Hepatic, Splenic, and Bone Marrow Gaucheromas: A Case Series and Systematic Literature Review.

BACKGROUND AND AIMS: Gaucher disease (GD) is one of the most common lysosomal storage diseases. It is characterized by the accumulation of glucocerebroside lipids in the macrophages, with liver, spleen and bone marrow frequently affected. The affected organs can develop tumor-like lesions (Gaucheromas), which are difficult to diagnose. We present the Gaucheromas and their ultrasonographic characteristics. METHODS: We selected Gaucheromas and their ultrasonographic characteristics found in the last 5 years during the periodical evaluation of 74 adult GD patients in Romania. All the patients had magnetic resonance imaging examination for comparison. A systematic review of all the Gaucheroma-related articles was performed to compare our results with the literature. RESULTS: Gaucheromas were found in 7 adult patients: 4 in the spleen, 2 in the liver and one affecting the bone. No malignancy ultrasound characteristics were found and neither on MRI exams. In the literature, 10 articles reported Gaucheromas, most of them in the liver and spleen in type 1 GD patients. All our patients were also type 1 GD, and the ultrasound aspect did not change during the 5 years follow-up. CONCLUSIONS: Gaucheromas can be found in any patient with GD. Malignancies have to be considered unless proven otherwise. Imaging characterization (ultrasound and MRI) are useful as histopathologic examination is difficult to obtain in all cases.

An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance.

Implementation of precision medicine in lung cancer has benefited from intense research in the past years, developing subsequently an improved quality of life and increased overall survival of the patients. Targeted therapy has become one of the most important therapeutic innovations for the non-small cell lung cancer (NSCLC) category with anaplastic lymphoma kinase (ALK) gene rearrangement. The aim of this review is to provide a through overview of the main molecules of ALK tyrosine kinase inhibitors (TKI) with their general and particular mechanisms of resistance, the main methods of ALK gene detection, each with advantages and limits and the future perspectives currently under research which try to overcome the mechanisms of resistance. We have used two of the most reliable medical databases EMBASE and PubMed to properly select the latest and the most relevant articles for this topic. Encouraged by the promising results, the clinical practice was enriched by the approval of tyrosine kinase inhibitor molecules, three generations being developed, each one with more powerful agents than the previous ones. Unfortunately, the resistance to TKI eventually occurs and it may be induced by several mechanisms, either known or unknown. Crizotinib was the most intensely studied TKI , becoming the first molecule approved into clinical practice and although four other drugs have been broadly used (alectinib, ceritinib, brigatinib and lorlatinib) it seems that even the most recently developed one remains imperfect due to the resistance mutations that developed. There are two types of resistance generally described for the entire class and for the particular drugs, but half of them remain unknown.

Increased Vascular Endothelial Growth Factor Serum Level and the Role of +936C/T Gene Polymorphism in Chronic Obstructive Pulmonary Disease.

Background and Objectives: Chronic obstructive pulmonary disease (COPD) represents a debilitating disease, with rising morbidity and mortality. Vascular endothelial growth factor (VEGF) plays a major role in angiogenesis, vascular permeability, and airway remodeling. The purpose of this study was to investigate the relationship between VEGF serum levels and VEGF +936 C/T gene polymorphism (rs3025039) with COPD, for the first time in a Romanian population. Materials and Methods: In total, 120 participants from Transylvania were included in this case-control study. Serum levels of VEGF were determined using an enzyme-linked immune-sorbent assay and rs3025039 was investigated by high molecular weight genomic deoxyribonucleic acid (DNA). Spirometric values, arterial blood gas analysis, and the Six Minute Walk Test (6MWT) outcome were also determined. Results: The serum level of VEGF was higher in the COPD group versus controls (p < 0.001), with a positive correlation with the 6MWT outcome. No significant difference was observed in the VEGF serum levels between VEGF +936C/T genotypes. There was no difference in the VEGF +936C/T genotype between COPD patients and healthy subjects (chi2 test p = 0.92, OR = 1.04, 95%CI = 0.41-2.62), but the presence of the T allele was significantly linked to the presence of COPD (chi2 test p = 0.02, OR = 2.36, 95%CI = 1.12-4.97). Conclusions: Higher VEGF serum levels were found in moderate and severe COPD and were positively correlated with the distance in the 6MWT. No significant difference was found between CC, CT, and TT genotypes of rs3025039 and the presence of COPD. The presence of the T allele was found to be linked to COPD and also to the degree of airway obstruction.

