Clinical Correlation of Multiple Sclerosis Immunopathologic Subtypes

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012782
Author(s):  
W. Oliver Tobin ◽  
Alicja Kalinowska-Lyszczarz ◽  
Stephen D. Weigand ◽  
Yong Guo ◽  
Nirubol Tosakulwong ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Disease ◽  
Clinical Course ◽  
Initial Attack ◽  
Long Term Outcomes ◽  
Common Pathway ◽  
Term Survival ◽  
Cns Demyelination

Objective:To compare clinical characteristics across immunopathological subtypes of patients with multiple sclerosis.Methods:Immunopathological subtyping was performed on specimens from 547 patients with biopsy and/or autopsy confirmed CNS demyelination.Results:The frequency of immunopathological subtypes were pattern I (23%), II (56%), and III (22%). Immunopatterns were similar in terms of age at autopsy/biopsy (median age 41 years, range 4-83 years, p=0.16) and proportion female (54%, p=0.71). Median follow-up after symptom onset was 2.3 years (range 0-38y). In addition to being overrepresented among autopsy cases (45% vs. 19% in biopsy cohort, p<0.001), index attack-related disability was higher in pattern III vs. pattern II (median EDSS 4 vs. 3, p=0.02). Monophasic clinical course was more common in patients with pattern III than pattern I or II (59% vs. 33% vs. 32%, p<0.001). Similarly, patients with pattern III pathology were likely to have progressive disease compared to patients with patterns I or II, when followed for ≥5 years (24% overall, p=0.49), with no differences in long-term survival, despite a more fulminant attack presentation.Conclusion:All three immunopatterns can be detected in active lesions, although they are found less frequently later into the disease due to the lower number of active lesions. Pattern III is associated with a more fulminant initial attack than either pattern I or II. Biopsied patients appear to have similar long-term outcomes irrespective of their immunopatterns. Progressive disease is less associated with the initial immunopattern and suggests convergence into a final common pathway related to the chronically denuded axon.

Clinical Course of Different Types of Immune Reactions following Keratoplasty

2021 ◽  
Author(s):  
Philip Keye ◽  
Thabo Lapp ◽  
Daniel Böhringer ◽  
Sonja Heinzelmann ◽  
Philip Maier ◽  
...  
Keyword(s):  
Clinical Course ◽  
Corneal Graft ◽  
Long Term Outcomes ◽  
Immune Mediated ◽  
Corneal Graft Rejection ◽  
Different Types ◽  
Lost To Follow Up

Abstract Background Immune-mediated corneal graft rejection (IR) is a leading cause of corneal graft failure. The endothelium, stroma, epithelium, or a combination can be affected. Little is known about the long-term outcomes of different types of IR. Methods We reviewed the medical records of all keratoplasties that had been performed at our eye centre between 2003 and 2016 (n = 3934) for any kind of IR that occurred between the surgery and 2019. All patients with a definite diagnosis of IR and sufficient clinical data were included in the analysis. IRs were grouped according to the affected part of the graft (endothelial, stromal, epithelial, and mixed). We analysed the dynamics of recovery and the clinical outcomes. Results We identified a total of 319 patients with IR. Twenty-seven of those were lost to follow-up and were excluded from further analysis. Of the IRs, 89% affected the endothelium. Endothelial IR resulted more frequently in a considerable loss of endothelial cell density than other forms of IR. Stromal IR showed a lower relapse rate and a better visual recovery than other types of IR and resulted less often in a failure of the graft. Conclusions We herein report comprehensive data about the prognosis regarding functional recovery after different types of IR following keratoplasty. Our data underline that timely recognition and correct classification of IR are important because they determine the clinical course and prognosis.

