Comparison of Vertebral and Femoral Strength Between White and Asian Adults Using Finite Element Analysis of Computed Tomography Scans

Given non-optimal testing rates for dual-energy X-ray absorptiometry (DXA) and the high use of computed tomography (CT) in some Asian countries, biomechanical computed tomography analysis (BCT)-based bone strength testing, which utilizes previously taken clinical CT scans, may improve osteoporosis testing rates. However, an understanding of ethnic differences in such bone strength measurements between Whites and Asians is lacking, which is an obstacle to clinical interpretation. Using previously taken CT and DXA scans, we analyzed bone strength and bone mineral density (BMD) at the hip and spine in two sex- and age-matched community-based cohorts, aged 40 to 80 years: Whites (Rochester, MN, USA) and Koreans (Seoul, South Korea). For both the spine and femur, the age dependence of bone strength was similar for both groups, White (n = 371; women n = 202, 54.5%) and Korean (n = 396; women n = 199, 50.3%). For both sexes, mean spine strength did not differ between groups, but femur strength was 9% to 14% higher in Whites (p ≤ 0.001), an effect that became non-significant after weight adjustment (p = 0.375). For Koreans of both sexes, the fragile bone strength thresholds for classifying osteoporosis, when derived from regional DXA BMD T-score references, equaled the clinically validated thresholds for Whites (in women and men, femoral strength, 3000 N and 3500 N; vertebral strength 4500 N and 6500 N, respectively). Using these thresholds, classifications for osteoporosis for Koreans based on bone strength versus based on DXA BMD T-scores were consistent (89.1% to 94.4% agreement) at both the hip and spine and for both sexes. The BCT-based, clinically validated bone strength thresholds for Whites also applied to Koreans, which may facilitate clinical interpretation of CT-based bone strength measurements for Koreans. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Chronic Pancreatitis with Benign Biliary Obstruction: Management Issues

Background

Benign biliary obstruction (BBO) is an important complication in patients with advanced chronic pancreatitis (CP). Its presentation varies from an incidental finding to overt jaundice. Thus it presents certain management issues. The present study was therefore performed to analyze the clinical presentation and management of biliary obstruction in patients with CP.

Methods

Retrospective analysis was performed from a prospectively collected database of 155 CP patients managed at our institute from October 2003 to June 2012.

Results

Among 43 (28 %) CP patients with biliary obstruction, 3 patients had evidence of malignancy on follow-up examination and were excluded from the final analysis. The various presentations include chronic nonprogressive elevation of serum alkaline phosphatase (SAP) (n = 15), a progressive increase in SAP with episodes of jaundice (n = 17), and persistent jaundice (n = 8). Of 15 patients with chronic nonprogressive elevation of SAP, 5 were managed conservatively, and the remaining 10 underwent only a pancreatic drainage procedure. During a median follow-up of 41 months (range 11–90 months), none of the 15 patients developed complications related to biliary obstruction. All patients with progressive increase in SAP levels and persistent jaundice underwent the biliary drainage procedure [choledochojejunostomy (CDJ, n = 20) and choledochoduodenostomy (CDD, n = 3)]. During a median follow-up of 30 months (range 10–89 months), two patients died of unrelated causes and two patients had an asymptomatic elevation of SAP.

Conclusions

BBO is common in patients with CP; however, biliary drainage is not indicated for chronic nonprogressive elevation of SAP. In patients with a progressive increase in SAP or persistent jaundice, both CDJ and CDD provide effective biliary drainage.     

Studies on angiotensin II and analogs: impact of substitution in position 8 on conformation and activity.

Affinity, residual agonist activity, and inhibitor properties of a series of angiotensin II analogs modified at the COOH-terminal position (X8-substituted peptides) have been probed for structure/conformation-biological activity relationships. The results emphasize (i) the large impact that subtle conformational variations caused by structural alterations in the position 8 side chain have on biological properties, (ii) the implication of the COOH-terminal carboxyl group in both affinity and intrinsic activity, and (iii) the influence that the bulkiness of the side chain in position 8 of antagonists has on the local conformation at the COOH terminus and thus on the inhibitory properties. In the hormone, the phenylalanine-8 ring is required for its steric influence and aromaticity to ensure a fully active conformation at the COOH terminus. Especially, correct orientation of the position 8 carboxyl group relative to the phenyl group of the phenylalanine residue may be necessary for agonistic activation of the angiotensin receptor complex. Replacement of the aromatic ring on the COOH-terminal residue by a nonaromatic group leads to incorrect orientation of the carboxyl group and causes the appearance of antagonist properties. Although the steric effects of the side chain can be modulated by specific interaction of its chemical groups (if any) with the peptide backbone, we found a good correlation between the size of the side chain-e.g., the steric parameter V gamma (the van der Waals volume consisting of the C alpha, C beta, and C gamma atoms), the conformational properties in the backbone (3J HC alpha-NH), and the binding capacities in all compounds tested.     