A Prospective Study of CPAP Therapy in Relation to Cardiovascular Outcome in a Cohort of Romanian Obstructive Sleep Apnea Patients.

BACKGROUND: Despite efforts at treatment, obstructive sleep apnea (OSA) remains a major health problem, especially with increasing evidence showing an association with cardiovascular morbidity and mortality. The treatment of choice for OSA patients is Continuous Positive Airway Pressure (CPAP), which has been proven in randomized controlled trials to be an effective therapy for this condition. The impact of CPAP on the cardiovascular pathology associated with OSA remains, however, unclear. Although the effect of CPAP has been previously studied in relation to cardiovascular outcome, follow-up of the treatment impact on cardiovascular risk factors at one year of therapy is lacking in a Romanian population. Thus, we aimed to evaluate the one-year effect of CPAP therapy on lipid profile, inflammatory state, blood pressure and cardiac function, assessed by echocardiography, on a cohort of Romanian OSA patients. METHODS: We enrolled 163 participants and recorded their baseline demographic and clinical characteristics with a follow-up after 12 months. Inflammatory and cardiovascular risk factors were assessed at baseline and follow up. RESULTS: Our results show that CPAP therapy leads to attenuation of cardiovascular risk factors including echocardiographic parameters, while having no effect on inflammatory markers. CONCLUSION: Treatment of OSA with CPAP proved to have beneficial effects on some of the cardiovascular risk factors while others remained unchanged, raising new questions for research into the treatment and management of OSA patients.

Alveolar proteinosis - an underdiagnosed condition in young people.

Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by an abnormal intra-alveolar accumulation of surfactant derived lipoproteinaceous compounds, leading to dyspnea and, in severe cases, to respiratory failure. The most common form of PAP is the auto-immune one. Secondary PAP has been recognized in myeloid leukemia, non-hematological neoplasms, lung infections or environmental exposure to noxious particles. Mutations in several genes (such as MARS, SFTPB, TTF1) are responsible for the alteration of surfactant production. Diagnosis tools include high-resolution computed tomography, bronchoalveolar lavage. Although over the past 20 years the pathophysiology of PAP has become more clear, the therapeutic strategies still need improvement. A national programme for patients with PAP might be useful in Romania.

Gaucher disease - therapeutic aspects in Romania.

Gaucher disease is a rare autosomal recessive disease caused by the beta-glicosidase activity deficiency, which will lead to substrate accumulation mainly in the liver, spleen or bone marrow. The main symptoms are liver and spleen enlargement, anemia and low platelet count, bone crisis and fatigue. Several treatment options are available, as enzyme replacement therapy, substrate reduction therapy, or chaperones treatment whose effect is still studied. There are 77 adult patients treated at this time in Romania, 54 with intravenous enzyme replacement ant 23 with oral substrate reduction therapy. No severe adverse effects have been reported by now. All patients had improved disease related symptoms after the receiving of the treatment.

Gaucher disease - bone involvement.

Gaucher disease (GD) is a rare genetic disease caused by the enzymatic deficiency of beta-glucocerebrosidase. This will lead to the accumulation of sphingolipids in various organs, such as liver, spleen, bone marrow. Bone involvement is frequent in Gaucher patients, leading to bone pain, necrosis and even fractures or growth deficiency in children, with painful surgeries and progressively decreasing quality of life. The early treatment initiation in symptomatic patients is very important in lowering bone complications frequency and improve general status. We present the case of a young patient whose first manifestation of GD was a bone cystic lesion and the clinical evolution until treatment.

Neutrophil-to-lymphocyte ratio, platelets-to-lymphocyte ratio, and eosinophils correlation with high-resolution computer tomography severity score in COVID-19 patients.