Long-Term Survival Analysis of the North American Intergroup Study C9011 Comparing Fludarabine (F) and Chlorambucil (C) in Previously Untreated Patients with Chronic Lymphocytic Leukemia (CLL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 536-536 ◽  
Author(s):  
Kanti R. Rai ◽  
Bercedis L. Peterson ◽  
Frederick R. Appelbaum ◽  
Martin S. Tallman ◽  
Andrew Belch ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Initial Treatment ◽  
Conflicts Of Interest ◽  
High Morbidity ◽  
Second Malignancies ◽  
Long Term Outcomes ◽  
Term Survival ◽  
Prolymphocytic Leukemia

Abstract Abstract 536 Long-term outcomes following novel therapies for CLL have rarely been reported. Between 10/90 and 12/94, 509 eligible, untreated patients (pts) with symptomatic CLL were enrolled by 4 cooperative groups onto study C9011; 179 were randomized to F, 193 to C, and 137 to F+C. After slightly more than 5 years median follow up, with the time of last follow-up in June 1999, we reported in 2000 (NEJM 343:1750) that F provided significantly higher response rates and longer remission duration and progression-free survival (PFS) than C (p<0.001 for all 3 endpoints). The combination arm with F+C was stopped early because of high morbidity and mortality. There was no difference in overall survival (OS) among the 3 groups. Nearly 10 years have now elapsed since this report. Therefore, with the time of last follow-up in January 2009, we analyzed the long term outcomes of pts enrolled on the study. PFS was defined as the time between randomization and the occurrence of progressive disease or death due to any cause. Results: Of the 509 pts, 85% have now died; among pts on the F and C arms, 92% have progressed. We found that F treatment resulted in significantly longer PFS than did C (p < 0.001), with notable differences in PFS at 2, 3, and 4 years (Table). While the F and C arms had the same OS during the initial 5 years following randomization, our current analysis with longer follow-up shows that pts treated on the F arm had better survival than did those on the C arm during the ensuing years (Figure). The p-values for this difference are 0.04 (unadjusted for covariates) and 0.07 (covariate-adjusted). The emergence of improved survival following initial F treatment, appearing only after 5-6 years, is an unexpected and noteworthy finding. Reporting second malignancies was required on this study. There were 27 epithelial cancers reported (9 on F, 11 on C, 7 on F+C), involving colon, lung, breast, prostate, pancreas, liver, bladder and skin (6 squamous, 2 melanoma). Seven therapy-related myeloid neoplasms (t-MN) were reported; 6 were on F+C; 1 on F. Richter's transformation to non-Hodgkin lymphoma was reported in 34 pts; prolymphocytic leukemia occurred in 10; Hodgkin lymphoma in 6; myeloma in 2; hairy cell leukemia in 1. These cases were distributed with 18 on F, 18 on C, and 17 on F+C. Thus, the overall incidence of second malignancies reported was 17%. Conclusion: Initial treatment with F provides better long-term outcomes than initial treatment with C. Second malignancies are common, but the overall incidence is not increased on the F-containing treatment arms except for t-MN. Disclosures: No relevant conflicts of interest to declare.

Long-term survival of kidney grafts in lupus nephritis: a Mexican cohort

Lupus ◽  
2018 ◽  
Vol 27 (8) ◽  
pp. 1303-1311 ◽  
Author(s):  
J C Ramirez-Sandoval ◽  
H Chavez-Chavez ◽  
M Wagner ◽  
O Vega-Vega ◽  
L E Morales-Buenrostro ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Immunosuppressive Treatment ◽  
Graft Loss ◽  
Matched Pair ◽  
Long Term Outcomes ◽  
Term Survival

Kidney transplant for patients with lupus nephritis (LN) has satisfactory outcomes in studies with short-term or mid-term follow up. Nevertheless, information about long-term outcomes is scarce. We performed a retrospective matched-pair cohort study in 74 LN recipients compared with 148 non-LN controls matched by age, sex, immunosuppressive treatment, human leukocyte antigen (HLA) matches, and transplant period in order to evaluate long-term outcomes of kidney transplant in LN recipients. Matched pairs were predominantly females (83%), median age at transplant surgery of 32 years (interquartile range 23–38 years), and 66% received a graft from a living related donor. Among LN recipients, 5-, 10-, 15-, and 20-year graft survival was 81%, 79%, 57% and 51%, respectively, and it was similar to that observed in controls (89%, 78%, 64%, and 56%, respectively). Graft loss (27% vs. 21%, p = 0.24) and overall survival ( p = 0.15) were not different between LN recipients and controls. Also, there was no difference in episodes of immunological rejection, thrombosis, or infection. Only six LN recipients had biopsy-proven lupus recurrence and three of them had graft loss. In a cohort with a long follow up of kidney transplant recipients, LN recipients had similar long-term graft survival and overall outcomes compared with non-lupus recipients when predictors are matched between groups.

