bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of newly diagnosed HIV‐infected patients who are lost to follow up
Authors: Fridman V , Bello N , Lasala M
Published: November 2012

Purpose of the study

We previously identified that a great amount of newly diagnosed HIV‐infected patients were lost to follow up after the diagnosis. The aim of the present study is to describe the characteristics of the newly diagnosed HIV‐infected patients who are lost to follow up.

Methods

We reviewed the clinical charts of the adult (>18 y/o) patients who attended for the first time our HIV clinic between 1/Jan/2005 and 31/Dec/2010. Among the patients who were newly diagnosed with HIV infection, we identified those who consulted the clinic only once. We considered patients were lost to follow up if they never came back within 12 months. We compared age, gender, nationality, education level and socioeconomic characteristics between those patients who were lost to follow and those who continue HIV care. We considered the first visit the one in which the patient was informed about his/her HIV seropositive condition.

Summary of results

We included 504 patients, 179 (35.5%) never came back after the first visit. Patients who were lost to follow up (A) were younger (mean age 33.8 vs. 39.07 y/o) than those who continue follow up (B). We identified 11/179 patients older than 50 years in A and 52/325 in B; P = 0.001 (OR 0.34, 95% CI 0.16–0.70). In A 136/179 were male and 232/325 in B. 142/179 were Argentinian in A and 289/325 in B; P = 0.003 (OR 0.48, 95% CI 0.28–0.81). In A 61/179 lived alone and 39/325 in B; P = 0.000 (OR 3.79, 95% CI 0.64–1.37). 41/179 had health insurance in A and 162/325 in B; P = 0.003 (OR 0.30, 95% CI 0.28‐0.81). A university or tertiary degree was reached in 33/179 in A and 110/325 in B; P = 0.000 (OR 0.44, 95% CI 0.28–0.70).

Patients lost to follow up, n=179
Patients who continue follow up, n=325

Male/female
136/43
232/93
P=1.24 OR 1.27 (95% CI 0.82–1.97)

Mean age (years)
33.8
39.07

Older than 50 years old
11
62
P=0.001 OR 0.34 (95% CI 0.16–0.70)

Argentinian
142
289
P=0.003 OR 0.48 (95% CI 0.28–0.81)

Health insurance
41
162
P=0.003 OR 0.30 (95% CI 0.28–0.81)

Tertiary/university degree
33
110
P=0.000 OR 0.44 (95% CI 0.28–0.70)

Living alone
61
39
P=0.000 OR 3.79 (95% CI 0.64–1.37)

Employed
83
156
P=0.72 OR 0.94 (95% CI 0.64–1.37)

Conclusions

We must continue reinforcing need for consistent clinical care in the newly diagnosed HIV patients, especially those who are younger, foreigners and socially excluded.
SCORE underestimates cardiovascular risk (CVR) of HIV+ patients
Authors: Ramírez R , Márquez J , Tasias M , Ruiz S , Delegido A , Díaz A , Araújo O , Hernández S , Tikhomirova L , Creus C , Alonso‐Villaverde C , Pedrol E
Published: November 2012

The new European Guidelines of Dislipidemia Management of the European Societies of Cardiology and Arteriosclerosis consider HIV+ as patients at high risk of developing cardiovascular events and deaths. The objective of the study was to evaluate cardiovascular events and deaths in a series of HIV+ patients. Observational, cross‐sectional study, including a cohort of HIV+ and HIV− patients from 2008. CVR was calculated using the SCORE‐CVR chart. Variation on lipid profile and incidence of cardiovascular events, cardiovascular death or death related to any cause were recorded. Data was analyzed using SPSS version 20.0 for MAC. 154 HIV+ and 155 HIV− patients were included. Mean age: 44.8±9.5 vs 55.2±14.3 y and 69.5% vs 49% males respectively (p<0.01). Mean time since HIV+ diagnosis was 11±6.2 y. Mean BMI and systolic blood pressure were lower in HIV+ (25.1±6.7 kg/m2 vs 28.7±5.1 kg/m2, (p<0.01) and 119.6±19.4 vs 124.7±14.7 mmHg, (p=0.044; respectively)). A lower proportion of hypertense, diabetic and obese patients was observed in HIV+ (25.5% vs 6.5%; 20.6% vs 3.9% and 36.8% vs 12.3%) but a larger proportion of smokers (68.8% vs 29.7%) was observed (p<0.01 in all cases). Mean cholesterol and LDLc were lower in HIV+ (191.2±41.4 vs 218.5±44.6 mg/dl and 109.5±33.9 vs 134.6±37.7 mg/dl; p<0.01; respectively) but with a lower mean HDLc and higher TG (50.3±19 mg/dl vs 55.2±14.9 mg/dl; p=0.013 and 156.7±85.7 vs 135.8±66.2 mg/dl; p=0.017; respectively). There was no significant difference in mean CVR‐SCORE (3.5±3.6% vs 4.4±3.8%; p=0.091). With this SCORE, 5.2±5.3 and 6.7±5.8 cardiovascular events or deaths should be expected in HIV+ and HIV− respectively at 10 y. Four years later cholesterol, LDLc, HDLc, TG in HIV+ and HIV− patients did not vary compared with those obtained 4 y before. 5 events and 1 death were seen at 4 y follow‐up in HIV+, and in HIV− patients. The incidence of events in HIV+ patients is similar to the expected according to their SCORE at 10 y. We could suppose that once the 10 y follow‐up is reached, this incidence would be higher. On the other side, in HIV− at 4 y just 3 events ocurred, far from the 6.7 events expected. There were no significant differences between lipid profiles in any of the cohorts. Lipid profile with low HDLc and high TG is persistent in HIV+ patients at 4 y follow‐up. Understimation of CVR in HIV+ patients by SCORE charts could be present as soon as 4 y after the first assesment. This supports the stratification of HIV+ patients as high‐risk patients in new guidelines.
Effect of the treatment of hepatitis C with interferon (IFN) and ribavirin (RBV) in body composition measurement by DEXA in HIV‐HCV infected patients
Authors: De Los Santos I , Sanz J , Manzano Luque M
Published: November 2012

Purpose of the study

HIV infection and antiretroviral therapy (ART) have been associated with lipodystrophy (LD), but we unknown the effect of IFN/RBV on the body composition, mainly body fat, in HIV patients, already with a degree of LD. Our objective: to assess the body composition in HIV‐HCV patients that start treatment with IFN/RBV and the changes at its ending.

