Novel biomarkers predict liver fibrosis in hepatitis C patients: alpha 2 macroglobulin,vitamin D binding protein and apolipoprotein AI

Background  

The gold standard of assessing liver fibrosis is liver biopsy, which is invasive and not without risk. Therefore, searching for noninvasive serologic biomarkers for liver fibrosis is an importantly clinical issue.     

Role of chromosome stability and telomere length in the production of viable cell lines for somatic cell nuclear transfer

Background  

Somatic cell nuclear transfer (SCNT) provides an appealing alternative for the preservation of genetic material in non-domestic and endangered species. An important prerequisite for successful SCNT is the availability of good quality donor cells, as normal embryo development is dependent upon proper reprogramming of the donor genome so that embryonic genes can be appropriately expressed. The characteristics of donor cell lines and their ability to produce embryos by SCNT were evaluated by testing the effects of tissue sample collection (DART biopsy, PUNCH biopsy, post-mortem EAR sample) and culture initiation (explant, collagenase digestion) techniques.     

Significant difference between three observers in the assessment of intraepidermal nerve fiber density in skin biopsy

Background  

The determination of Intraepidermal Nerve Fiber Density (IENFD) in skin biopsy is a useful method for the evaluation of different types of peripheral neuropathies. To allow a reliable use of the method it is necessary to determine interobserver reliability. Previous studies dealing with this topic used limited suitable statistical methods.     

Concurrent genotyping of <Emphasis Type="Italic">Helicobacter pylori</Emphasis>virulence genes and human cytokine SNP sites using whole genome amplified DNA derived from minute amounts of gastric biopsy specimen DNA

Background  

Bacterial and cellular genotyping is becoming increasingly important in the diagnosis of infectious diseases. However, difficulties in obtaining sufficient amount of bacterial and cellular DNA extracted from the same human biopsy specimens is often a limiting factor. In this study, total DNA (host and bacterial DNA) was isolated from minute amounts of gastric biopsy specimens and amplified by means of whole genome amplification using the multiple displacement amplification (MDA) technique. Subsequently, MDA-DNA was used for concurrent Helicobacter pylori and human host cellular DNA genotyping analysis using PCR-based methods.     

Apoptosis is increased and cell proliferation is decreased in out-of-phase endometria from infertile and recurrent abortion patients

Background  

Various endometrial abnormalities have been associated with luteal phase deficiency: a significant dyssynchrony in the maturation of the glandular epithelium and the stroma and a prevalence of out-of-phase endometrial biopsy specimens. Out-of phase endometrium is a controversial disorder related to failed implantation, infertility and early pregnancy loss. Given that the regulation of the apoptotic process in endometrium of luteal phase deficiency is still unknown, the aim of this study was to evaluate cell proliferation, apoptosis and the levels of the main effector caspase, caspase-3 in the luteal in-phase and out-of-phase endometrium.     

An ELISA-based procedure for assaying proteins in digests of human leukocytes and cell lines, using specifically selected peptides and appropriate antibodies

Background  

We describe the application of an ELISA-based assay (the Peptidomatrix) that can be used to simultaneously identify and quantitate a number of proteins in biological samples. The biological sample (blood component, biopsy, culture or other) is first lysed to release all the proteins, without any additional separation. The denatured proteins in the sample are then digested in bulk with the desired proteolytic enzyme(s). The peptides in the digest are then assayed by appropriate antibodies, using a competition ELISA protocol.     

Identification of an unusual <Emphasis Type="Italic">Brucella</Emphasis> strain (BO2) from a lung biopsy in a 52 year-old patient with chronic destructive pneumonia

Background  

Brucellosis is primarily a zoonotic disease caused by Brucella species. There are currently ten Brucella spp. including the recently identified novel B. inopinata sp. isolated from a wound associated with a breast implant infection. In this study we report on the identification of an unusual Brucella-like strain (BO2) isolated from a lung biopsy in a 52-year-old patient in Australia with a clinical history of chronic destructive pneumonia.     

