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Objectives: To investigate the effect of vestibular rehabilitation exercises supported with virtual reality containing real-life environments on dizziness, static and dynamic balance, functional mobility, fear of falling, anxiety, and depression in elderly patients with dizziness. Methods: In this prospective randomized controlled study, 32-patients aged 65-years and older who applied to the otorhinolaryngology clinic with dizziness complaint randomly assigned to 2 groups. In Group 1 (n = 16), vestibular rehabilitation program, supported with virtual reality, and in Group 2 (n = 16), conventional vestibular rehabilitation program was applied 30-min a day, 5 sessions per week, 15 sessions in total for 3 weeks. Subjects were evaluated with The Vertigo Symptom Scale (VSS), Dizziness Handicap Inventory (DHI), Berg Balance Test (BBT) and Timed Up & Go Test (TUG), Falls Efficacy Scale-International (FES-I), Postural Stability Test (PST), Geriatric Depression Scale (GDS), Hamilton Anxiety Scale (HAS) at baseline, at the end of the treatment and 6-months after the treatment. Results: Statistically significant improvements were seen in the DHI emotional subscale and TUG in Group 1 compared to Group 2 at the end of the treatment in elderly with dizziness (p < 0.05). Also, there were significant improvements in the VSS, all DHI subgroups, and total scores, BBT, HAS in Group 1 compared to Group 2 at the 6-months after the treatment (p < 0.05). Conclusion: The application of vestibular rehabilitation in a virtual reality environment can lead to additional improvements especially in dizziness symptoms, disability, balance, and mobility in the elderly with chronic dizziness. © 2021 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial

Prior studies have reported increased cortical excitability in people with Alzheimer’s disease (AD), but findings have been inconsistent, and how excitability relates to dementia severity remains incompletely understood. The objective of this study was to investigate the association between a transcranial magnetic stimulation (TMS) measure of motor cortical excitability and measures of cognition in AD. A retrospective cross-sectional analysis tested the relationship between resting motor threshold (RMT) and the Alzheimer’s Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) across two independent samples of AD participants (a discovery cohort, n=22 and a larger validation cohort, n=129) and a control cohort of cognitively normal adults (n=26). RMT was correlated with ADAS-Cog in the discovery-AD cohort (n=22, β=−.70, p

Background: Crohn’s disease (CD) is a chronic inflammatory disorder affecting the gastrointestinal tract with disease behaviour based on the depth and severity of mucosal injury. Cumulative injury can result in complications including stricture formation and penetrating complications which often require surgical resection of diseased segments of the intestine resulting in significant morbidity. Accurate assessment of disease activity and appropriate treatment is essential in preventing complications. Summary: Treatment targets in the management of CD have evolved with the advent of more potent immunosuppressive therapy. Targeting the resolution of sub-clinical inflammation and achieving mucosal healing is associated with the prevention of stricturing and penetrating complications. Identifying non-invasive modalities to assess mucosal healing remains a challenge. Key Messages: Mucosal healing minimizes the risk of developing disease complications, prolongs steroid-free survival, and reduces hospitalization and the need for surgical intervention.

PURPOSE OF REVIEW Treat-to-target (T2T) approach has improved outcomes in chronic diseases. The aim of this review is to discuss the long-term goals and review the evidence for possible targets that would predict the achievement of these goals for developing a T2T strategy for Behcet's syndrome. RECENT FINDINGS There are no trials comparing a tight control strategy to standard care in Behcet's syndrome but recent studies suggest better outcomes with earlier use of biologic agents compared with sustained conventional treatment. Fluorescein angiography may be a reliable tool for assessing remission in uveitis as fluorescein angiography findings were shown to predict relapses and long-term visual outcome. Good recanalization on Doppler ultrasonography can be a target for venous involvement as this was the only predictor of relapse. Fecal calprotectin levels were associated with small intestinal and colonic ulcers and may be used as a surrogate for remission of gastrointestinal involvement. SUMMARY There are several new treatment modalities that are tried for Behcet's syndrome and ongoing work on outcome measures for reliable disease assessment. In order to ensure the wise and efficient use of treatment modalities, development and implementation of T2T strategies are needed through multidisciplinary and multinational efforts that include patient research partners.

Objectives This study sought to determine the level of understanding and opinion among rheumatologist and pulmonologists regarding risk factors, diagnostic approach and treatment of RA-associated interstitial lung disease (RA-ILD). Methods We conducted an international electronic survey of rheumatologists and pulmonologists utilizing two separate Redcap-based surveys with questions on the epidemiology, workup and management of RA-ILD as well as ILD screening questions using case-based scenarios directed at rheumatologists. The survey also collected demographic data on participants including their practice setting, years in practice and country of practice. Results We received a total of 616 responses (354 rheumatologists and 262 pulmonologists) from six continents. There were significant differences in responses between pulmonologists and rheumatologists in estimated prevalence and mortality, risk factors for the development of ILD in RA and medications that are effective or should be avoided. Rheumatologists were much less likely to consider assessment for ILD in high risk, asymptomatic patients compared with high-risk patients with either symptoms or exam findings suggestive of ILD. Conclusion Our study brought to light the variability in disease assessment and clinical practice among providers caring for patients with RA-ILD and indicate that greater education is needed to optimize clinical decision making in the risk assessment, screening and treatment of RA-ILD. Research questions that address appropriate screening and treatment strategies for RA-ILD will be valuable for rheumatologists given their central role in the overall health and lung health of patients with RA.

Detectable minimal residual disease (MRD) after therapy for acute lymphoblastic leukemia (ALL) is the strongest predictor of hematologic relapse. The objective of the study was to assess disease-free survival (DFS) and overall survival (OS) of patients with ALL according with MRD status at the end of induction therapy in a Colombian population.We assessed a retrospective cohort to compare DFS and OS in adults with de novo ALL according to MRD status at the end of induction chemotherapy, and the type of postinduction consolidation strategy used.A total of 165 adults with ALL were included in the MRD part of the study, 73 patients in the MRD-negative group and 92 in the MRD-positive group. Median DFS for the MRD-positive group was 11 months (95% confidence interval, 11.7-22.2) and was not reached for the MRD-negative group (P .001). At 3 years, DFS was 18% and 55%, respectively (P .001). The median OS for MRD-positive patients was 16 months (95% confidence interval, 8.8-23.15) and was not reached in the MRD-negative group. At 3 years, OS was 26% and 51% for the former and latter group, respectively. Among subjects who did not receive a transplant, median DFS was 21 months for MRD-negative patients and 9 months for MRD-positive patients (P .001). The median DFS was not reached in either group, whereas 3-year DFS was 64% for MRD-negative and 70% for MRD-positive patients who underwent transplantation in first remission (P = .861).MRD status at the end of induction is an independent prognostic factor for DFS and OS in adult ALL. Allogeneic transplantation in first remission could overcome the adverse prognostic impact of MRD.

