light-chain amyloidosis-AL) the fibrils consist of light-chain immunoglobulins produced by a clonal plasma cell population in bone marrow. b) In CA related to transthyretin (transthyretin-related amyloidosis - ATTR), whether familial amyloid cardiomyopathy or senile systemic amyloidosis, monomers or dimers of the normally tetrameric protein of transthyretin are deposited in the myocardium. Today, definitive diagnosis of cardiac amyloid disease is based on endomyocardial biopsy in conjunction with immunohistochemical parameters or, in ambiguous cases, with mass spectroscopy. Several radiotracers have been hitherto tried in the detection of CA. SUBJECTS AND METHODS: In this pilot study technetium-99m pyrophosphate ((99m)Tc-PYP) was administered to patients suffering from CA, aiming to differentiate scintigraphically between AL and ATTR. Twelve patients (8 males, aged [mean±SD] 70,6±13,2y; 4 females, aged 65,7±9,9y) were enrolled for the discrimination between AL and ATTR. Diagnosis was confirmed by biopsy combined with the clinical and laboratory evaluation of the patients. Myocardial scintigraphy (planar and tomographic imaging) was conducted at 1, 2 and/or 3h after intravenous administration of 555-925MBq (99m)Tc-PYP. Myocardial radiotracer uptake was evaluated optically and also by a semiquantitative method. Two regions of interest (ROI) were drawn: one over the heart and another over the contralateral hemithorax, to calculate the corresponding heart-to-contralateral (H/CL) count ratio. According to established reference standards, a cut-off H/CL value of 1.5 best discriminates between the two conditions. (99m)Tc-PYP scintigraphy revealed diffuse intense myocardial uptake upon visual evaluation that was also verified semi-quantitatively in 6 patients, all of which had ATTR. Faint or no myocardial tracer uptake was found in 4 patients who were diagnosed with AL. Two AL patients had a borderline positive scan on visual evaluation but their H/CL ratios did not exceed the value of 1.5. In three patients, we also attempted scintigraphy with the tracer pentavalent (99m)Tc-dimercaptosuccinic acid. Results and possible mechanisms of uptake are discussed. The sensitivity and specificity of scintigraphy with (99m)Tc-PYP was high, albeit the small number of patients. IN CONCLUSION: These preliminary results are compatible with current international literature, and demonstrate that scintigraphy with (99m)Tc-PYP may prove a simple, non-invasive and widely available method in the identification of patients with the ATTR subtype, thus optimizing therapeutic decisions.

Gender specific association of decreased bone mineral density in patients with epilepsy.

OBJECTIVE: To evaluate whether epilepsy or certain antiepileptic drugs render patients prone to develop low bone mineral density (BMD) and osteoporosis risk. METHODS: Thirty-eight (27 males, 11 females) consecutive adult epileptic patients receiving antiepileptic drugs (AEDs) and 71 control individuals matched for race, gender, age and body mass index (BMI) were subjected to dual energy X-ray absorptiometry (DXA). RESULTS: The mean lumbar spine and total hip BMD values were lower in the patients compared to control group (0.90±0.24 g/cm2 vs 1.04±0.14 g/cm2, p<0.001 and 0.92±0.14 g/cm2 vs 0.99±0.13 g/cm2, p=0.02, respectively). At the same skeletal sites, male patients had significantly reduced BMD compared to control males (0.90±0.21 g/cm2 vs 1.03±0.15 g/cm2, p=0.004 and 0.93±0.14 g/cm2 vs 1.02±0.13 g/cm2, p=0.009, respectively) while there was a trend but no significant differences in females. This BMD reduction was independent of AED type. CONCLUSION: Adult epileptic, predominantly male patients have lower BMD and could be screened with densitometry for early diagnosis and prevention of osteoporosis.

Growth and function in childhood of a normal solitary kidney from birth or from early infancy.

BACKGROUND: Children with a solitary kidney (SK) have an increased long-term risk of hypertension, albuminuria and glomerulosclerosis. In this study, we assessed the early signs of impaired glomerular filtration in children with a SK from birth or from early infancy. METHODS: Renal growth and function at ages 4-15.5 years were studied in 38 children with SK and 40 matched control subjects in terms of accelerated growth. RESULTS: The systolic/diastolic blood pressure Z-scores (p = 0.01/<0.05) and the resistance index (RI) of the arcuate arteries (p = 0.05) were higher in the children with SK. Creatinine clearance and 24-h protein and albumin urinary excretion showed no difference. All but seven children with SK had 99mTc diethylene-triamine pentaacetic acid glomerular filtration rate values of >80 ml/min/1.73 m(2). An independent positive correlation was found between length of the follow-up time and 24-h albumin urinary excretion (ß = 0.54, p < 0.01). Accelerated postnatal growth was positively related with kidney volume (ß = 0.35, p < 0.05). CONCLUSIONS: Among our patient cohort, renal function was well preserved at ages 4-15.5 years in children who were born with a SK. However, both their higher blood pressure and RI and the correlation of 24-h albumin urinary excretion with length of follow-up time underline the need for monitoring to detect early signs of glomerular hyperfiltration and, if necessary, implement timely intervention. SK hypertrophy was found to be correlated with postnatal growth.