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OBJECTIVE Motor vehicle collisions (MVCs) are a common source of traumatic stress, which could lead to the development of posttraumatic stress disorder. However, the natural course of symptom development is still poorly understood. The current study aimed to prospectively examine the expression of traumatic stress symptoms in mild-moderate injured MVC survivors, using a novel daily life repeated measurement approach. METHOD Participants (N = 70) were screened and recruited upon hospital arrival. Daily assessments of traumatic stress symptoms were conducted via mobile phones, and the data during days 2-6 (acute phase) and 27-31 (1-month phase) following the MVC were used for the current study. RESULTS Latent growth curve analyses showed that at the acute phase, traumatic stress symptoms followed a reducing trajectory, with significant intercept and negative slope factors. At the 1-month phase, traumatic stress symptoms followed a low-stable trajectory, with a lower intercept and a nonsignificant slope factor. The acute-phase intercept and slope were both positively associated with 1-month symptomatology, such that higher initial symptoms and slower recovery rates were associated with greater traumatic stress symptoms at 1-month post-MVC. Trauma history and peritraumatic perceived life threat were indirectly associated with the 5-days end-of-the-month traumatic stress symptoms, through the mediation of the acute-phase intercept. CONCLUSIONS An early screen of traumatic stress symptoms in the first few days following trauma exposure, together with trauma history and perceived peritraumatic life threat, may assist in identifying individuals at risk for subsequent posttraumatic psychopathology. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

PurposeData on myopia progression during its entire course are scarce. The aim of this study is to investigate myopia progression in Europeans as a function of age and degree of myopia from first prescription to final refractive error.MethodsThe Drentse Refractive Error and Myopia Study assessed data from a branch of opticians in the Netherlands from 1985 onwards in a retrospective study. First pair of glasses prescribed was defined as a spherical equivalent of refraction (SER) ≤−0.5 D to ≥−3.0 D. Subjects with prescriptions at an interval of at least 1 year were included in the analysis.ResultsA total of 2555 persons (57.3% female) met the inclusion criteria. Those with first prescription before the age of 10 years showed the strongest progression (−0.50 D; IQR: −0.75 to −0.19) and a significantly (pConclusionOur trajectories of the natural course of myopia progression may serve as a guide for myopia management in European children. SER at 10 years is an important prognostic indicator and will help determine treatment intensity.

Aortic pathology is always a challenge for the clinician, and must be diagnosed and treated by a multidisciplinary team due to the technical and technological complexity of the resources used. Ongoing efforts to implement a systematic, protocolized approach involving "Aortic teams" made up of cardiologists, cardiac surgeons, vascular surgeons, anaesthesiologists and radiologists, among others are now leading to improved outcomes. The aim of this consensus document drawn up by the Aortic working groups of the Spanish Society of Anaesthesiology, Resuscitation and Pain Therapy (SEDAR) and the Spanish Society of Thoracic and Cardiovascular Surgery (SECTCV) is to disseminate a set of working protocols. The latest consensus document of the European Association for Cardio-Thoracic Surgery (EACTS) and the European Society for Vascular Surgery (ESVS) define the concept of "AORTIC TEAM"(1). The aortic team should be closely involved from diagnosis to treatment and finally follow-up, and should be formed of cardiac and vascular surgeons working together with anaesthesiologists, cardiologists, radiologists and geneticists. Treatment of aortic pathologies should be centralised in large centres, because this is the only way to effectively understand the natural course of the disease, provide the entire range of treatment options under one umbrella and treat potential complications. A streamlined emergent care pathway (24/7 availability), adequate transportation and transfer capabilities, as well as rapid activation of the multidisciplinary team must be available. In light of the complexity and constant evolution of therapeutic options, we present this first version of the Anaesthesiology and surgical guidelines for surgery of the ascending aorta and aortic arch. Some questions will no doubt remain unanswered, and future versions will include new techniques that, though implemented in some centres, are still not widely recommended.

Background and Purpose: The purpose of this study was to investigate the natural course of cerebral cavernous malformations (CCM) in the pediatric population, with special emphasis on the risk of first and recurrent bleeding over a 5-year period. Methods: Our institutional database was screened for patients with CCM treated between 2003 and 2020. Patients ≤18 years of age with complete magnetic resonance imaging data set, clinical baseline characteristics, and ≥1 follow-up examination were included. Surgically treated individuals were censored after CCM removal. We assessed the impact of various parameters on first or recurrent intracerebral hemorrhage (ICH) at diagnosis using univariate and multivariate logistic regression adjusted for age and sex. Kaplan-Meier and Cox regression analyses were performed to determine the cumulative 5-year risk for (re)hemorrhage. Results: One hundred twenty-nine pediatric patients with CCM were analyzed. Univariate logistic regression identified brain stem CCM (odds ratio, 3.15 [95% CI, 1.15−8.63]; P =0.026) and familial history of CCM (odds ratio, 2.47 [95% CI, 1.04−5.86]; P =0.041) as statistically significant predictors of ICH at diagnosis. Multivariate logistic regression confirmed this correlation (odds ratio, 3.62 [95% CI, 1.18−8.99]; P =0.022 and odds ratio, 2.53 [95% CI, 1.07−5.98]; P =0.035, respectively). Cox regression analysis identified ICH as mode of presentation (hazard ratio, 14.01 [95% CI, 1.80−110.39]; P =0.012) as an independent predictor for rehemorrhage during the 5-year follow-up. The cumulative 5-year risk of (re)bleeding was 15.9% (95% CI, 10.2%−23.6%) for the entire cohort, 30.2% (20.2%−42.3%) for pediatric patients with ICH at diagnosis, and 29.5% (95% CI, 13.9%−51.1%) for children with brain stem CCM. Conclusions: Pediatric patients with brain stem CCM and familial history of CCM have a higher risk of ICH as mode of presentation. During untreated 5-year follow-up, they revealed a similar risk of (re)hemorrhage compared to adult patients. The probability of (re)bleeding increases over time, especially in cases with ICH at presentation or brain stem localization.

As the number of individuals vaccinated against SARS-CoV-2 rises worldwide, population-level data regarding the vaccines' ability to reduce infection are being generated. Randomised trials have shown that these vaccines dramatically reduce symptomatic COVID-19; however, less is known about their effects on transmission between individuals. The natural course of infection with SARS-CoV-2 involves infection of the respiratory epithelia and replication within the mucosa to sufficient viral titres for transmission via aerosol particles and droplets. Here we discuss the available data on the existing, approved SARS-CoV-2 vaccines' capacity to reduce transmissibility by reducing primary infection, viral replication, capacity for transmission, and symptomaticity. The potential for mucosal-targeted SARS-CoV-2 vaccine strategies to more effectively limit transmission than intramuscular vaccines is considered with regard to known immunological mechanisms. Finally, we enumerate the population-level effects of approved vaccines on transmission through observational studies following clinical trials and vaccine distribution in real-world settings.