Natural killer T-cell lymphoma (NKTCL) is an aggressive type of non-Hodgkin’s lymphoma. While FDG-PET/CT imaging has been increasingly utilized for disease assessment, its prognostic value and potential utility in NKTCL patient stratification remain controversial. We aim to investigate the prognostic utility of FDG-PET/CT and its role in complementing clinical indices. We conducted a retrospective review of 72 patients from a tertiary National Cancer Centre with biopsy-proven NKTCL and available FDG-PET/CT data (either baseline, end of treatment or both). Survival analysis was performed using the Kaplan–Meier method and multivariable Cox proportional regression. High initial SUVmax was significantly associated with advanced Ann-Arbor stage (p = 0.0352), elevated LDH levels (p = 0.0059) and plasma EBV DNA detection (p = 0.0278). SUVmax correlated with worse progression-free survival (PFS) (HR 3.68, 95% CI 1.56–8.69, p = 0.0030) and a trend toward worse overall survival (OS) (HR 2.06, 95% CI 0.95–4.45, p = 0.0676). End of treatment Deauville scores of 4–5, as compared to scores of 1–3, was associated with worse PFS (HR 2.72, 95% CI 1.04–7.12, p = 0.0419). Notably, while all patients with scores of 5 developed progressive disease, only 2 of 5 patients with scores of 4 eventually relapsed. Clinical indices (NABS score) were still able to stratify survival outcomes regardless of end-of-treatment Deauville scores. A Deauville score of 5 is more diagnostic of true disease progression than a score of 4, and NABS score may be used in patients who achieve Deauville scores of 1–3 for further risk stratification. A higher SUVmax at baseline portends a worse prognosis in NKTCL.

Purpose To investigate the predictive significance of different pneumonia scoring systems in clinical severity and mortality risk of patients with severe novel coronavirus pneumonia. Materials and methods A total of 53 cases of severe novel coronavirus pneumonia were confirmed. The APACHE II, MuLBSTA and CURB-65 scores of different treatment methods were calculated, and the predictive power of each score on clinical respiratory support treatment and mortality risk was compared. Results The APACHE II score showed the largest area under ROC curve in both noninvasive and invasive respiratory support treatment assessments, which is significantly different from that of CURB-65. Further, the MuLBSTA score had the largest area under ROC curve in terms of death risk assessment, which is also significantly different from that of CURB-65; however, no difference was noted with the APACHE II score. Conclusion For patients with COVID, the APACHE II score is an effective predictor of the disease severity and mortality risk. Further, the MuLBSTA score is a good predictor only in terms of mortality risk.

Objective: To share experience of 1000 patients who underwent functional endoscopic sinus surgery (FESS) in 4different hospitals for various diseases over span of 9 years. Study Design: Prospective observational study. Place and Duration of Study: Sheikh Khalifa Hospital Muzaffarabad, Combined Military Hospital Sialkot, PakEmirates Military Hospital Rawalpindi and CMH Quetta, from Jun 2009 to Jun 2018. Methodology: We included 1000 patients who underwent Functional endoscopic sinus surgery (FESS) in fourdifferent military hospitals, suffering with various diseases discussed later. Patients were operated after failureto get response to medical therapy. All the patients had preoperative endoscopic examination and CT-scan paranasal sinuses (PNS) done for disease assessment. Patients were examined post operatively at 1, 15 days and 2 months. All patients were documented for the level of satisfaction at end of 2 months post-operative period. Results: Most patients were suffering from rhino sinusitis 364 (36.4%). Bilateral ethmoidal polyps constitutedthe second largest group at 289 (28.9%) patients. About 837 (83.7%) of patients were completely free of symptom, 104 (10.4%) with partial improvement whereas, 59 (5.9%) patients did not report any improvement in symptoms. 899 (89.9%) of patients were discharged on their first post operation day meaning less hospital stay and quick recovery.Conclusion: Functional endoscopic sinus surgery (FESS) can be employed to treatment variety of common nasal diseases (chronic rhino-sinusitis, nasal polyps) & non-nasal diseases like cerebrospinal fluid (CSF) rhinorrhea & as approach to skull base. This method of treatment was quite effective in alleviating symptoms of patients.

INTRODUCTION Many new markers are being evaluated to increase the sensitivity and applicability of multicolor flow cytometry (MFC)-based measurable residual disease (MRD) monitoring. However, most of the studies are limited to childhood B-cell lymphoblastic leukemia/lymphoma (B-ALL), and reports in adult B-ALL are extremely scarce and limited to small cohorts. We studied the expression of CD304/neuropilin-1 in a large cohort of adult B-ALL patients and evaluated its practical utility in MFC-based MRD analysis. METHODS CD304 was studied in blasts from adult B-ALL patients and normal precursor B cells (NPBC) from non-B-ALL bone marrow samples using MFC. CD304 expression intensity and pattern were studied with normalized-mean fluorescent intensity (nMFI) and coefficient of variation of immunofluorescence (CVIF), respectively. MFC-based MRD was performed at end of induction (EOI; day-35), end of consolidation (EOC; day 78-80), and subsequent follow-up (SFU) time points. RESULTS CD304 was positive in 120/214(56.07%) and was significantly associated with BCR-ABL1 fusion (P = .001). EOI-MRD and EOC-MRD were positive in 129/214(60.3%) and 50/81(61.72%), respectively. CD304 was positive in a significant percentage of EOI (48%, 62/129) and EOC (52%, 26/50) MRD-positive B-ALL samples. Its expression was retained, lost, and gained in 73.7%, 26.3%, and 11.3% of EOI-MRD and 85.7%, 14.3%, and none of EOC-MRD samples, respectively. Low-level MRD (

In recent years, 18F-Sodium Fluoride (NaF)-PET/CT has seen its role in the detection and management of osteoporosis increase. This article reviews the extent of this application in the literature, its efficacy compared with other comparable imaging tools, and how total-body PET/CT combined with global disease assessment can revolutionize measurement of total osteoporotic disease activity. NaF-PET/CT eventually can be the modality of choice for metabolic bone disorders, especially with these advances in technology and computation.

PET with 18F-fluorodeoxyglucose (FDG) is used to assess a wide array of inflammatory and neoplastic disorders. FDG-PET has shown particular utility in the evaluation of disorders of the central nervous system (CNS). Although fused PET/computed tomography (CT) is frequently used across the globe for these diseases, recent evidence has pointed to PET/magnetic resonance (MR) imaging as a more sensitive and specific molecular imaging modality. This article reviews the literature regarding the advantages of PET/MR imaging compared with PET/CT imaging, especially in CNS disease. It also introduces a new concept for PET-based evaluation of patients with neurodegenerative disorders: global disease assessment.

OBJECTIVE To assess the relationship between measures of disease assessment in patients with large vessel vasculitis. METHODS Patients with giant cell arteritis (GCA) or Takayasu arteritis (TAK) were recruited into a prospective, observational cohort. Assessments within the following outcomes were independently recorded: 1) patient-reported outcomes (Multidimensional Fatigue Inventory, patient global assessment of disease activity [PtGA], Short Form 36 health survey [SF-36], Brief Illness Perception Questionnaire), 2) physician global assessment of disease activity (PhGA), 3) laboratory outcomes (C-reactive protein [CRP] level, erythrocyte sedimentation rate [ESR]), and 4) imaging outcomes (PETVAS, a qualitative score of vascular 18 F-fluorodeoxyglucose-positron emission tomography activity). RESULTS Analyses were performed on 112 patients (GCA = 56, TAK = 56), over 296 visits, with a median follow-up of 6 months. Correlation network analysis revealed assessment measures clustered independently by type of outcome. PhGA was centrally linked to all other outcome types, but correlations were modest (ρ = 0.12-0.32; P < 0.05). PETVAS, CRP level, and PtGA were independently associated with clinically active disease. All 4 patient-reported outcomes strongly correlated with each other (ρ = 0.35-0.60; P < 0.0001). Patient-reported outcomes were not correlated with PETVAS, and only PtGA correlated with CRP level (ρ = 0.16; P < 0.01). Patients whose clinical assessment changed from active disease to remission (n = 29) had a corresponding significant decrease in ESR, CRP level, and PETVAS at the remission visit. Patients whose clinical assessment changed from remission to active disease (n = 11) had a corresponding significant increase in CRP level and PtGA at the active visit. CONCLUSION Measures of disease assessment in large vessel vasculitis consist of independent, yet complementary, outcomes, supporting the need to develop composite outcome measures or a standard set of measures covering multiple types of outcomes.

