Rate Of Progression In Patients Research Articles

Neuroinflammation and glycosylation-related cerebrospinal fluid proteins for predicting functional decline in amyotrophic lateral sclerosis: a proteomic study.

The rate of disease progression varies widely among patients with amyotrophic lateral sclerosis (ALS). Prognostic assessment using biomarkers is highly anticipated to improve clinical trial design. We aimed to explore the cerebrospinal fluid (CSF) for prognostic biomarkers to predict future functional decline in patients with ALS. We collected CSF samples from 64 patients with ALS and 25 disease controls. The prospective progression rate was calculated using the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) at CSF collection and in 6 months. The ALS patients were classified into slow, intermediate, and fast progression groups. We performed comprehensive proteomic analyses of the CSF samples. Factors with significant changes between slow and fast progression groups were investigated via receiver operating characteristic curve analyses. Moreover, the correlation of the CSF factors with progression rate was evaluated by multiple regression analyses. In total, 26 proteins changed significantly (p < 0.05 and q < 0.10), with levels varying within a large dynamic range (fold change of >1.5 or < 0.5). A receiver operating characteristic curve analyses showed that the following proteins showed high discrimination power between slow and fast progression groups: glycoprotein non-metastatic melanoma protein B (GPNMB; area under the curve [AUC], 0.88), glial fibrillary acidic protein (AUC, 0.81), glypican-1 (GPC1; AUC, 0.79), alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (AUC, 0.74), and chitinase-3-like protein 2 (CHI3L2; AUC, 0.73). Of these, GPNMB, GPC1, and CHI3L2 were significantly correlated to prognostic progression rate. This study demonstrated that CSF levels of neuroinflammation and glycosylation-related proteins were significantly correlated with prospective progression rates in patients with ALS. These proteins could be useful prognostic biomarkers for ALS.

The Tissue Systems Pathology Test Objectively Risk-Stratifies Patients With Barrett's Esophagus: Results From a Multicenter US Clinical Experience Study.

Barrett's esophagus (BE) is a diagnosis of esophageal intestinal metaplasia, which can progress to esophageal adenocarcinoma (EAC), and guidelines recommend endoscopic surveillance for early detection and treatment of EAC. However, current practices have limited effectiveness in risk-stratifying patients with BE. This study aimed to evaluate use of the TSP-9 test in risk-stratifying clinically relevant subsets of patients with BE in clinical practice. TSP-9 results for tests ordered by 891 physicians for 8080 patients with BE with clinicopathologic data were evaluated. Orders were from nonacademic (94.3%) and academic (5.7%) settings for nondysplastic BE (NDBE; n=7586; 93.9%), indefinite for dysplasia (IND, n=312, 3.9%), and low-grade dysplasia (LGD, n=182, 2.3%). The TSP-9 test scored 83.2% of patients with low risk, 10.6% intermediate risk, and 6.2% high risk, respectively, for progression to HGD/EAC within 5 years. TSP-9 provided significant risk-stratification independently of clinicopathologic features, within NDBE, IND, and LGD subsets, male and female, and short- and long-segment subsets of patients. TSP-9 identified 15.3% of patients with NDBE as intermediate/high-risk for progression, which was 6.4 times more than patients with a pathology diagnosis of LGD. Patients with NDBE who scored intermediate or high risk had a predicted 5-year progression risk of 8.1% and 15.3%, respectively, which are similar to and higher than published progression rates in patients with BE with confirmed LGD. The TSP-9 test identified a high-risk subset of patients with NDBE who were predicted to progress at a higher rate than confirmed LGD, enabling early detection of patients requiring management escalation to reduce the incidence of EAC. TSP-9 scored the majority of patients with NDBE as low risk, providing support to adhere to 3- to 5-year surveillance per guidelines.

Durability of immune checkpoint inhibitor (ICI) response following treatment discontinuation in advanced merkel cell carcinoma (MCC).