Material and Methods

Pilot and prospective study of HIV‐HCV patients. We performed (baseline and at the end of treatment) clinical and laboratory parameters, HIV and HCV‐related. Total and regional body fat contents were measured in the same periods with DEXA (dual‐energy X‐ray absorptiometry) scanners. For LD diagnostic we used the definition of fat/mass ratio (FMR): absence, <1, obvious >1.5, and between 1–1.5 it could have LD but is better to see the evolution. Data are expressed in median.

Results

We included 10 male patients; age 45 yo; time on ART 115 months. HIV VL < 20 in 9; CD4 count 577/mm3. Genotype 1 in 8, and 3 in 2. Time on IFN/RBV: 10 months. At the end of the treatment we observed a decrease in the level of total, HDL and LDL‐cholesterol (expressed in percentage: 4, 16 and 1.5 respectively) and a slightly increase in the level of TGR (9%). The total body mass decreased 7% (from 76.2 kg to 70.6), the total body fat decreased 18.4% (from 21.060 g to 17.172) and the total lean mass decreased only 3%. Results expressed in percentage and by regional parts, we observed also a decrease in all the parameters: 11% in total body fat (from 26.3 to 23.4), 6% in the fat in arms (21.9 to 20.5), 10% in total fat in legs (22.5 to 20.3) and 12.5% in total trunk fat (30.3 to 26.5). The FMR also decreased from 1.5 to 1.4.

Conclusions

Trend to LD at baseline, as the FMR was 1.5. After 10 months on treatment with IFN/RBV there was a decrease in the total body mass (7%), mainly due to the loss of total body fat and less in the lean mass. Regarding the percentage of fat loss, we observed the biggest decrease in the trunk fat and the lesser in the limb fat. So, the FMR also decreased. This effect does not get worse the baseline LD; on the contrary it improves it, although very slightly (decrease of 0.1 in FMR), and could serve to advise the patients and not to be afraid of a possible worsening of LD. The study is ongoing and the next objective will be to perform DXA one year after the end of treatment and to expand the cohort to study clinical or laboratory factors related with these results.
Iron overload, an immunosuppression marker in HIV‐infected patients
Authors: López‐Calderón C , Palacios R , Cobo A , Moreno T , Ruiz J , Nuño E , Márquez M , Santos J
Published: November 2012

Purpose

Iron overload (IO) has been associated with increased cardiovascular risk (CVR) and metabolic syndrome (MS) in the general population; both elevated CVR and MS are frequent in HIV‐patients. Our aim was to analyze the prevalence of IO in a cohort of asymptomatic patients with HIV infection, and related factors.

Methods

Cross‐sectional study of a cohort of HIV outpatients in regular follow‐up. Demographic, epidemiological, clinical, analytical and therapeutic data were collected. Patients completed a questionnaire about CVR factors and 10‐year CV disease risk estimation (Framingham score), underwent a physical exam, and a fasting blood analysis. IO was defined as a plasma ferritin level higher than 200 μ/L in women and 300 μ/L in men.

Results

571 patients (446 men, 125 women), with a mean age of 43.2 years, sexual transmission of HIV in 68.5%, median CD4 count 474 cell/μL (IQR: 308–666), and 36.3% Aids cases. 86.2% were on antiretroviral therapy (ART), and 74.8% of them had undetectable HIV viral load. 14.6% met MS criteria, and mean CVR at 10 years was 6.67%. IO was detected in 11% of cases. Patients with IO were more immunosuppressed (CD4 count 369 vs 483/μL, p<0.0001), presented a higher prevalence of detectable HIV viral load (17.6% vs 8.9%; p<0.005), and of Aids cases (14.9% vs 8.7%; p<0.023), and lower plasma levels of cholesterol, HDLc and LDLc (154 vs 183, 34 vs 43, 93 vs 110 mg/dL, respectively; p<0.0001. In the multivariate analysis, the only related factor was CD4 count <350 cell/μL (OR 2.86, 95% CI 1.6–4.9; p<0.0001). IO was not associated with CVR nor with MS.

Conclusions

IO is not uncommon in HIV patients, and it is only related with immunosuppression defined as CD4 count <350 cell/μL, and in contrast to general population, it is not related with increased CVR nor with MS.
Maraviroc shows differential effects on glucose uptake and lipolysis in human subcutaneous cultured adipocytes in comparison with omental adipocytes
Authors: Perez‐Matute P , Perez‐Martinez L , Rus A , Jareño M , Blanco J , Oteo J
Published: November 2012