Introduction Studies have demonstrated the high agreement of several remote neuropsychological tests using video teleconferencing (VTC) with face-to-face (FTF) tests. However, the reliability of the remotely administered Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS-cog), one of the most commonly used neuropsychological tests to detect cognitive decline, has not been substantially elucidated, particularly in Japanese populations. Therefore, this study aimed to evaluate the reliability of the remotely administered ADAS-cog compared with FTF-administered ADAS-cog among elderly Japanese participants. Methods Participants aged ≥60 years with and without cognitive impairment, i.e. those with mild cognitive impairment (MCI), those with dementia and healthy controls (HCs), were assessed with the ADAS-cog using VTC and FTF testing at an interval of >2 weeks and Results A total of 73 participants were included in the study (36 men; age, 76.3 ± 7.6 years). The ICC for the ADAS-cog total score was high in the entire sample (0.86), whereas ICCs were moderate to high for the subgroups (MCI: 0.63, dementia: 0.80 and HC: 0.74). Discussion The results indicate that a VTC-administered ADAS-cog could be an alternative for an FTF-administered ADAS-cog, although further replication studies with larger sample sizes and a wider range of cognitive functionalities are warranted.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) has been changing for nearly 20 years. GOLD has moved from single assessment using spirometry to a more comprehensive assessment of chronic obstructive pulmonary disease using spirometry, symptoms and exacerbation history. And subsequently, a new assessment system for chronic obstructive pulmonary disease separated spirometric grades from the old assessment system, and classified patients only according to their symptoms and history of exacerbation. The distribution, clinical characteristics, treatment, and prognosis of the new subgroups were different from the old ones. In this review, we will present a brief profile of changes made to the disease assessment method of GOLD, based on the relevant existing literature.

Artificial intelligence (AI) has been studied in ophthalmology since availability of digital information in ophthalmic care. The significant turning point was availability of commercial digital color fundus photography in the late 1990s, which caused digital screening for diabetic retinopathy (DR) to take off. Automated Retinal Disease Assessment software was then developed using machine learning to detect abnormal lesions in fundus to screen DR. The use of this version of AI had not been generalized because the specificity at 45% was not high enough, although the sensitivity reached 90%. The recent breakthrough in machine learning is the invent of deep learning, which accelerates its performance to be on par with experts. The first 2 breakthrough studies on deep learning for screening DR were conducted in Asia. The first represented collaboration of datasets between Asia and the United States for algorithms development, whereas the second represented algorithms developed in Asia but validated in different populations across the world. Both found accuracy for detecting referable DR of >95%. Diversity and variety are unique strengths of Asia for AI studies. There are many more studies of AI ongoing in Asia not only as prospective deployments in DR but in glaucoma, age-related macular degeneration, cataract, and systemic disease, such as Alzheimer's disease. Some Asian countries have laid out plans for digital health care system using AI as one of the puzzle pieces for solving blindness. More studies on AI and digital health are expected to come from Asia in this new decade.

There is a lack of an international consensus on adenomyosis classification that is useful for clinical practice and research. This article reviews advancements in the classification of adenomyosis, and the existing limitations. We collected a literature search from PubMed and Embase database up to March 2019. The proposed adenomyosis classification is based on magnetic resonance imaging and clinically relevant parameters. Adenomyosis is not a disease of homogeneity but is composed of multiple heterogeneous subtypes. Adenomyosis represents a spectrum of lesions, ranging from increased thickness of the junctional zone to focal or diffuse lesions involving the entire uterine wall. Potentially important parameters to be included in the classification could be affected area (internal or external adenomyosis), pattern (focal or diffuse), size or volume (myometrial involvement 2/3 of uterine wall), concomitant pathologies (none, peritoneal endometriosis, ovarian endometrioma, deep infiltrating endometriosis, uterine fibroids, or others) and localization (anterior, posterior, left lateral, right lateral, or fundal). We propose a simplified classification system to monitor symptom severity against morphological types or extent of adenomyosis using the combination of previously published classifications as a starting point. More studies are needed to investigate whether this classification represents a useful tool for disease assessment in clinical practice and research.

Introduction: Executive dysfunction is common in dementia with Lewy bodies (DLB). The pulvinar nucleus plays a role in executive control and synchronizes with cortical regions in the salience network that are vulnerable to Lewy pathology. Objective: We investigated the pulvinar subregions in patients with mild DLB and their associations with executive function. Methods: The sample consisted of 38 DLB patients and 38 age- and sex-matched normal controls. We evaluated cognitive function using the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet. We obtained four pulvinar nuclei using preprocessed T1-weighted magnetic resonance images. We compared volumes and textures of the DLB patients and the normal controls for each nucleus. We used a linear regression to determine the association of textures and neuropsychological test scores. Results: The DLB patients showed comparable volumes to the normal controls in all pulvinar nuclei. However, the DLB patients showed different texture of the left medial pulvinar (PuM) from the normal controls. The entropy, contrast, and cluster shade were lower but autocorrelation of left PuM was higher in the DLB patients compared to the normal controls. These texture features of the left PuM were associated with the set-shifting performance measured by the Trail Making Test. Conclusions: In DLB, the left PuM may be altered from early stage, which may contribute to the development of executive dysfunction.

The objective of this research is to identify the relationship between the neuropsychiatric symptoms (NPSs) of patients with major neurocognitive disorder (mNCD), their quality of life, illness intrusiveness and the caregiver’s burden. We assessed 131 patients with mNCD. Examination methods included WHO well-being index short version, illness intrusiveness rating scale, Alzheimer’s Disease Assessment Scale-Cog, Mini Mental State Examination and neuropsychiatric inventory. The results were analysed using standard statistical tests. In our sample, the prevalence of NPSs is 100%. A significant correlation (p < 0.0001) was observed with quality of life and illness intrusiveness. Additionally, a strong relationship was observed between NPSs and the caregiver’s burden (r = 0.9). The result is significantly twice as much stronger in comparison to the relationship between NPS and cognitive symptoms (r = 0.4). This is the first study in Hungary to assess the impact of NPS on the burden of relatives and quality of life. NPS had twice stronger impact on caregivers’ burden than cognitive decline. However, further studies are needed to assess the sub-syndromes in mNCD in relation to NPS.

Objectives Right ventricular (RV) failure with pulmonary hypertension (PH) is frequently encountered in patients with advanced left-sided heart disease (LHD). However, RV energetics in patients with postcapillary PH because of LHD has not been well studied. The authors investigated intraoperative RV energetics in patients with PH due to LHD based on pressure–volume curves with three-dimensional transesophageal echocardiography and pulmonary artery catheterization. Design Exploratory study. Setting National center. Participants Thirty-three patients who underwent cardiac surgery for LHD were enrolled. Ten patients had PH (mean pulmonary artery pressure ≥ 25 mmHg). Interventions None. Measurements and Main Results RV stroke work index (RVSWI) was calculated by integrating the area bounded by the pressure–volume curve. RV minute work index (RVMWI) was calculated as RVSWI × heart rate. Right ventriculo-arterial coupling was estimated as stroke volume divided by end-systolic volume (SV/ESV). The authors compared RV energetics between patients with and without PH because of LHD. RVSWI and RVMWI were significantly higher in patients with PH (690.7 mmHg·mL/m2 [601.6-737.1] v 440.9 mmHg·mL/m2 [330.8-585.3], p = 0.015, and 60,068 mmHg·mL/m2/min [35,547-68,741] v 26,351 mmHg·mL/m2/min [17,316-32,517], p = 0.011, respectively), although cardiac index was nearly identical. SV/ESV was significantly lower in patients with PH (0.520 [0.305-0.810] v 0.820 (0.650-1.090), p = 0.007). Conclusions Although cardiac index was similar, RVSWI and RVMWI were significantly higher and SV/ESV was significantly lower in patients with PH because of LHD, suggesting that patients with postcapillary PH have inefficient RV performance.