9596 Background: Advanced MCC has a high response rate to ICI therapy, but the durability of responses once treatment is discontinued remains unclear. We therefore reviewed the long-term outcomes of advanced MCC patients at our institution who discontinued ICI treatment after achieving favorable initial response. Methods: In an IRB-approved single institution retrospective review of advanced MCC patients, we analyzed all patients who received at least one dose of anti-PD(L)1 monotherapy for unresectable or metastatic disease, achieved stable disease (SD) or better, and discontinued treatment for a reason other than disease progression. Duration of response and outcomes of subsequent therapy were assessed. Results: Of 195 advanced MCC patients treated with ICI, we identified 45 who met study criteria. Of these, 21 (47%) had a complete response (CR) to initial ICI treatment, 23 (51%) a partial response (PR) and 1 (2%) SD. Twenty-five (56%) patients discontinued ICI electively and 20 (44%) discontinued due to toxicity. In total, 21 of the 45 patients (47%) experienced disease progression at a median of 11.2 months (range 2.1-22.7 months) from ICI cessation. The median follow-up after ICI discontinuation for patients who have not experienced progression is 22.8 months (5.8-82.0 months). There was a lower rate of progression in patients who achieved CR vs. non-CR (24% vs 67%, p=0.006) and a trend towards a lower rate in those who discontinued electively vs. due to toxicity (36% vs 60%, p=0.14). For patients in whom the molecular subtype was known, there was a higher risk for progression in patients with viral MCC (12 of 16, 75%) compared to UV-associated MCC (4 of 13, 31%, p=0.02). Fifteen of the 21 patients (71%) who experienced progression were rechallenged with ICI therapy, including both single agent (12 patients, 57%) and combination (3, 14%) therapy. The remaining patients received locally-directed therapy only (3, 14%), chemotherapy (1, 5%), declined further treatment (1, 5%), or transferred care and were lost to follow up (1, 5%). Eleven of 15 ICI-retreated patients (73%) achieved an objective response to rechallenge, including all 3 patients who received combination therapy with ipilimumab+nivolumab. Twelve of the 45 patients have expired; 6 due to progressive MCC and remaining 6 known or suspected from unrelated causes. Conclusions: Patients with advanced MCC have a substantial risk of disease progression following treatment discontinuation despite initial favorable ICI response, 47% in our series with a median time to event of 11.2 months, particularly in those that achieve less than a complete response. In the setting of disease progression post-ICI discontinuation, most patients maintain sensitivity to retreatment with the same drug class. Virus-positive MCC may be a risk factor for post-discontinuation relapse, which should be validated in future studies.

Protocol of the Comparison of Intravesical Therapy and Surgery as Treatment Options (CISTO) study: a pragmatic, prospective multicenter observational cohort study of recurrent high-grade non-muscle invasive bladder cancer

BackgroundBladder cancer poses a significant public health burden, with high recurrence and progression rates in patients with non-muscle-invasive bladder cancer (NMIBC). Current treatment options include bladder-sparing therapies (BST) and radical cystectomy, both with associated risks and benefits. However, evidence supporting optimal management decisions for patients with recurrent high-grade NMIBC remains limited, leading to uncertainty for patients and clinicians. The CISTO (Comparison of Intravesical Therapy and Surgery as Treatment Options) Study aims to address this critical knowledge gap by comparing outcomes between patients undergoing BST and radical cystectomy.MethodsThe CISTO Study is a pragmatic, prospective observational cohort trial across 36 academic and community urology practices in the US. The study will enroll 572 patients with a diagnosis of recurrent high-grade NMIBC who select management with either BST or radical cystectomy. The primary outcome is health-related quality of life (QOL) at 12 months as measured with the EORTC-QLQ-C30. Secondary outcomes include bladder cancer-specific QOL, progression-free survival, cancer-specific survival, and financial toxicity. The study will also assess patient preferences for treatment outcomes. Statistical analyses will employ targeted maximum likelihood estimation (TMLE) to address treatment selection bias and confounding by indication.DiscussionThe CISTO Study is powered to detect clinically important differences in QOL and cancer-specific survival between the two treatment approaches. By including a diverse patient population, the study also aims to assess outcomes across the following patient characteristics: age, gender, race, burden of comorbid health conditions, cancer severity, caregiver status, social determinants of health, and rurality. Treatment outcomes may also vary by patient preferences, health literacy, and baseline QOL. The CISTO Study will fill a crucial evidence gap in the management of recurrent high-grade NMIBC, providing evidence-based guidance for patients and clinicians in choosing between BST and radical cystectomy. The CISTO study will provide an evidence-based approach to identifying the right treatment for the right patient at the right time in the challenging clinical setting of recurrent high-grade NMIBC.Trial registrationClinicalTrials.gov, NCT03933826. Registered on May 1, 2019.