Pelodera (syn. Rhabditis) strongyloides as a cause of dermatitis – a report of 11 dogs from Finland

Background  

Pelodera (Rhabditis) strongyloides is a small saprophytic nematode that lives in decaying organic matter. On rare occasions, it can invade the mammalian skin, causing a pruritic, erythematous, alopecic and crusting dermatitis on skin sites that come into contact with the ground. Diagnosis of the disease is based on case history (a dog living outdoors on damp straw bedding) with characteristic skin lesions and on the demonstration of typical larvae in skin scrapings or biopsy. Pelodera (rhabditic) dermatitis cases have been reported mainly from Central European countries and the United States.     

The histologic detection of Helicobacter pylori in seropositive subjects is affected by pathology and secretory ability of the stomach

Background

Helicobacter pylori is unevenly distributed in hypochlorhydric environments. The study aim was to elucidate the risk factors for a negative Giemsa staining finding in seropositive subjects by measuring the secretory ability of the stomach.

Methods

Subjects aged over 18 years were included consecutively after endoscopic biopsy at gastric lesions with color or structural changes. Blood was sampled for the serum pepsinogen (PG) assay and H. pylori serology test. After excluding the subjects with past H. pylori eradication, the risk factors for a negative Giemsa staining finding in seropositive subjects were analyzed.

Results

Among 872 included subjects, a discrepancy between the serum anti‐H. pylori IgG and Giemsa staining findings was found in 158 (18.1%) subjects, including 145 Giemsa‐negative, seropositive subjects. Gastric adenocarcinoma/adenoma (OR = 11.090, 95% CI = 3.490‐35.236) and low serum PG II level (OR = 0.931, 95% CI = 0.899‐0.963) were the independent risk factors for a negative Giemsa staining finding in seropositive subjects. The cutoff value of serum PG II level was 7.45 ng/mL (area under curve [AUC] = 0.904, 95% CI = 0.881‐0.927). Follow‐up studies of Giemsa staining at different sites of the stomach revealed that 75% of the Giemsa‐negative seropositive subjects with adenocarcinoma are positive, whereas none of those with low serum PG II level of <7.45 ng/mL revealed positive findings.

Conclusions

The risk of a negative Giemsa staining finding in seropositive subjects is increased in gastric adenocarcinoma/adenoma specimens and in subjects with a diminished gastric secretory ability with low serum PG II level of <7.45 ng/mL. A false‐negative Giemsa staining finding is common in subjects with adenocarcinoma, and therefore, additional biopsies at different sites should be performed in these subjects.     

The Value of Routine Biopsy during Percutaneous Kyphoplasty for Vertebral Compression Fractures

Objective

Percutaneous kyphoplasty (PKP) is now widely performed to treat VCF, which is usually caused by osteoporosis. Previous researches have reported unsuspected malignancies found by biopsy. However, the safety and cost-effective profiles of routine biopsy during PKP are unclear. The purpose of this study was to evaluate the feasibility of routine biopsy during PKP in treatment of VCF.

Methods

Ninety-three patients (September 2007–November 2010) undergoing PKP without biopsy were reviewed as the control group. One hundred and three consecutive patients (November 2010–September 2013) undergoing PKP with biopsy of every operated vertebral level were prospectively enrolled as the biopsy group. The rate of unsuspected lesions was reported, and the severe adverse events, surgical duration, cement leakage rate and pain control were compared between the two groups.

Results

No statistically significant differences were found between the two groups, regarding the severe adverse events, surgical duration, cement leakage rate and pain control. Four unsuspected lesions were found in the biopsy group, three of which were malignancies with a 2.9% (3/103) unsuspected malignancy rate. The economic analysis showed that routine biopsy was cost-effective in finding new malignancies comparing with a routine cancer screening campaign.

Conclusions

Routine biopsy during PKP was safe and cost-effective in finding unsuspected malignancies. We advocate routine biopsy in every operated vertebral level during PKP for VCF patients.     

Profiling of serum and tissue high abundance acute-phase proteins of patients with epithelial and germ line ovarian carcinoma

Background  

Acute-phase response involves the simultaneous altered expression of serum proteins in association to inflammation, infection, injury or malignancy. Studies of the acute-phase response usually involve determination of the levels of individual acute-phase serum proteins. In the present study, the acute-phase response of patients with epithelial (EOCa) and germ-line (GOCa) ovarian carcinoma was investigated using the gel-based proteomic approach, a technique which allowed the simultaneous assessment of the levels of the acute-phase serum high abundance proteins. Data obtained were validated using ELISA and immunostaining of biopsy samples.     