Maraviroc (MVC), the first approved CC‐chemokine receptor 5 (CCR5) antagonist, is used for treating HIV‐1‐infected patients with CCR5 tropism. MVC has been proved safe in all respects and showed beneficial effects on lipid profile of HIV patients with dislipidemia. Adipocyte dysfunction seems to be responsible for many metabolic alterations such as insulin resistance and dislipidemia. Subcutaneous and visceral fat depots are not only physiologically but also metabolically different and metabolic disturbances are more closely associated with visceral than subcutaneous fat accumulation. It has been suggested that antiretrovirals affect both fat depots in a different extent. Thus, whether isolated human adipocytes display regio‐specific sensitivity to the metabolic effects of MVC have been tested in this study. Human subcutaneous and omental preadipocytes were used as the source of human adipocytes. These cells were treated with therapeutic concentrations of MVC (0.5–25 µM) at day 14 post‐differentiation (4 and 24 hours of treatment). Glucose utilization, lactate production and glycerol released into the media were measured using an autoanalyzer. Adiponectin secretion was determined by an ELISA array. A dose‐dependent increase in glucose uptake was observed in subcutaneous adipocytes treated with MVC (+72% of stimulation for MVC 25 µM, p < 0.01). This stimulatory effect was tissue specific, as no effects were observed in omental adipocytes. MVC did not exert any significant effect on adiponectin secretion. No significant effects were observed on lactate production neither in subcutaneous nor omental adipocytes. Interestingly, 4 hours of treatment with MVC induced a significant increase in the amount of glycerol released into the media by subcutaneous adipocytes (p < 0.001), but this effect disappeared with longer exposure of adipocytes to MVC (24 h). No effects were observed on lipolysis in omental adipocytes although a slight tendency to decrease lipolysis was observed (p = 0.08). These data suggest that MVC exerts direct and differential effects on adipocytes depending on their origin. Thus, a stimulation of glucose uptake has been reported in subcutaneous but not in omental adipocytes and a slight decrease of lipolysis was observed in omental adipocytes whereas no effects were observed in subcutaneous adipocytes. These actions could underline the neutral and even beneficial effects demonstrated for MVC in lipid and glucose metabolism of HIV‐infected patients.
Experience with polymethylmethacrylate 30% (PMMA) facial filling in patients with facial HIV lipoatrophy using of local anesthesia dentistry
Authors: Matsuda E , Soares F , Brigido L
Published: November 2012

Background

HIV‐associated lipoatrophy in a common and stigmatizing side effect of HIV infection, is aggravated by antiretroviral therapy; its presence causes distress and compromises adherence to therapy. PMMA filling is often associated with pain and discomfort.

Objective

To evaluate outpatient intervention using local dentistry anesthesia.

Methods

Patients complaining of facial lipoatrophy, from 10/2007 to 11/2011, were offered the filling with PMMA. Cases with bleeding potential, acute or decompensated chronic diseases or use of immunosuppressors or chemotherapy were excluded. Inclusion criteria: perception of distressing malar lipoatrophy and both the assisting physician and the applicant agreeing with potential benefit. After informed consent, patients were infused with 30 mg prilocaine/0.03 IU felypressin in 1.8 ml, using a carpule type syringe aiming to block the posterior superior alveolar nerve. This was followed by PMMA infiltration in different points at the malar region. At first return a simple questionnaire evaluating pain, satisfaction, grading 0 to 10 and if would repeat the procedure.

Results

All 64 eligible patients were included. Mean age 46 (13 to 73) years, mostly white (71.87%), males (68.75%), 37.5% of them MSM. Arterial hypertension was the most prevalent comorbidity (17%), 78% with viral load <50 c/mL, with a median 585 CD4 cells/mL (95–2063). On a median of 8 years on treatment, 1/3 had been exposed to three classes (NRTI/ NNRTI/PI), one antiretroviral‐naïve. Of the 12 patients who had detectable viral load in the first procedure, seven were suppressed to below 50 copies/mL during follow up. Two of the five patients remaining with detectable viremia died from other causes, 2 transferred and 1 remained naïve. 127 procedures were made in 64 patients, a median of 2 (1–6) per patient. After a mean follow‐up of 33 weeks, no infection or late complications were observed. Mean dispensed volume was 9 mL (1.5 to 22). Pain grade was documented in 105 procedures; grade <4 reported by 46%, 4–6 by 34%; 7–8 by 16%, 9 by 2%. All reported that the pain would not hamper future procedures; 94% refer an overall satisfaction from 8 to 10.

Conclusion

The use of local anesthesia in dental facial filling with PMMA in patients with HIV lipoatrophy of the face is safe, decreases pain to tolerable levels and allows high levels of satisfaction with the procedure. The procedure may improve patient adherence to ARV.
Tenofovir‐induced acute kidney injury in HIV‐infected patients in western India: a resource limited setting perspective
Authors: Sadre A , Munshi N , Dhande S , Dravid A
Published: November 2012

Background and objective

Tenofovir use in HIV positive patients is associated with 0.5–2.5% risk of acute kidney injury (AKI). Data on AKI due to tenofovir use in resource limited settings like India is sparse. Objective of this study is to determine incidence, risk factors and outcome of tenofovir‐induced acute kidney injury (serum creatinine>2 mg/dl or creatinine clearance decrease by 50% compared to baseline) in HIV infected patients attending tertiary level HIV clinic in Western India.

Methods

All patients enrolled at the clinic from 2009 to 2012 who were initiated on tenofovir‐based ART and had regular follow up creatinine clearance values available were included in this retrospective observational cohort analysis. Patients already on tenofovir‐based ART during enrollment were also included.

Summary of results

512 patients were enrolled in the study with 70% being males. Average age of the cohort was 41 years, average body weight 56 kilograms and median baseline CD4 count 164 cells/mm3. Mean baseline creatinine clearance was 90 ml/min. Median duration of follow up was 26 months. Tenofovir‐induced AKI developed in 25 patients (incidence 4.88 %). Median time to developing AKI was 6 months. On stopping tenofovir, 15 patients had complete recovery of renal function, 5 had partial recovery while 5 patients died. Hemodialysis as a treatment option was used in 3 patients. Age>50 yrs (p=0.001), baseline creatinine clearance<50 ml/min (p=0.0001), diabetes mellitus (p=0.0001), use of tenofovir with protease inhibitors (p=0.001), presence of renal calculus disease (p =0.0001) and use of concomitant nephrotoxic medications (p=0.001) were significantly associated with risk of tenofovir AKI on applying Pearson's Chi square test.