Purpose A model was calculated during the first Austrian coronavirus disease-2019 (COVID-19) pandemic lockdown to estimate the effect of a short-term treatment interruption due to healthcare restrictions on visual acuity (VA) in neovascular age-related macular degeneration (nAMD). The model was compared to the real-life outcomes before treatment re-started. Methods Retrospective data-collection of 142 eyes in 142 patients receiving repeated intravitreal injections with anti-VEGF at a retina unit in Vienna in a personalized pro-re-nata regimen prior to the COVID-19 associated lockdown, when treatment was deferred between March 16 and May 4, 2020. During the lockdown, the preliminary data was integrated into pre-existing formulae based on the natural course of the disease in untreated eyes in the long term. Patients were re-scheduled and treated after gradually opening operating rooms. The calculation model was compared to the effective VA change. Results The model calculated an overall VA loss of 3.5 ± 0.8 letters early treatment diabetes retinopathy study (ETDRS) ( p Conclusion The herein presented calculation model might not be suitable to estimate the effective VA loss correctly over time, although untreated eyes and eyes under therapy show similarities after short-term treatment interruption. However, this study demonstrated the potentially negative impact of the COVID-19 pandemic lockdown on patients compromised by nAMD.

Chronic rotator cuff pathology is often complicated by fatty degeneration of the rotator cuff (FDRC) muscles, an insidious process associated with poor prognosis with or without surgical intervention. Currently there is no treatment for FDRC, and many studies have described a natural course for this disease almost always resulting in further degeneration and morbidity. Recapitulating FDRC using animal injury models, and using imaging-based studies of human FDRC, the pathophysiology of this disease continues to be further characterized. Researchers studying mesenchymal stem cell–derived progenitor cells and known fibrogenic and adipogenic signaling pathways implicated in FDRC seek to clarify the underlying processes driving these changes. While new cell- and molecular-based therapies are being developed, currently the strongest available avenue for improved management of FDRC is the use of novel imaging techniques which allow for more accurate and personalized staging of fatty degeneration. This narrative review summarizes the evidence on the molecular and pathophysiologic mechanisms of FDRC and provides a clinical update on the diagnosis and management of this condition based on the existing knowledge. We also sought to examine the role of newer biologic therapies in the management of RC fatty degeneration and to identify areas of future research.

Purpose Mucolipidosis (ML) II, MLIII alpha/beta, and MLIII gamma are rare autosomal recessive lysosomal storage disorders. Data on the natural course of the diseases are scarce. These data are important for counseling, therapies development, and improvement of outcome. The aim of this study is to gain knowledge on the natural history of ML by obtaining data on survival, symptom onset, presenting symptoms, diagnosis, and pathogenic variants associated with the MLII or MLIII phenotype. Methods A systematic review on all published MLII and MLIII cases between 1968 and August 2019 was performed. Results Three hundred one articles provided data on 843 patients. Median age at diagnosis: 0.7 for MLII and 9.0 years for MLIII. Median survival: 5.0 for MLII and 62.0 years for MLIIIII. Median age of death: 1.8 for MLII and 33.0 years for MLIII. Most frequent causes of death in all ML were pulmonary and/or cardiac complications. Pathogenic variants were described in 388 patients (GNPTAB: 571, GNPTG 179). Conclusion This review provides unique insights into the natural history of MLII and MLIII, with a clear genotype–phenotype correlation with the most frequent pathogenic variant c.3503_3504del in MLII and in MLIII alpha/beta c.22A>G for GNPTAB. All pathogenic GNPTG variants resulted in MLIII gamma.

Objective: Gastric intestinal metaplasia (GIM) is considered as a predisposing lesion for the development of gastric cancer and isrecommended to be kept under surveillance in designated intervals. We aimed to assess the natural course of GIM in a large Turkishcohort.Materials and Methods: We retrospectively reviewed findings from pathology reports of gastric biopsies conducted between 2011 to2018 to reveal patients diagnosed with solitary GIM in their index pathology report. Progression of GIM was pre-defined as; lowgradedysplasia (LGD), high-grade dysplasia (HGD), or gastric malignancy.Results: The median follow-up period of the study population was 34 (12-128) months. Out of 109 patients with GIM at the entry, 54(49.6%) patients had stable GIM, whereas 53 (48.6%) cases had no signs of GIM at their final endoscopy. Only two (1.8%) patientsprogressed to LGD, but no HGD or malignancy was detected in the follow-up.Conclusion: Although, considered as a premalignant lesion and offered surveillance globally, progression of GIM was very low in alarge Turkish cohort. Further prospective studies in larger cohorts are required to enlighten the obscure strategies in the surveillanceof gastric malignancy.

Background: Given the strong relationship between depression and anxiety, there is an urge to investigate their shared and specific long-term course determinants. The current study aimed to identify and compare the main determinants of the 9-year trajectories of combined and pure depression and anxiety symptom severity. Methods: Respondents with a 6-month depression and/or anxiety diagnosis (n=1,701) provided baseline data on 152 sociodemographic, clinical and biological variables. Depression and anxiety symptom severity assessed at baseline, 2-, 4-, 6- and 9-year follow-up, were used to identify data-driven course-trajectory subgroups for general psychological distress, pure depression, and pure anxiety severity scores. For each outcome (class-probability), a Superlearner (SL) algorithm identified an optimally weighted (minimum mean squared error) combination of machine-learning prediction algorithms. For each outcome, the top determinants in the SL were identified by determining variable-importance and correlations between each SL-predicted and observed outcome ( ρ p r e d ) were calculated. Results: Low to high prediction correlations ( ρ p r e d : 0.41-0.91, median=0.73) were found. In the SL, important determinants of psychological distress were age, young age of onset, respiratory rate, participation disability, somatic disease, low income, minor depressive disorder and mastery score. For course of pure depression and anxiety symptom severity, similar determinants were found. Specific determinants of pure depression included several types of healthcare-use, and of pure-anxiety course included somatic arousal and psychological distress. Limitations: Limited sample size for machine learning. Conclusions: The determinants of depression- and anxiety-severity course are mostly shared. Domain-specific exceptions are healthcare use for depression and somatic arousal and distress for anxiety-severity course.

Objective. To analyze the natural course of type 1 spinal muscular atrophy in children with the onset of the disease up to 6 months in the Russian population.Material and methods. The retrospective multicenter study included data of 54 children with an established diagnosis of type 1 spinal muscular atrophy who did not receive therapy with nusinersen, risdiplam, branaplam, onasemogen abeparvovec-xioi, or other anti-sense oligonucleotides / selective SMN2 splicing modifiers or genetherapy drugs for SMN1 genetransduction. Basedon medical records, the scientists have collected all available information on the health status of children, the need for respiratory support and death or start of long-term mechanical ventilation.Results. The median time from birth to the onset of the combined event (death or initiation of long-term respiratory support), determined using the Kaplan-Meier method, was 365 [269; 409] days (12 months). The date of death was known in 22 out of 54 children. The median age of death was 301,5 [181; 375] days (9,9 months). The initiation date of long-term respiratory support was known in 15 of 54 patients, the median was 180 [91; 276] days (5,9 months). Both the start date of long-term respiratory support and the date of death were known in 5 of 54 children; whileit was found that the median time from the initiation of long-term respiratory support to death in these children was 361 [135; 619] day (11,87 months).In a subgroup of 32 children with available date of initiation of long-term respiratory support and / or the date of death, the median time from birth to the combined event was 245,5 [173; 331] days (8,07 months).Conclusion. In the course of a retrospective study, the authors obtained the information on the date of the onset of constant respiratory support and the date of death from the date of birth in the absence of pathogenetic treatment in children with type 1 spinal muscular atrophy. The data obtained in the Russian population are comparable with the published international data. This information can be useful for additional assessment of the health status of patients who received drugs affecting the level of SMN protein in the body, as well as reference data for the development of new approaches to therapy.

