Investigation of sensor placement for accurate fall detection

Fall detection is typically based on temporal and spectral analysis of multi-dimensional signals acquired from wearable sensors such as tri-axial accelerometers and gyroscopes which are attached at several parts of the human body. Our aim is to investigate the location where such wearable sensors should be placed in order to optimize the discrimination of falls from other Activities of Daily Living (ADLs). To this end, we perform feature extraction and classification based on data acquired from a single sensor unit placed on a specific body part each time. The investigated sensor locations include the head, chest, waist, wrist, thigh and ankle. Evaluation of several classification algorithms reveals the waist and the thigh as the optimal locations. © ICST Institute for Computer Sciences, Social Informatics and Telecommunications Engineering 2017

Impact of minimal residual disease detection by next-generation flow cytometry in multiple myeloma patients with sustained complete remission after frontline therapy

Minimal residual disease (MRD) was monitored in 52 patients with sustained CR (≥2 years) after frontline therapy using next-generation flow (NGF) cytometry. 25% of patients initially MRD- reversed to MRD+. 56% of patients in sustained CR were MRD+; 45% at the level of 10−5; 17% at 10−6. All patients who relapsed during follow-up were MRD+ at the latest MRD assessment, including those with ultra-low tumor burden. MRD persistence was associated with specific phenotypic profiles: higher erythroblasts’ and tumor-associated monocytes/macrophages’ predominance in the bone marrow niche. NGF emerges as a suitable method for periodic, reproducible, highly-sensitive MRD-detection at the level of 10−6

Nonselective proteasome inhibitors in multiple myeloma and future perspectives

Introduction: Proteasome inhibition can lead to inhibition of tumor cell proliferation, and therefore it constitutes a potential therapeutic anticancer approach especially in the therapeutic algorithm of patients with multiple myeloma. Areas covered: Three different proteasome inhibitors are currently approved, bortezomib, carfilzomib, and ixazomib, and they have been investigated in multiple myeloma and other hematological malignancies. However, these agents lack specificity, since they target both the constitutive proteasome and the immunoproteasome. Targeting the constitutive proteasome is the main reason for side toxicity due to the effect on normal tissues. In contrary, immunoproteasome inhibition may reduce the adverse events while maintaining the therapeutic efficacy. In this review, the authors present the role of the available proteasome inhibitors in myeloma therapeutics and future perspectives of both selective and nonselective proteasome inhibitors. Expert opinion: The available nonselective proteasome inhibitors have changed the therapeutics of multiple myeloma the last 10 years and have significantly improved the clinical outcomes of the patients. Furthermore, selective proteasome inhibitors are now under preclinical investigation and there is hope that their optimization will come with an improved safety profile with at least comparable efficacy. © 2021 Informa UK Limited, trading as Taylor & Francis Group

Clinical utility of selinexor/dexamethasone in patients with relapsed or refractory multiple myeloma: A review of current evidence and patient selection

Multiple myeloma (MM) is one the most common hematological malignan-cies, and despite the survival prolongation offered by proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs) and anti-CD38 monoclonal antibodies, the need for novel agents is prominent. Selinexor is a first-in-class, oral, selective inhibitor of exportin-1 (XPO1), a vital protein for the exportation of more than 200 tumor sup-pressor proteins from the nucleus. Both in solid tumors and hematologic malignancies, selinexor-mediated inhibition of nucleus export seems to effectively lead to cancer cell death. Selinexor in combination with dexamethasone (Sd) received an accelerated FDA approval on July 2019 for heavily pretreated patients with relapsed/refractory MM (RRMM) based on the promising results of the Phase II STORM trial. The preliminary results of the randomized Phase III BOSTON trial have shown a 47% increase in progression-free survival among PI-sensitive, RRMM patients who received selinexor with bortezomib-dexamethasone compared with bortezomib-dexamethasone alone. Several different selinexor-containing triplet regimens are currently being tested in the RRMM setting in an umbrella trial, and the preliminary results seem promising. Furthermore, the addition of selinexor in other anti-myeloma agents seems to overcome drug-acquired resistance in preclinical studies. The main toxicities of selinexor are gastrointestinal disorders and hematologic toxicities (mainly thrombocytopenia); how-ever, they are manageable with proper supportive measures. In conclusion, selinexor is a new anti-myeloma drug that seems to be effective in patients who have no other therapeutic options, including patients who have received novel cellular therapies such as CAR-T cells. Its potential role earlier in the therapeutic algorithm of MM is currently under clinical investigation. © 2020 Malandrakis et al

Multiple myeloma bone disease: Implication of micrornas in its molecular background

