Search Results (47)

Background: Idiopathic pulmonary fibrosis (IPF) and emphysema often coexist in patients with lung cancer (LC), forming a syndrome with combined pulmonary fibrosis and emphysema (CPFE). The three share the pathogenic mechanisms of smoking, chronic inflammation, and oxidative stress. The clinical management of CPFE patients is challenging, but its impact on tumor characteristics, acute exacerbation (AE), and prognosis is still controversial. The purpose of this study was to clarify the effect of CPFE on tumor biological behavior, AE risk, and survival outcome in patients with IPF-LC so as to optimize individualized treatment strategies. Methods: This was a retrospective and single-center study. Newly diagnosed LC patients with IPF, COPD, and normal lungs were recruited in the west China hospital. Patients with IPF were further categorized into CPFE-LC and isolated IPF-LC groups based on the presence of emphysema. Clinical and tumor features, lung function parameters, and prognosis were obtained and compared. Results: Patients with IPF and LC were more common in older men and heavy smokers. IPF-associated tumors had a higher proportion of carrying EGFR wild-type, occurring in the lower lobe of the lung and developing adenocarcinoma and squamous cell carcinoma. Among IPF-LC patients, 68.2% (103/151) met CPFE criteria. Pulmonary function tests demonstrated preserved VC% but significantly reduced FEV1/FVC in CPFE versus non-emphysema IPF (76.3% vs. 80.7%, p = 0.004), alongside elevated CPI and impaired DLCO. CPI ≥ 40 (HR = 2.087, 95%CI: 1.715–6.089, p = 0.012), combined with COPD (HR = 2.281, 95%CI: 1.139–4.569, p = 0.040), isolated IPF (HR = 5.703, 95%CI: 2.516–12.925, p < 0.001), and CPFE (HR = 6.275, 95%CI: 3.379–11.652, p < 0.001), were independent prognostic risk factors in LC patients. The incidence of treatment-induced AEs (49.5% vs. 29.2%, p = 0.038) and AE-related mortality (28.0% vs. 11.8%, p = 0.045) were significantly higher in the CPFE group than in the isolated IPF group. Logistic regression analysis showed that CPFE (OR: 3.494, 95%CI: 2.014–6.063, p = 0.001) was independently associated with the risk of AE-related mortality in patients with LC and IPF. Conclusions: Compared to LC patients with solely IPF, the presence of emphysema had no significant impact on overall survival, but CPFE increased the risk of treatment-triggered AE and was associated with AE-related mortality. In patients with LC, CPFE with AEs had a worse prognosis than IPF with AEs. Full article

Background: Diabetes mellitus (DM) is an independent risk factor for severe SARS-CoV-2 infection and is linked to higher incidences of infections and adverse outcomes in patients with DM. This study examines the association between DM and multidrug-resistant Gram-negative bacteria (MDR-GNB) in critically ill, intubated COVID-19 patients in the intensive care unit (ICU) and evaluates mortality rates and clinical factors contributing to unfavorable outcomes. Methods: This retrospective observational study included intubated COVID-19 patients diagnosed with secondary infections due to MDR-GNB. Patients were treated for acute respiratory distress syndrome (ARDS) in a tertiary care university hospital ICU between October 2020 and February 2022. Collected data included demographics, comorbidities, medication, and laboratory parameters including blood tests and culture samples. Results: Among 416 COVID-19 patients, 112 (26.9%) had T2DM. Cultures from lower respiratory tract specimens revealed a significantly higher likelihood of isolating Acinetobacter baumannii in patients with DM (OR: 2.18, 95% CI: 1.40–3.40, p < 0.001), and DM is an independent predictor of isolation Acinetobacter baumannii in bronchial secretions of COVID-19 intubated patients (OR: 2.046, 95% CI: 1.256–3.333. p < 0.004). DM was not significantly associated with differences in length of stay (LOS) until discharge or death (HR: 0.76, 95% CI: 0.51–1.12, p = 0.16; HR: 0.91, 95% CI: 0.70–1.19, p = 0.50) or 28-day ICU mortality (OR: 1.12, 95% CI: 0.52–2.41, p = 0.77). Age was linked to an increased 28-day mortality risk in patients with DM (OR: 1.10, 95% CI: 1.02–1.18, p = 0.011). Conclusions: In critically ill intubated COVID-19 patients, DM emerged as a significant and independent predictor for the isolation of Acinetobacter baumannii from bronchial secretions, highlighting a key link between DM and specific multidrug-resistant pathogens, even though no broader association with MDR-GNB-related secondary infections was observed. Full article

