Východisko: Vícenásobné nádorové onemocnění plic je poměrně vzácnou nozologickou jednotkou, cílem této kazuistiky je její připomenutí a poukázání na úskalí její diagnostiky a následné terapie. Případ: Pacientka, 62 let, po ablaci pravého prsu s disekcí axily v roce 1993 pro invazivní duktální adenokarcinom byla indikována k operační terapii pro nemalobuněčný plicní nádor středního laloku pravé plíce, diagnostikovaném při screeningovém vyšetření. Perioperačně bylo odstraněno další ložisko v dolním laloku téže plíce, které bylo následně také hodnoceno jako primární plicní karcinom, tedy synchronní plicní nádor. Závěr: Jedná se o vzácnou nozologickou jednotku, při které je nádorové onemocnění plic prezentováno více než jedním primárním plicním ložiskem. Dělí se na synchronní nebo metachronní variantu. Synchronní forma je charakterizována záchytem ložisek v době primární diagnózy, naproti tomu u metachronního výskytu je druhý, primární plicní nádor diagnostikován s časovým odstupem. Incidence se zvyšuje díky dřívější diagnostice, úspěšnější léčbě nádorového onemocnění v raném stadiu s prodloužením přežívání pacientů, a tedy i prodloužením intervalu pro možnost vzniku dalšího primárního plicního tumoru. Jedním z hlavních rizikových faktorů je kouření. Diagnostika je obtížnější s nutností vyloučení metastatického onemocnění. Základní informaci o povaze ložisek získáváme z histologického došetření. U pacientů s více než jedním plicním ložiskem by měl být proveden velmi pečlivě staging, zejména v případě zvažované kurativní resekce, s vyloučením extrapulmonálních metastáz pomocí MRI mozku a celotělového PET/CT došetření.
Background: Multiple primary lung cancer is a relatively rare nosological entity. This case report is a reminder and points out the pitfalls of its diagnosis and therapy. Case report: A 62-year-old patient was indicated for surgical therapy for non-small cell lung cancer of the middle lobe and right lung, which were diagnosed during a screening investigation after the patient had undergone previous mastectomy of the right breast with axillary dissection for invasive ductal adenocarcinoma. Another infiltration in the lower lobe of the same lung was removed at the same time and was classified as a primary lung carcinoma; it was a synchronous lung cancer. Conclusion: Lung cancer presenting with more than one primary lesion in the lung is a rare nosological entity that can be classified into two types; synchronous and metachronous. Whereas synchronous cancers arise in the lung at the same time, metachronous cancers develop after treatment of the initial lesion. The incidence of multiple lung cancer is increasing due to earlier diagnosis and because successful treatment of the initial cancer at an early stage has led to an increase in patient survival, resulting in an increase in the interval between detection of the initial cancer and detection of the second. Smoking is one of the main risk factors. Diagnosis is made difficult because metastatic disease must be excluded. Basic information is obtained from a biopsy of the tumor. The staging of more than one primary lung cancer is complex and needs to be meticulous if curative resection is being contemplated. Magnetic resonance imaging of the brain and fluorodeoxyglucose positron emission tomography should be performed to evaluate for extra-thoracic metastases.
- MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasms, Multiple Primary * diagnosis surgery pathology MeSH
- Lung Neoplasms diagnosis surgery pathology MeSH
- Carcinoma, Non-Small-Cell Lung * diagnosis surgery pathology MeSH
- Pneumonectomy MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- Review MeSH
Glioblastoma multiforme (GBM) is the most malignant primary brain tumor. The prognosis of GBM patients varies considerably and the histopathological examination is not sufficient for individual risk estimation. MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and were repeatedly proved to play important roles in pathogenesis of GBM. In our study, we performed global miRNA expression profiling of 58 glioblastoma tissue samples obtained during surgical resections and 10 non-tumor brain tissues. The subsequent analysis revealed 28 significantly deregulated miRNAs in GBM tissue, which were able to precisely classify all examined samples. Correlation with clinical data led to identification of six-miRNA signature significantly associated with progression free survival [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.33-2.94, P < 0.001] and overa+ll survival (HR 2.86, 95% CI 1.91-4.29, P < 0.001). O(6)-methylguanine-DNA methyltransferase methylation status was evaluated as reference method and Risk Score based on six-miRNA signature indicated significant superiority in prediction of clinical outcome in GBM patients. Multivariate Cox analysis indicated that the Risk Score based on six-miRNA signature is an independent prognostic classifier of GBM patients. We suggest that the Risk Score presents promising prognostic algorithm with potential for individualized treatment decisions in clinical management of GBM patients.
