Myocardial perfusion imaging-derived left ventricular strain: Regional abnormalities associated with transthyretin cardiac amyloidosis.

Background: Transthyretin (ATTR) cardiac amyloidosis is associated with an apical-sparing strain pattern on TTE. We hypothesize that strain indices derived from myocardial perfusion imaging (MPI) can identify this abnormality. Methods: A group with ATTR amyloidosis was compared to age-matched controls with LVH but without amyloidosis who underwent PET or SPECT MPI. Strain values were used to calculate the apical strain index (ASI), apex-to-base ratio (ABR), and ejection fraction to global strain ratio in multiple planes. Results: A direct comparison using Welch's t-tests reveals 6 statistically significant metrics. After regression analysis, the circumferential ASI and ABR at rest remain significantly greater in the ATTR group compared to controls. Conclusion: MPI-derived strain from the circumferential plane at rest may distinguish cardiac amyloidosis from other forms of LVH. If these findings are confirmed with validation studies, routine MPI-derived strain analysis could identify patients with subclinical amyloidosis who may benefit from further testing.

A Pilot Study of Neurobiological Mechanisms of Stress and Cardiovascular Risk.

Objective: Coronary heart disease is a leading cause of death and disability. Although psychological stress has been identified as an important potential contributor, mechanisms by which stress increases risk of heart disease and mortality are not fully understood. The purpose of this study was to assess mechanisms by which stress acts through the brain and heart to confer increased CHD risk. Methods: Coronary Heart Disease patients (N=10) underwent cardiac imaging with [Tc-99m] sestamibi single photon emission tomography at rest and during a public speaking mental stress task. Patients returned for a second day and underwent positron emission tomography imaging of the brain, heart, bone marrow, aorta (indicating inflammation) and subcutaneous adipose tissue, after injection of [18F]2-fluoro-2-deoxyglucose for assessment of glucose uptake followed mental stress. Patients with (N=4) and without (N=6) mental stress-induced myocardial ischemia were compared for glucose uptake in brain, heart, adipose tissue and aorta with mental stress. Results: Patients with mental stress-induced ischemia showed a pattern of increased uptake in the heart, medial prefrontal cortex, and adipose tissue with stress. In the heart disease group as a whole, activity increase with stress in the medial prefrontal brain and amygdala correlated with stress-induced increases in spleen (r=0.69, p=0.038; and r=0.69, p=0.04 respectfully). Stress-induced frontal lobe increased uptake correlated with stress-induced aorta uptake (r=0.71, p=0.016). Activity in insula and medial prefrontal cortex was correlated with post-stress activity in bone marrow and adipose tissue. Activity in other brain areas not implicated in stress did not show similar correlations. Increases in medial prefrontal activity with stress correlated with increased cardiac glucose uptake with stress, suggestive of myocardial ischemia (r=0.85, p=0.004). Conclusions: These findings suggest a link between brain response to stress in key areas mediating emotion and peripheral organs involved in inflammation and hematopoietic activity, as well as myocardial ischemia, in Coronary Heart Disease patients.

Determination of [N-13]-ammonia extraction fraction in patients with coronary artery disease by calibration to invasive coronary and fractional flow reserve.

BACKGROUND: This study presents a new extraction fraction (EF) model based on physiological measures of invasive coronary flow reserve (CFR) and fractional flow reserve (FFR) in patients with suspected coronary artery disease (CAD) and normal index microcirculatory resistance (IMR). To ascertain the clinical relevance of the new EFs, flow measurements using the newly patient-determined EFs were compared to flow measurements using traditional animal-determined EFs. METHODS: 39 patients were retrospectively selected that included a total of 91 vascular territories with invasive coronary angiography physiological measures. [N-13]-ammonia dynamic rest/adenosine-stress PET imaging was conducted in all patients and absolute myocardial flow was estimated using four published compartmental models. The extraction fraction during hyperemic flow was iteratively estimated by maximizing the agreement between invasive CFR and FFR with the non-invasive analogs myocardial flow reserve (MFR) and relative flow reserve (RFR) at similar physiological states, respectively. RESULTS: Using the new patient-determined EFs, agreement between CFR vs MFR for Model 1 and 2 was moderate and poor for Model 3 and 4. All models showed moderate agreement for FFR vs RFR. When using published models of animal-determined EFs, agreement between CFR vs MFR remained moderate for Model 1 and 2, and poor for Model 3 and 4. Similarly, all models showed moderate agreement for FFR vs RFR using animal-determined EF values. None of the observed differences were statistically significant. CONCLUSIONS: Flow measurements using extraction fraction correction for [N-13]-ammonia based on calibration to invasive intracoronary angiography physiological measures in patients with CAD were not discordant from those reported in the literature. Either patient-determined or traditional animal-determined EF correction, when used with the appropriate flow model, yields moderate agreement with invasive measurements of coronary flow reserve and fractional flow reserve.