Antibiotics resistance of Helicobacter pylori in children with upper gastrointestinal symptoms in Hangzhou,China

Background

The decreasing eradication rate of Helicobacter pylori is mainly because of the progressive increase in its resistance to antibiotics. Studies on antimicrobial susceptibility of H. pylori in children are limited. This study aimed to investigate the resistance rates and patterns of H. pylori strains isolated from children.

Materials and Methods

Gastric mucosa biopsy samples obtained from children who had undergone upper gastrointestinal endoscopy were cultured for H. pylori, and susceptibility to six antibiotics (clarithromycin, amoxicillin, gentamicin, furazolidone, metronidazole, and levofloxacin) was tested from 2012‐2014.

Results

A total of 545 H. pylori strains were isolated from 1390 children recruited. The total resistance rates of H. pylori to clarithromycin, metronidazole, and levofloxacin were 20.6%, 68.8%, and 9.0%, respectively. No resistance to amoxicillin, gentamicin, and furazolidone was detected. 56.1% strains were single resistance, 19.6% were resistant to more than one antibiotic, 16.7% for double resistance, and 2.9% for triple resistance in 413 strains against any antibiotic. And the H. pylori resistance rate increased significantly from 2012‐2014. There was no significant difference in the resistance rates to clarithromycin, metronidazole, and levofloxacin between different gender, age groups, and patients with peptic ulcer diseases or nonulcer diseases.

Conclusions

Antibiotic resistance was indicated in H. pylori strains isolated from children in Hangzhou, and it increased significantly during the 3 years. Our data strongly support current guidelines, which recommend antibiotic susceptibility tests prior to eradication therapy.     

Comparison of LPS-stimulated release of cytokines in punch versus transwell tissue culture systems of human gestational membranes

Background  

Cytokine signaling within the amnionic, chorionic and decidual extraplacental gestational membranes plays an important role in membrane rupture and the timing of birth. The predominant in vitro explant culture system for evaluating cytokine induction in human gestational membranes has been the free-floating biopsy punch culture. Punch systems have been used to investigate the impact of various toxicants, pharmaceuticals and genetic variation on expression of pro-inflammatory cytokines. More recently, a dual compartment transwell culture system has been developed that more closely mimics the intrauterine compartment. The current study compares these two systems with respect to release of pro- and anti-inflammatory cytokines in response to lipopolysaccharide (LPS), a model stimulant.     

Operator Dependent Choice of Prostate Cancer Biopsy Has Limited Impact on a Gene Signature Analysis for the Highly Expressed Genes IGFBP3 and F3 in Prostate Cancer Epithelial Cells

Background

Predicting the prognosis of prostate cancer disease through gene expression analysis is receiving increasing interest. In many cases, such analyses are based on formalin-fixed, paraffin embedded (FFPE) core needle biopsy material on which Gleason grading for diagnosis has been conducted. Since each patient typically has multiple biopsy samples, and since Gleason grading is an operator dependent procedure known to be difficult, the impact of the operator''s choice of biopsy was evaluated.

Methods

Multiple biopsy samples from 43 patients were evaluated using a previously reported gene signature of IGFBP3, F3 and VGLL3 with potential prognostic value in estimating overall survival at diagnosis of prostate cancer. A four multiplex one-step qRT-PCR test kit, designed and optimized for measuring the signature in FFPE core needle biopsy samples was used. Concordance of gene expression levels between primary and secondary Gleason tumor patterns, as well as benign tissue specimens, was analyzed.

Results

The gene expression levels of IGFBP3 and F3 in prostate cancer epithelial cell-containing tissue representing the primary and secondary Gleason patterns were high and consistent, while the low expressed VGLL3 showed more variation in its expression levels.

Conclusion

The assessment of IGFBP3 and F3 gene expression levels in prostate cancer tissue is independent of Gleason patterns, meaning that the impact of operator''s choice of biopsy is low.     