- MeSH
- Algorithms MeSH
- DNA Modification Methylases genetics MeSH
- DNA Repair Enzymes genetics MeSH
- Glioblastoma genetics mortality pathology MeSH
- Humans MeSH
- DNA Methylation MeSH
- MicroRNAs genetics MeSH
- Survival Rate MeSH
- Brain metabolism MeSH
- Biomarkers, Tumor genetics MeSH
- Tumor Suppressor Proteins genetics MeSH
- Brain Neoplasms genetics mortality pathology MeSH
- Follow-Up Studies MeSH
- Prognosis MeSH
- Cell Proliferation * MeSH
- Promoter Regions, Genetic genetics MeSH
- Retrospective Studies MeSH
- Neoplasm Staging MeSH
- Gene Expression Profiling * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
We investigated the evolution of cortical atrophy in patients with early relapsing-remitting (RR) multiple sclerosis (MS) and its association with lesion volume (LV) accumulation and disability progression. 136 of 181 RRMS patients who participated in the Avonex-Steroids-Azathioprine study were assessed bimonthly for clinical and MRI outcomes over 2 years. MS patients with disease duration (DD) at baseline of ≤24 months were classified in the early group (DD of 1.2 years, n = 37), while patients with DD > 24 months were classified in the late group (DD of 7.1 years, n = 99). Mixed effect model analysis was used to investigate the associations. Significant changes in whole brain volume (WBV) (P < 0.001), cortical volume (CV) (P < 0.001), and in T2-LV (P < 0.001) were detected. No significant MRI percent change differences were detected between early and late DD groups over 2 years, except for increased T2-LV accumulation between baseline and year 2 in the early DD group (P < 0.01). No significant associations were found between changes in T2-LV and CV over the followup. Change in CV was related to the disability progression over the 2 years, after adjusting for DD (P = 0.01). Significant cortical atrophy, independent of T2-LV accumulation, occurs in early RRMS over 2 years, and it is associated with the disability progression.
BACKGROUND: The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is currently the most widely validated, patient-reported outcome measure assessing patients' perception of the impact of multiple sclerosis (MS) on walking ability. To date, the majority of previous studies investigating the MSWS-12 have focused on the total score despite individual items being potentially informative. Therefore, our objective was to examine the associations between the individual items of the MSWS-12 and mobility and whether these associations depend on disability level. METHODS: Participants completed the MSWS-12, Two-Minute Walk Test (2MWT), Timed 25-Foot Walk (T25FW), Timed Up and Go Test (TUG) and the Four Square Step Test (FSST). Subsequently, they were divided into two groups according to their disability level, classified as either "mildly" or "moderately-severely" disabled. The correlation between individual items of the MSWS-12 and clinical measures of mobility were separately examined by Spearman's correlation coefficients; linear regression analyses were performed for each disability group, with/without adjusting for cognition, age and gender. RESULTS: 242 people with MS (PwMS), 108 mildly and 134 moderately-severely disabled, were included. Stronger correlations between the MSWS-12 items and mobility tests were found in the mildly disabled compared to the moderately-severely disabled group. The linear regression analysis showed that in the mildly disabled, item 9 (use of support outdoors) explained 35.4%, 30.8%, and 23.7% of the variance related to the 2MWT, T25FW and TUG, respectively. As for the moderately-severely disabled, the linear regression analysis presented a model which included item 8 (use of support indoors), explaining 31.6%, 18.0%, 20.2% and 9.5% of the variance related to the 2MWT, T25FWT, TUG and FSST, respectively. CONCLUSIONS: Items 8 and 9 of the MSWS-12 focusing on the patient's use of walking support in and outdoors, provide a robust indicator of mobility capabilities for mildly and moderately-severely disabled PwMS.