The natural course of chronic hepatitis B virus (HBV) infection is widely studied; however, follow-up studies of the same patients are scanty. Here, we studied the dynamic changes of serum HBV RNA and cytokines in hepatitis B virus e antigen (HBeAg)-positive patients treated with entecavir (ETV) to explore the relationship between the HBV serum viral nucleic acids and host immunity.Thirty-three chronic hepatitis B patients who are HBeAg-positive, with high virus load (HBV DNA20,000 IU/mL), and received standard nucleos(t)ide analogue (NA) antiviral therapy (ETV) for more than 48 weeks were included. The serum levels of HBV nucleic acids and selected cytokines were measured at 0, 12, 24, and 48 weeks respectively.Serum HBV RNA could still be detected while serum HBV DNA had fallen below the detection limit in patients treated with ETV. There was a strong positive correlation between HBV RNA and HBeAg, with a concomitant decrease in the secretion of cytokines from type 1 helper T (Th1)/type 2 helper T (Th2)/interleukin (IL)-17 producing T (Th17) cells. IL-4 and IL-10 were the main cytokines negatively associated with serum HBV RNA.HBeAg can be used to reflect the load of HBV RNA indirectly, because serum HBV RNA has not been widely used in clinical practice. Meanwhile, serum IL-4 and IL-10 might be explored in combination with HBV RNA in guiding future clinical antiviral therapy.

Background: A paucity of literature exists regarding trajectories of functional and sports-specific recovery after hip arthroscopy for femoroacetabular impingement syndrome (FAIS). Purpose: To determine if subgroups of patients exist based on the recovery trajectory of patient-reported outcomes (PROs) after hip arthroscopy for FAIS in the short-term period and to determine clinical predictors for these subgroups of patients. Study Design: Case-control study; Level of evidence, 3. Methods: A prospectively maintained repository was queried for patients who had undergone primary hip arthroscopy for the treatment of FAIS between January 2012 and May 2018. Patients who completed the preoperative, 1-year, and 2-year International Hip Outcome Tool–12 (iHOT-12) or the Hip Outcome Score Sports Subscale (HOS-SS) were included. The latent class growth analysis (LCGA) and growth mixture models (GMMs) were used to identify subgroups of patients based on trajectories of recovery for the iHOT-12 and the HOS-SS utilizing preoperative, 1-year, and 2-year follow-ups. LCGA and GMM models using 1 to 6 classes for each PRO were performed, and the best-fit model for each PRO was selected. After final model selection, a multivariable multinomial logistic regression was performed, with the largest class being the reference group to determine clinical predictors of subgroup membership. Results: A total of 443 and 556 patients were included in the iHOT-12 and HOS-SS analyses, respectively. For the iHOT-12, we identified the following 3 subgroups: early progressors (70%), late regressors (22.3%), and late progressors (7.7%). Predictors of late regression were workers’ compensation status, psychiatric history, preoperative chronic pain, and lower preoperative iHOT-12 scores; and late progressors were less likely to participate in sports. For the HOS-SS, we identified the following 4 subgroups: early progressors (47.7%), late regressors (17.4%), late progressors (6.8%), and steady progressors (28.1%). Predictors of less favorable recovery trajectories (late regressors and late progessors) were older age, male sex, back pain, psychiatric history, preoperative chronic pain, greater alpha angle, and lower preoperative HOS-SS scores. Conclusion: Using the growth mixture modeling, 3 natural courses of health-related quality of life (early progression, late regression, and late progression) and 4 natural courses of recovery of athletic function (steady progression, late regression, late progression, and early progression) were identified. Preoperative psychiatric conditions, chronic pain, workers’ compensation status, and lower iHOT-12 scores were predictive of less than favorable trajectories of recovery according to the iHOT-12, and male sex, older age, back pain, preoperative narcotic use, and lower preoperative HOS-SS were predictors of less favorable recovery trajectories according to the HOS-SS.

Introduction COVID‐19 pandemic and associated lockdown measures have deeply modified the natural course of seasonal viral infections, such as respiratory syncytial virus (RSV). Methods We analyzed French national data from three networks: emergency departments (ED) of French hospitals, general practitioners (GP), and hospital laboratories. We compared the number of ED or GP visits for bronchiolitis in children

Aortic pseudoaneurysms are rare entities caused by infection, trauma, atherosclerotic plaque rupture, or aortic instrumentation. Their natural course remains unknown; however, repair is invariably recommended. We present a case of a 71-year-old man with a history of recurrent deep venous thrombosis and pulmonary embolisms who underwent an inferior vena cava filter placement 8 years prior and was found to have a 3.6-cm contained ruptured infrarenal aortic pseudoaneurysm on imaging performed for abdominal pain. His pseudoaneurysm was excluded using a Gore Excluder Endoprosthesis. We further reviewed literature on the subject to highlight the various surgical approaches to this lethal condition.

The review deals with the development and achievements in a new scientific direction in medicine studying the pathogenesis of various human diseases — clinical pathophy­siology over the last decades. The latest low-traumatic intravital highly sensitive research methods used in pathophysiology for studying the important vital physiological and immunological processes in an organism of patients with type 1 and type 2 diabetes mellitus made it possible to show that the etiopathogenesis of these diseases in humans significantly differs from that in animals with experimental diabetes mellitus. This made it possible to obtain more accurate information about the causes and natural course of diabetes mellitus in humans that requires the development of new methods for its diagnosis, especially at the preclinical stage of development and to stimulate the development of more effective agents for the prevention and treatment of this disease.

Background This study aimed to assess the baseline levels of D-dimer, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) and monitor the natural course of these serum markers after uneventful primary total joint arthroplasty. Methods This prospective study enrolled 81 patients undergoing primary total knee arthroplasty or total hip arthroplasty. The level of serum D-dimer, CRP, and ESR was measured preoperatively and on postoperative days 1, 3, 5, 15, and 45. Mean peak values, peak times, and distribution were compared between D-Dimer, CRP, and ESR. Results The mean preoperative serum D-dimer, CRP, and ESR level was 412 ± 260 (range 200-980) ng/mL, 2.93 ± 2.1 (range 1-18) mg/L, and 22.88 ± 17.5 (range 3-102) mm/h, respectively. The highest mean peak for D-dimer, CRP, and ESR was at postoperative day 1, 3, and 5, respectively. Conclusion D-dimer levels reached peak levels on postoperative day 1 and then declined rapidly to a plateau level by postoperative day 3. A second, albeit small, peak in the level of D-dimer occurred on postoperative day 15. The level of CRP and ESR remained elevated for much longer with CRP returning to baseline on postoperative day 45 and the level of ESR had not returned back to normal on postoperative day 45.