Conclusions

Incidence of tenofovir‐induced AKI in our cohort is higher than previously reported and could be attributed to lower body weight, lower baseline creatinine clearance, higher incidence of advanced HIV disease and higher incidence of co‐morbidities in our patients.
Association of fibroblast growth factor 23 and hypophosphatemia in well‐suppressed HIV‐infected patients receiving antiretroviral therapy
Authors: Avihingsanon A , Praditpornsilpa K , Avihingsanon Y , Wongsabut J , Klongpetch C , Ubolyam S , Ruxrungtham K
Published: November 2012

Introduction

Prolong hypophosphatemia may result in future bone loss which will have effect on patient's quality of life. Hypophosphatemia is observed in 4–31% of HIV‐infected patients receiving highly active antiretroviral therapy (HAART). Fibroblast growth factor 23 (FGF‐23), a potent phosphaturic hormone, has not been well studied in HIV‐infected Thai patients. We aimed to investigate whether FGF‐23 is involved in the etiology of hypophosphatemia in our HIV‐positive patients on HAART.

Method

This study was a case‐controlled study at HIV‐NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand during June 2011‐May 2012. Serum and urine phosphate was studied in 696 well‐suppressed HIV‐infected patients. Hypophosphatemia was defined as a serum phosphate level <2.5 mg/dl. All fasting blood and urine samples were taken between 7.00 and 10.00 hr to measure serum phosphate, calcium, 1,25 OHD, parathyroid hormone (PTH), FGF‐23 and urinary phosphate excretion. The renal phosphate threshold tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR) was calculated. eGFR was calculated using the MDRD.

Results

Totally 65 (9.3%) subjects were identified for hypophosphatemia. The prevalence of hypophosphatemia was not difference between TDF exposure [(46/544: 8.5%) and TDF unexposure (19/154: 12.5%), p=0.13]. However, only 56 subjects for a case group (hypophosphatemia group) and 65 subjects with normal phosphate (normophosphatemia group were included in this analysis. In the hypophosphatemia group, they were more likely younger, less female, and lower CD4 cell counts than the control group. About 80% and 74% of the case and control group had TDF exposure, respectively. The renal phosphate reabsorption threshold was significantly lower in hypophosphatemia group than in the control [43 (2.19–2.6) vs 3.16 (2.92–3.61) mg/dl, p<0.001]. FGF‐23 was significantly higher in hypophosphatemia group [31.9 (24.7–40.0) vs 26.2 (19.3–34.1) pg/dl, p<0.017]. TmP/GFR was strongly related to FGF‐23 levels (p<0.04), but not for PTH (p<0.06), and urine calcium (p<0.07).

Conclusion

FGF‐23 is involved in pathogenesis of hypophosphatemia in our HIV‐positive patients on HAART.
Hierachically Structured Hollow Silica Spheres for High Efficiency Immobilization of Enzymes
Authors: Cao Shunsheng , Fang Long , Zhao Zhiyuan , Ge Yi , Piletsky Sergey , Turner Anthony P. F.
Published: November 2012

In this work, the first example of a hierarchically structured hollow silica system is reported without any chemical modification to the enzyme involved in the process. The leaching of the physically adsorbed enzyme is substantially restrained in comparison to pure hollow silica supports. The hierarchical architecture is composed of the ordered hollow silica spheres with a shell‐in‐shell structure. This rationally integrated architecture, which serves as the host for glucose oxidase immobilization, displays many significant advantages, including increases in mechanical stability, enzyme loading, and bioactivity, and a decrease in enzyme leaching compared to existing pure hollow silica matrices. This facilitates further multifarious applications for enhanced enzyme immobilization, biosensors, and biocatalysis.
Influence of the polymer structure on the drug–polymer interactions in the micellar nanoparticles: Mixed homopolymer and copolymerized cores
Authors: Hassanzadeh Salman , Khoee Sepideh
Published: November 2012

The two strategies of mixing and copolymerizing were used to incorporate more drug‐compatible butylene adipate (BA) repeating units into the less drug‐compatible unsaturated poly(cis‐2‐butene adipate) (PCBA) core of micelles. Novel parameters were defined on the basis of the hydrodynamic radius of the particles. A comparison of the encapsulation capabilities of the different copolymerized and mixed micelles was performed with these parameters. Both the mixed and core‐copolymerized micelles were indicated to have spherical morphologies and synergic properties of the copolymerized and mixed repeating units. They exhibited a higher encapsulation of the drug, a lower critical micelle concentration, and more controlled release behavior compared to the pure PCBA micelles. In addition, a comparative study of the two strategies was performed in the presence of same molar ratios of BA in the core. The mixed micelle formulation was found to be more effective in making a core more compatible to quercetin (as a model anticancer hydrophobic drug) with better pharmaceutical properties. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Dysfunctional cortico–basal ganglia–thalamic circuit and altered hippocampal–amygdala activity on cognitive set‐shifting in non‐neuropsychiatric systemic lupus erythematosus
Authors: Ren Tao , Ho Roger Chun‐Man , Mak Anselm
Published: November 2012

Objective

To explore sequential brain activities throughout cognitive set‐shifting, which is critical to understanding the basic pathophysiology of cognitive dysfunction, in patients with new‐onset systemic lupus erythematosus (SLE) without neuropsychiatric symptoms.

Methods

Fourteen patients with new‐onset SLE but without neuropsychiatric symptoms and 14 healthy controls matched for age, sex, education level, and intelligence quotient with the patients performed a cognitive set‐shifting task derived from the Wisconsin Card Sorting Test while they were undergoing event‐related functional magnetic resonance imaging of the brain. Blood oxygen level–dependent signals were compared between different stages of cognitive set‐shifting in the lupus patients and in the healthy subjects.