scholarly journals Long-term Outcomes of Pregnancy-Associated Breast Cancer: A Single Institution Experience

2021 ◽  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Long Term Outcomes ◽  
Single Institution ◽  
Term Survival ◽  
Long Term Survival ◽  
Response To Chemotherapy ◽  
Her 2

Background: The incidence of pregnancy-associated breast cancer (PABC) is increasing, especially in the developed countries. Herein, we report the long-term outcomes of PABC from a single institution in an Arab country. Methods: Consecutive patients diagnosed to have PABC between 2005 and 2012 at a tertiary referral hospital from a Gulf cooperation council country were the subjects of the study. Long-term outcomes are reported, with a minimum follow-up of 8 years. Results: A total of 16 patients were evaluable for long-term survival analysis. The median age at the time of diagnosis was 31.5 (26-40) years. Nine (56%) patients were multiparous (> 5 previous pregnancies). The mean gestational age at diagnosis was 19.7±7.4 weeks. Immunohistochemistry revealed the following phenotypes: Luminal A 3 (18.8%); HER-2 enriched 8 (50%); triple-negative 5 (31.2%). Three patients underwent modified radical mastectomy as the initial treatment, of which 2 received adjuvant chemotherapy during pregnancy. For patients who received neoadjuvant or palliative chemotherapy, the response rate was 75% (pCR 2; CR 1; PR 6). After a median follow-up of 60 months, median progression-free survival was 36 months (95%CI 24.2 to 47.8), while the overall survival was 59 months (95%CI 31.6 – 86.4). Age, marker status, Ki-67 score, clinical stage and differentiation grade did not affect the PFS or OS on univariate analysis. Conclusions: Fifty percent of the patient with PABC expressed HER-2/neu protein, and 1/3rd had triple-negative disease. The rate of response to chemotherapy, and long-term survival may help to set a benchmark for studies from the region. Larger cohort studies may help to draw firm conclusions.

scholarly journals Surgical Aortic Mitral Curtain Replacement: Systematic Review and Metanalysis of Early and Long-Term Results

2021 ◽  
Vol 10 (14) ◽  
pp. 3163
Author(s):  
Ilaria Giambuzzi ◽  
Giorgia Bonalumi ◽  
Michele Di Mauro ◽  
Maurizio Roberto ◽  
Silvia Corona ◽  
...  
Keyword(s):  
Infective Endocarditis ◽  
Pacemaker Implantation ◽  
Early Mortality ◽  
Long Term Results ◽  
High Complexity ◽  
Long Term Outcomes ◽  
Term Survival ◽  
Double Valve Replacement

The Commando procedure is challenging, and aims to replace the mitral valve, the aortic valve and the aortic mitral curtain, when the latter is severely affected by pathological processes (such as infective endocarditis or massive calcification). Given the high complexity, it is seldomly performed. We aim to review the literature on early (hospitalization and up to 30 days) and long-term (at least 3 years of follow-up) results. Bibliographical research was performed on PubMed and Cochrane with a dedicated string. Papers regarding double valve replacement or repair in the context of aortic mitral curtain disease were included. The metaprop function was used to assess early survival and complications (pacemaker implantation, stroke and bleeding). Nine papers (540 patients, median follow-up 41 (IQR 24.5–51.5) months) were included in the study. Pooled proportion of early mortality, stroke, pacemaker implant and REDO for bleeding were, respectively 16.2%, 7.8%, 25.1% and 13.1%. The long-term survival rate ranged from 50% to 92.2%. Freedom from re-intervention was as high as 90.9% when the endocarditis was not the first etiology and 78.6% in case of valvular infection (one author had 100%). Freedom from IE recurrences reached 85% at 10 years. Despite the high mortality, the rates of re-intervention and infective endocarditis recurrences following the Commando procedure are satisfactory and confirm the need for an aggressive strategy to improve long-term outcomes.