Lissencephaly is a malformation of cortical development associated with deficient neuronal migration and abnormal formation of gyri. The natural course includes developmental delay, mental retardation, epileptic seizures, and microcephaly. Early diagnosis of lissencephaly is very important to give couples reproductive choices. Cranial ultrasonography is often used for the initial evaluation of intracranial abnormalities in fetuses and infants, and we believe that it is a safe and cost-efficient alternative to MRI and CT in many cases. This study combines a case of lissencephaly in our hospital and related literature review, to explore the clinical manifestations, epileptic seizures and ultrasonographic features of the disease, in order to improve the understanding of the disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has various known complications in its natural course of the illness. Pneumothorax is one of the emerging complications in coronavirus disease 2019 (COVID-19)-positive patients, not initiated on invasive mechanical ventilation. Case studies and autopsy reports across the globe suggest alveolar pathology to be responsible for the outcome.COVID-19 infection in humans caused by the SARS-CoV-2 virus has various known complications in its natural course of the illness. Pneumothorax is one of the emerging complications in COVID-19-positive patients. Prior identification and anticipation of such life-threatening complications aid in the treatment of COVID-19-positive patients.

Objective. Renal sympathetic denervation (RDN) is one of the invasive treatment options for the patients with hypertension (HTN) who are resistant to antihypertensive therapy (AHT). The short-term efficacy of RDN has been proven in a number of randomized clinical trials, but remains controversial, the data on its long-term efficacy are limited. The aim of our study was to evaluate the natural course of HTN, to assess long-term major adverse cardiovascular events (MACE) and other outcomes, as well as AHT efficacy and its features in patients with resistant HTN after bilateral RDN during extended prospective follow-up. Design and methods. We included 22 patients with truly resistant HTN (median 57 y. o., 9 males), in whom RDN was performed during 2012–2015 in the clinical center of excellence. We assessed initial and further (after 1 year and after ≥ 5 years) clinical, laboratory and anthropometric parameters, as well as detailed AHT history. Long-term MACE and other clinically significant outcomes were recorded. At baseline and follow-up, the quality of life (QoL) was determined with the use of EQ-5D questionnaire at all time points. Multiple linear regression was used to find possible predictors of the efficacy of RDN. Results. A significant and sustained drop in office and ambulatory systolic blood pressure (SBP) and diastolic blood pressure (DBP) was observed at 12 months after RDN compared to baseline values (∆ –24 and –12 mm Hg, p < 0,005; ∆ –10 and –7 mm Hg, p < 0,05, respectively). There were 7 patients with office SBP on-target, and 12 patients were considered responders (∆ SBP > 10 mm Hg). These numbers increased to 10 and 14 patients after ≥ 5 years after RDN. A causal relationship between changes in office SBP was found only for the baseline SBP (β -0,6, p = 0,02). No differences in the number of medications were noted during follow-up (4,4; 4,1 and 4,1 drugs, p = 0,41). During the follow-up 10 MACE occurred and 5 patients were diagnosed with various types of cancer; there were no fatal outcomes. The QoL significantly improved a year after RDN (+9,7 points, p = 0,01), however, a negative trend was observed in the next 5 years with return to reference level. No association was observed between BP and QoL changes at two timepoints. Conclusions. The RDN shows a pronounced clinical effect in patients with resistant HTN up to 5 years, and is not accompanied by an AHT intensification, but is not associated with QoL changes. The initial positive trend for QoL completely harked back after 5 years which may be associated with the development of MACE. The only predictor of RDN positive effect is baseline SBP level.

Background The value of the single-breath diffusing capacity of the lungs for carbon monoxide (D lco ) relates to outcomes for patients with COPD. However, little is known about the natural course of D lco over time, intersubject variability, and factors that may influence D lco progression. Research Question What is the natural course of D lco in patients with COPD over time, and which other factors, including sex differences, could influence this progression? Study Design and Methods We phenotyped 602 smokers (women, 33%), of whom 506 (84%) had COPD and 96 (16%) had no airflow limitation. Lung function, including D lco, was monitored annually over 5 years. A random coefficients model was used to evaluate D lco changes over time. Results The mean (± SE) yearly decline in D lco % in patients with COPD was 1.34% ± 0.015%/y. This was steeper compared with non-COPD control subjects (0.04% ± 0.032%/y; P = .004). Sixteen percent of the patients with COPD, vs 4.3% of the control subjects, had a statistically significant D lco % slope annual decline (4.14%/y). At baseline, women with COPD had lower D lco values (11.37% ± 2.27%; P lco annual decline of 0.89% ± 0.42%/y (P = .039). Interpretation Patients with COPD have an accelerated decline in D lco compared with smokers without the disease. However, the decline is slow, and a testing interval of 3 to 4 years may be clinically informative. The lower and more rapid decline in D lco values in women, compared with men, suggests a differential impact of sex in gas exchange function. Trial Registry ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov

PURPOSE The aim of this study was to determine the natural course of vitreomacular traction (VMT) in patients with diabetic retinopathy and to evaluate the factors associated with VMT relief. METHODS Seventy-four eyes of 65 patients with VMT accompanying diabetic retinopathy were evaluated retrospectively. The presence of intravitreal injection and the presence of panretinal photocoagulation were obtained from the medical records of the patients. Spontaneous release of VMT, the horizontal length of vitreomacular traction, the presence of hyperreflective retinal spots, the presence of the epiretinal membrane, and the grade of VMT were evaluated from the spectral-domain optical coherence tomography images. Factors associated with the spontaneous release of VMT were evaluated by logistic regression analysis. RESULTS Spontaneous release was observed in 28 eyes (37.8%). The horizontal length of VMT was lower in the release of the VMT group compared with the persistent VMT group (P = 0.03). The persistent VMT group had a higher rate of hyperreflective retinal spots and epiretinal membrane compared with the release of the VMT group (respectively; P = 0.003 and P = 0.031). No statistically significant difference was observed between the release of VMT and persistent VMT groups in terms of intravitreal injection and panretinal photocoagulation treatment (respectively; P = 0.938 and P = 0.36). The absence of hyperreflective retinal spots was the most important prognostic factor for the spontaneous release of VMT (P = 0.029). CONCLUSION Spontaneous release of VMT observed higher rates of patients without hyperreflective retinal spots, epiretinal membrane, and patients with lower horizontal length of VMT.

Introduction. The natural course of some interstitial lung diseases (ILD) is characterized by progressive fibrosing phenotype resembling idiopathic pulmonary fibrosis (IPF). Until recently, the antifibrotic drug nintedanib was approved for treatment of the only fibrosing ILD which was IPF. A new indication for this drug which has been registered in Russian Federation in 2021 includes other fibrosing ILDs with progressive phenotype (PF-ILDs) and ILD associated with systemic scleroderma (SS-ILD).The aim of this publication is to describe general considerations of the decision of Multidisciplinary Expert Board on diagnosis and treatment of PF-ILDs including SS-ILD.Results. According to the extension in nintedanib use mentioned above, the Expert Board created an algorithm for diagnosis and treatment of patients with PF-ILDs and criteria for nuntedanib administration in PF-ILDs.Conclusion. Antifibrotic therapy is needed for patients with PF-ILDs with the failure of the stanrard therapy. In those patients antifibrotic treatment should be initiated as early as possible to better preserve the lung function.