Repeat Targeted Prostate Biopsy under Guidance of Multiparametric MRI-Correlated Real-Time Contrast-Enhanced Ultrasound for Patients with Previous Negative Biopsy and Elevated Prostate-Specific Antigen: A Prospective Study

Objectives

To prospectively determine whether multi-parametric MRI (mpMRI) - contrast-enhanced ultrasound (CEUS) correlated, imaging-guided target biopsy (TB) method could improve the detection of prostate cancer in re-biopsy setting of patients with prior negative biopsy.

Methods

From 2012 to 2014, a total of 42 Korean men with a negative result from previous systematic biopsy (SB) and elevated prostate-specific antigen underwent 3T mpMRI and real-time CEUS guided TB. Target lesions were determined by fusion of mpMRI and CEUS. Subsequently, 12-core SB was performed by a different radiologist. We compared core-based cancer detection rates (CaDR) using the generalized linear mixed model (GLIMMIX) for each biopsy method.

Results

Core-based CaDR was higher in TB (17.92%, 38 of 212 cores) than in SB (6.15%, 31 of 504 cores) (p < 0.0001; GLIMMIX). In the cancer-positive TB cores, CaDR with suspicious lesions by mpMRI was higher than that by CEUS (86.8% vs. 60.5%, p= 0.02; paired t-test) and concordant rate between mpMRI and CEUS was significantly different with discordant rate (48% vs. 52%, p=0.04; McNemar’s test).

Conclusion

The mpMRI-CEUS correlated TB technique for the repeat prostate biopsy of patients with prior negative biopsy can improve CaDR based on the number of cores taken.     

Cost effectiveness of fibrosis assessment prior to treatment for chronic hepatitis C patients

Background and Aims

Chronic hepatitis C (HCV) is a liver disease affecting over 3 million Americans. Liver biopsy is the gold standard for assessing liver fibrosis and is used as a benchmark for initiating treatment, though it is expensive and carries risks of complications. FibroTest is a non-invasive biomarker assay for fibrosis, proposed as a screening alternative to biopsy.

Methods

We assessed the cost-effectiveness of FibroTest and liver biopsy used alone or sequentially for six strategies followed by treatment of eligible U.S. patients: FibroTest only; FibroTest with liver biopsy for ambiguous results; FibroTest followed by biopsy to rule in; or to rule out significant fibrosis; biopsy only (recommended practice); and treatment without screening. We developed a Markov model of chronic HCV that tracks fibrosis progression. Outcomes were expressed as expected lifetime costs (2009 USD), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICER).

Results

Treatment of chronic HCV without fibrosis screening is preferred for both men and women. For genotype 1 patients treated with pegylated interferon and ribavirin, the ICERs are $5,400/QALY (men) and $6,300/QALY (women) compared to FibroTest only; the ICERs increase to $27,200/QALY (men) and $30,000/QALY (women) with the addition of telaprevir. For genotypes 2 and 3, treatment is more effective and less costly than all alternatives. In clinical settings where testing is required prior to treatment, FibroTest only is more effective and less costly than liver biopsy. These results are robust to multi-way and probabilistic sensitivity analyses.

Conclusions

Early treatment of chronic HCV is superior to the other fibrosis screening strategies. In clinical settings where testing is required, FibroTest screening is a cost-effective alternative to liver biopsy.     

Efficacité et innocuité du prélèvement percutané de sperme testiculaire dans la prise en charge de l’infertilité masculine

Objective

To assess the efficacy and safety of percutaneous testicular biopsy to provide sperm cells for ICSI in male patients with azoospermia not amenable to surgical treatment.

Materials and methods

From October 1995 to December 2001, 175 biopsies were performed in men with azoospermia to provide material for intracytoplasmic sperm injection. Azoospermia was obstructive (OA) in 41 cases and non-obstructive (NOA) in 134 cases. Open biopsy was performed in the first 15 patients in the series and percutaneous biopsy was performed on an outpatient basis, under local anesthesia, with a Biopty Gun® (14G needle), in the subsequent patients as the first step in management. Open surgical biopsies were performed in another 15 patients following a sperm cell-negative percutaneous biopsy.

