Sarcoidosis is a granulomatous disease of unknown etiology that can affect almost any organ. Although the acute form can have spontaneous regression, a certain number of patients can have a chronic ...form, which leads to an increase in mortality and a decrease in the quality of life. Considering that the risk factors are still unknown, we wanted to compare the characteristics of patients with acute and chronic forms of sarcoidosis in Serbia in order to determine significant differences between them with hopes of contributing to everyday clinical practice. A total of 2380 patients treated in our clinic were enrolled in this study. They were separated into the following two groups: 1126 patients with acute form and 1254 patients with chronic form. They were further compared by gender, smoking status, radiological status, exposition, biomarkers for sarcoidosis, organ involvement, and other comorbidities; the distribution of patients according to regions of Serbia was also noted. Statistical significance was found in radiological findings (p < 0.001), biomarkers (calcium in 24 h urine p < 0.001; chitotriosidase p = 0.001), and the affliction of organs (p < 0.001). The differences noted in this paper could help improve our understanding of this disease.
Introduction
Sarcoidosis is a multiorgan, multisystem chronic disease of unknown etiology and unpredictable course. Health status is reduced in sarcoidosis and assessing it is a difficult multitask ...effort due to many faces this disease might have. Recently, a new questionnaire for assessing health status in sarcoidosis was developed by a group of authors from England–King’s Sarcoidosis Questionnaire (KSQ). The benefit of KSQ is the ability to develop the best care plan for the patient, as well as to differentiate the efficacy of the administered treatment.
Objective
The aim of this study was to validate the KSQ in Serbian speaking population of sarcoidosis patients. The test itself is a modular, multi-organ health status measure for patients with sarcoidosis for use in clinic and the evaluation of therapies. The correlation of KSQ with different clinical course of sarcoidosis (acute vs chronic disease) and with the clinical outcome status (COS) in sarcoidosis was also investigated.
Methods
A total of 159 biopsy positive sarcoidosis patients participated in this study. The average age of the participants was 49.67, majority was female (67.3%) and majority had only pulmonary form of sarcoidosis (71.7%). KSQ ‐ new disease-specific health status instrument, was compared with 5 other already existing instruments already used and validated in sarcoidosis (Saint George Respiratory Questionnaire- SGRQ, Daily Activity List -DAL, Fatigue Assessment Scale- FAS, Medical Research Council dyspnea scale–MRC, Borg Dyspnea Scale and 15D as general questionnaire.
Results
KSQ has significant correlation with other quality of life questionnaires already used in sarcoidosis. Translated version of KSQ shows significant internal reliability, similar to the original KSQ. Serbian version of KSQ has significant correlation with different clinical course of sarcoidosis and with COS as well. The translated version of KSQ is reliable sarcoidosis specific instrument for assessing health status in these patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
It has been reported that high‐density lipoprotein (HDL) particles have anti‐inflammatory and antioxidant roles thanks to different enzymes such as paraoxonase 1 (PON1). Under inflammatory ...and oxidative stress conditions, HDL particles may lose their protective properties. Sarcoidosis is an inflammatory disease characterized by excessive oxidative stress. Serum amyloid A (SAA) is produced in liver and in granulomas, and its concentration increases in inflammatory conditions contributing to increased catabolism of HDL particles. The aim of our study was to determine PON1 activity, SAA concentration and their associations in patients with sarcoidosis.
Materials and methods
Inflammatory high‐sensitive C‐reactive protein (hsCRP), angiotensin‐converting enzyme (ACE), SAA, lipid total cholesterol (TC), HDL‐cholesterol (HDL‐c), low‐density lipoprotein cholesterol (LDL‐c), triglycerides (TG) oxidative stress status parameters total oxidant status (TOS), malondialdehyde (MDA), pro‐oxidant–antioxidant balance (PAB), sulfhydryl (SH) groups and PON1 activities were determined in serum of 72 patients with sarcoidosis and 62 healthy subjects.
Results
HsCRP (P < 0·05), TC, LDL‐c, TG, SAA, TOS, MDA and PAB (P < 0·001) were significantly higher, whereas HDL‐c, SH groups and PON1 activity (P < 0·001) were significantly lower in patients with sarcoidosis when compared with controls. PON1 showed significant association with SAA, MDA and PAB. It was shown that 71% of decrease in PON1 activity may be explained by increase in TOS, PAB and SAA concentration.
Conclusions
We found decreased PON1 activity and increased SAA concentration in patients with sarcoidosis. Inflammatory condition presented by high SAA was implicated in impaired HDL functionality evident through dysregulated PON1 activity. Excessive oxidative stress was also involved in dysregulation of PON1 activity.