scholarly journals Secondary Progressive Multiple Sclerosis: New Insights

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012323
Author(s):  
Bruce Anthony Campbell Cree ◽  
Douglas L Arnold ◽  
Jeremy Chataway ◽  
Tanuja Chitnis ◽  
Robert J. Fox ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Disease ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Response To Treatment ◽  
Disability Progression ◽  
Long Term Outcomes ◽  
Secondary Progressive ◽  
Relapsing Remitting

In most cases, multiple sclerosis (MS) begins with a relapsing–remitting course followed by insidious disability worsening that is independent from clinically apparent relapses and is termed secondary progressive multiple sclerosis (SMPS). Major differences exist between relapsing–remitting MS (RRMS) and SPMS, especially regarding therapeutic response to treatment. This review provides an overview of the pathology, differentiation, and challenges in the diagnosis and treatment of SPMS. We emphasize the criticality of conversion from a relapsing–remitting to a secondary progressive disease course not only because such conversion is evidence of disability progression, but also because, until recently, treatments that effectively reduced disability progression in relapsing MS were not proven to be effective in SPMS. Clear clinical, imaging, immunological, or pathological criteria marking the transition from RRMS to SPMS have not yet been established. Early identification of SPMS will require tools which, together with the use of appropriate treatments, may result in better long-term outcomes for the population of patients with SPMS.

scholarly journals L-Asparaginase Toxicity in the Treatment of Children and Adolescents with Acute Lymphoblastic Leukemia

2021 ◽  
Vol 10 (19) ◽  
pp. 4419
Author(s):  
Madalina-Petronela Schmidt ◽  
Anca-Viorica Ivanov ◽  
Daniel Coriu ◽  
Ingrith-Crenguta Miron
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Children And Adolescents ◽  
Lymphoblastic Leukemia ◽  
Event Free Survival ◽  
Long Term Outcomes ◽  
Term Survival ◽  
Free Survival ◽  
The Impact

Asparaginase is a basic component of chemotherapy in pediatric acute lymphoblastic leukemia (ALL) and has played a crucial role in improving the long-term survival of this disease. The objectives of this retrospective study were to elucidate the toxicity profile associated with asparaginase in children and adolescents with ALL, to analyze the impact of each type of toxicity on long-term outcomes, and to identify risk factors. We analyzed the medical charts of 165 patients diagnosed with ALL at Sf. Maria Iasi Children’s Hospital from 2010 to 2019 and treated according to a chemotherapeutic protocol containing asparaginase. The median duration of follow-up was 5 years (0.1–11.5 years). Groups of patients with specific types of toxicity were compared to groups of patients without toxicity. We found the following incidence of asparaginase-associated toxicity: 24.1% clinical hypersensitivity, 19.4% hepatotoxicity, 6.7% hypertriglyceridemia, 4.2% hyperglycemia, 3.7% osteonecrosis, 3% pancreatitis, 2.4% thrombosis, and 1.2% cerebral thrombosis. Overall, 82 patients (49.7%) had at least one type of toxicity related to asparaginase. No type of toxicity had a significant impact on overall survival or event-free survival. Being older than 14 years was associated with a higher risk of osteonecrosis (p = 0.015) and hypertriglyceridemia (p = 0.043) and a lower risk of clinical hypersensitivity (p = 0.04). Asparaginase-related toxicity is common and has a varied profile, and its early detection is important for realizing efficient and appropriate management.