Objective Osteonecrosis (ON), also known as avascular necrosis, is characterized by the collapse of the architectural bone structure secondary to the death of the bone marrow and trabecular bone. Osteonecrosis may accompany many conditions, especially rheumatic diseases. Among rheumatic diseases, osteonecrosis is most commonly associated with systemic lupus erythematosus (SLE). We assessed prevalence and distribution pattern of symptomatic ON in patients with SLE and compare the natural courses of hip and knee ON. Methods 912 SLE patients admitted between 1981 and 2012 were reviewed. SLE patients with symptomatic ON were retrospectively identified both from the existing SLE/APS database. The prevalence of symptomatic ON was calculated; with ON, the joint involvement pattern was determined by examining the distribution of the joints involved, and then the data about the hip and knee joints were entered in the Kaplan-Meier analysis. Kaplan-Meier methods were used to calculate 5- and 10-year rates of ON-related hip (the hip group) and knee survival (the knee group). Results Symptomatic ON developed in various joints in 97 of 912 patients with SLE, and the overall prevalence of ON was detected as 10.6%. The mean age at the time of SLE and ON diagnoses were 27.9 ± 9.9 (14–53) and 34.2 ± 11.3 (16–62) years, respectively. The mean duration from diagnosis of SLE to the first development of ON was 70.7± 60.2 (range = 0–216) months. The most common site for symptomatic ON was the hips (68%, n=66), followed by the knees (38%, n = 37). According to Kaplan-Meier analysis, hip and knee joint survival rates associated with 5-year ON were 51% and 88%, and 10-year survival rates were 43% and 84%, respectively. Conclusion We observed that the prevalence of symptomatic ON in patients with SLE was 10.6%. With the estimated 10-year survival rates of 40% versus 84% for the hip and knee joints, respectively, hip involvement may demonstrate a more aggressive course to end-stage osteoarthritis than the knee involvement.

BACKGROUND Spontaneous HDV-RNA fluctuations, assessed by nonstandardised in-house assays, have been reported during the course of chronic hepatitis delta (CHD). AIMS To evaluate changes in serum HDV-RNA concentrations in untreated CHD patients and correlate these changes with other HBV markers. METHODS A total of 323 consecutive serum samples from 56 CHD patients (detectable HDV-RNA) followed for >3 years were retested for HDV-RNA levels by a sensitive technique using the first WHO international HDV-RNA standard. Quantitative HBsAg, HBV-DNA, and HBV-RNA were also determined. RESULTS Most participants were male, middle-aged, white European, and HBeAg-negative (82%). Almost half had liver cirrhosis and 64% were receiving nucleos(t)ide analogues. At inclusion, median-HDV-RNA was 5.3 (4.2-6.5) log10 IU/mL, HBsAg 4.0 (3.5-4.3) log10 IU/mL, and HBV-DNA 1.6 (1.0-2.6) log10 IU/mL; ALT values were normal in 13 (23%). During a mean follow-up of 5.6 (3-16) years, 14 (25%) showed ≥2log10 HDV-RNA decline, including 11 (20%) who spontaneously achieved undetectable HDV-RNA. Four patients (7%) lost HBsAg, with undetectable HDV-RNA. The remaining 42 (75%) had persistently detectable HDV-RNA. During follow-up, patients with a ≥2log10 HDV-RNA decline showed a greater HBsAg drop (-0.7 ± 1.1 vs -0.09 ± 0.9 log IU/mL; P = 0.039) than those with a

A large number of patients who have recovered from the acute phase of COVID 2019 (COVID-19), caused by the new “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2), have a host of long-term symptoms. Around 10% of suffer from long-term symptoms beyond three weeks, and a smaller proportion for months. Among them, more than half suffer from fatigue. In the above article fatigue in post-infections syndromes is described. In addition, selected hypothesis on pathophysiology of long Covid and current guidelines on approach in rehabilitation are discussed. Long Covid has a rich symptomatology with a chronic fatigue as one of many symptoms that patients might suffer from. Therefore, rehabilitation programme should be conducted in an interdisciplinary approach to aim to improve function of many body systems. Self-support should be advised, however, ideally patients should be supported throughout rehabilitation process. Further studies on natural course of long Covid and underlying pathological mechanism would be helpful in development of pharmacological and non-pharmacological long Covid treatments. If the symptomatology of long Covid patients would be as heterogenous as in Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients, then development of individual approach in rehabilitation might be necessary to obtain high efficacy and low adverse effects rate. (JNNN 2021;10(2):77–81)

Introduction The use of TKIs in CML has dramatically altered the natural course of the disease and improved outcomes for patients. TKIs overall have a very favorable safety profile. Dasatinib, a second generation TKI, is commonly used as a first-line treatment option in CML. Case report We describe the first two reported cases of first-line dasatinib induced aplastic anemia in CML. In both patients, pancytopenia occurred within one year of diagnosis/starting dasatinib. Both bone marrow biopsies showed hypocellularity with mild fibrosis and persistent BCR-Abl1 positivity. Management & outcome Dose reduction was attempted without success in both patients. In one patient, multiple TKIs were trialed, while in the other, growth factor support was attempted; neither regimen was effective. Ultimately, the cytopenias associated with dasatinib were only resolved after immunosuppression in one patient and allogeneic stem cell transplant in the other patient. Discussion Prior reports have shown that aplasia/aplastic anemia can rarely be associated with imatinib and nilotinib. Here we show that dasatinib can lead to this phenomenon as well. This diagnosis should be considered in patients with CML who unexpectedly develop cytopenias.

Aim:Specific allergen immunotherapy (SIT) is the only disease-modifying therapy for allergic diseases. We aimed to examine the effect of subcutaneous specific allergen immunotherapy (SCIT) applications on the prognosis of asthma and allergic rhinitis in pediatric cases in real-life settings.Methods:The study was designed as a retrospective cohort study. Patients with asthma and/or allergic rhinitis aged between 5 and 18 years old were enrolled between 2010 and 2015. The groups who received SCIT and who did not receive were compared in terms of disease severity parameters in follow-up recorded in their files.Results:A total of 298 cases, among which 140 received subcutaneous specific allergen immunotherapy. The frequency of asthma, allergic rhinitis, and co-morbidity was similar between the two groups. In the first year of the follow-up, asthma symptoms severity was not significant between the two groups; however, both asthma and allergic rhinitis symptoms were significantly lower in the SCIT patients at the end of the third year of follow-up. While the follow-up rate for three years or more was 62% in the group that received subcutaneous specific allergen immunotherapy, it was 38% in the group that did not receive.Conclusion:These results showed that SIT is an effective treatment modality in real-life settings with low side effects in pediatric patients with uncontrolled asthma and allergic rhinitis despite medical treatment.