Results

Lupus patients and healthy subjects demonstrated comparable cognitive function performance, but the cortico–basal ganglia–thalamic–cortical circuit and amygdala–hippocampus coupling, which were involved in response inhibition and active forgetting–learning dynamics, respectively, were demonstrated to be compromised in patients with SLE. Moreover, an increase in contralateral cerebellar–frontal activity was found to compensate for the compromised cortico–basal ganglia–thalamic–cortical circuit in lupus patients in order to maintain their cognitive test performance as comparable to that of the healthy subjects.

Conclusion

Our study revealed significant differences in the sequential brain signals during cognitive set‐shifting between patients with SLE without neuropsychiatric symptoms and healthy subjects. The results prompt further in‐depth investigation for the functional neural basis of cognitive dysfunction involving the aforementioned neural circuits and compensatory pathways in patients with SLE.
Single‐fraction radiotherapy versus multifraction radiotherapy for palliation of painful vertebral bone metastases—Equivalent efficacy, less toxicity, more convenient
Authors: Howell David D. , James Jennifer L. , Hartsell William F. , Suntharalingam Mohan , Machtay Mitchell , Suh John H. , Demas William F. , Sandler Howard M. , Kachnic Lisa A. , Berk Lawrence B.
Published: November 2012

BACKGROUND:

The Radiation Therapy Oncology Group (RTOG) trial 97‐14 revealed no difference between radiation delivered for painful bone metastases at a dose of 8 gray (Gy) in 1 fraction (single‐fraction radiotherapy [SFRT]) and 30 Gy in 10 fractions (multifraction radiotherapy [MFRT]) in pain relief or narcotic use 3 months after randomization. SFRT for painful vertebral bone metastases (PVBM) has not been well accepted, possibly because of concerns about efficacy and toxicity. In the current study, the authors evaluated the subset of patients that was treated specifically for patients with PVBM.

METHODS:

PVBM included the cervical, thoracic, and/or lumbar spine regions. Among patients with PVBM, differences in retreatment rates and in pain relief, narcotic use, and toxicity 3 months after randomization were evaluated.

RESULTS:

Of 909 eligible patients, 235 (26%) had PVBM. Patients with and without PVBM differed in terms of the percentage of men (55% vs 47%, respectively; P = .03) and the proportion of patients with multiple painful sites (57% vs 38%, respectively; P < .01). Among those with PVBM, more patients who received MFRT had multiple sites treated (65% vs 49% for MFRT vs SFRT, respectively; P = .02). There were no statistically significant treatment differences in terms of pain relief (62% vs 70% for MFRT vs SFRT, respectively; P = .59) or freedom from narcotic use (24% vs 27%, respectively; P = .76) at 3 months. Significant differences in acute grade 2 through 4 toxicity (20% vs 10% for MFRT vs SFRT, respectively; P = .01) and acute grade 2 through 4 gastrointestinal toxicity (14% vs 6%, respectively; P = .01) were observed at 3 months, with lower toxicities seen in the patients treated with SFRT. Late toxicity was rare. No myelopathy was recorded. SFRT produced higher 3‐year retreatment rates (5% vs 15%; P = .01).

CONCLUSIONS:

Results for the subset of patients with PVBM in the RTOG 94‐17 randomized controlled trial were comparable to those for the entire population. SFRT produced less acute toxicity and a higher rate of retreatment than MFRT. SFRT and MFRT resulted in comparable pain relief and narcotic use at 3 months. Cancer 2013. © 2012 American Cancer Society.
Neoadjuvant therapy with weekly docetaxel and cisplatin, 5‐fluorouracil continuous infusion, and concurrent radiotherapy in patients with locally advanced esophageal cancer produced a high percentage of long‐lasting pathological complete response
Authors: Pasini Felice , de Manzoni Giovanni , Zanoni Andrea , Grandinetti Antonio , Capirci Carlo , Pavarana Michele , Tomezzoli Anna , Rubello Domenico , Cordiano Claudio
Published: November 2012

BACKGROUND:

This phase 2 study was aimed at defining the pathological response rate of a neoadjuvant schedule including weekly docetaxel and cisplatin, continuous infusion (c.i.) of 5‐fluorouracil (5‐FU) and concomitant radiotherapy (RT) in untreated stage II‐III adenocarcinoma and squamous cell carcinoma of mid‐distal thoracic esophagus.

METHODS:

The schedule consisted of a first phase of chemotherapy alone and of a second phase of concurrent chemoradiation. Doses were as follows: docetaxel 35 mg/m2 and cisplatin 25 mg/m2 on days 1, 8, 15, 29, 36, 43, 50, and 57 plus 5‐FU c.i. (180 mg/m2 on days 1‐21 and 150 mg/m2 on days 29‐63); RT (50 Gy) started at day 29. Surgery was planned 6 to 8 weeks after the completion of chemoradiation.

RESULTS:

A total of 74 patients were enrolled; pathological complete remission (pCR) was found in 47% (35 of 74) and near pCR (microfoci of tumor cells on the primary tumor without lymph nodal metastases) (pnCR) in 15% of the patients (11 of 74). Grade 3‐4 neutropenia, nonhematological toxicity, and toxic deaths occurred in 13.5%, 32.4%, and 4% of the patients, respectively. Median follow‐up was 55 months (range, 3‐108 months). Median survival of all 74 patients was 55 months, whereas it was not reached in the pCR subset. The 3‐ and 5‐year survival rates were, respectively, 83% and 77% for pCR, 73% and 44% for pnCR, and 21% and 14% for Residual Tumor subsets (P < .001).

CONCLUSIONS:

This study shows that 1) this intensive weekly schedule produced a high pathological response rate, 2) responders had high and long‐term durable survival rates. Cancer 2013. © 2012 American Cancer Society.
Correlation of TP53 and MDM2 genotypes with response to therapy in sarcoma
Authors: Ohnstad Hege O. , Castro Russell , Sun Jinchang , Heintz Karen‐Marie , Vassilev Lyubomir T. , Bjerkehagen Bodil , Kresse Stine H. , Meza‐Zepeda Leonardo A. , Myklebost Ola
Published: November 2012

BACKGROUND:

Relatively few sarcomas harbor TP53 (tumor protein p53) mutations, but in many cases, amplification of MDM2 (murine double minute 2) effectively inactivate p53. The p53 pathway activity can also be affected by normal genetic variation.