Background. The molecular mechanisms underlying acute coronary syndrome (ACS) have been extensively investigated, with a particular focus on the role of circulating microvesicles (MVs) as carriers of regulatory elements that influence hemodynamic changes and coronary flow. Endothelial and platelet dysfunction during ACS alters MV composition, impacting clinical outcomes. This study explores the levels of miR–126–5p and miR–223–3p in circulating MVs and their association with the Thrombolysis in Myocardial Infarction (TIMI) coronary flow classification scale, proposing their potential as biomarkers. Methods. Bioinformatic tools identified miRNAs linked to ACS. Plasma MVs were isolated from ACS patients and healthy controls through high-speed centrifugation. miRNA levels were quantified using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and compared across TIMI 0 and TIMI 3 groups. Diagnostic efficacy was assessed via receiver operating characteristic (ROC) curve analysis. Results. The bioinformatic analysis identified miR–126 and miR–223 present in ACS. miR–126–5p and miR–223–3p were significantly reduced in MVs from TIMI 0 patients compared to TIMI 3. ROC analysis showed high diagnostic accuracy for miR–126–5p (AUC = 0.918; 95% CI: 0.818–1.00; p = 0.001) and miR–223–3p (AUC = 1.00; 95% CI: 1.00–1.00; p < 0.001). Conclusions. Reduced levels of miR–126–5p and miR–223–3p in circulating MVs are strongly associated with impaired coronary flow, positioning these miRNAs as potential biomarkers for ACS risk stratification and therapeutic targeting. Full article

This review aims to provide a comprehensive overview of the main types, subtypes, clinical manifestations, and current therapeutic strategies for multiple sclerosis, emphasizing recent advancements and clinical challenges. Multiple Sclerosis (MS) is a demyelinating, chronic, autoimmune, and inflammatory disease that affects the Central Nervous System (CNS). Its classification has the following subtypes: Relapsing-Remitting (RRMS), Secondary-Progressive (SPMS), and Primary-Progressive (PPMS), including rarer subtypes such as Clinically Isolated Syndrome (CIS), Radiologically Isolated Syndrome (RIS), Balo’s Concentric Sclerosis (BCS), Schilder’s Disease (SD), and Progressive-Relapsing MS (PRMS). This article divides the various treatments for MS into the following three categories: acute relapse management, symptomatic treatments, and Disease-Modifying Treatments (DMTs). The latter represents revolutionary research in MS, since they are the drugs considered as the best treatment alternatives for this disease. Full article

Background and Objectives: In this study, we evaluated clinical factors associated with implementing a rehabilitation program for patients with COVID-19-associated acute respiratory distress syndrome (ARDS) requiring mechanical ventilation (MV) during the quarantine period. Materials and Methods: This observational study was conducted in the National Designated Isolated ICU, a dedicated COVID-19 center with 18 beds, from 30 December 2020 to 30 May 2022. One hundred and fifty-four patients (mean age: 67.3 ± 13.4 years; male: 59.7%) were enrolled. The ICU rehabilitation program included early mobilization, chest physiotherapy, and dysphagia treatment. Results: Forty-five patients (29.3%) participated in the rehabilitation program. Multivariate logistic regression identified three significant factors: tracheostomy (odds ratio [OR], 2.796; 95% confidence interval [CI], 1.238–6.316; p = 0.013), body mass index ≥ 25.0 kg/m² (OR, 2.724; 95% CI, 1.276–5.817; p = 0.010), and extracorporeal membrane oxygenation (OR, 2.931; 95% CI, 1.165–7.377; p = 0.022); patients with all three factors were younger (median 44 vs. 70 years, p < 0.001) and had significantly lower Acute Physiology and Chronic Health Evaluation II scores (median 12 vs. 16, p = 0.002) on the MV day. One-year cumulative mortality rates for patients with 0 to 3 factors were 66.7%, 50.8%, 38.9%, and 15.4%, respectively, with a significant difference among them (log-rank, p < 0.001). Conclusions: Three clinical factors associated with implementing a rehabilitation program during the quarantine period for COVID-19-associated ARDS patients were identified. The program was feasible and beneficial, particularly for younger patients with lower illness severity and fewer comorbidities on the day of MV. Full article