Connective tissue disorders are common in women of reproductive age, and hence are seen frequently in maternal medicine clinics. The disorders, and their treatments, may have significant adverse effects on fertility, the developing fetus, and on pregnancy outcomes. In turn pregnancy may affect the natural course of the illness. Pre-pregnancy planning and multidisciplinary management are vital to optimise maternal and fetal outcomes. This review will cover a general approach and specific management points of common autoimmune and genetic conditions. Alterations in the maternal immune system affect the disease course of pre-existing skin conditions during pregnancy, and pharmacotherapy may be limited due to effects on the fetus. Some dermatological conditions arise de novo during pregnancy. Women may present to maternity services directly; therefore obstetricians must be able to diagnose, investigate and initiate management of pregnancy dermatoses, with input from dermatologists where available.

The natural course of coronavirus disease 2019 (COVID‐19) patients without clinical intervention has not yet been documented. One hundred and fifty‐eight patients from two hospitals were enrolled to identify the indicators of severe COVID‐19 and observe the natural course of COVID‐19 patients without clinical intervention. The total computed tomography (CT) score, a quantitative score based on assessment of the number, quadrant, and area of the lesions in CT, tended to perform better than assessment based only on the number or area of the lesions (p = 0.0004 and p = 0.0887, respectively). Multivariate logistic regression showed that the total CT score, chest tightness, lymphocyte, and lactate dehydrogenase (LDH) were independent factors for severe COVID‐19. For patients admitted in 2 weeks from onset to hospitalization, the frequency of severe COVID‐19 was gradually increased with the delayed hospitalization. The symptoms of fatigue, dry cough, sputum production, chest tightness, and polypnea were gradually more frequent. The levels of C‐reactive protein, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, γ‐glutamyl transpeptidase, LDH, and d‐dimer were also gradually increased, as well as the scores based on CT. Conversely, the lymphocyte count and the albumin level were gradually decreased with the delayed hospitalization. Detail turning points of the above alterations were observed after 10–14 days from onset to hospitalization. Total CT score was a simple and feasible score for identifying severe COVID‐19. COVID‐19 patients without clinical intervention deteriorated gradually during the initial 10–14 days but gradually improved thereafter., Highlights Present study developed a simple and feasible score based on CT to identify severe COVID‐19.Present study was the first to investigate the natural course of COVID‐19 patients without clinical intervention.COVID‐19 patients without clinical intervention deteriorated gradually during the initial 10‐14 days but gradually improved thereafter.

Introduction Recently, based on data from the PREDICT study, the European Foundation for the Study of Chronic Liver Failure (EF‐CLIF) consortium proposed pathophysiological/prognostic groups in hospitalized patients with cirrhosis: stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre‐acute‐on‐chronic liver failure (pre‐ACLF), and ACLF. We evaluated the outcomes of these subgroups in a real‐life cohort of hospitalized patients with cirrhosis. Methods Patients with cirrhosis developing first AD between 09/2010 and 12/2017 at the Vienna General Hospital were evaluated for this retrospective analysis. Results Two hundred and ten patients with cirrhosis (aged 57.6 ± 11.8 years) including n = 45 (21.4%) SDC, n = 100 (47.6%) UDC, n = 28 (13.3%) pre‐ACLF, and n = 37 (17.6%) with ACLF were considered. The proposed AD subgroups discriminated between patients with favorable (1‐year mortality: SDC: 6.7% and UDC: 19.6%) and dismal prognosis (90‐day mortality: pre‐ACLF: 42.9%). Interestingly, systemic inflammation gradually increased (e.g., C‐reactive protein, SDC: 0.9 mg/dl, vs. UDC: 2.0 mg/dl vs. pre‐ACLF: 3.2 mg/dl, p

Introducción: La enfermedad de Pompe de inicio tardío es una enzimopatía sumamente rara que se caracteriza por daño neuromuscular incapacitante y progresivo. Aun no existe consenso acerca del tratamiento, pero ensayos clínicos han mostrado que el reemplazo enzimático con alfa glucosidasa ácida recombinante podría enlentecer el curso natural de la enfermedad y mejorar el pronóstico. Caso clínico: Varón de 67 años con diagnóstico de enfermedad de Pompe desde hace 4 años, en tratamiento con rehabilitación física. Ingresó al servicio por celulitis de miembro inferior derecho que descompensa su cuadro de fondo llevándolo a una insuficiencia respiratoria severa. Es ingresado a ventilación mecánica, su evolución es tórpida debido a múltiples sobreinfecciones bacterianas asociadas a ventilador. Luego de 7 meses en ventilación mecánica a pesar de múltiples intentos de destete, se propone el tratamiento de reemplazo enzimático con alfa glucosidasa ácida recombinante. Dos semanas después inicia mejoría de parámetros ventilatorios y es dado de alta luego de 11 meses de estancia hospitalaria. Conclusión: El tratamiento de reemplazo enzimático con alfa glucosidasa ácida recombinante, mostró un efecto positivo en la evolución de nuestro paciente.

ObjectiveTo explore the natural course of hip osteoarthritis (OA) in a population of first-time presenters with hip complaints.MethodsData were collected at baseline and after 2, 5, 8 and 10 years on participants from the Cohort Hip and Cohort Knee study with early symptomatic hip OA. Descriptive statistics were used to analyse the natural course of the hip complaints with respect to clinical signs and symptoms, physical functioning and radiographic osteoarthritis (ROA) features.ResultsIn total, 588 participants were included with hip complaints and 86% completed the 10-year follow-up. The 10-year follow-up showed that 12% (69 participants) underwent hip replacement (HR), an increase of ROA of the hip (Kellgren and Lawrence score≥2) from 19% to 49%, and an increase in clinical hip OA according to the American College of Rheumatology criteria from 27% to 43%. All Western Ontario and McMaster Osteoarthritis Index subscales and physical activity remained on average constant during the 10-year follow-up for those who did not undergo an HR. The use of pain medication increased from 43% at baseline to 50% after 10 years.ConclusionOne out of nine participants with early hip problems received an HR during the 10-year follow-up. Prevalence of clinical hip OA and hip ROA increased steadily during the 10-year follow-up. Overall, we observed more hip OA, but fewer or stable complaints with respect to clinical signs and symptoms, and physical functioning. So it could be cautiously concluded that after 10 years, first-time presenters with hip complaints either received an HR or their symptoms remained stable.

Tough ectopic male breast cancer is extremely rare, non-axillary ectopic male breast cancer is even rare. To date, the natural course and prognosis of this disease are not fully understood. Consequently, the appropriate treatment for this disease has not been established. We report on a patient with ectopic male breast cancer in the suprapubic area that relapsed with hematogenous metastasis 3 years after complete surgical resection and adjuvant treatment despite an early diagnosis. This unusual case highlights the need for new prognostic factors such as genomic profiling to predict whether ectopic male breast cancer is aggressive and to guide on the duration between follow-ups and the appropriate method for conducting them.

