Serum vascular endothelial growth factor as a tumor marker for hepatocellular carcinoma in hepatitis C virus-related cirrhotic patients

BACKGROUNDHepatocellular carcinoma (HCC) accounts for 8.2% of all cancer-related deaths worldwide. Being a vascular tumor, vascular endothelial growth factor (VEGF) plays a vital role in HCC pathogenesis, growth, and spread.AIMTo determine the accuracy of serum VEGF and VEGF/platelet (PLT) as tumor markers in the early detection of HCC cases in patients with hepatitis C virus (HCV)-related liver cirrhosis.METHODSWe conducted a case-control study with HCV patients from the outpatient and inpatient hepatology clinics. Patients were classified into three groups: (1) HCC group; (2) Cirrhosis group; and (3) HCV without cirrhosis (control group). Patients were clinically evaluated, and blood samples were drawn for the analysis; serum VEGF levels were measured by a specific VEGF human recombinant enzyme-linked immunosorbent assay kit. Data from the three study groups were compared by the one-way analysis of variance or Kruskal-Wallis test. Receivers operating characteristic curves were constructed to determine the optimal cut-off values of alpha fetoprotein (AFP), VEGF, and VEGF/PLT that provided the best diagnostic accuracy. The sensitivity and specificity at the optimal cut-off value of each biomarker were then calculated. RESULTSThis study included one hundred patients (HCC, cirrhosis, and control groups: n = 40, 30, 30, respectively). HCC patients had significantly higher serum VEGF and VEGF/PLT levels than the non-HCC groups (P = 0.001). Serum VEGF and VEGF/PLT showed significant positive correlations with and HCC tumor size, stage, vascular invasion, and Child-Pugh classification. Moreover, a VEGF cut-off the value of 250 pg/mL provided 80% sensitivity and 81.7% specificity for discriminating HCC patient from non-HCC patients. Similarly, the ratio of VEGF/PLT provided sensitivity and specificity of 77.5% and 80%, respectively which is higher than the accuracy provided by AFP. The combination of AFP, VEGF, and VEGF/PLT increases the accuracy of diagnosing HCC to > 95%.CONCLUSIONIn HCV patients, serum VEGF and VEGF/PLT separately or in combination with AFP are reliable biomarkers for early and accurate HCC diagnosis.     

The Use of Herbal Therapy to Improve the Quality of Life among Cancer Patients in the Southern Region of Peninsular Malaysia

Objective: To investigate the impact of herbal therapy on the quality of life (QoL) among cancer patients and to evaluate the relationship of QoL with age, gender, cancer stage, cancer type, and history of conventional treatment.Methodology: A prospective study was targeted on cancer patients receiving herbal therapy from a Traditional and Complementary Medicine (T&CM) clinic in a public hospital from 1st January 2016 to 31st August 2018. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTCQLQ-C30) was distributed to the patients prior to herbal therapy (baseline) and after the sixth and twelfth week of herbal therapy. Socio-demographic and clinical data were collected and analyzed using SPSS version 16. Results: The majority of the patients were females (60.0%) and were from the Chinese ethnic group (77.4%) with a mean age of 58.72 ± 12.17 years. Approximately 42.4% of patients were in advanced cancer stages at the time of study and 60.7% of patients had undergone radiotherapy before receiving herbal therapy. The most commonly prescribed herbs were Bai Hua She She Cao (90.6%) and Zhen Ren Huo Ming Yin (57.6%). Significant differences in mean score were observed in global health status, overall functional scales, and symptom scales after the sixth and twelfth week of receiving herbal therapy. QoL in terms of global health status and overall functional scales improved with higher scores while symptom scales recorded a lower score after twelve weeks of receiving herbal therapy in the T&CM clinic. Herbal therapy has a significant effect (p < 0.05) on the improvement of QoL of cancer patients. However, gender, cancer stage, cancer type, age, history of radiotherapy, and history of chemotherapy has no effect (p > 0.05). Conclusion: Herbal therapy did improve the QoL of cancer patients in the southern region of Peninsular Malaysia.     

Functional aberrant expression of CCR2 receptor on chronically activated NK cells in patients with TAP-2 deficiency

Chemokines play a pivotal role in homeostatic and inflammatory migration of naive and activated natural killer (NK) subsets. Recent studies have shown that aberrant chemokine receptor expression on certain immune cells underlies the pathogenesis of clinical conditions in which recruitment of such cells is altered. Progressive accumulation of activated NK cells, subsequently resulting in the formation of chronic granulomatous lesions in the respiratory tract and the skin, has been described in a number of patients with transporter associated with antigen processing 2 (TAP-2) deficiency in the later stages of disease. Therefore, the goal of the present study was to elucidate whether the dysregulation of chemoattracting receptor expression on NK cells could explain abnormal navigation of these cells in TAP-2 deficiency. High-throughput proteomic comparison, followed by verification with flow cytometry, revealed that chronically activated NK cells derived from 3 newly identified patients with TAP-2 deficiency consistently expressed aberrant levels of CC chemokine receptor 2 (CCR2) chemokine receptor in vitro and in vivo. This expression pattern translated into specific responsiveness of chronically activated NK cells derived from patients with TAP-2 deficiency to multiple ligands of CCR2. Moreover, the in vivo elevated levels of interleukin-2 (IL-2) and monocyte chemoattractant protein-1 (MCP-1) detected in serum and bronchoalveolar lavage samples derived from these patients highlight the potential involvement of the CCR2 pathway in aberrant NK-cell retention at chronic inflammatory sites.     