Does medial branch radiofrequency neurotomy accelerate degenerative lumbar spondylolisthesis compared to natural progression? A cross-sectional cohort study

BackgroundLumbar radiofrequency neurotomy (LRFN) effectively treats lumbar zygapophyseal joint pain by coagulating medial branch nerves (MBNs) carrying nociceptive signals. MBNs also innervate deep paraspinal muscles. There is a paucity of literature on whether LRFN accelerates the progression of vertebral displacement in patients with degenerative lumbar spondylolisthesis (DLS). ObjectiveCompare the rate of spondylolisthesis progression in adults with DLS who underwent LRFN to the 2% annual rate of progression expected by natural history. DesignCross-sectional cohort study. MethodsConsecutive patients with pre-existing DLS who underwent LRFN for zygapophyseal joint-mediated low back pain were identified. Patient demographics, LRFN procedure details, and radiographic images confirming Meyerding Grade (I-II) spondylolisthesis were collected from electronic medical records. The quantitative magnitude of spondylolisthesis progression and the annualized rate were calculated from pre-and post-LRFN radiographs. Data were analyzed using Wilcoxon signed-rank tests and a linear regression model. Results152 patients (mean age 65.9 ± 12.3 years; 59.2% female) met eligibility criteria and were included in the analyses. Average time to radiographic follow-up was 35.6 ± 24.7 months post-LRFN. The average spondylolisthesis progression rate of 1.63 ± 2.91% per year calculated for the LRFN cohort was significantly lower than the 2% annual rate of progression associated with natural history (p < 0.001). None of the included covariates, such as age, BMI, LRFN laterality, number of levels denervated, or history of prior lumbar spinal surgery, were significantly associated with the average annual rate of progression. ConclusionsOur results suggest that spondylolisthesis progression rate is no different or worse than the expected natural progression rate in patients with pre-existing DLS who have undergone LRFN.

The effect of plasma cortisol on hippocampal atrophy and clinical progression in mild cognitive impairment.

Both elevated cortisol and hippocampal volume have been linked to an increased risk for the development of Alzheimer's disease (AD). This longitudinal study assessed the effects of plasma cortisol on hippocampal atrophy and clinical progression rates in patients with mild cognitive impairment (MCI). Patients with amnestic MCI (n=304) were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) based on availability of baseline plasma cortisol and hippocampal volume measures, assessed at baseline and during follow-ups. We investigated associations between plasma cortisol, hippocampal volume, and risk of clinical progression to AD over a study period of up to 100 months (mean follow-up time 36.8 months) using linear mixed models, Cox proportional hazards models, and Kaplan-Meier estimators. Plasma cortisol predicted greater hippocampal atrophy, such that participants with higher cortisol showed faster decline in hippocampal volume over time (interaction: β=-0.15, p=0.004). Small hippocampal volume predicted a higher risk of clinical progression to AD (haard ratio [HR]=2.15; confidence in terval [CI], 1.64-2.80; p<0.001). A similar effect was not found for cortisol (HR=1.206; CI, 0.82-1.37; p=0.670) and there was no statistical evidence for an interaction between hippocampal volume and cortisol on clinical progression (HR=0.81; CI, 0.57-0.17; p=0.260). Our findings suggest that higher cortisol predicts higher hippocampal atrophy, which in turn is a risk factor for progression to AD. Regulation of the hypothalamic-pituitary-adrenal axis through stress-reducing lifestyle interventions might be a protective factor against hippocampal degeneration at the prodromal stage of AD.

24-Hour Monitoring of Intraocular Pressure Fluctuations Using a Contact Lens Sensor: Diagnostic Performance for Glaucoma Progression.