Choroid plexus (CP) can be seen as a watchtower of the central nervous system (CNS) that actively regulates CNS homeostasis. A growing body of literature suggests that CP alterations are involved in the pathogenesis of multiple sclerosis (MS) but the underlying mechanisms remain elusive. CPs are enlarged and inflamed in relapsing-remitting (RRMS) but also in clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) stages, far beyond MS diagnosis. Increases in the choroid plexus/total intracranial volume (CP/TIV) ratio have been robustly associated with increased lesion load, higher translocator protein (TSPO) uptake in normal-appearing white matter (NAWM) and thalami, as well as with higher annual relapse rate and disability progression in highly active RRMS individuals, but not in progressive MS. The CP/TIV ratio has only slightly been correlated with magnetic resonance imaging (MRI) findings (cortical or whole brain atrophy) and clinical outcomes (EDSS score) in progressive MS. Therefore, we suggest that plexus volumetric assessments should be mainly applied to the early disease stages of MS, whereas it should be taken into consideration with caution in progressive MS. In this review, we attempt to clarify the pathological significance of the temporal CP volume (CPV) changes in MS and highlight the pitfalls and limitations of CP volumetric analysis. Full article

Usher syndrome (US) is a clinically and genetically heterogeneous disorder that involves three main features: sensorineural hearing loss, retinitis pigmentosa (RP), and vestibular impairment. With a prevalence of 4–17/100,000, it is the most common cause of deaf-blindness worldwide. Genetic research has provided crucial insights into the complexity of US. Among nine confirmed causative genes, MYO7A and USH2A are major players in US types 1 and 2, respectively, whereas CRLN1 is the sole confirmed gene associated with type 3. Variants in these genes also contribute to isolated forms of hearing loss and RP, indicating intersecting molecular pathways. While hearing loss can be adequately managed with hearing aids or cochlear implants (CIs), approved RP treatment modalities are lacking. Gene replacement and editing, antisense oligonucleotides, and small-molecule drugs hold promise for halting RP progression and restoring vision, enhancing patients’ quality of life. Massively parallel sequencing has identified gene variants (e.g., in PCDH15) that influence CI results. Accordingly, preoperative genetic examination appears valuable for predicting CI success. To explore genetic mutations in CI recipients and establish correlations between implant outcomes and involved genes, we comprehensively reviewed the literature to gather data covering a broad spectrum of CI outcomes across all known US-causative genes. Implant outcomes were categorized as excellent or very good, good, poor or fair, and very poor. Our review of 95 cochlear-implant patients with US, along with their CI outcomes, revealed the importance of presurgical genetic testing to elucidate potential challenges and provide tailored counseling to improve auditory outcomes. The multifaceted nature of US demands a comprehensive understanding and innovative interventions. Genetic insights drive therapeutic advancements, offering potential remedies for the retinal component of US. The synergy between genetics and therapeutics holds promise for individuals with US and may enhance their sensory experiences through customized interventions. Full article