METHODS:

The mutation status of TP53 and expression of MDM2, TP53, and their genetic variants SNP309 and R72P (Arg72Pro) were investigated in 125 sarcoma patient samples and 18 sarcoma cell lines. Association of the different genotypes and gene aberrations with chemotherapy response and survival, as well as response to MDM2 antagonists in vitro was evaluated.

RESULTS:

Twenty‐two percent of the tumors had mutant TP53 and 20% MDM2 gene amplification. Patients with wild‐type TP53 (TP53Wt) tumors had improved survival (P < .001) and TP53Wt was an independent prognostic factor (hazard ratio = 0.41; 95% confidence interval = 0.23‐0.74; P = .03). Interestingly, there was a trend toward longer time to progression after chemotherapy for tumors with the apoptosis‐prone p53 variant R72 (P = .07), which was strongest with doxorubicin/ifosfamide‐based regimens (P = .01). Liposarcomas had low R72 frequency (33% versus 56%), but increased levels of MDM2 and MDM4 (51% and 11%, P < .001). MDM2 overexpression on a TP53Wt background predicted better response to MDM2 antagonist Nutlin‐3a, irrespective of R72P or SNP309 status.

CONCLUSIONS:

Improved survival after chemotherapy was found in patients with TP53Wt tumors harboring the R72 variant. MDM2 overexpression in TP53Wt tumors predicted good response to MDM2 antagonists, irrespective of R72P or SNP309 status. Thus, detailed TP53 and MDM2 genotype analyses prior to systemic therapy are recommended. Cancer 2013. © 2012 American Cancer Society.
The risk of primary and contralateral breast cancer after ovarian cancer in BRCA1/BRCA2 mutation carriers
Authors: Vencken Peggy M. L. H. , Kriege Mieke , Hooning Maartje , Menke‐Pluymers Marian B. , Heemskerk‐Gerritsen Bernadette A. M. , van Doorn Lena C. , Collée Margriet M. , Jager Agnes , van Montfort Cees , Burger Curt W. , Seynaeve Caroline
Published: November 2012

BACKGROUND:

The objective of this study was to assess the incidence of primary breast cancer (PBC) and contralateral breast cancer (CBC) in patients who had BRCA1/BRCA2‐associated epithelial ovarian cancer (OC).

METHODS:

From the database of the Rotterdam Family Cancer Clinic, patients who had BRCA‐associated OC without a history of unilateral breast cancer (BC) (at risk of PBC; n = 79) or with a history of unilateral BC (at risk of CBC; n = 37) were selected. The control groups consisted of unaffected BRCA mutation carriers (n = 351) or mutation carriers who had a previous unilateral BC (n = 294), respectively. The risks of PBC and CBC were calculated using the Kaplan‐Meier survival method with death considered as a competing risk event.

RESULTS:

Women with BRCA‐associated OC had lower 2‐year, 5‐year, and 10‐year risks of PBC (3%, 6%, and 11%, respectively) compared with unaffected mutation carriers (6%, 16%, and 28%, respectively; P = .03), although they had a considerably higher mortality rate at similar time points (13%, 33%, and 61%, respectively, vs 1%, 2%, and 2%, respectively; P < .001). In BRCA mutation carriers with a previous unilateral BC, the 2‐year, 5‐year, and 10‐year risks of CBC were nonsignificantly lower in patients with OC than in those without OC (0%, 7%, and 7%, respectively, vs 6%, 16%, and 34%, respectively; P = .06), whereas the mortality rate was higher in patients with OC (19%, 34%, and 55%, respectively, vs 4%, 11%, and 21%, respectively; P < .001).

CONCLUSIONS:

Patients with BRCA‐associated OC had a lower risk of developing a subsequent PBC or CBC than mutation carriers without OC, whereas the risk of dying from OC was greater than the risk of developing BC. These data may facilitate more tailored counseling for this patient subgroup, although confirmative studies are warranted. Cancer 2013. © 2012 American Cancer Society.
Outcome of children treated for relapsed acute lymphoblastic leukemia in Central America
Authors: Marjerrison Stacey , Antillon Federico , Fu Ligia , Martinez Roxana , Vasquez Roberto , Bonilla Miguel , Howard Scott C. , Sung Lillian
Published: November 2012

BACKGROUND:

Outcomes for relapsed childhood acute lymphoblastic leukemia (ALL) have not been documented in resource‐limited settings. This study examined survival after relapse for children with ALL in Central America.

METHODS:

A retrospective cohort study was performed and included children with first relapse of ALL in Guatemala, Honduras, or El Salvador between 1990 and 2011. Predictors of subsequent event‐free survival (EFS) and overall survival (OS) were examined.

RESULTS:

There were 755 children identified with relapsed disease. The median time from diagnosis to relapse was 1.7 years (interquartile range, 0.8‐3.1 years). Most relapses occurred during (53.9%) or following (24.9%) maintenance chemotherapy, and the majority occurred in the bone marrow (63.1%). Following the initial relapse, subsequent 3‐year EFS (± standard error) and OS were 22.0% ± 1.7%, and 28.2% ± 1.9%, respectively. In multivariable analysis, worse postrelapse survival was associated with age ≥ 10 years, white blood cell count ≥ 50 × 109/L, and positive central nervous system status at the original ALL diagnosis, relapse that was not isolated central nervous system or testicular, and relapse < 36 months following diagnosis. Site and time to relapse were used to identify a favorable risk group whose 3‐year EFS and OS were 50.0% ± 8.9% and 68.0% ± 8.1%, respectively.