The purpose of this study was to compare 24-hour intraocular pressure (IOP) related fluctuations monitoring between 2 groups of visual field progression rates in patients with open angle glaucoma (OAG). Cross-sectional study performed at Bordeaux University Hospital. Twenty-four-hour monitoring was performed using a contact lens sensor (CLS; Triggerfish; SENSIMED, Etagnières, Switzerland). Progression rate was calculated using a linear regression of the mean deviation (MD) parameter of the visual field test (Octopus; HAAG-STREIT, Switzerland). Patients were allocated into two groups: group 1 with an MD progression rate <-0.5dB/year and group 2 with an MD progression rate ≥-0.5dB/year. An automatic signal-processing program was developed and a frequency filtering of the monitoring by wavelet transform analysis was used to compare the output signal between the two groups. A multivariate classifier was performed for prediction of the faster progression group. Fifty-four eyes of 54 patients were included. The mean progression rate was -1.09 ± 0.60 dB/year in group 1 (n = 22) and -0.12 ± 0.13 dB/year in group 2 (n = 32). Twenty-four-hour magnitude and absolute area under the monitoring curve were significantly higher in group 1 than in group 2 (group 1: 343.1 ± 62.3 millivolts [mVs] and 8.28 ± 2.10 mVs, respectively, group 2: 274.0 ± 75.0 mV and 6.82 ± 2.70 mVs respectively, P < 0.05). Magnitude and area under the wavelet curve for short frequency periods ranging from 60 to 220 minutes were also significantly higher in group 1 (P < 0.05). The 24-hour IOP related fluctuations characteristics, as assessed by a CLS, may act as a risk factor for progression in OAG. In association with other predictive factors of glaucoma progression, the CLS may help adjust treatment strategy earlier.

Is there a new role for oral therapy to treat peyronie's disease? Commentary on Daily low-dose tadalafil may reduce the penile curvature progression rate in patients with acute Peyronie's Disease: a retrospective comparative analysis.

Is there a new role for oral therapy to treat peyronie's disease? Commentary on Daily low-dose tadalafil may reduce the penile curvature progression rate in patients with acute Peyronie's Disease: a retrospective comparative analysis.

Evaluation of CD4+ cells infiltration as a prognostic factor in cervical intraepithelial neoplasia 2.

To identify candidate predictors for the prognosis of cervical intraepithelial neoplasia 2 (CIN2) lesions and evaluate the prognostic value of the local immune response. One hundred fifteen CIN2 patients were enrolled. The percentage of p16-, minichromosome maintenance complex component 2- or apolipoprotein B mRNA editing enzyme catalytic subunit 3G (APOBEC3G)-positive cells was determined immunohistochemically. Tumor-infiltrating lymphocytes (TILs) in intertumoral lesions were scored using an automated system. CIN3 disease progression and regression rates were estimated by the Kaplan-Meier method. A case-control study was conducted to screen CIN2 prognostic factors in 10 regression and 10 progression patients. Selected factors were examined in a cohort study to determine their prognostic value for CIN2. Among all participants, the cumulative progression and regression rates at 60 months were 0.477 and 0.510, respectively. In the case-control study, p16- and APOBEC3G-positive cells were higher in the progression group (p=0.043, p=0.023). Additionally, CD4+ cell infiltration was enhanced in the regression group (p=0.023). The cohort study revealed a significantly increased progression rate in patients with elevated p16-positive cells (p<0.001), and increased CD4+ TIL infiltration was associated with better regression (p=0.011). Kaplan-Meier analysis according to human papillomavirus (HPV) positivity revealed a greater CIN3 development risk in HPV16-positive patients than in HPV16-negative cases. Finally, multivariate analysis identified HPV16 infection and CD4+ TIL infiltration as independent prognostic factors in CIN2 regression. CD4+ TIL infiltration in intertumoral lesions was related with CIN2 regression. Our findings suggest CD4+ TIL infiltration may be useful for the triage of CIN2 patients.

Daily low-dose tadalafil may reduce the penile curvature progression rate in patients with acute Peyronie's disease: a retrospective comparative analysis.

The aim of this study was to evaluate the clinical outcomes of patients in acute phase of Peyronie's disease (PD) treated with daily low-dose of Tadalafil. An observational retrospective study involving patients in acute phase of PD with erectile dysfunction (ED) was designed. All subjects were offered Tadalafil 5 mg one tablet a day. Men who accepted treatment were compared to patients who refused Tadalafil. Penile curvature progression was chosen as the primary outcome. PD Questionnaire (PDQ) and IIEF-5 scores were selected as secondary outcomes. A total of 191 patients were included in the study (108 intervention vs. 83 control). Penile curvature progression rate was significantly lower in subjects taking Tadalafil at 12 weeks (25.9% vs. 39.7%, p = 0.042). Mean IIEF-5 score improved in the intervention group, becoming significantly higher compared to the observation group at 12 weeks (19.3 vs. 11.2 points, p < 0.001). Mean PDQ-Overall and PDQ-Penile Pain scores only improved in the intervention group and the statistically significant differences at baseline between groups became not statistically significant at 12 weeks (p = 0.001 vs. p = 0.232 and p < 0.001 vs. p = 0.078, respectively). Daily low-dose Tadalafil in patients with acute phase of PD seems to significantly reduce the penile curvature progression rate compared to observation, especially when it is administrated early. It also appears to improve erectile function and PD-related symptoms.