Anti-synthetase syndrome (ASS) is a rare autoimmune disease. Since the knowledge of ASS remains limited, we conducted the retrospective study aiming to describe clinical characteristics and identify variables associated with interstitial lung disease (ILD) and mortality among patients with ASS. Patients diagnosed with ASS from January 2013 to October 2022 were included. Patient demographics, clinical manifestations, myositis auto-antibody profiles, HRCT findings, and laboratory tests were collected. Variables associated with mortality risk and ILD were evaluated using the Cox proportional hazards model and the logistic regression model, respectively. A total of 82 patients with ASS were included. Clinical manifestations included arthritis (57%), Raynaud’s phenomenon (32%), mechanic’s hands (29%), fever (26%), and myositis (17%). The myositis auto-antibody profiles included anti-PL-7 (29%), anti-Jo-1 (27%), anti-EJ (17%), anti-PL-12 (16%), and anti-OJ (11%). ILD was observed in 64 patients (78%). Among patients with ILD, 21 initially presented with ILD before developing other ASS clinical manifestations, 29 simultaneously presented with ILD and other symptoms, and 14 had isolated ILD throughout follow-up. Overall, 6 patients presented with rapid-progressive ILD. With a median follow-up time of 2.5 years, mortality was observed in 10 patients (12.2%). Factors associated with mortality included increased lymphocyte counts (adjusted HR, 0.74; 95% CI, 0.61–0.91; p < 0.01), isolated ILD (adjusted HR, 9.59; 95% CI, 1.52–60.61; p = 0.02) and the presence of anti-Ro52 antibodies (adjusted HR, 0.14; 95% CI, 0.02–0.93; p = 0.04). Factors associated with ILD included age (adjusted OR, 1.10; 95% CI, 1.03–1.18; p = 0.01), presence of anti-Ro52 antibodies (adjusted OR, 17.92; 95% CI, 2.13–138.68; p = 0.01), and presence of arthritis (adjusted OR, 0.09; 95% CI, 0.01–0.75; p = 0.03). Our study demonstrated a favorable overall mortality rate among ASS patients. Full article

Objective: Critically ill patients with acute respiratory distress syndrome (ARDS) due to viral infection are at risk for secondary complications, including invasive aspergillosis. Our study aimed to characterize the clinical significance and outcome of Aspergillus species isolated from lower-respiratory-tract samples of critically ill OVID-19 patients at a single center. Design: We conducted a retrospective cohort study to evaluate the characteristics of patients with COVID-19 and aspergillus isolated from the lower respiratory tract and to identify predictors of outcomes in this population. Setting: The setting was a single-center hospital system within the metropolitan Detroit region. Results: The prevalence of Aspergillus isolated in hospitalized COVID-19 patients was 1.18% (30/2461 patients), and it was 4.6% in critically ill ICU patients with COVID-19. Probable COVID-19-associated invasive pulmonary aspergillosis (CAPA) was found in 21 critically ill patients, and 9 cases were classified as colonization. The in-hospital mortality of critically ill patients with CAPA and those with aspergillus colonization were high but not significantly different (76% vs. 67%, p = 1.00). Furthermore, the in-hospital mortality for ICU patients with or without Aspergillus isolated was not significantly different 73.3% vs. 64.5%, respectively (OR 1.53, CI 0.64–4.06, p = 0.43). In patients in whom Aspergillus was isolated, antifungal therapy (p = 0.035, OR 12.3, CI 1.74–252); vasopressors (0.016, OR 10.6, CI 1.75–81.8); and a higher mSOFA score (p = 0.043, OR 1.29 CI 1.03–1.72) were associated with a worse outcome. In a multivariable model adjusting for other significant variables, FiO₂ was the only variable associated with in-hospital mortality in patients in whom Aspergillus was isolated (OR 1.07, 95% CI 1.01–1.27). Conclusions: The isolation of Aspergillus from lower-respiratory-tract samples of critically ill patients with COVID-19 is associated with high mortality. It is important to have a low threshold for superimposed infections such as CAPA in critically ill patients with COVID-19. Full article

Multiple sclerosis (MS) is a clinically heterogenous disease. Currently, we cannot identify patients with more active disease who may potentially benefit from earlier interventions. Previous data from our lab identified the CXCL13 index (I_CXCL13), a measure of intrathecal production of CXCL13, as a potential biomarker to predict future disease activity in MS patients two years after diagnosis. Patients with clinically isolated syndrome (CIS) or radiologically isolated syndrome (RIS) underwent a lumbar puncture and blood draw, and the I_CXCL13 was determined. They were then followed for at least 5 years for MS activity. Patients with high I_CXCL13 were more likely to convert to clinically definite MS (82.4%) compared to those with low I_CXCL13 (10.0%). The data presented below demonstrate that this predictive ability holds true in CIS and RIS patients, and for at least five years compared to our initial two-year follow-up study. These data support the concept that I_CXCL13 has the potential to be used to guide immunomodulatory therapy in MS. Full article