Lesions of the paraventricular nucleus of the thalamus differentially affect sign‐ and goal‐tracking conditioned responses

Recently, evidence has emerged suggesting a role for the paraventricular nucleus of the thalamus (PVT) in the processing of reward‐associated cues. However, the specific role of the PVT in these processes has yet to be elucidated. Here we use an animal model that captures individual variation in response to discrete reward‐associated cues to further assess the role of the PVT in stimulus–reward learning. When rats are exposed to a Pavlovian conditioning paradigm, wherein a discrete cue predicts food reward, two distinct conditioned responses emerge. Some rats, termed sign‐trackers, approach and manipulate the cue, whereas others, termed goal‐trackers, approach the location of reward delivery upon cue presentation. For both sign‐ and goal‐trackers the cue is a predictor, but only for sign‐trackers is it also an incentive stimulus. We investigated the role of the PVT in the acquisition and expression of these conditioned responses using an excitotoxic lesion. Results indicate that PVT lesions prior to acquisition amplify the differences between phenotypes – increasing sign‐tracking and attenuating goal‐tracking behavior. Lesions of the PVT after rats had acquired their respective conditioned responses also attenuated the expression of the goal‐tracking response, and increased the sign‐tracking response, but did so selectively in goal‐trackers. These results suggest that the PVT acts to suppress the attribution of incentive salience to reward cues, as disruption of the functional activity within this structure enhances the tendency to sign‐track.     

Renal Arcuate Vein Microthrombi-Associated AKI

Backgrounds and objectives

This report describes six patients with AKI stages 2–3 (median admission creatinine level, 2.75 mg/dl [range, 1.58–5.44 mg/dl]), hematuria (five with hemoproteinuria), and unremarkable imaging with an unusual and unexplained histologic diagnosis on renal biopsy.

Design, setting, participants, & measurements

The patients were young adults who presented to two neighboring United Kingdom nephrology centers over a 40-month period (between July 2010 and November 2013). Four were male, and the median age was 22.5 years (range, 18–27 years). Their principal symptoms were flank pain or lower back pain. All had consumed alcohol in the days leading up to admission.

Results

Renal biopsy demonstrated microthrombi in the renal arcuate veins with a corresponding stereotypical, localized inflammatory infiltrate at the corticomedullary junction. All patients recovered to baseline renal function with supportive care (median, 17 days; range, 6–60 days), and none required RRT. To date, additional investigations have not revealed an underlying cause for these histopathologic changes. Investigations have included screening for thrombophilic tendencies, renal vein Doppler ultrasonographic studies, and testing for recreational drugs and alcohol (including liquid chromatography–mass spectrometry of urine) to look for so-called designer drugs. Inquiries to the United Kingdom National Poisons Information Centre have identified no other cases with similar presentation or histologic findings.

Conclusions

Increased awareness and additional study of future cases may lead to a greater understanding of the underlying pathophysiologic mechanisms that caused AKI in these patients.     

Cross-protection by B subunit-whole cell cholera vaccine against diarrhea associated with heat-labile toxin-producing enterotoxigenic Escherichia coli: results of a large-scale field trial

The B subunit (BS) of cholera toxin and that of the heat-labile enterotoxin (LT) of enterotoxigenic Escherichia coli (ETEC) are antigenically similar. We therefore assessed whether a combined cholera toxin BS/whole-cell (BS-WC) oral vaccine against cholera conferred cross-protection against LT-producing ETEC (LT-ETEC) diarrhea in a randomized, double-blind field trial among rural Bangladeshi children and women. The 24,770 persons who ingested two or more doses of BS-WC vaccine were compared with 24,842 controls who took two or more doses of killed whole-cell (WC) oral cholera vaccine. Sixty-seven percent fewer episodes of LT-ETEC diarrhea were noted in the BS-WC group than in the WC group during short-term (three-month) follow-up (P less than .01), but no reduction was evident during the ensuing nine months. Short-term protection was particularly notable against LT-ETEC diarrhea causing life-threatening dehydration (protective efficacy, 86%; P less than .05).     

Determination of the natural radioactivity levels in north west of Dukhan, Qatar using high-resolution gamma-ray spectrometry

This study is aimed at the determination of the activity concentrations of naturally occuring and technologically enhanced levels of radiation in 34 representative soil samples that have been collected from an inshore oil field area which was found to have, in a previous study, the highest observed value of 226Ra concentration among 129 soil samples. The activity concentrations of 238U and 226Ra have been inferred from gamma-ray transitions associated with their decay progenies and measured using a hyper-pure germanium detector. Details of the sample preparation and the gamma-ray spectroscopic analysis techniques are presented, together with the values of the activity concentrations associated with the naturally occuring radionuclide chains for all the samples collected from NW Dukhan. Discrete-line, gamma-ray energy transitions from spectral lines ranging in energy from ～100 keV up to 2.6 MeV have been associated with characteristic decays of the various decay products within the 235.8U and 232Th radioactive decay chains. These data have been analyzed, under the assumption of secular equilibrium for the U and Th decay chains. Details of the sample preparation and the gamma-ray spectroscopic analysis techniques are presented. The weighted mean value of the activity concentrations of 226Ra in one of the samples was found to be around a factor of 2 higher than the values obtained in the previous study and approximately a factor of 10 higher than the accepted worldwide average value of 35 Bq/kg. The weighted mean values of the activity concentrations of 232Th and 40K were also deduced and found to be within the worldwide average values of 30 and 400 Bq/kg, respectively. Our previous study reported a value of 201.9±1.5Stat.±13Syst.Bq/kg for 226Ra in one sample and further investigation in the current work determined a measured value for 226Ra of 342.00±1.9Stat.±25Syst.Bq/kg in a sample taken from the same locality. This is significantly higher than all the other investigated soil samples in the current and previous works. Notably, the Th levels in the same sample are within the worldwide average expectations, implying that the increased 226Ra concentration arises from TENORM processes.