Heart rate variability in human immunodeficiency virus-positive individuals

Torsade de pointes is a form of polymorphic ventricular tachycardia occurring in a setting of prolonged QT interval on surface electrocardiogram. Congenital causes of prolonged QT interval occur in individuals with genetic mutations in genes that control expression of potassium and sodium channels and acquired causes are numerous, predominantly drugs causing prolonged QT interval by blockade of potassium channels. Among the drugs, antiarrhythmic agents most notably quinidine, sotalol, dofetilide and ibutilide have the potential to induce the fatal torsade de pointes. Many non-antiarrhythmic drugs can also cause torsade de pointes. Although it is important to distinguish between the congenital and the acquired forms of long QT syndrome as the later can often be reversed by correction of the underlying disorder or discontinuation of the offending drug, both forms are not mutually exclusive. Clinical considerations and management of torsade de pointes are described.     

Epidemiology of sarcopenia

OBJECTIVES: To examine patterns of muscle mass change with aging and to estimate the prevalence of sarcopenia. DESIGN: Cross-sectional survey. SETTING: Population-based study in Rochester, Minnesota. PARTICIPANTS: Age-stratified sample of men and women from the community. MEASUREMENTS: Muscle mass estimated from total body scans by dual-energy X-ray absorptiometry. Sarcopenia was defined as muscle mass more than 2 standard deviations below the sex-specific young-normal mean. RESULTS: Total lean body mass (exclusive of bone) and total skeletal muscle mass both were greater in men than women and declined linearly with age as judged from these cross-sectional data. Adjustment for height reduced the gender difference. The age- and sex-adjusted prevalence of sarcopenia varied from 6 to 15% among subjects 65 years of age or over, depending on the muscle mass parameter that was evaluated, but prevalence rates were quite sensitive to the normal values used to define cutoff levels. Subjects with sarcopenia appeared to have more physical limitations than the others. CONCLUSIONS: Late in life, a substantial portion of the population reaches low levels of muscle mass that are associated with increased physical disability. However, additional efforts are needed to validate an operational definition of sarcopenia.     

Sacrococcygeal teratoma growth rate predicts adverse outcomes

Purpose

The purpose of this study was to characterize the growth rate of sacrococcygeal teratomas (SCTs) and determine its relationship to adverse outcomes.

Methods

A retrospective review of all pathology-confirmed isolated SCT patients evaluated with at least two documented ultrasounds and followed through hospital discharge between 2005 and 2012 was conducted. SCT growth rate was calculated as the difference between tumor volumes on a late- and early-gestation ultrasound divided by the difference in time. Outcomes were death, high-output cardiac failure (HOCF), hydrops, and preterm delivery. Student's t-test, receiver operator characteristics, Fisher's Exact test, and Pearson's correlation were performed.

Results

Of the 28 study subjects, there were 3 in utero demises and 2 neonatal deaths. Significantly faster SCT growth rates were seen in all adverse outcomes, including death (p < 0.0001), HOCF (p = 0.005), and preterm delivery (p = 0.009). There was a significant association with adverse outcomes at > 61 cm³/week (AUC = 0.87, p = 0.001, LR = 4.52). Furthermore, there was an even greater association with death at > 165 cm³/week (AUC = 0.93, p = 0.003, LR = 18.42). Growth rate was directly correlated with the percent of solid tumor (r = 0.60, p = 0.0008).

Conclusion

Faster SCT growth is associated with adverse outcomes. SCT growth rate determined by ultrasound is an effective prognostic indicator for adverse outcomes and easily applied to patient management.     

