Optimising Intraoperative Fluid Management in Patients Treated with Adolescent Idiopathic Scoliosis-A Novel Strategy for Improving Outcomes.

Scoliosis surgery is a challenge for the entire team in terms of safety, and its accomplishment requires the utilization of advanced monitoring technologies. A prospective, single centre, non-randomised controlled cohort study, was designed to assess the efficacy of protocolised intraoperative haemodynamic monitoring and goal-directed therapy in relation to patient outcomes following posterior fusion surgery for adolescent idiopathic scoliosis (AIS). The control group (n = 35, mean age: 15 years) received standard blood pressure management during the surgical procedure, whereas the intervention group (n = 35, mean age: 14 years) underwent minimally invasive haemodynamic monitoring. Arterial pulse contour analysis (APCO) devices were employed, along with goal-directed therapy protocol centered on achieving target mean arterial pressure and stroke volume. This was facilitated through the application of crystalloid boluses, ephedrine, and noradrenaline. The intervention group was subjected to a comprehensive protocol following Enhanced Recovery After Surgery (ERAS) principles. Remarkably, the intervention group exhibited notable advantages (p < 0.05), including reduced hospital stay durations (median 7 days vs. 10), shorter episodes of hypotension (mean arterial pressure < 60 mmHg-median 8 vs. 40 min), lesser declines in postoperative haemoglobin levels (-2.36 g/dl vs. -3.83 g/dl), and quicker extubation times. These compelling findings strongly imply that the integration of targeted interventions during the intraoperative care of AIS patients undergoing posterior fusion enhance a set of treatment outcomes.

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.

BDNF G196A (Val66Met) polymorphism associated with cognitive impairment in Parkinson's disease.

Brain-derived neurotrophic factor (BDNF) is a neurotrophin widely expressed in the mammalian brain, regulating neuronal survival and known to influence dopaminergic neurons and cognitive processes. The present study investigated the BDNF Val66Met polymorphism associations with PD risk, and cognitive impairment in PD. A total of 486 study subjects (244 PD and 242 age and sex matched controls) were included in the study. UPDRS score, Hoehn-Yahr staging and the Schwab-England scale were used to assess motor abilities and activity during daily life. The patients were classified into groups with dementia (PDD, n=69) and without it (nPDD, n=166) on the basis of neuropsychological assessment. The most common functional polymorphism in BDNF Val66Met (rs6265, G196A) gene was determined using TaqMan real-time PCR assay. Frequencies of evaluated BDNF alleles and genotypes were similar in PD and the controls. The mean age of disease onset among BDNF Met/Met carriers was later (65.00±6.13) in comparison to Val/Val (57.45±10.68) and Val/Met (56.33±10.91) subjects (p=0.077). The studied BDNF polymorphism was not associated with cognitive status in PD patients. However, patients with Met/Met alleles demonstrated better delayed recall of information than patients with Val/Val alleles. The results of multivariate logistic regression analysis revealed age (p=0.0003) and the disease stage (p=0.002) as independent risk factors predisposing to PD dementia.

Association of COMT, MTHFR, and SLC19A1(RFC-1) polymorphisms with homocysteine blood levels and cognitive impairment in Parkinson's disease.

INTRODUCTION: Elevated plasma homocysteine (Hcy) concentration is an independent risk factor for cardiovascular disease, and its involvement in endothelial cell dysfunction is well established. However, the role of Hcy and folate in the pathogenesis of Parkinson's disease (PD) remains controversial. OBJECTIVES: The study was aimed at evaluating the relationships between Hcy, vitamin B12, and folic acid levels in the blood and cognitive status in PD patients with the genetic polymorphisms of MTHFR (rs1801133: C>T-677C>T, rs1801131: A>C-1298A>C), COMT (rs4680: A>G-Val158Met, rs6269: A>G, rs4633: C>T, rs4818: C>G), or SLC19A1 (rs1051266: G>A-80G>A). METHODS: A total of 502 participants (248 with PD and 254 age-matched and sex-matched controls) were included in the study. The Unified Parkinson's Disease Rating Scale score, Hoehn-Yahr staging, and the Schwab-England scale were used to assess motor abilities and activity during daily life. Complex psychological examination with a battery of tests was used to classify patients into groups with (PDD) and without (nPDD) dementia. Blood samples were examined for Hcy, vitamin B12, and folic acid levels, as well as polymorphisms in genes related to Hcy metabolism, such as COMT, MTHFR, and SLC19A1(RFC-1). RESULTS: The frequency of homozygous COMT rs4680G and rs4633C allele carriers was significantly decreased in PD patients in comparison with the controls (P=0.015; odds ratio=0.60; 95% confidence interval 0.41-0.90 and P=0.020; odds ratio=0.619; 95% confidence interval 0.42-0.92, respectively). No significant differences in the distribution of MTHFR 677C>T, 1298A>C, and SLC19A1 80G>A alleles and genotypes between PD patients and the controls were found. Hcy levels were significantly increased in PD patients (18±7.8 µmol/l) as compared with the controls (14.0±9.6 µmol/l, P=10(-8)) and were significantly associated with the MTHFR 677C>T polymorphism both in PD patients and controls, in which T allele carriers were characterized by markedly elevated Hcy plasma concentrations. No association was observed between Hcy plasma level and COMT and SLC19A polymorphisms. The results of multivariate logistic regression analysis revealed age (P=0.0003) and Hcy plasma levels (P=0.07) as independent risk factors predisposing individuals to PD dementia. The studied polymorphisms were not associated with cognitive status in PD patients. CONCLUSION: The genetic factors studied were not associated with cognitive status in PD patients. Only age and Hcy plasma levels were found to be independent risk factors predisposing individuals to PD dementia. However, COMT: rs4680: A>G and rs4633: C>T polymorphisms were found to significantly affect PD risk, and the MTHFR 677C>T polymorphism helped determine plasma Hcy concentrations.