Efficacy of Azacitidine Post-Transplant Maintenance for FLT3-Negative Acute Myeloid Leukemia and Myelodysplastic Syndrome

Introduction: For patients with myeloid malignancies undergoing allogeneic hematopoietic transplantation (alloHCT), disease relapse remains the most common cause of transplant failure and mortality. Treatment of relapse after alloHCT remains extremely challenging. Post-transplant maintenance with fms-like tyrosine kinase 3 (FLT3) inhibitors has shown benefit in preventing relapse in the minority of patients with FLT3 mutated acute myeloid leukemia (AML). For the remaining patients, the efficacy of hypomethylating agents (HMA) as post-transplant maintenance yields conflicting results. There is a paucity of data regarding the role of HMA as post-transplant maintenance administered outside the context of a clinical trial. We aimed to evaluate the efficacy of azacitidine (AZA) as post-alloHCT maintenance in a real-world setting in patients with FLT3-negative AML or myelodysplastic syndrome (MDS). Methods: We conducted a single center retrospective matched-control comparative analysis. The study group (AZA group) included adults, aged ³18, with FLT3-negative AML or MDS who received their first alloHCT between 2013 and 2020; and were treated post-transplant with AZA maintenance therapy, initiated within 180 days after alloHCT. All patients in the AZA group initiated maintenance while in complete remission (CR) without minimal residual disease (MRD), assessed by multi-color flow cytometry. We compared the AZA group to a matched control group of contemporaneous patients with AML or MDS who did not receive any maintenance. We matched the control group according to disease type (AML or MDS), disease risk category (by ELN12 for AML and IPSS-R for MDS) and disease status at transplant. Matched controls were required to have count recovery (ANC>1000 X 106 cells/L and PLT>20K/µL) within ±7 days of initiation of AZA in their counterparts. We excluded controls if they had positive MRD, overt relapse or if they died prior to the initiation of AZA in their counterparts; grade 2-4 acute graft versus host disease (GVHD) within +/-7 days, or chronic GVHD within +/-15 days of initiation of AZA in their counterparts. The primary endpoint was disease progression, evaluated considering death before progression as a competing event. Results: We identified 93 consecutive patients who received AZA maintenance. A total of 357 unique matched controls were identified at a 2/1, 3/1, 4/1 matching ratio for 1 (1%), 13 (14%), and 79 (85%) of cases, respectively. The AZA and control groups had comparable patient and disease characteristics except for older age (median: 61 vs. 57 years, p=0.01) and lower hematopoietic comorbidity index (HCT-CI) (median: 2 vs. 3, p=0.04) in the AZA group (Table 1). Patients in the AZA group received a median of 8 (range 1-60) cycles of AZA. Outcomes were compared starting at the time of initiation of AZA in the case. Median follow-up among surviving patients was 35 and 44 months in the AZA and control groups, respectively. The 3-year cumulative incidence of disease progression was 29% and 33% (HR 0.7, 95% CI 0.4-1.1; p=0.09), respectively. Subset analyses showed that the protective effect of AZA on disease progression was limited to patients with high risk AML or MDS [HR 0.4, 95% CI 0.2-0.8, p=0.009] (Figure 1 B,D).There was no beneficial effect for AZA for patients with low or intermediate risk disease [HR 1.04, 0.6-1.8, p=0.9] (Figure 1 A,C). The use of AZA was also associated with a lower rate (4% vs. 22%, p=0.001) of non-relapse mortality independent of the disease risk category. These effects translated into a significantly superior overall (74% vs. 51%, p<0.001) and progression-free (67% vs. 46%, P<0.001) survival in the AZA group compared to the control group. Results were consistent when the analyses were repeated using a second independently selected matched control group (data not shown). Conclusion: Post-alloHCT AZA maintenance was associated with lower progression rate in patients with high-risk FLT3-negative AML or MDS. This effect is remarkable considering that matched controls had been in MRD-negative CR prior to initiation of AZA in their matched counterparts. Our results also indicate a low rate of non-relapse mortality associated with AZA maintenance which warrants evaluation in prospective studies. Collectively, our data suggest that AZA maintenance should be considered for post-alloHCT maintenance in high risk FLT3-negative AML and MDS patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Predictors and clinical impact of infarct progression rate in the ESCAPE-NA1 trial

BackgroundDetermining infarct progression rate in acute ischemic stroke (AIS) is important for patient triage, treatment decision-making, and outcome prognostication.ObjectiveTo estimate infarct progression rate in patients with AIS with large vessel...