CONCLUSIONS:

Prognosis after relapsed ALL in Central America is poor, but a substantial number of those with favorable risk features have prolonged survival, despite lack of access to stem cell transplantation. Stratification by risk factors can guide therapeutic decision‐making. Cancer 2013. © 2012 American Cancer Society.
Polyaniline/Prussian‐Blue‐Based Amperometric Biosensor for Detection of Uric Acid
Authors: Thakur Bhawana , Sawant Shilpa N.
Published: November 2012

Polyaniline/Prussian blue (PANI‐PB) composite was electrochemically deposited on a platinum electrode. The properties of the PANI‐PB‐modified electrode were exploited in terms of its response toward H2O2 sensing by using cyclic voltammetry, and were found to be more effectual than the PANI‐modified electrode in the low‐potential range. The PANI‐PB‐modified electrode was further used for the bioanalysis of uric acid by immobilization of the enzyme uricase. The electrode was characterized at various stages of modification by scanning electron microscopy (SEM), IR spectroscopy, and cyclic voltammetry. The biosensor gave a linear response for uric acid in the concentration range 10–160 μM with a sensitivity of 160 μA mM−1 cm−2. The main advantage of the PANI‐PB composite electrode is its low working potential (0 V vs. Ag/AgCl) for the estimation of uric acid, which enables the elimination of plausible interfering effects caused by analytes present in real samples. The biosensor was selective to uric acid and did not respond to analytes such as ascorbic acid, glucose, and urea. The sensor electrode retained its selectivity and sensitivity for seven days if stored at −18 °C. The biosensor also displayed a satisfactory performance for the detection of uric acid in human blood serum samples.
Real‐time cell viability assays using a new anthracycline derivative DRAQ7®
Authors: Akagi Jin , Kordon Magdalena , Zhao Hong , Matuszek Anna , Dobrucki Jurek , Errington Rachel , Smith Paul J. , Takeda Kazuo , Darzynkiewicz Zbigniew , Wlodkowic Donald
Published: November 2012

The exclusion of charged fluorescent dyes by intact cells has become a well‐established assay for determining viability of cells. In search for a noninvasive fluorescent probe capable of long‐term monitoring of cell death in real‐time, we evaluated a new anthracycline derivative DRAQ7. The novel probe does not penetrate the plasma membrane of living cells but when the membrane integrity is compromised, it enters and binds readily to nuclear DNA to report cell death. It proved to be nontoxic to a panel of cancer cell lines grown continuously for up to 72 h and did not induce any detectable DNA damage signaling when analyzed using laser scanning microscopy and flow cytometry. The DRAQ7 provided a sensitive, real‐time readout of cell death induced by a variety of stressors such as hypoxia, starvation, and drug‐induced cytotoxicity. The overall responses to anticancer agents and resulting pharmacological dose‐response profiles were not affected by the growth of tumor cells in the presence DRAQ7. Moreover, we for the first time introduced a near real‐time microflow cytometric assay based on combination of DRAQ7 and mitochondrial inner membrane potential (ΔΨm) sensitive probe TMRM. We provide evidence that this low‐dosage, real‐time labeling procedure provides multiparameter and kinetic fingerprint of anticancer drug action. © 2012 International Society for Advancement of Cytometry
Murine and human very small embryonic‐like cells: A perspective
Authors: Heider Andreas , Danova‐Alt Ralitza , Egger Dietmar , Cross Michael , Alt Rüdiger
Published: November 2012

In 2006, very small embryonic‐like (VSEL) stem cells were described as a pluripotent population of prospectively isolated stem cells in adult murine bone marrow (mBM) and human umbilical cord blood (hUCB). While rigorous proof of pluripotency is still lacking, murine VSEL cells have been shown to overlap with an independently identified population of neural crest derived mesenchymal stem cells (MSC). The presence of primitive mesenchymal precursors within the VSEL cell population may partially explain the findings that have led to the concept of an “embryonic‐like” stem cell in mBM. However, our own studies on human VSEL cells revealed very little similarity between murine VSEL cells and their reportedly equivalent population in hUCB. On the contrary, our data strongly suggest that human VSEL cells are an aberrant and inactive population that cannot expand in vitro and has neither embryonic nor adult stem cell like properties. Here we critically re‐examine the data supporting stemness and pluripotency of murine and human VSEL cells, respectively. © 2012 International Society for Advancement of Cytometry
Cytologic diagnosis of thyroid‐like follicular carcinoma of the kidney: A case report
Authors: Dhillon Jasreman , Mohanty Sambit K. , Krishnamurthy Savitri
Published: November 2012

Thyroid‐like follicular carcinoma of the kidney (TLFCK) is a recently described subtype of renal‐cell carcinoma that is not currently included in the World Health Organization classification. Few sporadic case reports and one series have been reported with emphasis on histopathologic features. However, cytological features have not been described in the literature to date.

A 34‐year‐old male presented with a renal mass. An intraoperative smear preparation of the tumor revealed a hypercellular smear with cells arranged in sheets without any follicular, papillary, or acinar arrangement. The most striking feature was the presence of acellular eosinophilic material associated with the neoplastic epithelial cells in the background of the smear. Individual tumor cells were oval, round, and plasmacytoid with mild nuclear pleomorphism, finely stippled nuclear chromatin, and inconspicuous nucleoli with moderate amount of eosinophilic cytoplasm and rare nuclear grooves. It was unclear at the time of the intraoperative assessment of the smear if the acellular eosinophilic material represented metachromatic matrix‐like extracellular material, mucin, colloid, amyloid, or hyaline material.

The differential diagnoses included a primary renal‐cell carcinoma versus a metastatic tumor.

