Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non-Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors.

Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma.

Assessing Tumor-infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method From the International Immunooncology Biomarkers Working Group: Part 1: Assessing the Host Immune Response, TILs in Invasive Breast Carcinoma and Ductal Carcinoma In Situ, Metastatic Tumor Deposits and Areas for Further Research.

Assessment of tumor-infiltrating lymphocytes (TILs) in histopathologic specimens can provide important prognostic information in diverse solid tumor types, and may also be of value in predicting response to treatments. However, implementation as a routine clinical biomarker has not yet been achieved. As successful use of immune checkpoint inhibitors and other forms of immunotherapy become a clinical reality, the need for widely applicable, accessible, and reliable immunooncology biomarkers is clear.

Wake-Up Stroke: Current Understanding.

Patients with wake-up strokes account for approximately 1 in 5 individuals presenting with an acute ischemic stroke. However, they are commonly excluded from acute stroke treatment. This article reviews the current understanding of wake-up strokes.

Real-Time Patient and Staff Radiation Dose Monitoring in IR Practice.

Purpose: Knowledge of medical radiation exposure permits application of radiation protection principles. In our center, the first dedicated real-time, automated patient and staff dose monitoring system (DoseWise Portal, Philips Healthcare) was installed. Aim of this study was to obtain insight in the procedural and occupational doses.

Fetal in vivo continuous cardiovascular function during chronic hypoxia.

Although the fetal cardiovascular defence to acute hypoxia and the physiology underlying it have been established for decades, how the fetal cardiovascular system responds to chronic hypoxia has been comparatively understudied. We designed and created isobaric hypoxic chambers able to maintain pregnant sheep for prolonged periods of gestation under controlled significant (10% O2) hypoxia, yielding fetal mean P(aO2) levels (11.5 ± 0.

The regenerative role of adipose-derived stem cells (ADSC) in plastic and reconstructive surgery.

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift in plastic and reconstructive surgery. The use of either embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) in clinical situations is limited because of regulations and ethical considerations even though these cells are theoretically highly beneficial. Adult mesenchymal stem cells appear to be an ideal stem cell population for practical regenerative medicine.

Novel Noxipoint Therapy versus Conventional Physical Therapy for Chronic Neck and Shoulder Pain: Multicentre Randomised Controlled Trials.

As chronic pain affects 115 million people and costs $600B annually in the US alone, effective noninvasive nonpharmacological remedies are desirable. The purpose of this study was to determine the efficacy and the generalisability of Noxipoint therapy (NT), a novel electrotherapy characterised by site-specific stimulation, intensity-and-submodality-specific settings and a immobilization period, for chronic neck and shoulder pain. Ninety-seven heavily pretreated severe chronic neck/shoulder pain patients were recruited; 34 and 44 patients were randomly allocated to different treatment arms in two patient-and-assessor-blinded, randomised controlled studies.

Sustained virological response and its treatment predictors in hepatitis C virus genotype 4 compared to genotypes 1, 2, and 3: a meta-analysis.

Background: Pegylated interferon and ribavirin (PEG-IFN+RBV) may be more cost-effective than direct-acting antivirals in resource-limited settings. Current literature suggests sustained virological response (SVR) in hepatitis C virus genotype 4 (HCV-4) is similar to genotype 1 (HCV-1), but worse than 2 and 3 (HCV-2/3). However, few studies have compared treatment response between these groups and these have been limited by small sample sizes with heterogeneous designs.

Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations.

Polycystic ovary syndrome (PCOS) is a common, highly heritable complex disorder of unknown aetiology characterized by hyperandrogenism, chronic anovulation and defects in glucose homeostasis. Increased luteinizing hormone relative to follicle-stimulating hormone secretion, insulin resistance and developmental exposure to androgens are hypothesized to play a causal role in PCOS. Here we map common genetic susceptibility loci in European ancestry women for the National Institutes of Health PCOS phenotype, which confers the highest risk for metabolic morbidities, as well as reproductive hormone levels.

Temporal variability of glucocorticoid receptor activity is functionally important for the therapeutic action of fluoxetine in the hippocampus.

Previous studies have shown inconsistent results regarding the actions of antidepressants on glucocorticoid receptor (GR) signalling. To resolve these inconsistencies, we used a lentiviral-based reporter system to directly monitor rat hippocampal GR activity during stress adaptation. Temporal GR activation was induced significantly by acute stress, as demonstrated by an increase in the intra-individual variability of the acute stress group compared with the variability of the non-stress group.

The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014.

Background: The morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) is gaining momentum as evidence strengthens for the clinical relevance of this immunological biomarker. Accumulating evidence suggests that the extent of lymphocytic infiltration in tumor tissue can be assessed as a major parameter by evaluation of hematoxylin and eosin (H&E)-stained tumor sections. TILs have been shown to provide prognostic and potentially predictive value, particularly in triple-negative and human epidermal growth factor receptor 2-overexpressing BC.

A disease-specific metabolic brain network associated with corticobasal degeneration.