Background: Multiple sclerosis (MS) is a common neurological disease affecting the optic nerve, directly or indirectly, through transsynaptic axonal degeneration along the visual pathway. New ophthalmological tools, arguably the most important being optical coherence tomography (OCT), could prove paramount in redefining MS diagnoses and shaping their follow-up protocols, even when the optic nerve is not involved. Methods: A prospective clinical study was conducted. In total, 158 eyes from patients previously diagnosed with relapsing remitting MS (RRMS)—with or without optic neuritis (ON), clinically isolated syndrome (CIS) with or without ON, and healthy controls were included. Each patient underwent an ophthalmologic exam and OCT evaluation for both eyes (a posterior pole analysis (PPA) and the optic nerve head radial circle protocol (ONH-RC)). Results: The macular retinal thickness (the 4 × 4, respectively, 2 × 2 grid) and thickness of the peripapillary retinal nerve fiber layer (pRNFL) were investigated. Various layers of the retina were also compared. Our study observed significant pRNFL thinning in the RRMS eyes compared to the control group, the pRNFL atrophy being more severe in the RRMS-ON eyes than the RRMS-NON eyes. In the ON group, the macular analysis showed statistically significant changes in the RRMS-ON eyes when compared only to the CIS-ON eyes, regarding decreases in the inner plexiform layer (IPL) thickness and inner nuclear layer (INL) on the central 2 × 2 macular grid. The neurodegenerative process affected both the inner retina and pRNFL, with clinical damage appearing for the latter in the following order: CIS-NON, CIS-ON, RRMS-NON, and RRMS-ON. In the presence of optic neuritis, SMRR patients presented an increase in their outer retina thickness compared to CIS patients. Conclusions: To differentiate the MS patients from the CIS patients, in the absence of optic neuritis, OCT Posterior Pole Analysis could be a useful tool when using a central 2 × 2 sectors macular grid. Retinal changes in MS seem to start from the fovea and spread to the posterior pole. Finally, MS could lead to alterations in both the inner and outer retina, along with pRNFL. Full article

Primary headaches are known to be associated with multiple sclerosis (MS), but previous studies concerning this relationship are not conclusive. Nowadays, there are no studies assessing the prevalence of headaches in Polish MS patients. The aim of the study was to assess the prevalence and characterise headaches in MS patients treated with disease-modifying therapies (DMTs). In a cross-sectional study of 419 consecutive RRMS patients, primary headaches were diagnosed according to the International Classification of Headache Disorders (ICHD-3) criteria. Primary headaches were observed in 236 (56%) of RRMS patients, with a higher prevalence in women (ratio of 2:1). The most common was migraine 174 (41%) (migraine with aura 80 (45%), migraine without aura 53 (30%), and probable migraine without aura 41 (23%); less frequent was tension-type headache 62 (14%). Female sex was a risk factor for migraines but not for tension-type headaches (p = 0.002). Migraines mostly started before MS onset (p = 0.023). Migraine with aura was associated with older age, longer disease duration (p = 0.028), and lower SDMT (p = 0.002). Longer DMT time was associated with migraine (p = 0.047), particularly migraine with aura (p = 0.035). Typical for migraine with aura were headaches during clinical isolated syndrome (CIS) (p = 0.001) and relapses (p = 0.025). Age and type of CIS, oligoclonal band presence, family MS history, EDSS, 9HTP, T25FW, and type of DMT did not correlate with headache. Headaches are present in more than half of MS patients treated with DMTs; migraines occur almost three times more frequently than tension-type headaches. Migraines with aura headaches during CIS and relapses are typical. Migraine in MS patients had high severity and typical migraine characteristics. DMTs had no correlation with the presence or type of headache. Full article

