T03.01.5 AGE, OVERWEIGHT, DIABETES AND INITIAL CYST SIZE ARE ASSOCIATED WITH THE RISK OF PROGRESSION OF BD-IPMN UNDERGOING FOLLOW-UP

ObjectivesTo develop a prediction model to guide annual assessment of systemic sclerosis (SSc) patients tailored in accordance to disease activity.MethodsA machine learning approach was used to develop a model that can identify patients without disease progression. SSc patients included in the prospective Leiden SSc cohort and fulfilling the ACR/EULAR 2013 criteria were included. Disease progression was defined as progression in ≥1 organ system, and/or start of immunosuppression or death. Using elastic-net-regularisation, and including 90 independent clinical variables (100% complete), we trained the model on 75% and validated it on 25% of the patients, optimising on negative predictive value (NPV) to minimise the likelihood of missing progression. Probability cutoffs were identified for low and high risk for disease progression by expert assessment.ResultsOf the 492 SSc patients (follow-up range: 2–10 years), disease progression during follow-up was observed in 52% (median time 4.9 years). Performance of the model in the test set showed an AUC-ROC of 0.66. Probability score cutoffs were defined: low risk for disease progression (<0.197, NPV:1.0; 29% of patients), intermediate risk (0.197–0.223, NPV:0.82; 27%) and high risk (>0.223, NPV:0.78; 44%). The relevant variables for the model were: previous use of cyclophosphamide or corticosteroids, start with immunosuppressive drugs, previous gastrointestinal progression, previous cardiovascular event, pulmonary arterial hypertension, modified Rodnan Skin Score, creatine kinase and diffusing capacity for carbon monoxide.ConclusionOur machine-learning-assisted model for progression enabled us to classify 29% of SSc patients as ‘low risk’. In this group, annual assessment programmes could be less extensive than indicated by international guidelines.

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Serum BCMA levels predict outcomes in MGUS and smoldering myeloma patients

Blood Cancer Journal ◽

10.1038/s41408-021-00505-4 ◽

2021 ◽

Vol 11 (6) ◽

Author(s):

A. Visram ◽

C. Soof ◽

S. V. Rajkumar ◽

S. K. Kumar ◽

S. Bujarski ◽

...

Keyword(s):

Monoclonal Gammopathy ◽

Serum Samples ◽

Risk Models ◽

Independent Validation ◽

Increased Risk ◽

Risk Of Progression ◽

Paired Serum ◽

Smoldering Myeloma ◽

Undetermined Significance

AbstractSoluble BCMA (sBCMA) levels are elevated in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). However, the association between sBCMA levels and prognosis in MGUS and SMM has not been studied. We retrospectively analyzed sBCMA levels in stored samples from 99 MGUS and 184 SMM patients. Baseline sBCMA levels were significantly higher in MGUS and SMM patients progressing to MM during clinical follow up. When stratified according to the median baseline sBCMA level for each cohort, higher levels were associated with a shorter PFS for MGUS (HR 3.44 comparing sBCMA ≥77 vs <77 ng/mL [95% CI 2.07–5.73, p < 0.001] and SMM (HR 2.0 comparing sBCMA ≥128 vs <128 ng/mL, 95% 1.45–2.76, p < 0.001) patients. The effect of sBCMA on PFS was similar even after adjusting for the baseline MGUS or SMM risk stratification. We evaluated paired serum samples and found that sBCMA increased significantly in MGUS and SMM patients who eventually progressed to MM, whereas among MGUS non-progressors the sBCMA level remained stable. While our results require independent validation, they suggest that sBCMA may be a useful biomarker to identify MGUS and SMM patients at increased risk of progression to MM independent of the established risk models.

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Family History of Gastric Cancer and the Risk of Progression of Gastric Premalignant Conditions: A Prospective, 10-Year Endoscopic Follow-up Study

10.1055/s-0041-1724309 ◽

2021 ◽

Author(s):

M Garrido ◽

JR Viscaíno ◽

M Dinis-Ribeiro ◽

F Carneiro ◽

I Pedroto ◽

...