Meta-analysis of the effect of perioperative intravenous lidocaine on return of gastrointestinal function after colorectal surgery.

BACKGROUND: Return of normal gastrointestinal (GI) function is a critical determinant of recovery after colorectal surgery. The aim of this meta-analysis was to evaluate whether perioperative intravenous (IV) lidocaine benefits return of gastrointestinal function after colorectal resection. METHODS: A comprehensive search of Ovid Medline, PubMed, Embase, Cochrane library, and clinicaltrials.org was performed on 1st July 2018. A manual search of reference lists was also performed. Inclusion criteria were as follows: randomized controlled trials (RCTs) of intravenous (IV) lidocaine administered perioperatively compared to placebo (0.9% saline infusion) as part of a multimodal perioperative analgesic regimen, human adults (> 16 years), and open or laparoscopic colorectal resectional surgery. EXCLUSION CRITERIA: non-colorectal surgery, non-placebo comparator, children, non-general anaesthetic, and pharmacokinetic studies. The primary endpoint was time to first bowel movement. Secondary endpoints were time to first passage of flatus, time to toleration of diet, nausea and vomiting, ileus, pain scores, opioid analgesia consumption, and length of stay. RESULTS: One hundred and ninety one studies were screened, with 9 RCTs meeting inclusion criteria (405 patients, four laparoscopic and five open surgery studies). IV lidocaine reduced time to first bowel movement compared to placebo [seven studies, 325 patients, mean weighted difference - 9.54 h, 95% CI 18.72-0.36, p = 0.04]. Ileus, pain scores, and length of stay were reduced with IV lidocaine compared with placebo. CONCLUSIONS: Perioperative IV lidocaine may improve recovery of gastrointestinal function after colorectal surgery. Large-scale effectiveness studies to measure effect size and evaluate optimum dose/duration are warranted.

Rb-82 PET/CT left ventricular mass-to-volume ratios.

Left ventricular (LV) mass:volume ratios indexed to body size (Mi/Vi) provide risk stratification for cardiac events. We sought to determine whether Rb-82 PET mass and volume indices are similar to MRI normal values for low likelihood subjects, and whether abnormal indices are related to abnormal myocardial blood flow (MBF). Data were analyzed retrospectively for 194 patients referred for rest/stress Rb-82 PET. LV EF, volume and mass values were calculated and mass:volume ratios were indexed to patients' height and weight. MBF was computed from the first pass dynamic component of PET data. 53 patients at low likelihood of CAD had PET Mi/Vi = 1.35 ± 0.27, consistent with the MRI literature range of 1.0-1.5. Compared to patients with normal indexed volume (Vi), patients with abnormally high Vi had lower rest MBF (0.56 ± 0.24 vs 0.93 ± 0.57 ml/g/min, p = 0.0001), and lower stress MBF (0.97 ± 0.52 vs. 1.83 ± 0.96 ml/g/min, p < 0.0001). Stress EF < 50% predicted abnormal Vi with 90% accuracy. Patients with Mi/Vi < 1.0 had abnormally low rest EF (45 ± 16% vs. 60 ± 15%, p < 0.0001) and low rest MBF (0.58 ± 0.25 vs. 0.96 ± 0.59 ml/g/min, p < 0.0001). In our study population, abnormal LV volume and mass correlated with lower rest and stress MBF and EF, suggesting that the pathophysiologic explanation of these patients' increased risk is more extensive obstructive CAD.

Arthroscopic treatment of labral tears in femoroacetabular impingement: a comparative study of refixation and resection with a minimum two-year follow-up.