Results

All biopsies performed for OA were positive, but only 51/134 biopsies (38%) were positive in the NOA group. The material provided by percutaneous biopsy, when positive for sperm cells, was always sufficient to perform ICSI. When percutaneous biopsy was negative, open surgical biopsy failed to give better results. Five men developed minor complications (acute hematocele) following percutaneous biopsies requiring reoperation for hemostasis (3.12%). No major complications were observed. Results were comparable in terms of fertilization and pregnancy rates whether fresh or frozen-thawed sperm was used.

Conclusion

Percutaneous testicular sperm extraction is a safe, well-tolerated and cost-effective procedure in the management of male-factor infertility related to azoospermia.     

Metabolism during anaesthesia and recovery in colic and healthy horses: a microdialysis study

Background  

Muscle metabolism in horses has been studied mainly by analysis of substances in blood or plasma and muscle biopsy specimens. By using microdialysis, real-time monitoring of the metabolic events in local tissue with a minimum of trauma is possible. There is limited information about muscle metabolism in the early recovery period after anaesthesia in horses and especially in the colic horse. The aims were to evaluate the microdialysis technique as a complement to plasma analysis and to study the concentration changes in lactate, pyruvate, glucose, glycerol, and urea during anaesthesia and in the recovery period in colic horses undergoing abdominal surgery and in healthy horses not subjected to surgery.     

What Is the Optimal Threshold at Which to Recommend Breast Biopsy?

Background

A 2% threshold, traditionally used as a level above which breast biopsy recommended, has been generalized to all patients from several specific situations analyzed in the literature. We use a sequential decision analytic model considering clinical and mammography features to determine the optimal general threshold for image guided breast biopsy and the sensitivity of this threshold to variation of these features.

Methodology/Principal Findings

We built a decision analytical model called a Markov Decision Process (MDP) model, which determines the optimal threshold of breast cancer risk to perform breast biopsy in order to maximize a patient’s total quality-adjusted life years (QALYs). The optimal biopsy threshold is determined based on a patient’s probability of breast cancer estimated by a logistic regression model (LRM) which uses demographic risk factors (age, family history, and hormone use) and mammographic findings (described using the established lexicon–BI-RADS). We estimate the MDP model''s parameters using SEER data (prevalence of invasive vs. in situ disease, stage at diagnosis, and survival), US life tables (all cause mortality), and the medical literature (biopsy disutility and treatment efficacy) to determine the optimal “base case” risk threshold for breast biopsy and perform sensitivity analysis. The base case MDP model reveals that 2% is the optimal threshold for breast biopsy for patients between 42 and 75 however the thresholds below age 42 is lower (1%) and above age 75 is higher (range of 3–5%). Our sensitivity analysis reveals that the optimal biopsy threshold varies most notably with changes in age and disutility of biopsy.

Conclusions/Significance

Our MDP model validates the 2% threshold currently used for biopsy but shows this optimal threshold varies substantially with patient age and biopsy disutility.     

Impact of Tumor Localization and Method of Preoperative Biopsy on Sentinel Lymph Node Mapping After Periareolar Nuclide Injection

Background

To evaluate whether tumor localization and method of preoperative biopsy affect sentinel lymph node (SLN) detection after periareolar nuclide injection in breast cancer patients.

Methods and Findings

767 breast cancer patients were retrospectively included. For lymphscintigraphy periareolar nuclide injection was performed and the SLN was located by gamma camera. Patient and tumor characteristics were correlated to the success rate of SLN mapping. SLN marking failed in 9/61 (14.7%) patients with prior vacuum-assisted biopsy and 80/706 (11.3%) patients with prior core needle biopsy. Individually evaluated, biopsy method (p = 0.4) and tumor localization (p = 0.9) did not significantly affect the SLN detection rate. Patients with a vacuum-assisted biopsy of a tumor in the upper outer quadrant had a higher odds ratio of failing in SLN mapping (OR 3.8, p = 0.09) compared to core needle biopsy in the same localization (OR 0.9, p = 0.5).

Conclusions

Tumor localization and preoperative biopsy method do not significantly impact SLN mapping with periareolar nuclide injection. However, the failure risk tends to rise if vacuum-assisted biopsy of a tumor in the upper outer quadrant is performed.