Keyword(s):

Gastric Cancer ◽

Family History ◽

Follow Up Study ◽

Risk Of Progression ◽

History Of ◽

Premalignant Conditions

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Long-Term Safety and Efficacy of Subcutaneous Cladribine Used in Increased Dosage in Patients with Relapsing Multiple Sclerosis: 20-Year Observational Study

Journal of Clinical Medicine ◽

10.3390/jcm10215207 ◽

2021 ◽

Vol 10 (21) ◽

pp. 5207

Author(s):

Konrad Rejdak ◽

Adriana Zasybska ◽

Aleksandra Pietruczuk ◽

Dariusz Baranowski ◽

Sebastian Szklener ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cumulative Dose ◽

Induction Dose ◽

Disability Status ◽

Risk Of Progression ◽

Dosing Regimens ◽

Favorable Safety ◽

Relapsing Multiple Sclerosis

Cladribine is currently registered as a 10-milligram tablet formulation with a fixed cumulative dosage of 3.5 mg/kg over 2 years. It is important to investigate if an increased dosage may lead to further clinical stability with preserved safety. This study used an off-label subcutaneous (s.c.) formulation of cladribine and compared outcomes (Expanded Disability Status Scale (EDSS) scores and disease progression) between 52 relapsing multiple sclerosis (RMS) patients receiving different s.c. dosing regimens with up to 20 years of follow-up. The study group received induction therapy with s.c. cladribine (1.8 mg/kg cumulative dose; consistent with 3.5 mg/kg of cladribine tablets). Patients were subsequently offered maintenance therapy (repeated courses of 0.3 mg/kg s.c. cladribine during 5–20-year follow-up). Forty-one patients received an increased cumulative dose (higher than the induction dose of 1.8 mg/kg); 11 received the standard induction dose. Risk of progression on the EDSS correlated with lower cumulative dose (p < 0.05) and more advanced disability at treatment initiation (p < 0.05) as assessed by EDSS change between year 1 and years 5 and 10 as the last follow-up. Maintenance treatment was safe and well-tolerated, based on limited source data. Subcutaneous cladribine with increased cumulative maintenance dosage was associated with disease stability and favorable safety over a prolonged period of follow-up (up to 20 years) in RMS patients.

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Urothelial Proliferation of Unknown Malignant Potential Involving the Bladder: Histopathologic Features and Risk of Progression in De Novo Cases and Cases With Prior Neoplasia

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2019-0005-oa ◽

2019 ◽

Vol 144 (7) ◽

pp. 853-862

Author(s):

Brett M. Lowenthal ◽

Debashis Sahoo ◽

Mahul B. Amin ◽

Donna E. Hansel

Keyword(s):

Median Time ◽

De Novo ◽

Clinical Findings ◽

Malignant Potential ◽

World Health ◽

Time To Progression ◽

Risk Of Progression ◽

Health Organization ◽

Subsequent Risk

Context.— Urothelial proliferation of unknown malignant potential (UPUMP) is a 2016 World Health Organization classifier that encompasses prior categories of flat and papillary urothelial hyperplasia. In addition, UPUMP occurs in settings of both de novo and prior bladder neoplasia. Objective.— To identify UPUMP features associated with subsequent neoplastic development. Design.— Sixty-eight patients were identified from the archives, including 26 patients with de novo and 42 patients with prior bladder neoplasia. Patient slides and clinical course were reviewed. Results.— Patients with de novo UPUMP were detected through clinical findings (26/26; 100%), whereas surveillance cystoscopy primarily detected UPUMP in patients with prior neoplasia (29/42; 69%). Histopathologic criteria evaluated included urothelial hyperplasia, urothelial cytology, vascular ingrowth, denudation, inflammation, edema, and fibrosis. Mean clinical follow-up was 68.9 months in patients with de novo neoplasia and 69.5 months in patients with prior neoplasia. Subsequent neoplasia developed in 4 of 26 (15.4%) of patients with de novo UPUMP and was associated with cystoscopic papillary appearance (P = .02) or microscopic thin papillary ingrowths or papillations (P = .02; median time to progression, 4.1 months). Of 42 patients with prior neoplasia, 17 (40.5%) had subsequent neoplasia, significantly associated with an absence of prominent lamina propria edema (P < .001; median time to progression, 11.0 months). A higher rate of progression to high-grade disease was present in patients with a prior neoplasia versus those with de novo disease (58.9% versus 25%). Conclusions.— Urothelial proliferation of unknown malignant potential shows subsequent risk of neoplastic development of 17% in patients with de novo disease and 40% in patients with prior neoplasia. The greatest risk of progression is associated with early papillary formation.

