Successful Treatment of Solitary Bone Metastasis of Non-Small Cell Lung Cancer with Bevacizumab and Hyperthermia

Non-small cell lung cancer (NSCLC) represents 85 % of all malignant lung cancers. In metastatic disease the principle goal of palliative therapy is to prolong survival with least toxicity and best patients’ quality of life. Bevacizumab (BEV) has been approved as first line treatment in combination with platinum based chemotherapy and maintenance therapy in NSCLC. BEV can be added safely to several chemotherapeutic agents, however there is no data on coadministration with thermotherapy. Even in localized disease no robust evidence exists about the beneficial effect of loco-regional thermotherapy on overall survival, but it might be used successfully in symptom palliation. In this article a successful co-administration of BEV and hyperthermia is reported in a patient with monolocalized bone metastasis from previously operated NSCLC. This case suggests that electrohyperthermia can probably be incorporated in palliative therapy added not only to radiotherapy or chemotherapy but also to anti-angiogenic BEV treatment.     

Carbohydrate recognition systems in autoimmunity

The immune system is a complex functional network of diverse cells and soluble molecules orchestrating innate and adaptive immunity. Biological information, to run these intricate interactions, is not only stored in protein sequences but also in the structure of the glycan part of the glycoconjugates. The spatially accessible carbohydrate structures that contribute to the cell's glycome are decoded by versatile recognition systems in order to maintain the immune homeostasis of an organism. Microbial carbohydrate structures are recognized by pathogen associated molecular pattern (PAMP) receptors of innate immunity including C-type lectins such as MBL, the tandem-repeat-type macrophage mannose receptor, DC-SIGN or dectin-1 of dendritic cells, certain TLRS or the TCR of NKT cells. Natural autoantibodies, a long known effector branch of this network-based operation, are effective to home in on non-self and self-glycosylation also. The recirculating pool of mammalian immune cells is recruited to inflammatory sites by a reaction pathway involving the self-carbohydrate-binding selectins as initial recognition step. Galectins, further key sensors reading the high-density sugar code, exert regulatory functions on activated T cells, among other activities. Autoimmune diseases are being associated with defined changes of glycosylation. This correlation deserves to be thoroughly studied on the levels of structural mimicry and dysregulation as well as effector molecules to devise innovative anti-inflammatory strategies. This review briefly summarizes data on sensor systems for carbohydrate epitopes and implications for autoimmunity.     

Improvement in pain intensity, spine stiffness, and mobility during a controlled individualized physiotherapy program in ankylosing spondylitis

Physical therapy in ankylosing spondylitis (AS) is important for maintaining or improving mobility, fitness, functioning, and global health. It also plays a role in the prevention and management of structural deformities. In this study we assessed the functional status of AS patients in relation to disease duration and activity. Furthermore, in volunteering patients we analyzed the efficacy of a controlled, individualized physiotherapeutic program. Altogether, clinical data of 75 AS patients were retrospectively analyzed. Anthropometrical data, duration since diagnosis and disease activity, pain intensity, tender points, sacroiliac joint involvement determined by X-ray, functional condition, and physical activity level were recorded. Subjective, functional, and physical tests were performed. Out of the 75 patients, 10 volunteered to undergo a complex physical exercise program twice a week for 3?months. The program included 1.5?h of general posture reeducation, manual mobilization of the spine, and pelvic-, upper-, and lower-extremity exercises, stretching with joint prevention strategies and functional exercises. In AS, pain intensity recorded on a 10-cm visual analog scale (VAS), BASFI, BASDAI, modified Schober index, chest expansion and occiput-to-wall distance values showed significant correlation with disease activity. The 3-month physical therapy improved several subjective and functional parameters, and markedly reduced pain intensity and spine stiffness. A complex, individualized physical therapy program may be useful and should be introduced to AS patients in order to maintain and increase spine mobility, preserve functional capacity, decrease the pain and stiffness.     