Fibroblast growth factor 22 is not essential for skin development and repair but plays a role in tumorigenesis.

Fibroblast Growth Factors play critical roles during development, tissue homeostasis and repair by controlling cell proliferation, survival, migration and differentiation. Of the 22 mammalian FGFs, FGF22, a member of the FGF7/10/22 subfamily, has been shown to have a clear role in synaptogenesis, but its roles in other tissues have not been studied. We have investigated the in vivo functions of FGF22 in mice. Fgf22 null animals were viable, fertile and did not display any obvious abnormalities. Despite the known expression profile of FGF22 in the skin, no differences in either skin or pelage were observed, demonstrating that FGF22 is dispensable during embryogenesis and in unchallenged adult skin. Mice lacking FGF22 were able to heal acute wounds just as efficiently as wild type mice. However, classical two-step skin carcinogenesis challenge revealed that FGF22 null mice developed fewer papillomas than wild type controls, suggesting a potential pro-oncogenic role for FGF22 in the skin.

The role of fibroblast growth factor receptor 2b in skin homeostasis and cancer development.

The epithelial isoform of fibroblast growth factor receptor 2 (Fgfr2b) is essential for embryogenesis, and Fgfr2b-null mice die at birth. Using Cre-Lox transgenics to delete Fgfr2b in cells expressing keratin 5, we show that mice lacking epidermal Fgfr2b survive into adulthood but display striking abnormalities in hair and sebaceous gland development. Epidermal hyperthickening develops with age, and 10% of mutant mice develop spontaneous papillomas, demonstrating the role of Fgfr2b in post-natal skin development and in adult skin homeostasis. Mice lacking epithelial Fgfr2b show great sensitivity to chemical carcinogenic insult, displaying several oncogenic ha-ras mutations with dramatic development of papillomas and squamous cell carcinomas. Mutant mice have increased inflammation in the skin, with increased numbers of macrophages and gammadeltaT cells with abnormal morphology. Mutant skin shows several changes in gene expression, including enhanced expression of the pro-inflammatory cytokine interleukin 18 and decreased expression of Serpin a3b, a potential tumor suppressor. Thus we describe a novel role of Fgfr2b and provide the first evidence of a tyrosine kinase receptor playing a tumor suppressive role in the skin.

[Paralysis of vocal fold as the first symptom of Vernet's syndrome in the course of jugular chemodectoma]. / Porazenie faldu glosowego jako pierwszy objaw zespolu Verneta w nastepstwie klbczaka otworu zyly szyjnej.

INTRODUCTION: Chemodectomas are relatively frequent tumors of the head and neck but their diagnosis in consideration of the slow growth is difficult. The aim of this study is pointing out of the attention on: (1) non-typical beginning of ill and diagnostic difficulties leading to delaying of putting the proper diagnosis, (2) symptoms which are cause of notifying the patient to the doctors of different specializations e.g. the laryngologist and the neurologist. MATERIAL AND METHODS: The case of 72-year-old man with the paraganglioma situated near to the foramen of the jugular vein is discribed. Clinical symptoms, giving at last typical picture of Vernet's syndrome, the diagnostic procedure as well as treatment of the entity are discussed in the report. CONCLUSIONS: (1) In cases of paralysis of any cranial nerve is necessary close cooperation among a laryngologist and a neurologist. (2) In idiopathical paralysis of the vocal fold, changes runing near by the internal jugular vein's foramen should be taken into account. (3) The computer scanning of skull's bases and angiograpy are the most useful in the differential diagnostics. (4) The radiotherapy allow to obtain good therapeutic's results especially in persons stricken in years.