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) ribonucleic acid (RNA) shedding is an important parameter for determining the optimal length of isolation period required for coronavirus disease 2019 (COVID-19) patients. However, the clinical (i.e., patient and disease) characteristics that could influence this parameter have yet to be determined. In this study, we aim to explore the potential associations between several clinical features and the duration of SARS-CoV-2 RNA shedding in patients hospitalized with COVID-19. A retrospective cohort study involving 162 patients hospitalized for COVID-19 in a tertiary referral teaching hospital in Indonesia was performed from June to December 2021. Patients were grouped based on the mean duration of viral shedding and were compared based on several clinical characteristics (e.g., age, sex, comorbidities, COVID-19 symptoms, severity, and therapies). Subsequently, clinical factors potentially associated with the duration of SARS-CoV-2 RNA shedding were further assessed using multivariate logistic regression analysis. As a result, the mean duration of SARS-CoV-2 RNA shedding was found to be 13 ± 8.44 days. In patients with diabetes mellitus (without chronic complications) or hypertension, the duration of viral shedding was significantly prolonged (≥13 days; p = 0.001 and p = 0.029, respectively). Furthermore, patients with dyspnea displayed viral shedding for longer durations (p = 0.011). The multivariate logistic regression analysis reveals that independent risk factors associated with the duration of SARS-CoV-2 RNA shedding include disease severity (adjusted odds ratio [aOR] = 2.94; 95% CI = 1.36–6.44), bilateral lung infiltrates (aOR = 2.79; 95% CI = 1.14–6.84), diabetes mellitus (aOR = 2.17; 95% CI = 1.02–4.63), and antibiotic treatment (aOR = 3.66; 95% CI = 1.74–7.71). In summary, several clinical factors are linked with the duration of SARS-CoV-2 RNA shedding. Disease severity is positively associated with the duration of viral shedding, while bilateral lung infiltrates, diabetes mellitus, and antibiotic treatment are negatively linked with the duration of viral shedding. Overall, our findings suggest the need to consider different isolation period estimations for specific clinical characteristics of patients with COVID-19 that affect the duration of SARS-CoV-2 RNA shedding. Full article

(1) Background: Multiple Sclerosis (MS) is a chronic, progressive, immune-mediated disorder that affects the Central Nervous System and is the most common cause of non-traumatic neurological disability in young adults. The study aimed to assess the levels of stress, resilience, well-being, sleep quality, and fatigue in Israeli people with MS (PwMS), and to examine the associations between these factors and the sociodemographic and clinical characteristics. These factors had never before been studied in conjunction in PwMS, nor had they been systematically addressed in Israel, the unique geopolitical situation of which may pose unique challenges. (2) Methods: This was a survey-based, cross-sectional study conducted through an Internet platform. (3) Results: Israeli PwMS who participated in the study were experiencing relatively high levels of stress and low resilience, poor sleep quality, and severe fatigue. The analysis revealed significant associations between resilience and stress, well-being, and anxiety, as well as stress and well-being, resilience, sleep quality, fatigue, and Clinically Isolated Syndrome (CIS). (4) Conclusions: the Israeli PwMS who participated in the study were experiencing higher levels of stress, lower resilience and worse sleep quality than PwMS in other countries, as compared to results previously reported in literature. The findings of this study ought to serve as a call to action for the MS care providers in Israel and warrant further research into the possible causes of the phenomenon and strategies to address it. Full article

Approximately 15% of multiple sclerosis (MS) patients develop a progressive form of disease from onset; this condition (primary progressive-PP) MS is difficult to diagnose and treat, and is associated with a poor prognosis. Extracellular vesicles (EVs) of brain origin isolated from blood and their protein cargoes could function as a biomarker of pathological conditions. We verified whether MBP and MOG content in oligodendrocytes-derived EVs (ODEVs) could be biomarkers of MS and could help in the differential diagnosis of clinical MS phenotypes. A total of 136 individuals (7 clinically isolated syndrome (CIS), 18 PPMS, 49 relapsing remitting (RRMS)) and 70 matched healthy controls (HC) were enrolled. ODEVs were enriched from serum by immune-capture with anti-MOG antibody; MBP and MOG protein cargoes were measured by ELISA. MBP concentration in ODEVs was significantly increased in CIS (p < 0.001), RRMS (p < 0.001) and PPMS (p < 0.001) compared to HC and was correlated with disease severity measured by EDSS and MSSS. Notably, MBP concentration in ODEVs was also significantly augmented in PPMS compared to RRMS (p = 0.004) and CIS (p = 0.03). Logistic regression and ROC analyses confirmed these results. A minimally invasive blood test measuring the concentration of MBP in ODEVs is a promising tool that could facilitate MS diagnosis. Full article