Background. Solithromycin, a novel macrolide antibiotic with both intravenous and oral formulations dosed once daily, has completed 2 global phase 3 trials for treatment of community-acquired ...bacterial pneumonia. Methods. A total of 863 adults with community-acquired bacterial pneumonia (Pneumonia Outcomes Research Team PORT class II-IV) were randomized 1:1 to receive either intravenous-to-oral solithromycin or moxifloxacin for 7 once-daily doses. All patients received 400 mg intravenously on day 1 and were permitted to switch to oral dosing when clinically indicated. The primary objective was to demonstrate noninferiority (10% margin) of solithromycin to moxifloxacin in achievement of early clinical response (ECR) assessed 3 days after first dose in the intent-to-treat (ITT) population. Secondary endpoints included demonstrating noninferiority in ECR in the microbiological ITT population (micro-ITT) and determination of investigator-assessed success rates at the short-term follow-up (SFU) visit 5-10 days posttherapy. Results. In the ITT population, 79.3% of solithromycin patients and 79.7% of moxifloxacin patients achieved ECR (treatment difference, –0.46; 95% confidence interval CI, –6.1 to 5.2). In the micro-ITT population, 80.3% of solithromycin patients and 79.1% of moxifloxacin patients achieved ECR (treatment difference, 1.26; 95% CI, –8.1 to 10.6). In the ITT population, 84.6% of solithromycin patients and 88.6% of moxifloxacin patients achieved clinical success at SFU based on investigator assessment. Mostly mild/moderate infusion events led to higher incidence of adverse events overall in the solithromycin group. Other adverse events were comparable between treatment groups. Conclusions. Intravenous-to-oral solithromycin was noninferior to intravenous-to-oral moxifloxacin. Solithromycin has potential to provide an intravenous and oral option for monotherapy for community-acquired bacterial pneumonia. Clinical Trials Registration. NCT01968733.
Sarcoidosis is an inflammatory disease characterised by enhanced production of reactive oxygen species and alterations in the circulating lipid profile. Both attributes are thought to play a role in ...its pathogenesis. However, current knowledge regarding the significance of blood oxidative stress/anti-oxidant defence as well as alterations in lipid status parameters in sarcoidosis is scarce. The aim of our study was to assess these parameters and their inter-relationships, as well as their potential for patient-control discrimination.
Oxidative stress status and anti-oxidant defence parameters were determined in serum and erythrocytes and lipid status parameters were assessed in the serum of 213 treated sarcoidosis patients and 90 controls.
Malondialdehyde, superoxide anion, total oxidant status, prooxidant–antioxidant balance and triglycerides were significantly higher whereas total anti-oxidant status, superoxide dismutase activity and HDL-cholesterol were significantly lower in sarcoidosis patients compared with controls. Total sulfhydryl group content was higher in patients compared with controls. Serum and erythrocyte malondialdehyde exhibited the strongest ability to predict disease presence. Elevated oxidative stress was characterised by higher clinical accuracy compared with lipid status abnormality. Some oxidative stress and lipid status markers were significantly associated in sarcoidosis.
Sarcoidosis is characterised by increased oxidative stress, diminished overall anti-oxidative protection and alterations in the circulating lipid profile. Both oxidative stress and lipid status parameters demonstrated the potential to discriminate sarcoidosis from controls which was particularly evident from the point of view of oxidative stress status parameters. Association between these parameters may indicate an increased risk for atherosclerosis development.
► Elevated serum and erythrocyte oxidative stress status were observed in sarcoidosis. ► Lipid status abnormality was noted in sarcoidosis. ► Serum and erythrocyte MDA strongly predict disease among oxidative stress markers. ► Serum oxidative stress parameters had the best discriminative potential. ► Connection between oxidative and lipid status may indicate risk for atherosclerosis.
Phenotypes of organ involvement in sarcoidosis Schupp, Jonas Christian; Freitag-Wolf, Sandra; Bargagli, Elena ...
The European respiratory journal,
01/2018, Letnik:
51, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in Sarcoidosis) project represents a European ...multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis.The baseline phenotype module of GenPhenReSa comprised 2163 Caucasian patients with sarcoidosis who were phenotyped at 31 study centres according to a standardised protocol.From this module, we found that patients with acute onset were mainly female, young and of Scadding type I or II. Female patients showed a significantly higher frequency of eye and skin involvement, and complained more of fatigue. Based on multidimensional correspondence analysis and subsequent cluster analysis, patients could be clearly stratified into five distinct, yet undescribed, subgroups according to predominant organ involvement: 1) abdominal organ involvement, 2) ocular-cardiac-cutaneous-central nervous system disease involvement, 3) musculoskeletal-cutaneous involvement, 4) pulmonary and intrathoracic lymph node involvement, and 5) extrapulmonary involvement.These five new clinical phenotypes will be useful to recruit homogenous cohorts in future biomedical studies.
Many studies include elevated activity of angiotensin-converting enzyme (ACE) in serum in sarcoidosis and in ocular sarcoidosis as well, but there are only a few analyzing ACE activities in aqueous ...humor. The aim of this study is to illuminate the diagnostic value of ACE in aqueous humor in patients with ocular sarcoidosis.
We analyzed twenty patients with ocular sarcoidosis and 18 patients with nonocular involvement. All patients have biopsy-positive sarcoidosis of the lungs and/or mediastinal lymph nodes. Blood samples for ACE serum levels were obtained from all patients. Aqueous humor samples were taken by paracentesis with a 25-gauge needle in local anesthesia. With appropriate statistical tests, we compared ACE activity in serum and aqueous humor in patients with and without ocular sarcoidosis.