Correlation of weight and body composition with disease progression rate in patients with amyotrophic lateral sclerosis

This study aims to observe the nutritional status of Chinese patients with amyotrophic lateral sclerosis (ALS), further investigating its effect on disease progression. One hundred consecutive newly diagnosed ALS patients and fifty controls were included. Weight and body composition were measured by bioelectrical impedance analysis at baseline and follow-ups. The revised ALS functional rating scale (ALSFRS-R) was used to calculate the rate of disease progression. Patients with ALS had a significantly lower BMI than controls, while no significant difference was found in body composition. Weight loss occurred in 66 (66%) and 52 (67.5%) patients at diagnosis and follow-up, respectively. Patients with significant weight loss (≥ 5%) at diagnosis had significantly lower BMI, fat mass (FM), and FM in limbs and trunk than those without. Fat-free mass (FFM), FM, and FM in limbs were significantly decreased along with weight loss at follow-up (p < 0.01). Patients with lower visceral fat index, lower proportion of FM, and higher proportion of muscle mass at baseline progressed rapidly during follow-ups (p < 0.05). Multivariate linear regression showed that FFM and weight at follow-up were independently correlated with disease progression rate at follow-up (p < 0.05). Weight loss is a common feature in ALS patients, along with muscle and fat wasting during the disease course. Body composition may serve as a prognostic factor and provide guidance for nutritional management in ALS patients.

Progression rates of medulla oblongata infarcts in clinical follow-up: A retrospective study

ObjectiveTo determine clinical progression rates in patients with medulla oblongata infarction (MOI). Materials and methodsThe data of patients diagnosed with MOI were analysed retrospectively. Dermographic characteristics of the patients; Age, gender, history and stroke etiology were evaluated. Radiological imagings were reviewed retrospectively. Intensive care unit (ICU) requirement, number of intubation days, failed extubation and death rates, good clinical outcome at discharge and 3 months [modified Rankin Scale (mRS 0–2)] and poor clinical outcome (mRS 3–6) rates were evaluated. In addition, the clinical results of patients with medial medullary infarction (MMI) and lateral medullary infarction (LMI) were compared. Results33 patients were included in the study, 22 (66.7 %) were male. The mean age of the patients was 72.0 (43.0–85.0). The characteristics of the patients (dermographic features, comorbidities, clinical symptoms, infarct localization, etc.) were evaluated. The results of MMI and LMI patients were compared. The intubation rate was 4 (44.4 %) in the MME group, while it was 8 (33.3 %) in the LME group. There was no statistically significant difference between the two groups in terms of failed extubation, tracheostomy, hospitalization and mortality rates. However, while discharge mRS was statistically significant between the two groups, the mRS at 3 months was not statistically significant. Twelve (36.4 %) of all patients were intubated due to severe clinical progression. In the clinical follow-up, 6 (50.0 %) of the intubated patients died, 3rd month mRS of 6 (50.0 %) patients who survived was 5. In all patients 3-month good clinical outcome rate was % 48,5. ConclusionIt should not be forgotten that life-threatening clinical progressions may develop at a considerable rate during the early treatment process of patients diagnosed with MOI.

Adipose Tissue Distribution as a Predictor of Rate of Progression in Patients with Amyotrophic Lateral Sclerosis (P3-13.008)

Adipose Tissue Distribution as a Predictor of Rate of Progression in Patients with Amyotrophic Lateral Sclerosis (P3-13.008)

Mouse Nerve Growth Factor Injection and Progression Rate in Patients With Amyotrophic Lateral Sclerosis: An Observational Study.