Inflammation has an important role in the progression of various viral pneumonia, including COVID-19. Circulating biomarkers that can evaluate inflammation and immune status are potentially useful in diagnosing and prognosis of COVID-19 patients. Even more so when they are a part of the routine evaluation, chest CT could have even higher diagnostic accuracy than RT-PCT alone in a suggestive clinical context. This study aims to evaluate the correlation between inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelets-to-lymphocytes ratio (PLR), and eosinophils with the severity of CT lesions in patients with COVID-19. The second objective was to seek a statically significant cut-off value for NLR and PLR that could suggest COVID-19. Correlation of both NLR and PLR with already established inflammatory markers such as CRP, ESR, and those specific for COVID-19 (ferritin, D-dimers, and eosinophils) were also evaluated. One hundred forty-nine patients with confirmed COVID-19 disease and 149 age-matched control were evaluated through blood tests, and COVID-19 patients had thorax CT performed. Both NLR and PLR correlated positive chest CT scan severity. Both NLR and PLR correlated positive chest CT scan severity. When NLR value is below 5.04, CT score is lower than 3 with a probability of 94%, while when NLR is higher than 5.04, the probability of severe CT changes is only 50%. For eosinophils, a value of 0.35% corresponds to chest CT severity of 2 (Se = 0.88, Sp = 0.43, AUC = 0.661, 95% CI (0.544; 0.779), p = 0.021. NLR and PLR had significantly higher values in COVID-19 patients. In our study a NLR = 2.90 and PLR = 186 have a good specificity (0.89, p = 0.001, respectively 0.92, p<0.001). Higher levels in NLR, PLR should prompt the clinician to prescribe a thorax CT as it could reveal important lesions that could influence the patient's future management.

Pulmonologists Adherence to the Chronic Obstructive Pulmonary Disease GOLD Guidelines: A Goal to Improve.

Background and objectives: Data about pulmonologist adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines showed a great variability and cannot be extrapolated. The present study investigates the current pharmacological prescribing practices in the treatment of chronic obstructive pulmonary disease (COPD) according to the 2017 GOLD guidelines, to determine the level of pulmonologist adherence and to identify possible factors that influence physician adherence. Materials and methods: This retrospective study took place between 1 February and 30 April 2018 in Pneumophtysiology Clinical Hospital Cluj-Napoca. We included 348 stable COPD outpatients classified according to the 2017 GOLD strategy in the ABCD risk groups. Pulmonologist adherence was defined as appropriate if the recommended pharmacological therapy was the first- or alternative-choice drug according to the guidelines, and inappropriate (overtreatment, undertreatment) if it was not in line with these recommendations. Results: The most prescribed treatment was the combination long-acting beta agonist (LABA) + long-acting antimuscarinic agent (LAMA) (34.77%), followed by LAMA + LABA + inhaled corticosteroid (ICS). Overall, pneumologist adherence was 79.02%. The most inappropriate therapies were in Group B (33.57%), followed by 33.33% in Group A. Compared to Groups C and D (analyzed together), Groups A and B had a 4.65 times higher chance (p = 0.0000001) of receiving an inappropriate therapy. Patients with cardiovascular comorbidities had a 1.89 times higher risk of receiving an inappropriate therapy (p = 0.021). ICS overprescription was the most common type of inappropriateness (17.81%). Groups C and D had a 3.12 times higher chance of being prescribed ICS compared to Groups A and B (p = 0.0000004). Conclusions: Pulmonologist adherence to the GOLD guidelines is not optimal and needs to be improved. Among the factors that influence the inappropriateness of COPD treatments, cardiovascular comorbidities and low-risk Groups A and B are important. ICS represent the most prescribed overtreatment. Further multicentric studies are needed to evaluate all factors that might influence the adherence rate.

Disease Perception and Coping with Emotional Distress During COVID-19 Pandemic: A Survey Among Medical Staff.

The novel coronavirus disease, COVID-19, is a highly contagious infectious disease declared by the World Health Organization to be a pandemic and a global public health emergency. During outbreaks, health care workers are submitted to an enormous emotional burden as they must balance the fundamental "duty to treat" with their parallel duties to family and loved ones. The aims of our study were to evaluate disease perceptions, levels of stress, emotional distress, and coping strategies among medical staff (COVID-19 versus non-COVID-19 departments) in a tertiary pulmonology teaching hospital in the first month after the outbreak of COVID-19. One hundred and fifteen health care workers completed four validated questionnaires (the brief illness perception questionnaire, perceived stress scale, the profile of emotional distress emotional, and the cognitive coping evaluation questionnaire) that were afterwards interpreted by one psychologist. There was a high level of stress and psychological distress among health care workers in the first month after the pandemic outbreak. Interestingly, there were no differences between persons that worked in COVID-19 departments versus those working in non-COVID-19 departments. Disease perceptions and coping mechanisms were similar in the two groups. As coping mechanisms, refocusing on planning and positive reappraisal were used more than in the general population. There is no difference in disease perceptions, levels of stress, emotional distress, and coping strategies in medical staff handling COVID-19 patients versus those staff who were not handling COVID-19 patients in the first month after the pandemic outbreak.