Background: Mild cognitive impairment (MCI) is a global-scale issue, due in large part to the rapidly growing elderly population. The main polyphenol contained in coffee beans, chlorogenic acid (CGA), improves attention in healthy individuals. The utility of CGAs for treating MCI, however, has not been evaluated. Objective: To determine the effects of continuous CGA intake on cognitive function, especially attention, in patients diagnosed with MCI. Methods: The study was a randomized controlled crossover trial including 34 patients with MCI. Participants were randomly divided into two groups: Those who first ingested a placebo beverage and those who first ingested an active beverage containing CGAs (553.6 mg/bottle) twice daily for 12 weeks. After a 4-week washout period, the subjects ingested the other beverage (i.e., placebo or active beverage) in the same manner. Endpoint measures included scores on the Japanese version of the Mini-Mental State Examination (MMSE), the Japanese version of the Alzheimer’s Disease Assessment Scale-cognitive component (ADAS-cog) testing overall cognitive function, and the Japanese version of the Trail Making Test (TMT-A, TMT-B) testing attention, along with the results of blood tests to evaluate safety. Results: In the TMT-B test, participants had a significantly reduced number of errors while ingesting the CGA beverage as compared with the placebo beverage (p

Background: To characterize the course of Alzheimer’s disease (AD) over a longer time interval, we aimed to construct a disease course model for the entire span of the disease using two separate cohorts ranging from preclinical AD to AD dementia. Methods: We used longitudinal data from 127 participants with preclinical AD and 309 participants with mild cognitive impairments (MCI) due to AD from the Alzheimer’s Disease Neuroimaging Initiative. In order to develop a model of progression from preclinical AD to AD dementia, we estimated Alzheimer’s Disease Assessment Scale–Cognitive Subscale 13 (ADAS-cog 13) scores according to the follow-up time for each cohort, determined the time point at which the estimated scores of ADAS-cog 13 for the two cohorts first overlapped, and shifted the ADAS-cog 13 scores for the latter cohort at this time point to connect the two cohorts and to combine the data into a single unified progression course. Results: The estimated years for progression from the median ADAS-cog 13 score in the preclinical AD cohort (9.3 points) to the median ADAS-cog 13 score at the time of progression in the participants who progressed from preclinical AD to MCI due to AD (16.0 points) was 7.8 years. The estimated years for progression from preclinical AD to the median ADAS-cog 13 score at the time of progression in those who progressed from MCI to due AD to AD dementia (26.8 points) was 15.2 years. ADAS-cog 13 scores deteriorated most rapidly in female APOE ε4 carriers and most slowly in male APOE ε4 non-carriers ( p < 0.001). Conclusion: Our results suggest that disease progression modelling from preclinical AD to AD dementia may help clinicians to estimate where patients are in the disease course and provide information on variation in the disease course by sex and APOE ε4 status.

Background and study aims Endoscopic ultrasound (EUS) may be a useful modality for disease assessment and risk stratification in ulcerative colitis. We assessed the reliability of a newly developed EUS index of inflammation called the EUS-Ulcerative Colitis (EUS-UC) score. Patients and methods The EUS-UC score components include total wall thickness, hyperemia, and depth of inflammation (DOI). Three blinded expert endosonographers assessed EUS videos of 58 patients with UC in triplicate. Intra- and inter-rater reliability of the hyperemia and DOI component scores were estimated using intra-class correlation coefficients (ICCs). Total wall thickness reliability estimates could not be assessed in this study. The ICCs were compared to the original indices from which they were derived. Results For hyperemia, the inter-class ICC was “moderate” at 0.556 (95 % CI = 0.434–0.651) and the intra class ICC was “almost perfect” at 0.884 (95 % CI = 0.835–0.920). The newly defined hyperemia score performed better than the original index from which is was derived. The DOI inter-class ICC was “fair” at 0.335 (95 % CI = 0.201–0.464), and the intra-class ICC was “substantial” at 0.732 (95 % CI = 0.642–0.802). The DOI reliability estimates were similar to the original index from which it was derived. Conclusions The hyperemia component of the EUS-UC score performed significantly better than the original index from which it was derived, but the reliability of the DOI component was suboptimal. Intra-class correlation was excellent for both components. The EUS-UC score is a promising instrument for assessment of UC and further validation is required.