ObjectivesAmyotrophic lateral sclerosis (ALS) is a progressive, fatal disease with no curative treatment up to now. This study aims to analyze ALS progression of patients treated with mouse nerve growth factor (mNGF), as well as the effects, side effects, and adverse events of the therapy.Materials and MethodsA retrospective, observational study was performed including 94 patients with ALS from July 2020 to July 2021. Thirty-two of them were treated with at least one course of mNGF on a regular riluzole use, and the rest 62 were treated with riluzole only. The declining rates of body mass index (BMI) and ALS Functional Rating Scale-Revised (ALSFRS-R) scores were compared between the two groups to indicate ALS progression.ResultsNo significant differences in ALS progression indicated by the declining rates of BMI and ALSFRS-R score were observed between the two cohorts. ALS progression before and after the first treatment course of mNGF also showed no discernible difference. However, we noticed a moderate 62.7 and 25.1% reduction in the declining rate of BMI and ALSFRS-R motor subscore when comparing mNGF + riluzole treatment to riluzole only. The mNGF treatment was overall safe and well-tolerated, and a rare case of diarrhea was reported after mNGF injection.ConclusionsOur study revealed that mNGF treatment was overall safe and well-tolerated in patients of ALS. Application of mNGF combined with regular riluzole treatment had no significant clinical effects on delaying ALS progression. Prospective cohort studies and randomized clinical trials based on larger cohorts and longer follow-up times are needed to make a more convincing conclusion.

Poor Prognosis With Intravesical Bacillus Calmette-Guérin History After Photodynamic Diagnosis-assisted Transurethral Resection Using 5-Aminolevulinic Acid.

Diagnostic efficacy and treatment outcome of orally administered 5 aminolevulinic acid (ALA) assessment for photodynamic diagnosis (PDD) in transurethral resection for non-muscle-invasive bladder cancer (NMIBC) in clinical practice. A retrospective analysis was performed of 105 patients who underwent PDD transurethral resection using orally administered ALA and were pathologically diagnosed with Ta, T1, or Tis at the Ishikawa Prefectural Central Hospital from December 2018 to May 2022. Fluorescent light had a significantly higher sensitivity but a lower specificity in detecting carcinoma compared to white light (91.7% vs. 77.1%; p<0.05 and 43.0% vs. 85.2%; p<0.05, respectively), as well as in detecting carcinoma in situ lesions (80.4% vs. 28.6%; p<0.05 and 23.3% vs. 84.5%; p<0.05, respectively). The cumulative frequency of recurrence and progression 1 year after treatment were 26.3% and 12.3%, respectively. Multivariate analyses indicated that a Bacillus Calmette-Guérin (BCG) history instillation was an independent predictive factor for intravesical recurrence (hazard ratio=4.439; p=0.002) and disease progression (hazard ratio=8.534; p=0.005). The 1-year cumulative recurrence rates were 66.2% and 16.5%, respectively (p<0.001), and progression rates for patients with and without prior BCG intravesical instillation were 50.4% and 3.5%, respectively (p<0.001). Sufficient diagnostic accuracy and relatively good treatment outcome was shown in PDD-transurethral resection using ALA. However, prior BCG intravesical instillation for NMIBC patients was a poor prognostic factor of cancer recurrence and progression, and may be useful for clinicians in their postoperative follow-up.

Automatic identification of MCI progressors significantly reduces the number of subjects in clinical trials

AbstractBackgroundAccurately predicting the progression rate in patients with mild cognitive impairment and mild dementia due to AD enables enrichment of trial populations. Here, we evaluate the potential use of our prognostic model (Abstract #54217) as a screening tool for enrichment in clinical trials in early AD.MethodData included 312 patients with mild AD from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and were chosen based on the Clinical Dementia Rating (CDR=0.5) and the Mini‐Mental State Exam (MMSE, range 24‐30) scores. We classified subjects into stable and progressive (defined by at least a 2‐point increase in CDR‐SB) using our automatic classification tool. Required sample sizes to detect a reduction in the mean annual rate of cognitive decline based on CDR‐SB score were estimated. We corrected for the annualized decline due to normal aging so as not to overestimate the benefit of enrichment when computing the treatment effect. We estimated and compared sample sizes for two groups of subjects: Using data from the mild AD subjects in the ADNI dataset that fit the selection criteria above (the unenriched group) and using only the subset of those ADNI MCI subjects identified as pMCI using baseline data and the classifier described above (the enriched group).ResultFigure 1 shows the required sample sizes for different treatment effects for both unenriched and enriched MCI cohorts. Using the unenriched group of MCI subjects, power analysis shows that 1075 subjects are required in a 2‐year (764 subjects for a 3‐year) trial of therapy with a hypothesized 25% effect size (80% power and 5% significance level) to reduce cognitive decline. When using the enriched cohort of MCI subjects, only 279 subjects are required for a 2‐year (373 for 3‐year) trial (solid lines in Fig. 3). These results demonstrate that enrichment using baseline HC, MoCA, ADAS‐13 and MMSE yields a 3.8‐fold decrease in the sample size for a 2‐year study (2.8‐fold decrease for a 3‐year study).ConclusionEnriching clinical trial cohorts of subjects in the early stages of AD with a higher chance of functional and cognitive decline will improve efficiency with smaller, faster, less expensive trials.