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P.04.12 ROLE OF CYST FEATURES AND PATIENTS' FACTORS IN PREDICTING THE RISK OF PROGRESSION IN BD-IPMN UNDERGOING FOLLOW-UP

Digestive and Liver Disease ◽

10.1016/s1590-8658(18)30480-8 ◽

2018 ◽

Vol 50 (2) ◽

pp. e160

Author(s):

G. Zerboni ◽

G. Vanella ◽

S. Stigliano ◽

L. Archibugi ◽

M. Signoretti ◽

...

Keyword(s):

Risk Of Progression

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Association of β-amyloid level, clinical progression and longitudinal cognitive change in normal older individuals

Neurology ◽

10.1212/wnl.0000000000011222 ◽

2020 ◽

pp. 10.1212/WNL.0000000000011222

Author(s):

Laura M. van der Kall ◽

Thanh Truong ◽

Samantha C Burnham ◽

Vincent Doré ◽

Rachel S Mulligan ◽

...

Keyword(s):

Proportional Hazards ◽

Cognitive Change ◽

Cox Proportional Hazards ◽

Imaging Biomarkers ◽

Older Individuals ◽

Mixed Effect ◽

Preclinical Ad ◽

Risk Of Progression ◽

Very High

Objective:To determine the effect of Aβ level on progression risk to MCI or dementia and longitudinal cognitive change in cognitively normal (CN) older individuals.Methods:All CN from the Australian Imaging Biomarkers and Lifestyle study (AIBL) with Aβ PET and ≥3 years follow-up were included (n=534; age 72±6 yrs; 27% Aβ positive; follow-up 5.3±1.7 yrs). Aβ level was divided using the standardised 0-100 Centiloid scale: <15 CL negative, 15-25 CL uncertain, 26-50 CL moderate, 51-100 CL high, >100 CL very high, noting >25 CL approximates a positive scan. Cox proportional hazards analysis and linear mixed effect models were used to assess risk of progression and cognitive decline.Results:Aβ levels in 63% were negative, 10% uncertain, 10% moderate, 14% high and 3% very high. Fifty-seven (11%) progressed to MCI or dementia. Compared to negative Aβ, the hazard ratio for progression for moderate Aβ was 3.2 (95% CI 1.3-7.6; p<0.05), for high was 7.0 (95% CI 3.7-13.3; p<0.001) and for very high was 11.4 (95% CI 5.1-25.8; p<0.001). Decline in cognitive composite score was minimal in the moderate group (-0.02 SD/year, p=0.05) while the high and very high declined substantially (high -0.08 SD/year, p<0.001; very high -0.35 SD/year p<0.001).Conclusion:The risk of MCI or dementia over 5 years in older CN is related to Aβ level on PET, 5% if negative vs 25% if positive but ranging from 12% if 26-50 CL to 28% if 51-100 CL and 50% if >100 CL. This information may be useful for dementia risk counselling and aid design of preclinical AD trials.

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Severe forms of neurocysticercosis: treatment with albendazole

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x1996000100014 ◽

1996 ◽

Vol 54 (1) ◽

pp. 82-93 ◽

Cited By ~ 26

Author(s):

Svetlana Agapejev ◽

Maria Dorvalina da Silva ◽

Anete K. Ueda

Keyword(s):

Intracranial Hypertension ◽

Ventriculoperitoneal Shunt ◽

Severe Form ◽

Cyst Size ◽

Multiple Symptoms ◽

Ivth Ventricle

Study of 22 patients with the severe form of neurocysticercosis treated with albendazole (ABZ) administered in 6 different schedules ranging from 15 to 30 mg/kg/day for 21 to 60 days. Dextrochloropheniramine and ketoprofen were the adjuvant drugs. Multiple symptoms were observed in 90.9% of patients. Intracranial hypertension was manifested in 90.9%. Hydrocephaly occurred in 86.4%. Evolution was satisfactory in 10 patients, 8 died and 4 had sequelae. Tomographic studies showed the appearance of an isolated IVth ventricle in 9 patients, after ventriculoperitoneal shunt, before ABZ treatment in 3 of them, during in 5 and after treatment in one. Median clinical follow-up duration was 10 months for the patients who died and 3-4 years for survivors. In 3 patients there was an increase in cyst size during the administration of the 15 mg/kg/day ABZ dose, which was not observed in any patient when the 30 mg/kg/day dose was used.

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