Labral tears are commonly associated with femoroacetabular impingement. We reviewed 151 patients (156 hips) with femoroacetabular impingement and labral tears who had been treated arthroscopically. These were subdivided into those who had undergone a labral repair (group 1) and those who had undergone resection of the labrum (group 2). In order to ensure the groups were suitably matched for comparison of treatment effects, patients with advanced degenerative changes (Tönnis grade > 2, lateral sourcil height < 2 mm and Outerbridge grade 4 changes in the weight-bearing area of the femoral head) were excluded, leaving 96 patients (101 hips) in the study. At a mean follow-up of 2.44 years (2 to 4), the mean modified Harris hip score in the labral repair group (group 1, 69 hips) improved from 60.2 (24 to 85) pre-operatively to 93.6 (55 to 100), and in the labral resection group (group 2, 32 hips) from 62.8 (29 to 96) pre-operatively to 88.8 (35 to 100). The mean modified Harris hip score in the labral repair group was 7.3 points greater than in the resection group (p = 0.036, 95% confidence interval 0.51 to 14.09). Labral detachments were found more frequently in the labral repair group and labral flap tears in the resection group. No patient in our study group required a subsequent hip replacement during the period of follow-up. This study shows that patients without advanced degenerative changes in the hip can achieve significant improvement in their symptoms after arthroscopic treatment of femoroacetabular impingement. Where appropriate, labral repair provides a superior result to labral resection.

Patterns of injury in mycophenolate mofetil-related colitis.

Mycophenolate mofetil (MMF) was introduced as a new immune-suppression drug in the mid-1990s. It is widely utilized in solid-organ transplantation immune-suppression regimens. Side effects include gastrointestinal (GI) toxicity in the form of nausea, vomiting, and diarrhea. Physicians tend to reduce the dose of MMF or switch their patients to an enterio-coated formula to overcome the side effects. Because GI side effects are well linked to MMF, colonoscopy is not utilized in most of the cases to investigate the diarrhea. However, Crohn's disease-like changes in the colon, erosive enterocolitis, and graft versus host disease-like colonic changes associated with the use of MMF have been reported. Colonic findings in five patients whose symptoms resolved after substituting another agent for MMF are described in the present report. Repeat colonoscopy 4 months following discontinuation of MMF showed reparative changes in one of our patients. MMF is an important drug in organ transplantation immune-suppression regimens; however, with its widespread usage, additional side effects continue to be recognized.

Renal disease in AIDS: it is not always HIVAN.

Human immunodeficiency virus (HIV) infection can cause a broad spectrum of clinical manifestations, ranging from an asymptomatic carrier state to severe immunodeficiency. The most common renal lesion, HIV-associated nephropathy (HIVAN), is a sclerosing glomerulopathy. However, potentially reversible causes of renal disease in HIV-infected patients should also be considered. We describe two cases of patients with acquired immune-deficiency syndrome (AIDS) who presented with rapidly progressive renal failure but were found to have reversible etiologies. The first case was found to have syphilis and the second, disseminated histoplasmosis; their renal injury resolved after initiation of a third-generation cephalosporin antibiotic and amphotericin B, respectively.

Exudative AMD subtypes and eligibility for treatment with ranibizumab.

PURPOSE: To ascertain the proportion of patients with neovascular age-related macular degeneration (AMD) eligible for intravitreal treatment with monoclonal antibodies to vascular endothelial growth factor, on the basis of inclusion criteria used in pivotal clinical trials. METHODS: We scrutinised an imaging database and extracted all fluorescein angiograms (FAs) captured between 1 January and 31 December 2001. Of the 1083 FA, we found 184 where features of AMD in one or both eyes that were observed. In 130 eyes with neovascular AMD, we measured the area of choroidal neovascularisation (CNV) and retinal angiomatous proliferation (RAP). If contiguous to the area of neovascularisation, any areas of blood, exudate, blocked fluorescence, fibrosis, and atrophy were also measured. Descriptive statistics on lesion location, size, and composition were generated and chi2-tests were used to test for associations. RESULTS: Of 130 eyes with neovascular AMD, a subfoveal CNV was present in over 75%. Overall, 24.6% were wholly or predominantly classic, and the remainder minimally classic or occult. Of this latter group, RAPs constituted nearly a third and were significantly associated with co-existent pigment epithelial detachment (PED). Using MARINA and ANCHOR study criteria, less than 50% would have been eligible for clinical trials for antiangiogenic therapy. CONCLUSIONS: The majority of CNV were ineligible for treatment with antiangiogenic therapies when assessed solely on angiographic features. RAPs accounted for some one-third of lesions classified as minimally classic or occult at presentation, and the majority of these would have been ineligible for inclusion in the pivotal randomized control trials.