Is nighttime bracing effective in the treatment of adolescent idiopathic scoliosis? A meta-analysis and systematic review based on scoliosis research society guidelines

Standard treatment for skeletally immature adolescents with moderate Adolescent Idiopathic Scoliosis (AIS) is a full-time spinal orthosis. However, adherence to full-time wear (≥ 18h/day) is often challenging for these patients. Nighttime bracing is an alternative option that may improve patient adherence and/or satisfaction. This systematic review and meta-analysis assessed the effectiveness of nighttime bracing in patients with AIS. A systematic review of studies evaluating nighttime bracing was performed. PubMed, Medline, Embase, CINAHL and Cochrane library databases were searched (01/1975-03/2020); two reviewers assessed eligibility. Eligible articles were peer reviewed, in English, and reported outcomes for patients who met Scoliosis Research Society (SRS) criteria. The primary outcome was curve progression ≥ 6°. Pooled progression rates were calculated from random effects meta-analyses with inverse-variance weights; 95% CIs were calculated. Nine studies (n = 595) were included. The overall pooled progression rate to ≥ 6° was 40.7% (95% CI: 30.4-51.5%). The pooled progression rate to surgical magnitude was 24.8% (95% CI: 4.5-53.6%). The most successful outcomes were in subjects with thoracolumbar/lumbar curves and subjects who initiated bracing at Risser 1/2 (pooled progression rates were 27.8% (95% CI: 17.0-40.0%) and 16.5% (95% CI: 11.7-21.8%), respectively). Univariate sub-analyses were conducted due to sample sizes. Progression rates in patients with primary thoracolumbar/lumbar curves and in patients who initiated nighttime bracing at Risser 1/2 were comparable to published progression rates for full-time bracing, indicating that nighttime bracing may be equally effective for these patients. However, the strength of these conclusions is limited by the sample size and the overall quality of included studies.

Disruption of the white matter structural network and its correlation with baseline progression rate in patients with sporadic amyotrophic lateral sclerosis

ObjectiveThere is increasing evidence that amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease impacting large-scale brain networks. However, it is still unclear which structural networks are associated with the disease and whether the network connectomics are associated with disease progression. This study was aimed to characterize the network abnormalities in ALS and to identify the network-based biomarkers that predict the ALS baseline progression rate.MethodsMagnetic resonance imaging was performed on 73 patients with sporadic ALS and 100 healthy participants to acquire diffusion-weighted magnetic resonance images and construct white matter (WM) networks using tractography methods. The global and regional network properties were compared between ALS and healthy subjects. The single-subject WM network matrices of patients were used to predict the ALS baseline progression rate using machine learning algorithms.ResultsCompared with the healthy participants, the patients with ALS showed significantly decreased clustering coefficient Cp (P = 0.0034, t = 2.98), normalized clustering coefficient γ (P = 0.039, t = 2.08), and small‐worldness σ (P = 0.038, t = 2.10) at the global network level. The patients also showed decreased regional centralities in motor and non-motor systems including the frontal, temporal and subcortical regions. Using the single-subject structural connection matrix, our classification model could distinguish patients with fast versus slow progression rate with an average accuracy of 85%.ConclusionDisruption of the WM structural networks in ALS is indicated by weaker small-worldness and disturbances in regions outside of the motor systems, extending the classical pathophysiological understanding of ALS as a motor disorder. The individual WM structural network matrices of ALS patients are potential neuroimaging biomarkers for the baseline disease progression in clinical practice.