Corticobasal degeneration is an uncommon parkinsonian variant condition that is diagnosed mainly on clinical examination. To facilitate the differential diagnosis of this disorder, we used metabolic brain imaging to characterize a specific network that can be used to discriminate corticobasal degeneration from other atypical parkinsonian syndromes. Ten non-demented patients (eight females/two males; age 73.

Endovascular treatment of a tentorial dural arteriovenous fistula.

Tentorial dural arteriovenous fistulae are rare intracranial fistulae, in which the fistula pocket is present within the leaves of tentorium cerebelli. These tentorial fistulae can be rarely present near the galenic complex, where they can engorge the deep venous system and cause symptoms of venous hypertension. We present an interesting case of endovascular treatment of a galenic tentorial dural arteriovenous fistula in a patient with headaches and imbalance.

Endovascular reconstruction of enlarging traumatic internal carotid artery pseudoaneurysm.

Traumatic dissecting pseudoaneurysms of the cervical and petrous internal carotid artery are often a result of blunt or penetrating trauma. These patients are at high risk for thromboembolic complications and are managed with antiplatelet agents. Patients who develop neurologic symptoms while on antiplatelet agents, or have interval enlargement of their pseudoaneurysms, may require repair of the vessel.

Endovascular management of cerebral venous sinus thrombosis.

Cerebral venous sinus thrombosis (CVST) is characterized by formation of widespread thrombus within the cerebral venous sinus system. CVST can cause venous hypertension, venous infarcts, hemorrhage and seizures. It is managed in most cases with systemic anticoagulation through the use of heparin to resolve the thrombus.

The impact of robotic surgery on the surgical management of prostate cancer in the USA.

Objective: To describe the surgeon characteristics associated with robot-assisted radical prostatectomy (RARP) adoption and determine the possible impact of this adoption on practice patterns and cost.

Patients And Methods: A retrospective cohort study with a weighted sample size of 489,369 men who underwent non-RARP (i.e.

Subdural hematoma after an epidural blood patch.

We report the case of a 37-year-old postpartum patient who developed a contained subacute spinal subdural hematoma causing mass effect on the cauda equina and severe spinal stenosis after undergoing an epidural blood patch for postdural puncture headache. Recovery occurred following administration of oral steroids.

Effect of Roux-en-Y gastric bypass on testosterone and prostate-specific antigen.

Background: Obese men have lower serum levels of testosterone, dehydroepiandrosterone (DHEA) and prostate-specific antigen (PSA), but an increased risk of dying from prostate cancer. The aim of this study was to examine the effect of surgically induced weight loss on serum testosterone, DHEA and PSA levels in obese men.

Methods: Consecutive men undergoing Roux-en-Y gastric bypass (RYGB) participated in a prospective, longitudinal study.

Procollagen 1 expression in atypical fibroxanthoma and other tumors.

Background: Procollagen (PC) is secreted by fibroblasts into the extracellular matrix, where it is cleaved to form collagen. The rat anti-human PC-1 monoclonal antibody has been reported to react with atypical fibroxanthoma (AFX), a poorly differentiated but usually benign skin lesion common in elderly patients. We have studied PC-1 staining in 50 tumors with AFX histological features (four of which were subsequently reclassified as non-AFX tumors) to confirm this prior observation.

Molecular epidemiology of tuberculosis.

Despite the almost 50 yrs since the introduction of curative antituberculosis drugs, Mycobacterium tuberculosis continues to exert an enormous toll on world health, and tuberculosis remains the world's leading cause of death due to a single infectious agent. This has stimulated research efforts into finding new tools to tackle the continuing tuberculosis pandemic. One of the few successes to date has been the development of a new discipline, molecular epidemiology.

Treatment of myelodysplastic syndrome with agents interfering with inhibitory cytokines.

Results of these trials provide evidence for biological activity and some clinical efficacy of agents potentially blocking inhibitory cytokines in patients with MDS. However, given the limited responses, it appears that factors additional to TNFalpha inhibitory activity contribute to the development of cytopenias in these patients. Further studies are warranted using anti-TNFalpha/anti-inhibitory cytokine approaches, either alone or in combination with other agents, capable of abrogating the effects of additional inhibitory mechanisms in MDS.

Hepatitis A in patients with chronic liver disease - severity of illness and prevention with vaccination.

Acute hepatitis A in patients with pre-existing chronic liver disease (CLD) may theoretically predispose such patients to a more severe outcome of infection. The results of reports covering epidemics and case series suggest but do not universally support this possibility. An analysis of the larger case series support the suggestion that acute hepatitis A superimposed on chronic hepatitis B infection is associated with higher peak laboratory abnormalities, more severe disease and a higher fatality rate.

New approaches to the investigation of focal hepatic lesions.

In the past few years, tremendous advances have been made in the fields of magnetic resonance imaging, computed tomography and ultrasonography. These include the development of novel contrast agents and new approaches to image acquisition and processing. This review provides an overview of the state-of-the-art of imaging investigation of focal hepatic lesions and highlights some of the most exciting emerging technologies.

Effects of TGFbeta on bone ingrowth in the presence of polyethylene particles.

We implanted bone harvest chambers (BHCs) bilaterally in ten mature male New Zealand white rabbits. Polyethylene particles (0.3+/-0.