The pathoanatomy of carpal instability is multifactorial and usually complex. A thorough medical history and clinical examination are essential, as well as profound knowledge of the specific instability patterns. The stability of the wrist is ensured by the carpal joint surfaces, by intact intra-articular (particularly the scapholunate interosseous ligament) and intracapsular ligaments, and by crossing extensor and flexor tendons, the latter making the proximal carpal row an “intercalated segment.” An important classification feature is the distinction between dissociative and nondissociative forms of carpal instability. Among others, scapholunate dissociation, lunotriquetral dissociation, midcarpal instability, and ulnar translocation are the most common entities. Early forms of instability are considered dynamic. In the natural course, static instability of the wrist and osteoarthritis will develop. This review focuses on the pathoanatomical fundamentals of the various forms of carpal instability.

In the past few decades, minimally-invasive esthetic treatments and the use of injectable Hyaluronic Acid Gels and other filling agents to treat facial esthetics have increased dramatically. Although extremely rare, a filler can cause ocular and orbital ischemia by retrograde flow from the ophthalmic artery when injected in any of the anastomosis of the face. Once filler reaches the central retinal artery, blindness is inevitable, and no treatment is effective. While the risk of blindness happening with any filler injection is rare, the life-altering irreversible consequence of a procedure that was anticipated to be simple and beautifying is a reality that each injector must be prepared for with every injection. The parameters associated with an iatrogenic stroke of the eye are the site of injection, the injection technique, patient characteristics, and the material injected. Understanding the interplay of each of these variables might help us reduce the possibility of blindness during the injection of a soft-tissue cosmetic filler. Here, we explore the causes of Hyaluronic Acid Gels Filler embolic phenomena, review the natural course of the process, and discuss appropriate immediate interventions. We also (1) propose an education plan for injectors and describe how to carry out a focused ophthalmologic examination and procedural activities for a referral to an ophthalmologist, (2) outline steps to prevent emboli during filler injection, and (3) how to manage and support a patient with a sudden loss of vision during or immediately after a Hyaluronic Acid Gels filler treatment.

Aims: Mucinous adenocarcinoma arising in congenital pulmonary airway malformation (CPAM) is a rare complication, with little being known about its natural course. The aims of this article are to describe a series of mucinous adenocarcinomas arising from CPAMs, and present their clinicopathological features, genetics, and clinical outcome. Methods and results: Thirty-seven cases were collected within a 34-year period, and the subtype of adenocarcinoma and CPAM, tumour location, stage, growth patterns, molecular data and follow-up were recorded. The cohort comprised CPAM type 1 (n = 33) and CPAM type 2 (n = 4). Morphologically, 34 cases were mucinous adenocarcinomas (21 in situ; 13 invasive), and three were mixed mucinous and non-mucinous adenocarcinoma. Seventeen cases showed purely extracystic (intra-alveolar) adenocarcinoma, 15 were mixed intracystic and extracystic, and five showed purely intracystic proliferation. Genetically, nine of 10 cases tested positive for KRAS mutations, four with exon 2 G12V mutation and five with exon 2 G12D mutation. Residual disease on completion lobectomy was observed in two cases, and three cases recurred 7, 15 and 32 years after the original diagnosis. Two patients died of metastatic invasive mucinous adenocarcinoma. Conclusions: Most adenocarcinoma that arise in type 1 CPAMs, are purely mucinous, and are early-stage disease. Intracystic proliferation is associated with lepidic growth, an absence of invasion, and indolent behaviour, whereas extracystic proliferation may be associated with more aggressive behaviour and advanced stage. Most cases are cured by lobectomy, and recurrence/residual disease seems to be associated with limited surgery. Long-term follow-up is needed, as recurrence can occur decades later.

Background Peri-implant bone level values have been used as the clinical standard of reference to describe the status of a dental implant, despite the fact that their significance for the long-term survival of the implant has never been properly assessed. Purpose To challenge the assumption that the natural course of peri-implant bone loss is the loss of the implant. Materials and methods This article is a narrative review on reasons and interpretations of marginal bone level changes around dental implants. Results and conclusions Different views regarding the pattern and progression of marginal bone loss depending on dental specialties have been identified. However, the present finding of a negative correlation between an increasing cumulative marginal bone loss and a decreasing risk of implant failures over time indicates that peri-implant marginal bone loss does not necessarily represent a condition of disease. Reduction of marginal bone levels may be observed in a majority of patients during follow-up time, with only a minority of those patients losing implants and implant-supported prostheses in the long term. Bone level changes seem often to occur as a consequence of physiological processes and/or as an adaptation to altered external as well as host response factors. Periodical radiological assessments of implant-restorations remain a valid diagnostic tool for the detection of potential implant fractures, loss of osseointegration, screws working loose and for the detection of the few cases with advanced, continuously progressing marginal bone loss during time. The detection of peri-implant marginal bone loss at one time point should not be immediately considered as a sign of ongoing pathology and of an increased risk of future loss of the implant in question.

Subcutaneous (SCIT) and sublingual (SLIT) immunotherapy methods are more commonly used to deliver the allergen to the patient. Both methods are able to alter the natural course of the disease and prevent the emergence of new sensitivities [6]. The use of ASIT leads to a reduction in the symptoms of the disease, a decrease in the need for treatment, and in addition has a long-term clinical effect by preventing the development of allergies and its symptoms. Treatment affects the underlying immunological mechanisms responsible for the development of clinical symptoms.

Interpreting natural course studies have been very difficult due to their retrospective design, lack of standardization, reliability of reported mucosal findings, liberal use of antireflux medications and accuracy of chart documentation. Studies provided a wide range of progression rates of patients from nonerosive reflux disease (NERD) to erosive esophagitis (EE). However, direct progression from NERD to Barrett's esophagus appears to be an uncommon phenomenon. Importantly, progression of NERD patients was commonly reported to low grades of EE, which are currently considered inconclusive of gastroesophageal reflux disease. Reports of progression rates from low grades to high grades EE also vary considerably. Progression of patients with EE, without metaplastic epithelium underneath the inflammation, to Barrett's esophagus is relatively uncommon. Recently, it was also recognized that regression from high grades to low grades EE and from EE to NERD is a common phenomenon affecting up to 25% of the patients from each group.

Background The coexistence of falcine and occipital sinuses is rare and its natural course has not been reported. Case reports Two patients with persistent falcine and occipital sinuses are described. Both patients had straight sinuses. In one, both the transverse and sigmoid sinuses were hypoplastic and the patient had an acquired Chiari I malformation. The other patient had no other venous anomalies and had a normal posterior cranial fossa. Conclusion The coexistence of falcine and occipital sinuses can lead to an acquired Chiari I malformation. These cases suggest the importance of checking other venous and brain anomalies in this situation.