Subsequent histopathologic examination was diagnostic of a rare, recently described primary neoplasm of the kidney called TLFCK. This work is a retrospective evaluation of the cytological features of TLFCK. It is important for cytopathologists to be aware of this entity and its cytological features to render a correct diagnosis for adequate management of these patients. Diagn. Cytopathol. 2014;42:273–277. © 2012 Wiley Periodicals, Inc.
Adenomatoid mesothelioma with intranuclear inclusion bodies: A case report with cytological and histological findings
Authors: Kawai Toshiaki , Kawashima Katsuhiko , Serizawa Hiromi , Miura Hiroyuki , Kyeongil Kim
Published: November 2012

We report a very unusual cytologic feature, intranuclear inclusion bodies, in mesothelioma of a predominantly adenomatoid type. The patient, a 57‐year‐old woman, was presented with dyspnea and right pleural effusion. Pleural aspiration cytology revealed many cohesive ball‐like clusters, with a tubular pattern, composed of small atypical cells displaying a high‐nuclear‐cytoplasmic ratio. They had a nuclear groove and irregular intranuclear inclusion bodies. Right lung partial resection with thoracoscopy revealed that a white tumor had proliferated along the pleural surface at S8. Histology revealed nodular tumor cells forming dilated structures mixed with small tubular or glandular structures similar to those seen in benign adenomatoid tumors. These tumor cells had invaded peripheral lung tissues. Such inclusion bodies have not been reported earlier in mesothelioma. On the basis of this observation, we propose that the adenomatoid type of malignant mesothelioma be added to the differential diagnosis of malignant effusions when tumor cells with nuclear grooves and intranuclear inclusions are found in pleural aspiration cytology. Diagn. Cytopathol. 2014;42:436‐440. © 2012 Wiley Periodicals, Inc.
Pulmonary neuroendocrine tumors: An entity in search of cytologic criteria
Authors: Huang Cheng Cheng , Collins Brian T. , Flint Andrew , Michael Claire W.
Published: November 2012

Pulmonary neuroendocrine tumors (PNET) are histologically subclassified into typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCLC). The criteria for subclassification in cytological specimens are not well defined. In this study, we reviewed histologically confirmed 18 TC, 8 AC, 10 LCNEC, and 10 SCLC cytologic specimens from 45 patients. The following features were reviewed: small clusters, geographic sheets, trabecular structures, pseudo‐rosettes, single cells, doublets, triplets or short cords, papillary‐like structures, capillary vasculatures, necrosis, smear background, cell size, cell pleomorphism, amount of cytoplasm, plasmacytoid cells, spindle cells, nuclear atypia, molding, palisading and smearing, chromatin textures, nucleoli, and mitotic figure count. Based on our results, geographic clusters and necrosis were often seen in LCNEC and SCLC; while AC only showed scattered single cell necrosis. TC and AC commonly exhibited trabecular structures. Papillary‐like structures and capillary vasculature were only present in TC, AC, and LCNEC. Cells forming doublets, triplets, and short cords were more commonly seen in SCLC and rarely seen in other entities. Plasmacytoid and spindle cells were only seen in TC and AC. Nuclear smearing was not identified in TC, rare in AC, focally present in LCNEC and obvious in SCLC. Mitotic figures were nearly absent in TC, ≤5/10 HPF in AT, and ≥10/10 HPF in SCLC. LCNEC showed a wide span of mitotic count ranging between 2 and 16/10 HPF. In this study, we propose a set of cytological features that are essential for subclassification of PNETs in cytologic specimens. Diagn. Cytopathol. 2013;41:689–696. © 2013 Wiley Periodicals, Inc.
High‐Quality Phenomics are Crucial for Informative Omics Studies
Authors: Gurwitz David
Published: November 2012

Preclinical Research
Evaluation of lower limb motor function using wireless motion sensors—a comparison of normal elderly subjects and those requiring Support Level 1
Authors: Miyoshi Hiroaki , Numata Takayuki , Kuwae Yutaka , Sekine Masaki , Tsuji Miwa , Okabe Ichiro , Hara Keita , Fujimoto Toshiro , Tamura Toshiyo
Published: November 2012

This study quantitatively compared lower limb motility of normal subjects and those requiring Support Level 1 (support_1). We developed a wireless inertial sensor with an embedded triaxial accelerometer and angular velocity sensor. Six normal elderly subjects and ten elderly subjects who were classified as support_1 by the Japanese care insurance system participated in the study. We attached the wireless motion sensors to the center of the lower back and both thighs of the subjects. The subjects were then asked to walk 10 m and perform a stepping exercise. For the evaluation, the cadence, pitch angle, and pitch angular velocity of the thigh autocorrelation function and root mean square (RMS) on the lower back were calculated. The autocorrelation coefficient function for the support_1 subjects was smaller than for the normal subjects, while the RMS was larger in support_1. These differences indicated that the gait and balance abilities of the support_1 subjects were poorer than those of the normal subjects. This suggests that our wireless motion sensor is useful for assessing the motility of the lower limbs while walking and climbing steps. © 2012 Wiley Periodicals, Inc. Electron Comm Jpn, 95(12): 37–45, 2012; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.11430
High‐speed generation of goal‐oriented scenarios using bidirectional combination of effect propagation on a qualitative and quantitative hybrid model
Authors: Samejima Masaki , Morita Yoshihiro , Akiyoshi Masanori
Published: November 2012

This paper addresses the high‐speed generation of goal‐oriented scenarios on a qualitative and quantitative hybrid model. The goal‐oriented scenarios can be generated efficiently by a bidirectional combination of forward propagation and backward propagation, if differences between the values related to each scenario are small on a certain time step. Thus, the method combines the scenarios when each value can be regarded as the same from qualitative value viewpoints. Furthermore, the proposed method decides the number of both propagations to generate the required number of goal‐oriented scenarios while decreasing the number of time‐consuming backward propagations. Experimental results show that the computational time for generating the required number of goal‐oriented scenarios is decreased by 98% compared to solely forward propagation. © 2012 Wiley Periodicals, Inc. Electron Comm Jpn, 95(12): 10–20, 2012; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.11443