Background: Measurable residual disease (MRD) by multiparameter flow cytometry (MFC) is highly prognostic for relapse and overall survival (OS) in patients (pts) with acute lymphoblastic leukemia (ALL). However, many pts with apparent "MRD negativity" by MFC still relapse. These relapses are likely due to residual leukemia that is present below the level of detection of MFC (generally ~1x10-4). In light of the limitations of conventional MRD assays, we sought to evaluate the clinical impact of a highly sensitive next-generation sequencing (NGS)-based MRD assay that is capable of detecting residual leukemia at a level of 1x10-6. Methods: We performed a retrospective study of 67 pts with previously untreated Philadelphia chromosome-negative ALL who received frontline therapy between 2/2012 and 7/2018 with a hyper-CVAD-based regimen (n=44) or a lower-intensity hyper-CVD-based regimen (n=23), which was usually combined with inotuzumab ozogamicin, and achieved complete remission (CR). Pts were selected for this study based on availability of banked samples at baseline and at sequential remission time points up to 4.5 months after start of therapy. Six-color MFC was performed as standard of care with an analytic sensitivity of 0.01% (1x10-4). Pretreatment genomic DNA derived from bone marrow was evaluated using a quantitative NGS MRD assay (Adaptive Biotechnologies Co., Seattle, WA) to identify dominant rearrangements within the B-cell receptor (IgH [VDJ and DJ], IgK and IgL). High throughput NGS of remission samples was subsequently performed to assess the target clonal rearrangements at an established analytic sensitivity of 0.0001% (1x10-6). Results: The baseline characteristics of the study population are shown in Table 1. Twenty pts (30%) underwent allogeneic stem cell transplant (alloSCT) in first remission. In the entire cohort, 14 pts relapsed (21%), including 2 with CNS-only relapses. The median duration of follow-up for the entire cohort was 51 months. Among the 109 remission samples, 84 were MRD-negative (MRDneg), 24 were MRD-positive (MRDpos), and 1 was indeterminate by MFC (Figure 1). All 24 MRDpos samples by MFC were also MRDpos by NGS. Among the 84 MRDneg samples by MFC, 32 (38%) were MRDpos by NGS. For these discordant cases, the median level of MRD by NGS was below the expected level of detection by MFC (median 0.002% [range 0.00002%-1.15%]). At the time of CR, 44/67 pts (66%), achieved MRDneg by MFC and 14/38 (37%) achieved MRDneg by NGS. The rates of MRDneg by MFC in pts treated with hyper-CVAD or hyper-CVD regimens were 61% and 74%, respectively, and by NGS were 32% and 46%, respectively. Achieving MRDneg by NGS at the time of CR better predicted the likelihood of durable remission than did achieving MRDneg by MFC. The 5-year cumulative incidence of relapse (CIR) of the 44 pts who achieved MRDneg by MFC and of 14 pts who achieved MRDneg by NGS was 27% and 8%, respectively. Only 1 out of 14 pts who achieved MRDneg by NGS at the time of CR subsequently relapsed. In contrast, MRD status by NGS did not predict for relapse when evaluated at post-CR time points. Among pts treated with a more intensive hyper-CVAD regimen, achievement of MRDneg by NGS at CR provided additional prognostic information compared to MRD status by MFC at the same time point and identified pts with an excellent long-term outcome. The 5-year OS rate for pts who achieved MRDneg by NGS at CR was 100% vs. 55% for those who were MRDpos by NGS (Figure 2A; P Conclusion: Early assessment of MRD using an ultrasensitive NGS assay can identify pts with ALL who have a very low risk of relapse and excellent long-term survival. Prospective studies are warranted to assess whether de-intensification of therapy is feasible for this favorable-risk group of pts who rapidly achieve MRDneg remission. Disclosures Short: Amgen: Honoraria; Astellas: Research Funding; AstraZeneca: Consultancy; Takeda Oncology: Consultancy, Honoraria, Research Funding. Kantarjian:Takeda: Honoraria; Amgen: Honoraria, Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Cyclacel: Research Funding; Pfizer: Honoraria, Research Funding; Agios: Honoraria, Research Funding; Novartis: Research Funding; Immunogen: Research Funding; AbbVie: Honoraria, Research Funding; BMS: Research Funding; Ariad: Research Funding; Jazz Pharma: Research Funding; Daiichi-Sankyo: Research Funding; Astex: Research Funding. Konopleva:F. Hoffmann La-Roche: Consultancy, Research Funding; Eli Lilly: Research Funding; Cellectis: Research Funding; Calithera: Research Funding; Rafael Pharmaceutical: Research Funding; Amgen: Consultancy; Sanofi: Research Funding; Stemline Therapeutics: Consultancy, Research Funding; Ablynx: Research Funding; Agios: Research Funding; AbbVie: Consultancy, Research Funding; Ascentage: Research Funding; AstraZeneca: Research Funding; Forty-Seven: Consultancy, Research Funding; Reata Pharmaceutical Inc.;: Patents & Royalties: patents and royalties with patent US 7,795,305 B2 on CDDO-compounds and combination therapies, licensed to Reata Pharmaceutical; Kisoji: Consultancy; Genentech: Consultancy, Research Funding. Jain:Cellectis: Research Funding; BMS: Research Funding; BeiGene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Fate Therapeutics: Research Funding; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Aprea Therapeutics: Research Funding; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics: Research Funding; TG Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Precision Bioscienes: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kebriaei:Kite: Other: Served on advisory board; Amgen: Other: Research Support; Ziopharm: Other: Research Support; Pfizer: Other: Served on advisory board; Novartis: Other: Served on advisory board; Jazz: Consultancy. Yilmaz:Pfizer: Research Funding; Daicho Sankyo: Research Funding; Pint Pharma: Honoraria. Issa:Celegene: Research Funding; Syndax: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees. Ravandi:BMS: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding; Xencor: Consultancy, Honoraria, Research Funding; Macrogenics: Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Orsenix: Consultancy, Honoraria, Research Funding. Jabbour:Amgen: Other: Advisory role, Research Funding; Adaptive Biotechnologies: Other: Advisory role, Research Funding; BMS: Other: Advisory role, Research Funding; Genentech: Other: Advisory role, Research Funding; AbbVie: Other: Advisory role, Research Funding; Takeda: Other: Advisory role, Research Funding; Pfizer: Other: Advisory role, Research Funding.

Arguably, the most important advances in modern clinical care have arisen not through the development of new drugs but instead through a recognition that the Gestalt approach to disease assessment is simply not adequate when it comes to selecting and assessing response to therapy. Accurate and regular assessment with an appropriate measurement instrument gives the clinician and patient reliable information to track disease trajectory and make treatment decisions. Achieving consensus on a single disease-specific instrument has considerable advantages, facilitating adoption of international treatment guidelines, and interpretation of data from trials, cohorts, and registries to make translation into routine care seamless1. In the context of rheumatoid arthritis (RA), the 28-joint count Disease Activity Score (DAS28) has been widely adopted as the most frequently used generally continuous measure of activity. The DAS28 has established cutpoints for high, moderate, and low disease activity and remission. The term near remission is increasingly preferred because it better differentiates those with some residual disease from those in true remission. Clinicians are used to the measure and what the numbers mean clinically, and this has allowed a smooth translation of research findings into clinical practice, including the implementation of treat to target and adoption of clinical guidelines. It has been harder to achieve this consensus in the field of psoriatic arthritis (PsA), with no current agreement on the most appropriate instrument to adopt. Why is this the case, and what are the key barriers2? The greatest challenge in the adoption of a composite measure for routine care in PsA has been philosophical: should we incorporate multiple domains of disease into a single measure to identify the totality of disease, or should we focus on 1 domain at a time for accurate assessment and to avoid diluting responsiveness? PsA may manifest in a variety … Address correspondence to W. Tillett, Royal National Hospital for Rheumatic Diseases, Upper Borough Walls, Bath BA1 1RL, UK. E-mail: w.tillett{at}nhs.net

Updated therapeutic guidelines for inflammatory bowel disease call for effective disease assessment, early intervention, and personalized patient care using a treat-to-target (T2T) approach. The ongoing, intensive monitoring of a T2T strategy is best facilitated by a multidisciplinary team, but the increased demand on health care systems impedes implementation. Therefore, advanced practice providers have a growing role in bridging the gap between T2T recommendations and clinical practice. Advanced practice providers can effectively facilitate patient-care team communication, deliver patient education, perform in-clinic and remote monitoring of symptoms and treatment response, and assist patients with self-management.

BACKGROUND Melanoma is a highly malignant skin tumour, and is one of the most rapidly growing malignant tumors in recent years. According to statistics, the morbidity of cancer increases with age, accounting for 1.6% of new cancer cases and 0.6% of deaths worldwide. Melanoma has a serious impact on society and families, thus it is of great significance to find biological markers related to the diagnosis and treatment of melanoma. AIM To explore the expression and predictive value of mir-489 and mir-21 in melanoma metastasis. METHODS A total of 60 patients with malignant melanoma treated at our hospital from June 2017 to December 2018 were selected as a research group, while 40 healthy subjects were selected as a control group. qRT-PCR technique was used to detect miR-489 and miR-21 in serum of the two groups. ROC curve was drawn to evaluate the predictive value and diagnostic efficiency. Spearman test was used for correlation analysis. Logistic single- and multiple-factor analyses were performed to identify the risk factors related to melanoma metastasis. RESULTS The expression of miR-489 in the research group was significantly lower than that in the control group (P < 0.001). However, the expression of miR-21 in the research group was significantly higher than that in the control group (P < 0.001). The expression of miR-489 and miR-21 was related to TNM stage and metastasis (P < 0.001). In the diagnosis of melanoma patients, the sensitivity, specificity, and AUC of miR-489 alone were 75.56%, 80.00%, and 0.852, respectively. The sensitivity, specificity, and AUC of miR-21 alone were 77.78%, 82.22%, and 0.844, respectively. MiR-489 was negatively correlated with TNM stage of melanoma (r = -0.612, P < 0.001), while miR-21 was positively correlated with TNM stage (r = 0.609, P < 0.001). Logistic single- and multiple-factor regression analyses showed that TNM stage, miR-489, and mir-21 were independent risk factors for malignant melanoma metastasis. CONCLUSION MiR-489 and miR-21 may participate in the process of melanoma occurrence, development, and metastasis, and can be used as potential serum biomarkers for melanoma metastasis diagnosis and disease assessment.