- MeSH
- Walking * MeSH
- Humans MeSH
- Postural Balance MeSH
- Disability Evaluation MeSH
- Multiple Sclerosis * diagnosis MeSH
- Time and Motion Studies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
BACKGROUND AND OBJECTIVES: Women with multiple sclerosis (MS) are at risk of disease reactivation in the early postpartum period. Ocrelizumab (OCR) is an anti-CD20 therapy highly effective at reducing MS disease activity. Data remain limited regarding use of disease-modifying therapies (DMTs), including OCR, and disease activity during peripregnancy periods. METHODS: We performed a retrospective cohort study using data from the MSBase Registry including pregnancies conceived after December 31, 2010, from women aged 18 years and older, with relapsing-remitting MS or clinically isolated syndrome. Women were classified by preconception exposure to DMTs, including OCR, rituximab (RTX), natalizumab (NAT), stratified into active (NAT-A; continued ≥28 weeks of gestation, restarted ≤1 month postpartum) or conservative (NAT-C; continued ≤4 weeks of gestation, restarted >1 month postpartum) strategies, dimethyl fumarate (DMF) or low-efficacy DMTs (interferon-beta, glatiramer acetate). Annualized relapse rates (ARRs) were calculated for 12-month prepregnancy, pregnancy, and 6-month postpartum periods. RESULTS: A total of 2,009 live births from 1,744 women were analyzed, including 73 live births from 69 women treated with preconception OCR. For OCR, no within-pregnancy relapse was observed and 3 women (4.1%) experienced 1 relapse in the postpartum period (ARR 0.09 [95% CI 0.02-0.27]). For NAT-A, 3 (3.7%) of 82 women relapsed during pregnancy (0.05 [0.01-0.15]) and 4 (4.9%) relapsed during postpartum (0.10 [0.03-0.26]). However, for NAT-C, 13 (15.9%) of 82 women relapsed within pregnancy (0.32 [0.20-0.51]) and 25 (30.5%) relapsed during postpartum (0.74 [0.50-1.06]). In the low-efficacy DMT group, 101 (7.6%) of 1,329 women experienced within-pregnancy relapse (0.12 [0.10-0.14]), followed by an increase in postpartum relapse activity with 234 women (17.6%) relapsing (0.43 [0.38-0.48]). This was similarly seen in the DMF group with 13 (7.9%) of 164 women experiencing within-pregnancy relapse (0.12 [0.06-0.20]) and 25 (15.2%) of 164 relapsing postpartum (0.39 [0.26-0.57]). Our RTX cohort had 0 of 24 women experiencing within-pregnancy relapse and 3 (12.5%) of 24 experiencing postpartum relapse. DISCUSSION: Women treated with OCR or NAT-A were observed to have low relapse rates during pregnancy and postpartum. NAT-C was associated with increased risk of relapses. There was no within-pregnancy relapse in our RTX cohort, although we caution overinterpretation due to our sample size. An effective DMT strategy with a favorable safety profile for the mother and infant should be discussed and implemented well in advance of planning a family. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for women with relapsing-remitting MS or clinically isolated syndrome who become pregnant, ocrelizumab, rituximab, and natalizumab (continued ≥28 weeks of gestation and restarted ≤1 month postpartum) were associated with reduced risk of relapses, compared with other therapeutic strategies.
- MeSH
- Adult MeSH
- Antibodies, Monoclonal, Humanized * pharmacology administration & dosage MeSH
- Immunologic Factors * pharmacology administration & dosage MeSH
- Pregnancy Complications * drug therapy MeSH
- Humans MeSH
- Young Adult MeSH
- Postpartum Period * MeSH
- Registries MeSH
- Multiple Sclerosis, Relapsing-Remitting drug therapy MeSH
- Retrospective Studies MeSH
- Multiple Sclerosis drug therapy MeSH
- Pregnancy MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: The Expanded Disability Status Scale (EDSS) has wide scientific and regulatory precedent but limited ability to detect clinically relevant disability progression in secondary progressive multiple sclerosis (SPMS) patients, partly due to a lack of meaningful measurement of short-distance ambulatory and upper-extremity function. OBJECTIVE: To present a rationale for a composite endpoint adding the timed 25-foot walk (T25FW) and 9-Hole Peg Test (9HPT) to EDSS for SPMS disability progression assessment. METHODS: Using the International Multiple Sclerosis Secondary Progressive Avonex Clinical Trial (IMPACT) placebo arm ( n = 215) data, we analyzed disability progression using a novel progression endpoint, "EDSS-Plus," defined as progression on ⩾1 of 3 components (EDSS, T25FW, and/or 9HPT) confirmed ⩾24 weeks apart and with a ⩾20% minimum threshold change for T25FW and 9HPT. RESULTS: Over 2 years, subjects classified as T25FW, 9HPT (dominant hand), or 9HPT (non-dominant hand) progressors worsened on average by 103.4%, 69.0%, and 59.2%, respectively, while non-progressors' times remained largely unchanged. Using EDSS-Plus, 59.5% of the patients had 24-week confirmed disability progression versus 24.7% (EDSS), 41.9% (T25FW), and 34.4% (9HPT (either hand)) on each component alone. CONCLUSION: The 24-week confirmed minimum worsening of ⩾20% for T25FW and 9HPT clearly separates SPMS progressors from non-progressors. We propose that EDSS-Plus may represent an improved endpoint to identify SPMS disability progression.