Favorable outcome after aggressive treatment of infection in a diabetic patient with MRSA-related IgA nephropathy.

IgA immune complex deposition is not commonly seen with acute postinfectious glomerulonephritis secondary to staphylococcal infections. Its deposition is usually indicative of IgA nephropathy or Henoch-Schonlein purpura nephritis. We describe a patient with a history of diabetes mellitus who was admitted with methicillin resistant Staphylococcus aureus bacteremia and subsequent demonstration on renal biopsy of crescentic glomerulonephritis associated with codominant IgA and C3 immune deposits and early changes of diabetic nephropathy. After aggressive treatment of infection, which included bilateral metatarsal amputation and subsequent left below-the-knee amputation as well as antibiotic administration for persistent osteomyelitis, the patient's renal function progressively improved with a reduction in serum creatinine concentration from 6.1 mg/dL (539 micromol/L) to 2.7 mg/dL (239 micromol/L). On a 3-year follow-up evaluation, his serum creatinine concentration was 1.7 mg/dL (150 micromol/L) and urine was negative for protein and blood.

Natural attenuation of a plume from an emplaced coal tar creosote source over 14 years.

An emplaced source of coal tar creosote within the sandy Borden research aquifer has documented the long-term (5140 days) natural attenuation for this complex mixture. Plumes of dissolved chemicals were produced by the essentially horizontal groundwater flowing at about 9 cm/day. Eleven chemicals have been extensively sampled seven times using a monitoring network of approximately 280, 14-point multilevel samplers. A model of source dissolution using Raoult's Law adequately predicted the dissolution of 9 of 11 compounds. Mass transformation has limited the extent of the plumes as groundwater has flowed more than 500 m, yet the plumes are no longer than 50 m. Phenol and xylenes have been removed and naphthalene has attenuated from its maximum extent on day 1357. Some compound plumes have reached an apparent steady state and the plumes of other compounds (dibenzofuran and phenanthrene) are expected to continue to expand due to an increasing mass flux and limited degradation potential. Biotransformation is the major process controlling natural attenuation at the site. The greatest organic mass lost is associated with the high solubility compounds. However, the majority of the mass loss for most compounds has occurred in the source zone. Oxygen is the main electron acceptor, yet the amount of organics lost cannot be accounted for by aerobic mineralization or partial mineralization alone. The complex evolution of these plumes has been well documented but understanding the controlling biotransformation processes is still elusive. This study has shown that anticipating bioattenuation patterns should only be considered at the broadest scale. Generally, the greatest mass loss is associated with those compounds that have a high solubility and low partitioning coefficients.

Investigation of emission-transmission misalignment artifacts on rubidium-82 cardiac PET with adenosine pharmacologic stress.

PURPOSE: This study was undertaken to determine if artifacts from misalignment of cardiac emission to transmission data is present in adenosine stress studies and if the artifact could be reproduced by intentional misalignment in normal exams. PROCEDURES: Seventy consecutive 82Rb myocardial perfusion studies were reviewed. Utilizing a quality control program, misalignment was assessed. The study was reprocessed after manual realignment to determine if the defect extent changed. Emission and transmission acquisitions in six normal studies also were intentionally misaligned. RESULTS: Twenty of 69 rest studies (29.0%) and 17 of 69 (24.6%) stress studies demonstrated misalignment. In four patients with stress misalignment, there was a significant change in clinical interpretation. Upon intentionally misaligning six normal studies, a lateral wall defect was reproduced. CONCLUSIONS: Emission-transmission misalignment occurs in 29.0% and 24.6% of 82Rb rest and adenosine stress studies, respectively. While there is a positive correlation of artifactual defects with misalignment, the presence and size of artifacts is variable and unpredictable at seemingly lesser degrees of misalignment.

Osteomalacia and secondary hyperparathyroidism after kidney transplantation: Relationship to vitamin D deficiency.