Hyperuricemia predicts adverse clinical outcomes after cardiac resynchronization therapy

Abstract

Objectives: Changes in the levels of serum creatinine and N-terminal of prohormone brain natriuretic peptide (NT-proBNP) are useful risk markers after cardiac resynchronization therapy (CRT). The diagnostic value of changes in serum uric acid levels has been established in chronic heart failure, but no data are available on the prognostic value of hyperuricemia in a CRT population. Design: We measured markers of renal function [creatinine, blood urea nitrogen (BUN) and uric acid] and NT-proBNP levels of 129 heart failure patients undergoing CRT in a prospective, observational study. The 5-year all-cause mortality and the 6-month clinical response (≥ 15% increase in the left ventricular ejection fraction) were considered as study end points. Results: In multivariable analyses, the uric acid was found to be a statistically significant predictor of the outcome. Uric acid levels exceeding 386?mmol/L before CRT increased the chances of mortality [n?=?55, hazard ratio?=?2.39 (1.30-4.39), p?<?0.01] and poor clinical response [n?=?37, odds ratio?=?2.89 (1.22-6.87), p?=?0.01] independently of serum NT-proBNP and other factors. Conclusions: Elevated uric acid concentrations in patients with CRT are associated with an increased risk of mortality and poor clinical response independently of the NT-proBNP levels and other relevant clinical factors.     

DNA hypermethylation is associated with invasive phenotype of malignant melanoma

Tumor cell invasion is one of the key processes during cancer progression, leading to life-threatening metastatic lesions in melanoma. As methylation of cancer-related genes plays a fundamental role during tumorigenesis and may lead to cellular plasticity which promotes invasion, our aim was to identify novel epigenetic markers on selected invasive melanoma cells. Using Illumina BeadChip assays and Affymetrix Human Gene 1.0 microarrays, we explored the DNA methylation landscape of selected invasive melanoma cells and examined the impact of DNA methylation on gene expression patterns. Our data revealed predominantly hypermethylated genes in the invasive cells affecting the neural crest differentiation pathway and regulation of the actin cytoskeleton. Integrative analysis of the methylation and gene expression profiles resulted in a cohort of hypermethylated genes (IL12RB2, LYPD6B, CHL1, SLC9A3, BAALC, FAM213A, SORCS1, GPR158, FBN1 and ADORA2B) with decreased expression. On the other hand, hypermethylation in the gene body of the EGFR and RBP4 genes was positively correlated with overexpression of the genes. We identified several methylation changes that can have role during melanoma progression, including hypermethylation of the promoter regions of the ARHGAP22 and NAV2 genes that are commonly altered in locally invasive primary melanomas as well as during metastasis. Interestingly, the down-regulation of the methylcytosine dioxygenase TET2 gene, which regulates DNA methylation, was associated with hypermethylated promoter region of the gene. This can probably lead to the observed global hypermethylation pattern of invasive cells and might be one of the key changes during the development of malignant melanoma cells.     

Pregnant intravenous drug user tricuspid valve infective endocarditis treated with a successful simultaneous valve replacement and Cesarean section

A 30‐year‐old female patient known to be an intravenous drug user (IVDU) was admitted to Bajcsy‐Zsilinszky Hospital Cardiology Intensive Care Unit at 29‐week gestation with severe sepsis and right heart failure. She had methicillin‐sensitive Staphylococcus aureus on blood culture. Echocardiography confirmed the diagnosis of tricuspid valve infective endocarditis (IE). She had acute deterioration and hemodynamic instability for which an emergency tricuspid valve replacement (TVR) with a simultaneous Cesarean section (CS) was performed simultaneously. Medical management is the standard treatment in IE of IVDU pregnant patients, but in case of life‐threatening complications, emergency TVR and CS are to be considered. This is the first reported case of IVDU IE treated with simultaneous TVR and CS.     

Corneal Manifestations of Systemic Sclerosis

Purpose: Corneal involvement in systemic sclerosis (SSc) is rare, but due to rich collagen composition cornea is especially vulnerable to connective tissue diseases. Therefore, our aim was to evaluate corneal parameters of SSc patients.

Methods: The study included 32 SSc patients and 39 control subjects with no ocular symptoms or ocular surface disorders. All study participants underwent Pentacam evaluation and objective signs of dry eye disease (DED), and clinical parameters were evaluated.

Results: All pachymetric values, most of the corneal front surface, corneal volume, as well as anterior chamber depth measurements were significantly lower in the SSc group than in the control group (p < 0.05). Significant negative correlation was found between corneal parameters and age on the one hand, and disease duration on the other.

Conclusions: Early recognition of corneal impairment, a possible extraintestinal manifestation of SSc, should be included in the check-up of the disease in order to reduce sight-threatening complications.