- MeSH
- Time Factors MeSH
- Multiple Sclerosis, Chronic Progressive diagnosis physiopathology MeSH
- Walking physiology MeSH
- Adult MeSH
- Upper Extremity physiopathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Persons with Disabilities rehabilitation MeSH
- Disability Evaluation MeSH
- Disease Progression MeSH
- Severity of Illness Index MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
OBJECTIVE: To investigate the individual occurrence of walking-related motor fatigue in persons with multiple sclerosis (PwMS), according to disability level and disease phenotype.Study design This was a cross-sectional, multinational study.Participants They were 208 PwMS from 11 centers with Expanded Disability Status Scale (EDSS) scores up to 6.5. METHODS: The percentage change in distance walked (distance walked index, DWI) was calculated between minute 6 and 1 (DWI(6-1)) of the 6-Minute Walk Test (6MWT). Its magnitude was used to classify participants into 4 subgroups: (1) DWI(6-1)[≥5%], (2) DWI(6-1)[5%; -5%], (3) DWI(6-1)[-5%; > -15%], and (4) DWI(6-1)[≤-15%]. The latter group was labeled as having walking-related motor fatigue. PwMS were stratified into 5 subgroups based on the EDSS (0-2.5, 3-4, 4.5-5.5, 6, 6.5) and 3 subgroups based on MS phenotype (relapsing remitting [RR], primary progressive [PP], and secondary progressive [SP]). RESULTS: The DWI6-1was ≥5% in 16 PwMS (7.7%), between 5% and -5% in 70 PwMS (33.6%), between -5% and -15% in 58 PwMS (24%), and ≤-15% in 64 PwMS (30.8%). The prevalence of walking-related motor fatigue (DWI(6-1)[≤-15%]) was significantly higher among the progressive phenotype (PP = 50% and SP = 39%; RR = 15.6%) and PwMS with higher disability level (EDSS 4.5-5.5 = 48.3%, 6 = 46.3% and 6.5 = 51.5%, compared with EDSS 0-2.5 = 7.8% and 3-4 = 16.7%;P< .05). Stepwise multiple regression analysis indicated that EDSS, but not MS phenotype, explained a significant part of the variance in DWI(6-1)(R(2)= 0.086;P< .001). CONCLUSION: More than one-third of PwMS showed walking-related motor fatigue during the 6MWT, with its prevalence greatest in more disabled persons (up to 51%) and in those with progressive MS phenotype (up to 50%). Identification of walking-related motor fatigue may lead to better-tailored interventions.
- MeSH
- Walking physiology MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Prevalence MeSH
- Cross-Sectional Studies MeSH
- Multiple Sclerosis complications epidemiology physiopathology MeSH
- Fatigue epidemiology etiology physiopathology MeSH
- Exercise Test MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Algorithms MeSH
- Autonomic Nervous System physiology MeSH
- Databases, Factual utilization MeSH
- Electrocardiography, Ambulatory utilization MeSH
- Atrial Fibrillation diagnosis MeSH
- Coronary Disease diagnosis etiology MeSH
- Humans MeSH
- Neural Networks, Computer MeSH
- Signal Processing, Computer-Assisted MeSH
- Arrhythmias, Cardiac diagnosis MeSH
- Heart Rate physiology MeSH
- Statistics as Topic MeSH
- Tachycardia, Supraventricular diagnosis MeSH
- Check Tag
- Humans MeSH
BACKGROUND AND PURPOSE: Characterization of iron deposition associated with demyelinating lesions of multiple sclerosis and neuromyelitis optica has not been well studied. Our aim was to investigate the potential of ultra-high-field MR imaging to distinguish MS from neuromyelitis optica and to characterize tissue injury associated with iron pathology within lesions. MATERIALS AND METHODS: Twenty-one patients with MS and 21 patients with neuromyelitis optica underwent 7T high-resolution 2D-gradient-echo-T2* and 3D-susceptibility-weighted imaging. An in-house-developed algorithm was used to reconstruct quantitative susceptibility mapping from SWI. Lesions were classified as "iron-laden" if they demonstrated hypointensity on gradient-echo-T2*-weighted images and/or SWI and hyperintensity on quantitative susceptibility mapping. Lesions were considered "non-iron-laden" if they were hyperintense on gradient-echo-T2* and isointense or hyperintense on quantitative susceptibility mapping. RESULTS: Of 21 patients with MS, 19 (90.5%) demonstrated at least 1 quantitative susceptibility mapping-hyperintense lesion, and 11/21 (52.4%) had iron-laden lesions. No quantitative susceptibility mapping-hyperintense or iron-laden lesions were observed in any patients with neuromyelitis optica. Iron-laden and non-iron-laden lesions could each be further characterized into 2 distinct patterns based on lesion signal and morphology on gradient-echo-T2*/SWI and quantitative susceptibility mapping. In MS, most lesions (n = 262, 75.9% of all lesions) were hyperintense on gradient-echo T2* and isointense on quantitative susceptibility mapping (pattern A), while a small minority (n = 26, 7.5% of all lesions) were hyperintense on both gradient-echo-T2* and quantitative susceptibility mapping (pattern B). Iron-laden lesions (n = 57, 16.5% of all lesions) were further classified as nodular (n = 22, 6.4%, pattern C) or ringlike (n = 35, 10.1%, pattern D). CONCLUSIONS: Ultra-high-field MR imaging may be useful in distinguishing MS from neuromyelitis optica. Different patterns related to iron and noniron pathology may provide in vivo insight into the pathophysiology of lesions in MS.