The objective of this study is to evaluate the effects of physical therapy on the cognitive and functional capacity of patients with Alzheimer’s Disease (AD). This is a systematic review of randomized or quasi-randomized clinical trials, using the descriptors: AD, dementia and physical therapy. Two studies were included with a total of 207 participants. In study 1, no statistically significant difference was found on the mini-mental state examination (MMSE) (MD 0.0, 95%CI −5.76 to 5.76), neuropsychiatric inventory (MD −4.50, 95%CI −21.24 to 12.24) and Pfeffer instrumental activities questionnaire (MD 0.0 95%CI −6.48 to 6.48). In study 2, there was no statistically significant difference on the MMSE (MD −1.60, 95% CI −3.57 to 0.37), clock-drawing test (MD −0.20, 95%CI −0.61 to 0.21) and Alzheimer’s Disease Assessment Scale - cognitive subscale (MD 1.0, 95%CI −2.21 to 4.21) after 12 months. There was no consistent evidence on the effectiveness of physiotherapeutic intervention in improving cognitive function and functional capacity of patients with AD. More studies should be conducted for better evidence. RESUMO O objetivo do estudo é avaliar os efeitos da fisioterapia na capacidade cognitiva e funcional de pacientes com doença de Alzheimer (DA). Trata-se de revisão sistemática de ensaios clínicos randomizados ou quasi-randomizados utilizando os descritores: DA, demência e fisioterapia. Dois estudos foram incluídos, com um total de 207 participantes. No Estudo 1, não houve diferença estatisticamente significativa no miniexame do estado mental (MEEM) (MD 0,0, IC 95% 5,76−5,76), inventário neuropsiquiátrico (MD −4,50, IC 95% 12,24−21,24) e questionário de atividades instrumentais Pfeffer (MD 0,0 IC 95% −6,48 a 6,48). No Estudo 2, não houve diferença estatisticamente significativa no MEEM (MD −1,60, IC 95% −3,57 a 0,37), teste do desenho do relógio (MD −0,20, IC95% −0,61 a 0,21) e escala de avaliação da doença de Alzheimer - subitem cognição (MD 1,0, IC95% −2,21 a 4,21) após 12 meses. Não houve evidência consistente da eficácia da intervenção fisioterapêutica na melhora da função cognitiva e capacidade funcional na DA. Recomenda-se a produção de mais estudos para encontrar possíveis evidências. RESUMEN El presente estudio tiene como objetivo evaluar los efectos de la fisioterapia en la capacidad cognitiva y funcional de pacientes con enfermedad de Alzheimer (EA). Se trata de una revisión sistemática de ensayos clínicos aleatorizados o casi-aleatorizados, en que se utilizó los descriptores: EA, demencia y fisioterapia. Se incluyeron dos estudios, con un total de 207 participantes. En el Estudio 1, no hubo diferencias estadísticamente significativas en el Miniexamen del estado mental (MEEM) (MD 0,0, IC 95%: 5,6 -5,76), en el inventario neuropsiquiátrico (MD -4,50, IC 95%: 12,24 -21,24) y en el cuestionario de actividades instrumentales de Pfeffer (MD: 0,0 IC 95% IC: -6,48 a 6,48). En el Estudio 2, no hubo diferencias estadísticamente significativas en el MEEM (MD −1,60, IC 95% −3,57 a 0,37), el test de diseño del reloj (MD −0,20, IC 95% −0,61 a 0,21) y la escala de evaluación de la enfermedad de Alzheimer: subítem de cognición (MD 1,0, IC 95% −2,21 a 4,21) tras 12 meses. No hubo evidencia consistente de la eficacia de la intervención fisioterapéutica en la mejora de la función cognitiva y de la capacidad funcional en la EA. Se recomienda realizar estudios adicionales para encontrar posibles evidencias.

Diabetes mellitus is common and complicates 2–5% of pregnancies in the UK, with an increasing prevalence of pre-existing diabetes mellitus in pregnancy. Hyperglycaemia directly correlates with adverse maternal and fetal outcomes, including congenital anomaly, miscarriage, pre-eclampsia, pre-term delivery, macrosomia, stillbirth and neonatal hypoglycaemia. Optimal glycaemic control before conception and during the antenatal period is paramount to reduce these risks. Pre-pregnancy preparation should focus on glycaemic control, medication review and end-organ disease assessment. All diabetic women of childbearing age not planning a pregnancy should be offered contraception. Antenatal care should focus on education from a multidisciplinary team. Women should understand the changes that occur in pregnancy and the need for more intense monitoring and tighter glycaemic control. Increased surveillance focuses on end-organ disease (retinal, renal), the development of pre-eclampsia and the presence of fetal complications. The postpartum period is valuable for reiterating the benefits of contraception and planning of future pregnancies. This article focuses on the management of pre-existing diabetes mellitus from pre-conception to the postpartum period.

Background: To explore the potential relationship of changes in classic serum tumor markers (CSTM) with differential diagnosis and disease assessment of upper tract urothelial carcinoma (UTUC).Methods: 60 UTUC (56 operated), 44 RCCC and 36 NTHN, were included into this retrospective analysis. The initial classic serum tumor markers (CSTMs), including CA242, CA199, CA125, CEA, AFP, SCC and CA724, were compared among the three groups. The preoperative, 1 month postoperative and 1 year postoperative/PD parameters (value and abnormal rate) of CSTMs were compared in UTUC group. A recommend test strategy was given and rechecked. The pathological manifestations of tumoral tissues and paracancerous tissues were analyzed.Results: The value of CA242, CA199 and CEA were higher in UTUC than in RCCC. The value of CEA was higher in UTUC than in NTHN. The value of CA199 and CEA were higher in UTUC than in RCCC+NTHN. The AR of CA199, CEA, SCC and CA724 were higher in UTUC than in RCCC. The AR of CEA and CA724 were higher in UTUC than in NTHN. The AR of CA199, CEA, SCC and CA724 were higher in UTUC than in RCCC+NTHN. The preoperative value of CA242 and CA199 were higher than 1 month postoperative ones in UTUC. The 1 year postop/PD value of CA242 and AFP were higher than 1 month postoperative ones in UTUC. For postop PD patients, the value during PD of CA242, CA199 and AFP were higher than 1 month postop ones. The preoperative AR of CA199 and CEA were higher than 1 month postoperative ones in UTUC. The recommended test strategy was given: CA242+CA199+CEA+AFP+SCC+CA724, and was rechecked. The P values were almost the lowest and the positive results covered all the comparisons. In 56 operated cases, the NAC in CSTMs by the recommended test strategy was statistically related with the tumor load. It appeared positive labelling by Ab of CA199, CA125, CEA, AFP and CA724 in UTUC tissues, while negative in paracancerous tissues.Conclusions: CSTMs may help to make differential diagnosis and disease assessment of UTUC. Group test (CA242+CA199+CEA+AFP+SCC+CA724) was recommended and more valuable.Trial registration: Not applicable

The recent scientific research has provided clinicians with the tools for substantially upgrading the standard of care in the field of bronchial asthma. Nevertheless, satisfactory asthma control still remains an unmet need worldwide. Identifying the major determinants of poor control in different asthma severity levels represents the first step towards the improvement of the overall patients’ management. The present review aims to provide an overview of the main unmet needs in asthma control and of the potential tools for overcoming the issue. Implementing a personalized medicine approach is essential, not only in terms of pharmacological treatments, biologic drugs or sophisticated biomarkers. In fact, exploring the complex profile of each patient, from his inflammation phenotype to his preferences and expectations, may help in filling the gap between the big potential of currently available treatments and the overall unsatisfactory asthma control. Telemedicine and e-health technologies may provide a strategy to both optimize disease assessment on a regular basis and enhance patients’ empowerment in managing their asthma. Increasing patients’ awareness as well as the physicians’ knowledge about asthma phenotypes and treatment options besides corticosteroid probably represent the key and more difficult goals of all the players involved in asthma management at every level.