Objective: The goal of this study was to examine the prevalence of anti-core+1 in “naive” patients with chronic hepatitis C and different stages of liver fibrosis infected by HCV subtypes 1b and 3a.Materials and methods: A total of 86 “naive” patients (37 men and 49 women) with CHC observed in the Botkin infectious disease hospital in 2017, were included in this study. The average age was 50,7±2,7. Laboratory tests included ALT and bilirubin. In 53 patients, the fibrosis stage in the liver tissue was evaluated by the TE method using Fibroscan (Echosens, France). The presence of antibodies to the core+1 protein in blood serum samples was determined by the “inhouse” indirect ELISA method using synthetic peptides F10 and F13, which amino acid sequences correspond to the antigenic determinants of core+1 protein of the HCV subtypes 1b and 3a, respectively.Results: In total, anti-core + 1 were detected in 27 (31,4%) subjects. It has been shown that the detection rate of anticore+1 does not depend on the HCV subtype. The study has indicated no statistically significant dependence between the presence of anti-core+1 and biochemical activity es of the infectious process (ALT, bilirubin). Anti-core+1 were detected in patients with all stages of fibrosis, however, the detection rate of anti-core+1 was statistically higher in patients with stage F4 fibrosis than in patients without liver fibrosis.Conclusion: The obtained results suggest a possible role of the core+1 protein in the development of fibrosis. In the natural course of HCV infection, the detection of anti-core+1 can be considered as a prognostic marker for the progression of fibrosis in the liver tissue.

Objective Cataplexy is a pathognomonic symptom of narcolepsy type 1. This study was conducted to clarify the clinical characteristics of cataplexy by staging, and to further analyse the correlations of clinical features and cataplectic stages in patients with narcolepsy type 1 (NT1). Methods We experimentally triggered patients with NT1 into cataplexy while under video-polysomnography (v-PSG) monitoring in the sleep lab. The most serious cataplectic attack from each patient was analysed. Each cataplectic episode was segmented into four stages according to the v-PSG. Correlations were analysed between cataplectic stages in pairs, and between cataplectic stages and other clinical features. Results We observed 81 cataplectic episodes in 21 patients with diverse triggers, including humorous or exciting videos, tickling, recalling horrible memories and exercising. Nine patients (43%) went through complete cataplectic attacks while the others experienced partial attacks. Four cataplectic stages (ie, triggering, resisting, atonic, and recovering) were identified according to clinical and electromyograms characteristics. Resisting stage is predominant (56.4%) in cataplexy, while atonic stage is most related with the total duration of cataplexy. The Epworth Sleepiness Scale score (ESS) has a positive correlation with the total duration of cataplexy. Both duration of cataplexy and ESS score are negatively correlated with disease course. However, medication history seems have no influence on either cataplexy duration or ESS score. Conclusion Four-stage segmentation shows the dynamic process of the cataplectic attack, which is different from the traditional classification of complete or partial cataplexy. Resisting stage is necessary for every cataplexy and might reflect the compensation mechanism, while atonic stage may be omitted in some patients. The severity of narcolepsy reduces with the extension of natural course regardless of medication history.

OBJECTIVES Data on the impact and course of uncorrected tricuspid regurgitation (TR) during left ventricular assist device (LVAD) implantation are scarce and inconsistent. This study explores the clinical impact and natural course of uncorrected TR in patients after LVAD implantation. METHODS The European Registry for Patients with Mechanical Circulatory Support was used to identify adult patients with LVAD implants without concomitant tricuspid valve surgery. A mediation model was developed to assess the association of TR with 30-day mortality via other risk factors. Generalized mixed models were used to model the course of post-LVAD TR. Joint models were used to perform sensitivity analyses. RESULTS A total of 2496 procedures were included (median age: 56 years; men: 83%). TR was not directly associated with higher 30-day mortality, but mediation analyses suggested an indirect association via preoperative elevated right atrial pressure and creatinine (P = 0.035) and bilirubin (P = 0.027) levels. Post-LVAD TR was also associated with increased late mortality [hazard ratio 1.16 (1.06–1.3); P = 0.001]. On average, uncorrected TR diminished after LVAD implantation. The probability of having moderate-to-severe TR immediately after an implant in patients with none-to-mild TR pre-LVAD was 10%; in patients with moderate-to-severe TR pre-LVAD, it was 35% and continued to decrease in patients with moderate-to-severe TR pre-LVAD, regardless of pre-LVAD right ventricular failure or pulmonary hypertension. CONCLUSIONS Uncorrected TR pre-LVAD and post-LVAD is associated with increased early and late mortality. Nevertheless, on average, TR diminishes progressively without intervention after an LVAD implant. Therefore, these data suggest that patient selection for concomitant tricuspid valve surgery should not be based solely on TR grade.

Background: This study was performed to investigate clinical characteristics and outcome after gamma knife radiosurgery (GKS) in patients with incidental, symptomatic unruptured, or ruptured arteriovenous malformations (AVMs). Methods: A total of 491 patients with brain AVMs treated with GKS from June 2002 to September 2017 were retrospectively reviewed. All patients were classified into the incidental (n = 105), symptomatic unruptured (n = 216), or ruptured AVM (n = 170) groups. Results: The mean age at diagnosis of incidental, symptomatic unruptured, and ruptured AVMs was 40.3, 36.7, and 27.6 years, respectively. The mean nidus volume was 3.9, 5.7, and 2.4 cm3, respectively. Deep venous drainage was identified in 34, 54, and 76% patients, respectively. There were no significant differences in obliteration rates after GKS between the 3 groups (64.8, 61.1, and 65.9%, respectively) after a mean follow-up period of 60.5 months; however, patients with incidental AVM had a significantly lower post-GKS hemorrhage rate than patients with symptomatic unruptured or ruptured AVMs (annual hemorrhage rate of 1.07, 2.87, and 2.69%; p = 0.028 and p = 0.049, respectively). Conclusions: There is a significant difference in clinical and anatomical characteristics between incidental, symptomatic unruptured, and ruptured AVMs. The obliteration rate after GKS is not significantly different between the 3 groups. Meanwhile, an older age at diagnosis and lower hemorrhage rate after GKS in incidental AVMs suggest that they have a more indolent natural course with a lower life-long risk of hemorrhage.

Can diabetes be reversed? Yes! The weight loss due to intensive lifestyle intervention leads to the recovery of islet β cell function, thus changing the natural course of type 2 diabetes.

Life expectancy over the past half century has increased significantly and by 2025 approximately one in six people on Earth will be over 60 years old, thus, age-related diseases become even more relevant, this also applies to menopausal syndrome in postmenopausal women. The average age of menopause is 5052 years. In the world 25 million women annually experience menopause and only 10% of them have no pathological manifestations. Genitourinar menopausal syndrome is the second most common marker of menopause. Urogenital disorders are a fairly common nosology, which is confirmed by numerous studies, but not every woman considers it necessary to report a problem to a doctor, considering this a natural course of aging. The increase in life expectancy and rejuvenation of the population is undoubtedly associated with socio-social development and the achievement of medicine, the purpose of which is also to increase the extension of the term of a healthy and quality life. Studies conducted in recent decades to study atrophic hypoestrogenic changes in the urogenital tract will allow us to reconsider our attitude to genitourinar menopausal syndrome and to select appropriate treatment for various groups of patients. But the inability of women, at times, to declare their symptoms associated with vulvovaginal atrophy, and the lack of active interest in this issue by doctors, especially gynecologists, leaves this problem unresolved.