- MeSH
- Algorithms MeSH
- Child MeSH
- Adult MeSH
- Electromagnetic Fields MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Brain Mapping MeSH
- Adolescent MeSH
- Young Adult MeSH
- Neuromyelitis Optica diagnostic imaging metabolism MeSH
- Infant, Newborn MeSH
- Image Processing, Computer-Assisted MeSH
- Child, Preschool MeSH
- Multiple Sclerosis diagnostic imaging metabolism MeSH
- Iron metabolism MeSH
- Imaging, Three-Dimensional MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Infant MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Infant, Newborn MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Patients with the 'aggressive' form of multiple sclerosis accrue disability at an accelerated rate, typically reaching Expanded Disability Status Score (EDSS) ≥ 6 within 10 years of symptom onset. Several clinicodemographic factors have been associated with aggressive multiple sclerosis, but less research has focused on clinical markers that are present in the first year of disease. The development of early predictive models of aggressive multiple sclerosis is essential to optimize treatment in this multiple sclerosis subtype. We evaluated whether patients who will develop aggressive multiple sclerosis can be identified based on early clinical markers. We then replicated this analysis in an independent cohort. Patient data were obtained from the MSBase observational study. Inclusion criteria were (i) first recorded disability score (EDSS) within 12 months of symptom onset; (ii) at least two recorded EDSS scores; and (iii) at least 10 years of observation time, based on time of last recorded EDSS score. Patients were classified as having 'aggressive multiple sclerosis' if all of the following criteria were met: (i) EDSS ≥ 6 reached within 10 years of symptom onset; (ii) EDSS ≥ 6 confirmed and sustained over ≥6 months; and (iii) EDSS ≥ 6 sustained until the end of follow-up. Clinical predictors included patient variables (sex, age at onset, baseline EDSS, disease duration at first visit) and recorded relapses in the first 12 months since disease onset (count, pyramidal signs, bowel-bladder symptoms, cerebellar signs, incomplete relapse recovery, steroid administration, hospitalization). Predictors were evaluated using Bayesian model averaging. Independent validation was performed using data from the Swedish Multiple Sclerosis Registry. Of the 2403 patients identified, 145 were classified as having aggressive multiple sclerosis (6%). Bayesian model averaging identified three statistical predictors: age > 35 at symptom onset, EDSS ≥ 3 in the first year, and the presence of pyramidal signs in the first year. This model significantly predicted aggressive multiple sclerosis [area under the curve (AUC) = 0.80, 95% confidence intervals (CIs): 0.75, 0.84, positive predictive value = 0.15, negative predictive value = 0.98]. The presence of all three signs was strongly predictive, with 32% of such patients meeting aggressive disease criteria. The absence of all three signs was associated with a 1.4% risk. Of the 556 eligible patients in the Swedish Multiple Sclerosis Registry cohort, 34 (6%) met criteria for aggressive multiple sclerosis. The combination of all three signs was also predictive in this cohort (AUC = 0.75, 95% CIs: 0.66, 0.84, positive predictive value = 0.15, negative predictive value = 0.97). Taken together, these findings suggest that older age at symptom onset, greater disability during the first year, and pyramidal signs in the first year are early indicators of aggressive multiple sclerosis.
- MeSH
- Adult MeSH
- Humans MeSH
- Disability Evaluation MeSH
- Disease Progression * MeSH
- Multiple Sclerosis * MeSH
- Sensitivity and Specificity MeSH
- Severity of Illness Index * MeSH
- Age of Onset MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
- Research Support, Non-U.S. Gov't MeSH