Background: Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory arthritis of childhood, characterized by various clinical phenotypes associated with variable prognosis. Significant progress has been achieved with the use of biologic treatments, which specifically block pro-inflammatory molecules involved in the disease pathogenesis. The most commonly used biologics in JIA are monoclonal antibodies and recombinant proteins targeting interleukins 1 (IL-1) and 6 (IL-6), and tumor necrosis factor α (TNF-α). Several biomarkers have been investigated in JIA.Aims: To assess the level of evidence available regarding the role of biomarkers in JIA related to guiding clinical and therapeutic decisions, providing disease prognostic information, facilitating disease activity monitoring and assessing biologic treatment response in JIA, as well as propose new strategies for biologic therapy-related biomarker use in JIA.Methods: We searched PubMed for relevant literature using predefined key words corresponding to several categories of biomarkers to assess their role in predicting and assessing biologic treatment response and clinical remission in JIA.Results: We reviewed serological, cellular, genetic, transcriptomic and imaging biomarkers, to identify candidates that are both well-established and widely used, as well as newly investigated in JIA on biologic therapy. We evaluated their role in management of JIA as well as identified the unmet needs for new biomarker discovery and better clinical applications.Conclusion: Although there are no ideal biomarkers in JIA, we identified serological biomarkers with potential clinical utility. We propose strategies of combining biomarkers of response to biologics in JIA, as well as routine implementation of clinically acceptable imaging biomarkers for improved disease assessment performance.

Background and Objective: Current evidence suggests that abnormalities within the default-mode network (DMN) play a key role in the broad-scale cognitive problems that characterize mild cognitive impairment (MCI). However, little is known about the alterations of DMN network homogeneity (NH) in MCI.Methods: Resting-state functional magnetic resonance imaging scans (rs-fMRI) were collected from 38 MCI patients and 69 healthy controls matched for age, gender, and education. NH approach was employed to analyze the imaging dataset. Cognitive performance was measured with the Chinese version of Alzheimer's disease assessment scale-Cognitive subscale (ADAS-Cog).Results: Two groups have no significant differences between demographic factors. And mean ADAS-Cog score in MCI was 12.02. MCI patients had significantly lower NH values than controls in the right anterior cingulate cortex and significantly higher NH values in the ventral medial prefrontal cortex(vmPFC) than those in healthy controls. No significant correlations were found between abnormal NH values and ADAS-Cog in the patients.Conclusions: These findings provide further evidence that abnormal NH of the DMN exists in MCI, and highlight the significance of DMN in the pathophysiology of cognitive problems occurring in MCI.

Micro/nanodevices have been widely applied for the real-time monitoring of intracellular activities and the delivery of exogenous substances in the past few years. This review focuses on miniaturized micro/nanodevices for assessment and treatment in stomatology and ophthalmology. We first summarize the recent progress in this field by examining the available materials and fabrication techniques, device design principles, mechanisms, and biosafety aspects of micro/nanodevices. Following a discussion of biochemical sensing technology from the cellular level to the tissue level for disease assessment, we then summarize the use of microneedles and other micro/nanodevices in the treatment of oral and ocular diseases and conditions, including oral cancer, eye wrinkles, keratitis, and infections. Along with the identified key challenges, this review concludes with future directions as a small fraction of vast opportunities, calling for joint efforts between clinicians and engineers with diverse backgrounds to help facilitate the rapid development of this burgeoning field in stomatology and ophthalmology.

We would like to thank Mr. Hall and coworkers for their interesting comments on our brief editorial review [1]. Owing to the emerging role of potential exocrine pancreatic insufficiency (EPI) in pa...

Prognosis of acute myeloid leukemia (AML) patients depends on patient-related features, disease manifestations at the time of presentation, and intrinsic disease-related genetic features, such as cytogenetic abnormalities and driver mutations. Prognostic stratification also depends on the therapeutic strategy and on response to treatment, including measurable residual disease assessment. This chapter reviews the influence of prognostic factors measured at the diagnosis of AML, with an emphasis on disease-related factors. The role of measurable residual disease and how prognostic stratification affects treatment decisions are covered in other chapters.

Venetoclax is a selective B-cell lymphoma 2 (BCL2) inhibitor, which is approved to treat elderly patients with newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). A total of 60 patients with a median age of 67 years from different centers were included in the final analysis. Our real-life data support the use of venetoclax in patients with both newly diagnosed and relapsed high-risk MDS and AML. Introduction: Venetoclax is a selective B-cell lymphoma 2 (BCL2) inhibitor, which is approved to treat elderly patients with newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) in combination with either low-dose cytarabine (ARA-C) or hypomethylating agents. We aimed to collect and share data among the efficacy and safety of venetoclax both as a monotherapy or in combination with other drugs used to treat high-risk MDS or AML. Materials and Methods: A total of 60 patients with a median age of 67 (30-83) years from 14 different centers were included in the final analysis. Thirty (50%) of the patients were women; 6 (10%) of the 60 patients were diagnosed with high-risk MDS and the remaining were diagnosed with AML. Results: The best objective response rate (complete remission [CR], complete remission with incomplete hematological recovery (CRi), morphological leukemia-free state [MLFS], partial response [PR]) was 35% in the entire cohort. Best responses achieved during venetoclax per patient number were as follows: 7 CR, 1 CRi, 8 MLFS, 5 PR, and stable disease. Median overall survival achieved with venetoclax was 5 months in patients who relapsed and not achieved in patients who were initially treated with venetoclax. Nearly all patients (86.7%) had experienced a grade 2 or more hematologic toxicity. Some 36.7% of these patients had received granulocyte colony stimulating factor (GCSF) support. Infection, mainly pneumonia (26.7%), was the leading nonhematologic toxicity, and fatigue, diarrhea, and skin reactions were the others reported. Conclusion: Our real-life data support the use of venetoclax in patients with both newly diagnosed and relapsed high-risk MDS and AML.

This paper presents a novel deep learning enabled, video based analysis framework for assessing the Unified Parkinsons Disease Rating Scale (UPDRS) that can be used in the clinic or at home. We report results from comparing the performance of the framework to that of trained clinicians on a population of 32 Parkinsons disease (PD) patients. In-person clinical assessments by trained neurologists are used as the ground truth for training our framework and for comparing the performance. We find that the standard sit-to-stand activity can be used to evaluate the UPDRS sub-scores of bradykinesia (BRADY) and posture instability and gait disorders (PIGD). For BRADY we find F1-scores of 0.75 using our framework compared to 0.50 for the video based rater clinicians, while for PIGD we find 0.78 for the framework and 0.45 for the video based rater clinicians. We believe our proposed framework has potential to provide clinically acceptable end points of PD in greater granularity without imposing burdens on patients and clinicians, which empowers a variety of use cases such as passive tracking of PD progression in spaces such as nursing homes, in-home self-assessment, and enhanced tele-medicine., Comment: Accepted by CVPR Workshops 2021

Castleman's disease is a rare lymphoproliferative syndrome involving several anatomical and clinical entities. We report two cases of Castleman's disease in patients with spondyloarthritis (with and without psoriasis) treated with Tumor Necrosis Factor-alpha blockers. During follow-up, imaging examinations, carried out for disease assessment, fortuitously revealed a pelvic mass close to the psoas or an atypical cervical adenopathy. Both lesions were in moderate hypermetabolism on Positron emission tomography-computed tomography. After surgical excision and histological analysis, Castleman's disease was diagnosed without signs of malignancy. To the best of our knowledge, these are the first cases of Castleman's disease diagnosed in a context of spondyloarthritis treated with Tumor Necrosis Factor-alpha blockers. The relationship between these two pathologies and the link with Tumor Necrosis Factor-alpha blockers agents has not been explored in the literature until now.