The majority of our patients with ocular sarcoidosis were female (12/20), also in the group with systemic sarcoidosis and without ocular involvement (12/6). Mean age of the whole analyzed group of sarcoidosis patients was 45 ± 6 years. There is no statistically significant difference in ACE activity in serum between two groups of patients (with and without ocular sarcoidosis). There is statistically significant difference in ACE activity in aqueous humor among patients with ocular and nonocular sarcoidosis. ACE activity in aqueous humor is significantly higher in patients with ocular sarcoidosis.
Increased ACE activity in aqueous humor can point to a diagnosis of ocular sarcoidosis, without the need for ocular biopsy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cough is frequent symptom in sarcoidosis and its impact on patient's quality of life (QoL) has not been adequately addressed so far.
The goal of this study was to determine the significant predictors ...of cough-specific and generic QoL in sarcoidosis patients.
In the prospective study 275 sarcoidosis patients administered Patient Reported Outcomes instruments for measurement of dyspnea (Borg and MRC scales) and fatigue (Fatigue Assessment Scale (FAS) and Daily Activity List (DAL)), as well as patients' QoL (cough-specific Leicester Cough Questionnaire (LCQ) and generic tool - 15D). The LCQ contains 3 domains covering physical, psychological and social aspects of chronic cough. Pulmonary function tests (spirometry and diffusing capacity for carbon monoxide) and serum angiotensin converting enzyme (sACE) were also measured.
Dyspnea measured by Borg scale and impairment of daily activities determined by DAL instrument as well as sACE were the strongest predictors of all cough-specific QoL domains. Mental aspect of patients' fatigue was significantly correlated with all domains except with psychological LCQ domain. Regarding the generic QoL, the following significant predictors were: dyspnea measured by MRC scale, overall fatigue determined by FAS and physical domain of the LCQ.
It is important to measure both cough-specific and generic QoL in sarcoidosis patients since they measure different health aspects and their predictors can be different. We demonstrated that physical domain of cough-specific QoL is significant predictor of generic QoL.
.
The careful monitoring of patients with mild/moderate COVID-19 is of particular importance because of the rapid progression of complications associated with COVID-19. For prognostic reasons and for ...the economic management of health care resources, additional biomarkers need to be identified, and their monitoring can conceivably be performed in the early stages of the disease. In this retrospective cross-sectional study, we found that serum concentrations of high-mobility group box 1 (HMGB1) and heme oxygenase-1 (HO-1), at the time of hospital admission, could be useful biomarkers for COVID-19 management. The study included 160 randomly selected recovered patients with mild to moderate COVID-19 on admission. Compared with healthy controls, serum HMGB1 and HO-1 levels increased by 487.6 pg/mL versus 43.1 pg/mL and 1497.7 pg/mL versus 756.1 pg/mL, respectively. Serum HO-1 correlated significantly with serum HMGB1, oxidative stress parameters (malondialdehyde (MDA), the phosphatidylcholine/lysophosphatidylcholine ratio (PC/LPC), the ratio of reduced and oxidative glutathione (GSH/GSSG)), and anti-inflammatory acute phase proteins (ferritin, haptoglobin). Increased heme catabolism/hemolysis were not detected. We hypothesize that the increase in HO-1 in the early phase of COVID-19 disease is likely to have a survival benefit by providing protection against oxidative stress and inflammation, whereas the level of HMGB1 increase reflects the activity of the innate immune system and represents levels within which the disease can be kept under control.
Sarcoidosis affects the central nervous system more frequently than it used to be believed. While the cranial nerves are most frequently affected, neurosarcoidosis can involve other nervous system ...tissues as well. TREATMENT OF NEUROSARCOIDOSIS: Although a lot of drugs have proved useful in treating neurosarcoidosis, corticosteroids are still the gold standard in treatment of these patients. Therapeutic protocols differ regarding the dose of these drugs. Symptomatic neurosarcoidosis should always be treated with pulse corticosteroid therapy. People with diabetes, high blood pressure, osteoporosis and tuberculosis should be carefully monitored, as they are prone to complications associated with treatment with corticosteroids. In cases when treatment with corticosteroids does not show the desired results or therapy is discontinued due to the development of side effects, there are other pharmacologic options, such as methotrexate, mycophenolate mofetil, cyclophosphamide, chloroquine, azathioprine, thalidomide, and infliximab. It should be noted that the treatment response to the above mentioned regimens, except for infliximab, is relatively slow compared to corticosteroids; therefore, corticosteroids should be taken into account in all states and particularly in the acute phase of the disease.
It is the existence of different forms of the disease, lack of local diagnostic criteria and different and non standardized therapy that makes the treatment of this disease difficult. Despite advances in pharmacotherapy and radiological diagnosis, it is necessary to develop better diagnostic strategies in order to set the optimal therapeutic approach.
PDF