Long-term survival of patients with multiple sclerosis in West France

2007 ◽  
Vol 13 (7) ◽  
pp. 865-874 ◽  
Author(s):  
E. Leray ◽  
SP Morrissey ◽  
J. Yaouanq ◽  
M. Coustans ◽  
E. Le Page ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
General Population ◽  
Fold Increase ◽  
French Population ◽  
Term Survival ◽  
Survival Probabilities ◽  
Clinical Onset ◽  
Disability Status

In France no data have been published about comparing survival in multiple sclerosis (MS) patients with the general French population. We estimated survival probabilities in MS patients from a major centre for MS in West France. We also compared MS survival with the general population and assessed prognostic parameters. All patients with MS onset after January 1976 and classified as dead or alive on 1 January 2004 were included. One thousand eight-hundred and seventy-nine patients (sex ratio W: M 2.3; relapsing/progressive onset 77.4%/22.6%) fulfilled these criteria, disease duration ranged from one to 28 years. By 2004, 68 patients died (51 due to MS) and the 15 and 25-year survival probabilities were 96% and 88%. Male gender, progressive course (either primary or secondary), polysymptomatic onset, and increased annual relapse rate during the first two years of MS were related to a worse prognosis. After a mean follow-up duration of 12.7 years since clinical onset, MS increased the number of deaths compared with the general population. However taking into account disability status, we found that less disabled MS patients had a better survival and highly disabled patients a worse survival (eight-fold increase of mortality) compared with the French population. Multiple Sclerosis 2007; 13: 865—874. http://msj.sagepub.com

scholarly journals Radiosurgery for multiple sclerosis–related trigeminal neuralgia: retrospective review of long-term outcomes

2019 ◽  
Vol 131 (5) ◽  
pp. 1583-1590 ◽  
Author(s):  
Colin J. Przybylowski ◽  
Tyler S. Cole ◽  
Jacob F. Baranoski ◽  
Andrew S. Little ◽  
Kris A. Smith ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Trigeminal Neuralgia ◽  
Retrospective Review ◽  
Pain Control ◽  
Facial Pain ◽  
Salvage Treatment ◽  
Long Term Outcomes ◽  
Facial Numbness

OBJECTIVEThe objective of this study was to assess long-term outcomes of facial pain and numbness after radiosurgery for multiple sclerosis (MS)–related trigeminal neuralgia (MS-TN).METHODSThe authors conducted a retrospective review of their Gamma Knife radiosurgeries (GKRSs) to identify all patients treated for MS-TN (1998–2014) with at least 3 years of follow-up. Treatment and clinical data were obtained via chart review and mailed or telephone surveys. Pain control was defined as a facial pain score of I–IIIb on the Barrow Neurological Institute (BNI) Facial Pain Intensity Scale. Kaplan-Meier analysis was performed to determine the rates of pain control after index and first salvage GKRS procedures. Patients could have had more than 1 salvage procedure. Pain control rates were based on the number of patients at risk during follow-up.RESULTSOf the 50 living patients who underwent GKRS, 42 responded to surveys (31 women [74%], median age 59 years, range 32–76 years). During the initial GKRS, the trigeminal nerve root entry zone was targeted with a single isocenter, using a 4-mm collimator with the 90% isodose line completely covering the trigeminal nerve and the 50% isodose line abutting the surface of the brainstem. The median maximum radiation dose was 85 Gy (range 50–85 Gy). The median follow-up period was 78 months (range 36–226 months). The rate of pain control after the index GKRS (n = 42) was 62%, 29%, 22%, and 13% at 1, 3, 5, and 7 years, respectively. Twenty-eight patients (67%) underwent salvage treatment, including 25 (60%) whose first salvage treatment was GKRS. The rate of pain control after the first salvage GKRS (n = 25) was 84%, 50%, 44%, and 17% at 1, 3, 5, and 7 years, respectively. The rate of pain control after the index GKRS with or without 1 salvage GKRS (n = 33) was 92%, 72%, 52%, 46%, and 17% at 1, 3, 5, 7, and 10 years, respectively. At last follow-up, 9 (21%) of the 42 patients had BNI grade I facial pain, 35 (83%) had achieved pain control, and 4 (10%) had BNI grade IV facial numbness (very bothersome in daily life).CONCLUSIONSIndex GKRS offers good short-term pain control for MS-TN, but long-term pain control is uncommon. If the index GKRS fails, salvage GKRS appears to offer beneficial pain control with low rates of bothersome facial numbness.

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