OBJECTIVE: Parkinson's disease (PD) is a neurodegenerative disorder that affects multiple neurological systems. Traditional PD assessment is conducted by a physician during infrequent clinic visits. Using smartphones, remote patient monitoring has the potential to obtain objective behavioral data semi-continuously, track disease fluctuations, and avoid rater dependency. METHODS: Smartphones collect sensor data during various active tests and passive monitoring, including balance (postural instability), dexterity (skill in performing tasks using hands), gait (the pattern of walking), tremor (involuntary muscle contraction and relaxation), and voice. Some of the features extracted from smartphone data are potentially associated with specific PD symptoms identified by physicians. To leverage large-scale cross-modality smartphone features, we propose a machine-learning framework for performing automated disease assessment. The framework consists of a two-step feature selection procedure and a generic model based on the elastic-net regularization. RESULTS: Using this framework, we map the PD-specific architecture of behaviors using data obtained from both PD participants and healthy controls (HCs). Utilizing these atlases of features, the framework shows promises to (a) discriminate PD participants from HCs, and (b) estimate the disease severity of individuals with PD. SIGNIFICANCE: Data analysis results from 437 behavioral features obtained from 72 subjects (37 PD and 35 HC) sampled from 17 separate days during a period of up to six months suggest that this framework is potentially useful for the analysis of remotely collected smartphone sensor data in individuals with PD. ispartof: Ieee Transactions On Biomedical Engineering vol:67 issue:12 pages:3491-3500 ispartof: location:United States status: published

Highlights • To summarize the blood CD4+ or CD8+ T cell count in COVID-19 patients. • The first meta-analysis on blood CD4+ or CD8+ T cell count between mild and severe COVID-19 patients. • The lower blood CD4+ or CD8+ T cell count could predict worse prognosis in COVID-19 patients., This study mainly focused on the very serious COVID-19 epidemic situation at present and provided a new insight for the treatment and monitor of patients with COVID-19. Through this meta-analysis, we could draw a conclusion that less expression of blood CD4+ and CD8+ T cells count might reflect the severity of infection and often accompanied by a poor prognosis. Hence, we inferred blood CD4+ and CD8+ T cells count could be a promising biomarker for disease assessment and monitor of patients with COVID-19.

The development of techniques and equipment for medical imaging has provided physicians with efficient, fast, and reliable resources for diagnostic tasks. Large volumes of three-dimensional (3D) data can be stored, analyzed, and visualized through non-invasive procedures, whose interpretation has led to advances in disease assessment, surgical planning, treatment monitoring, among other benefits in healthcare. This chapter describes relevant concepts related to medical imaging techniques for the construction of three-dimensional models for visualization and biofabrication.

Unlike IgG monoclonal proteins (MCPs), IgA MCP quantification is unreliable due to beta-migration of IgA MCPs on serum protein electrophoresis (SPEP). The utility of nephelometric quantitative IgA (qIgA) to monitor IgA multiple myeloma (MM) is unclear. We retrospectively studied disease response kinetics using qIgA versus MCPs by SPEP, and developed and validated novel qIgA disease assessment criteria in 491 IgA MM patients. The SPEP MCP nadir occurred a median of 41 (IQR 0–102) days before the qIgA. The median time to achieve a partial response (PR) was shorter using standard IMWG versus qIgA response criteria (32 vs 58 days, p

Long-term noise exposure often results in noise induced hearing loss (NIHL). Tinnitus, the generation of phantom sounds, can also result from noise exposure, although understanding of its underlying mechanisms are limited. Recent studies, however, are shedding light on the neural processes involved in NIHL and tinnitus, leading to potential new and innovative treatments. This review focuses on the assessment of NIHL, available treatments, and development of new pharmacologic and non-pharmacologic treatments based on recent studies of central auditory plasticity and adaptive changes in hearing. We discuss the mechanisms and maladaptive plasticity of NIHL, neuronal aspects of tinnitus triggers, and mechanisms such as tinnitus-associated neural changes at the cochlear nucleus underlying the generation of tinnitus after noise-induced deafferentation. We include observations from recent studies, including our own studies on associated risks and emerging treatments for tinnitus. Increasing knowledge of neural plasticity and adaptive changes in the central auditory system suggest that NIHL is preventable and transient abnormalities may be reversable, although ongoing research in assessment and early detection of hearing difficulties is still urgently needed. Since no treatment can yet reverse noise-related damage completely, preventative strategies and increased awareness of hearing health are essential.

Low-Level Laser Therapy (LLLT) has been investigated for the treatment of various dermatological disorders. Here, we investigate the efficacy of LLLT for the treatment of cutaneous leishmaniasis (CL). This study comprised of 53 patients (total 123 lesions) with a confirmed diagnosis of CL via positive smear of LD-bodies. The CL lesions were classified in Grade I (ie, papule of size ≤1 cm) to Grade V (ie, vesicle formation, ulceration, and superadded infection of size >4 cm). All the patients were divided into group 1 with low grade (ie, Grade I and II) CL lesions and group 2 with high-grade disease (ie, Grade III-V). Red laser light (wavelength = 635 nm) was used for the lesion irradiation, with a light dose of 75 J/cm2 and at a low power of 300 mW. The treatment was divided into four sessions, one session per week. Disease assessment at 10 months follow-up revealed complete response in 91% and partial response in 9% patients of group 1, while no response was observed in patients of group 2. LLLT offers a promising treatment modality for patients presenting with early-stage (ie, Grade I and II) CL lesions.

Total-body PET opens a new diagnostic paradigm with prospects for personalized disease treatment, yet the high cost of the current crystal-based PET technology limits dissemination of total-body PET in hospitals and even in research clinics. The J-PET tomography system is based on axially arranged low-cost plastic scintillator strips. It constitutes a realistic cost-effective solution of a total-body PET for broad clinical applications. High sensitivity of total-body J-PET and triggerless data acquisition enable multiphoton imaging, opening possibilities for multitracer and positronium imaging, thus promising quantitative enhancement of specificity in cancer and inflammatory disease assessment.

Background Autologous stem cell transplantation (ASCT) is one of the standard treatments of choice for eligible multiple myeloma (MM) patients. Herein, we aimed to analyze MM patients at our center and compare the clinical outcomes of single and double ASCT patients. Materials and methods Patients who were diagnosed as having MM and had undergone single or double ASCT in our clinic between the years 2003 and 2020 were retrospectively examined. Results In this study, the median time of second ASCT is approximately 3.6 years from the first ASCT. Overall survival (OS) duration of the single and double transplanted groups was 4,011 ± 266 vs 3,526 ± 326 days, respectively (p: 0.33). Progression-free survival (PFS) duration of the single and double transplanted groups was 2,344 ± 228 vs 685 ± 120 days, respectively (p: 0.22). Disease assessment after ASCT stable or progressive disease, partial remission, and very good partial or complete remission (CR) in single and double ASCT groups was 62/44/105 and 8/4/5, respectively (p: 0.22). Conclusion The present study points out that the second ASCT treatment option for MM patients may not be effective as suggested, especially in the era of novel MM drugs, since our results come from the past data that novel drugs were not exist. In conclusion, we found no benefit with second ASCT in MM patients in terms of PFS and OS or CR rates, and the novel anti-myeloma drugs might decrease the need for a second transplant.