Correlations between neutrophil to lymphocyte ratio, blood eosinophils and clinical characteristics in chronic obstructive pulmonary disease.

BACKGROUND AND AIMS: Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death worldwide, with increasing mortality and morbidity. The neutrophil to lymphocyte ratio (NLR) and blood eosinophils level (EOS) represent biomarkers of inflammation in various diseases, with current research in the field of COPD. The aim of this study was to determine correlations of NLR and EOS with certain characteristics of COPD in a group of patients without major comorbidities. METHODS: We conducted an observational study on COPD patients admitted to the Clinical Hospital of Pneumology in Cluj-Napoca, Romania. The smoking history, body mass index (BMI), NLR, EOS, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and the arterial partial pressure of oxygen (PaO2) were determined. Functional assessment consisted of spirometric and BODE index determinations. The duration of hospitalization was expressed as the length of stay (LOS). The patients were divided into 3 subgroups: active smokers (AS), former smokers (FS) and never smokers (NS). RESULTS: No significant differences between AS and FS were found when age, airway obstruction, BODE index, PaO2, ESR and CRP were considered. The NLR was higher in AS versus FS (p=0.035), while EOS was lower in AS group (p=0.061). COPD patients with ≥300 EOS/µL had lower CRP, ESR levels and NLR compared to those with eosinophilia <300/µL (p=0.020, p=0.009 and p=0.007, respectively). With a threshold of 3.5 for NLR, patients with lower NLR had lower CRP values (p=0.05). COPD patients with higher NLR had significant lower EOS levels (p=0.018). Overall, the NLR and EOS were not correlated with the investigated characteristics (p>0.05), but intragroup analysis (based on smoking status) revealed correlations with ESR (p=0.0001), CRP (p=0.053), BODE index (p=0.029) and LOS (p=0.042). CONCLUSIONS: AS have higher NLR and lower EOS levels versus FS. COPD patients with higher EOS level have lower CRP, ESR and NLR. In AS, EOS level is positively correlated with BODE index and negatively correlated with NLR.

Q10 Coenzyme Supplementation can Improve Oxidative Stress Response to Exercise in Metabolic Syndrome in Rats.

Background: The metabolic syndrome leads to high morbidity and mortality. Almost all pathological states are associated with oxidative stress (OS) disorders. This study evaluates the effects of Coenzyme Q10 (CoQ10) supplementation on different lifestyles, in relation to serum and tissue OS parameters. Materials and methods: Twelve Wistar rat groups (10 rats/group) were equally divided in three types of diets: standard (St), high fat (HF), high sugar (HS); within each diet group there was one sedentary group with CoQ10 supplementation (100 mg/kg body weight), one sedentary without CoQ10, one trained group with CoQ10 and one trained group without CoQ10 supplementation. After 28 days blood samples were collected as follows: after 12 hours of fasting (T0), 1 hour postprandial (T1) and after 1 hour of exercise (T2) or sedentary postprandial time (T3). Thiol groups (SH) and malondialdehyde (MDA) were determined from serum and liver homogenate. Results: Significant changes were observed in fasting MDA for HF (p = 0.024 for training, 0.028 for CoQ10). Postprandial, OS status altered, with highest MDA in HF sedentary non-CoQ10 group (3.92 ± 0.37 vs 2.67 ± 0.41 nmol/ml in St trained CoQ10). At T2 the untrained and non-CoQ10 groups had the highest MDA levels (up to 22.3% vs T1, p < 0.001 in HF) as SH dropped (34.4% decrease vs T1, p < 0.001 in HF). At T3 high MDA levels were observed, correlated with low SH (Pearson r = -0.423 overall), irrespective of the CoQ10 supplementation. CoQ10 improved the liver OS status (MDA and SH decreased), but not the exercise, in all diets. Conclusions: CoQ10 supplementation accompanied by chronic exercise improved the OS serum profile, irrespective of the daily diet. CoQ10 lowered liver MDA and SH concentrations.