Secondary hyperparathyroidism is highly prevalent in patients with end-stage renal disease. After successful kidney transplantation, however, parathyroid glands gradually involute to normal size with subsequent normalization of intact parathyroid hormone (PTH), serum calcium, and phosphorous concentrations. This report describes a 48-year-old diabetic end-stage renal disease patient who underwent a successful cadaveric kidney transplant. Serum calcium and phosphorous concentrations normalized within 6 months. Three years later, he presented with complaints of proximal muscle weakness that was progressively worsening. Physical examination revealed temporal wasting and proximal muscle weakness. Detailed neurologic examination was unremarkable except for decreased vibratory sensation in both feet. Laboratory data showed stable allograft function (serum creatinine, 1.3 mg/dL), hypocalcemia, and hypophosphatemia with markedly elevated alkaline phosphatase level (726 IU/L) and intact PTH level (947 pg/mL). Further laboratory evaluation revealed poor nutritional status and severe deficiency of 25(OH)D (4.0 ng/mL). Past medical history included remote episodes of acute pancreatitis due to prior alcohol abuse. Computed tomography of the abdomen showed calcific atrophic pancreas, and steatorrhea was confirmed on stool studies. Decreased bone mineral density was noted by computed tomography bone density scan. Secondary hyperparathyroidism and osteomalacia had developed due to severe vitamin D deficiency, occurring as a result of previously unrecognized, minimally symptomatic pancreatic exocrine insufficiency. Treatment with vitamin D, calcium, and pancreatic enzyme replacement led to remarkable resolution of clinical symptoms and secondary hyperparathyroidism (intact PTH, 65 pg/mL after therapy) and resulted in significant improvement in bone mineralization. Factors associated with vitamin D deficiency in the chronic kidney disease and post-transplant patient population are reviewed.

Regulation of iNOS by the p44/42 mitogen-activated protein kinase pathway in human melanoma.

Activating mutations of the genes for NRAS and BRAF, components of the p44/42 mitogen-activated protein kinase (MAPK) pathway, are common findings in melanoma. Recent evidence in several nonmelanoma cell systems supports the regulation of the inducible nitric oxide synthase (iNOS) gene by this pathway. On the basis of our data showing that melanoma iNOS expression predicts shortened patient survival, we formulated the hypothesis that activating mutations of NRAS or BRAF, which lead to constitutive activation of the p44/42 MAPK pathway, drive iNOS expression in human melanoma. In the present study, we have shown that inhibition of melanoma iNOS activity by S-methylisothiourea leads to decreased cell proliferation, confirming the importance of iNOS activity for melanoma cell growth. Regulation of melanoma iNOS expression by the p44/42 MAPK pathway was demonstrated by inhibition of the pathway by U0126, and by BRAF RNA interference. To explore this regulatory pathway in human tissue, 20 melanoma tumors were examined for NRAS and BRAF mutations, immunohistochemical evidence of ERK phosphorylation, and iNOS expression. A significant association was found among these three features. We conclude that in human melanoma, activating mutations of NRAS and BRAF drive constitutive iNOS expression and, implicitly, nitric oxide production, contributing to the poor survival of these patients.

The impact of socioeconomic and demographic factors on the utilization of smoking cessation medications in patients hospitalized with cardiovascular disease in Nova Scotia, Canada.

OBJECTIVE: To determine whether any demographic or socioeconomic factors affect the use of smoking cessation medications in patients hospitalized with heart disease. METHOD: Data were obtained from the Improving Cardiovascular Outcomes in Nova Scotia (ICONS) Canada database, which includes a registry of all hospitalized patients with a diagnosis of ischaemic heart disease, congestive heart failure, or atrial fibrillation since October 1997. Patients agreeing to provide follow-up were sent an enrollment survey to determine demographic and socioeconomic factors including household income, educational background and private drug insurance plans. RESULTS: Between 15 October 1997 and 31 December 2000, 5442 patients who were current smokers and 270 patients using a smoking cessation medication were admitted to hospital registered in the ICONS database. An enrollment survey was completed by 1071 current smokers and 77 patients using a smoking cessation agent. CONCLUSION: Higher education level, presence of private drug insurance plans, and less difficulty paying for basic needs were associated with higher use of smoking cessation medications.

Report of the use of hyperbaric oxygen therapy (HBO2) in an unusual case of secondary infertility.

We report the use of hyperbaric oxygen therapy (HBO2) in the treatment of an unusual case of secondary infertility. The patient had failed to conceive after a 1-year period of in-vitro fertilization, during which oral sildenafil had also been administered. However she became pregnant after an IVF cycle and the use of adjunctive HBO2 and sildenafil, which was administered intravaginally on this occasion. There is currently very little evidence to support the use of HBO2 in this context. The possible mechanisms of action of HBO2 in this case are discussed.