Cortical Porosity Identifies Women With Osteopenia at Increased Risk for Forearm Fractures

Most fragility fractures arise among the many women with osteopenia, not the smaller number with osteoporosis at high risk for fracture. Thus, most women at risk for fracture assessed only by measuring areal bone mineral density (aBMD) will remain untreated. We measured cortical porosity and trabecular bone volume/total volume (BV/TV) of the ultradistal radius (UDR) using high‐resolution peripheral quantitative computed tomography, aBMD using densitometry, and 10‐year fracture probability using the country‐specific fracture risk assessment tool (FRAX) in 68 postmenopausal women with forearm fractures and 70 age‐matched community controls in Olmsted County, MN, USA. Women with forearm fractures had 0.4 standard deviations (SD) higher cortical porosity and 0.6 SD lower trabecular BV/TV. Compact‐appearing cortical porosity predicted fracture independent of aBMD; odds ratio (OR) = 1.92 (95% confidence interval [CI] 1.10–3.33). In women with osteoporosis at the UDR, cortical porosity did not distinguish those with fractures from those without because high porosity was present in 92% and 86% of each group, respectively. By contrast, in women with osteopenia at the UDR, high porosity of the compact‐appearing cortex conferred an OR for fracture of 4.00 (95% CI 1.15–13.90). In women with osteoporosis, porosity is captured by aBMD, so measuring UDR cortical porosity does not improve diagnostic sensitivity. However, in women with osteopenia, cortical porosity was associated with forearm fractures. © 2014 American Society for Bone and Mineral Research.     

Death within the first year after kidney transplantation – an observational cohort study

The risk of death within the first year postkidney transplantation is not well described in the contemporary era. We extracted data on all kidney transplant procedures performed in England between April 2001 and March 2012. Data linkage analysis was performed between Hospital Episode Statistics and the Office for National Statistics to identify all deaths. Cox proportional hazard models were performed to identify factors associated with 1‐year mortality. 566 deaths (3.0%) occurred within the first year post‐transplant (from 19 103 kidney transplant procedures analysed). Infection, cardiovascular events and malignancy were classified in 21.6%, 18.3% and 7.4% of death certificates, respectively. Among recipients with prior myocardial infarct history who died within the first year, 38.8% of deaths were attributed to a cardiac‐related event. Malignancy‐related death was responsible for 61.5% of 1‐year mortality for allograft recipients with pretransplant cancer history. 22.1% of deaths included kidney failure as a contributory factor on the death certificate (3.3% specifically stated allograft failure). Variables associated with 1‐year mortality included deceased‐donor kidney, increasing age, residence in socioeconomically deprived area and history of select medical comorbidities pre‐operatively. We conclude 1‐year mortality postkidney transplantation is low, but in select allograft recipients, the risk of death increases considerably.     

Colorectal Cancer: Postoperative Follow-up and Surveillance

Follow-up and surveillance form an important aspect of care in patients with colorectal cancers (CRC). Most recurrences will occur within 2 years of surgery and 90% by 5 years. Follow up protocols have not been well defined in stage I disease and the approach should be individualized. As 40% of patients with stages II and III will develop recurrences, intensive postoperative follow-up strategy is recommended for them. It includes visit to the clinician for clinical examination, serum carcinoembryonic antigen (CEA), computed tomography (CT) of the chest and abdomen, colonoscopy, and flexible proctosigmoidoscopy in rectal cancers. Surveillance should be undertaken in those who are medically fit for repeat surgical procedures or for chemoradiotherapy. The concept of intensive post operative surveillance is based on the fact that some of these patients can have resectable/curable recurrence.     

Improving the Anticancer Activity of Curcumin Using Nanocurcumin Dispersion in Water

Curcumin is a highly potent, nontoxic bioactive agent found in turmeric and is known to have significant anticancer properties against different types of cancer cells. The major disadvantage associated with the use of curcumin, however, is its low systemic bioavailability due to its poor aqueous solubility. The focus of the present study was to generate nanoparticles of curcumin with improved aqueous phase solubility, and to investigate their efficacy in treating cancer cells. Curcumin nanoparticles having particle size in the range 2–40 nm and aqueous solubility of up to a maximum of 3 mg/mL were prepared. Evaluation of anticancer properties of curcumin nanodispersion was carried out in 3 different cancer cell lines: lung (A549), liver (HepG2), and skin (A431). The results demonstrated that under aqueous conditions curcumin nanoparticles exhibited similar or a much stronger antiproliferative effect on the cancer cells compared to normal curcumin in DMSO. Our results lead way toward unharnessed potential of curcumin in the form of its nanoparticles as an adjuvant therapy for clinical application in treating various cancers.