Multiple myeloma (MM) is a common hematological malignancy arising from terminally differentiated plasma cells. In the majority of cases, symptomatic disease is characterized by the presence of bone disease. Multiple myeloma bone disease (MMBD) is a result of an imbalance in the bone-remodeling process that leads to increased osteoclast activity and decreased osteoblast activ-ity. The molecular background of MMBD appears intriguingly complex, as several signaling pathways and cell-to-cell interactions are implicated in the pathophysiology of MMBD. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate the expression of their target mRNAs. Numerous miRNAs have been witnessed to be involved in cancer and hematological malignancies and their role has been characterized either as oncogenic or oncosuppressive. Recently, scientific research turned towards miRNAs as regulators of MMBD. Scientific data support that miRNAs finely regulate the majority of the signaling pathways implicated in MMBD. In this review, we pro-vide concise information regarding the molecular pathways with a significant role in MMBD and the miRNAs implicated in their regulation. Moreover, we discuss their utility as molecular bi-omarkers and highlight the putative usage of miRNAs as novel molecular targets for targeted therapy in MMBD. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Diabetes mellitus and multiple myeloma; common features of two distinct entities

Diabetes mellitus (DM) has attained the status of a global pandemic. Cardiovascular disease (CV) was the leading cause of morbidity in people with type 2 DM, however, a transition from CV to cancer as the leading contributor to DM related death has been observed lately. Multiple myeloma (MM) is the second most common haematological malignancy. Obesity is a common risk factor for both DM and MM. Although data are limited, studies have shown that DM might be associated with increased risk for the development of MM. The presence of DM might affect the course of patients with MM, since hyperglycemia may have an impact on both the efficacy and the adverse effects of antimyeloma therapy. In parallel, DM and MM share common clinical presentations, such as nephropathy, neuropathy, and CV. In terms of antidiabetic medications, metformin might present a synergistic effect with antimyeloma drugs and also prevent some of the adverse effects of these drugs; pioglitazone might have favourable effects when given as add on treatment in people with relapsed or refractory MM. No clinically important interactions have been observed between antidiabetic agents and the most commonly used antimyeloma drugs. Further data are needed to examine the effect of all classes of antidiabetic medication on MM and its complications. A baseline assessment of risk factors for glucose intolerance and close monitoring of glucose levels during therapy is strongly suggested for patients with MM. © 2022 John Wiley & Sons Ltd

The association between pulse wave velocity and peripheral neuropathy in patients with type 2 diabetes mellitus

Aims Diabetic peripheral neuropathy (DPN) is the most common diabetic complication, affecting up to half of the patients with type 2 diabetes mellitus (T2DM). Increased aortic stiffness, measured with the carotid-femoral pulse wave velocity (PWV), has been associated with incidence of cardiovascular disease independently of traditional risk factors. Previous data showed associations between risk factors for macroangiopathy and DPN in diabetes. However, the association between PWV and DPN is not well known. In this study we examined the association between PWV and presence as well as severity of DPN in subjects with T2DM. Material and methods A total of 381 patients with T2DM were recruited. Participants were classified as having DPN and not having DPN. PWV was measured at the carotid-femoral segment with a non-invasive method using applanation tonometry. DPN was assessed by determination of the Neuropathy Symptom Score (NSS) and the Neuropathy Disability Score (NDS). Results A hundred and seven participants (28.1%) had DPN. Patients with DPN were significantly more often male and older, had longer diabetes duration, higher height, larger waist circumference, higher systolic arterial blood pressure (SBP) and higher PWV (all P < 0.05). Furthermore, participants with DPN were treated more often with statins and had lower low density lipoprotein cholesterol; in addition, they were treated more often with antiplatelets, b-blockers and insulin than those without DPN. Univariative logistic regression analysis demonstrated that presence of DPN was significantly associated with age, male gender, longer diabetes duration, height, waist circumference, SBP, PWV, dyslipidemia, HbA1c, retinopathy, nephropathy and peripheral arterial disease. Multivariate logistic regression analysis, after adjustment for age, gender, waist circumference, SBP, nephropathy and use of b-blockers, demonstrated that the odds [OR (95% confidence intervals)] of peripheral neuropathy were associated significantly and independently only with diabetes duration [1.044 (1.009–1.081), P = 0.013], height [1.075 (1.041–1.110), P < 0.001], HbA1c [1.468 (1.164–1.851), P < 0.001], PWV [1.174 (1.054–1.309), P = 0.004], dyslipidemia [1.941 (1.015–3.713), P = 0.045], retinopathy [4.426 (2.217–8.837), P < 0.001] and peripheral arterial disease [4.658 (2.264–9.584), P < 0.001]. In addition, multivariate linear regression analysis, after controlling for age, gender, diabetes duration, SBP, HbA1c and nephropathy, demonstrated that an increased NDS was significantly and independently associated with height [standardized regression coefficient (beta = 0.229, P < 0.001)], PWV (beta = 0.197, P < 0.001), retinopathy (beta = 0.268, P < 0.001) and peripheral arterial disease (beta = 0.374, P < 0.001). Conclusion Increased PWV is associated strongly and independently not only with the presence but also with the severity of DPN in patients with T2DM, irrespective of known risk factors. © 2017 Elsevier Inc

Squamous cell carcinoma of the pancreas: A systematic review and pooled survival analysis

The diagnosis and treatment of squamous cell carcinoma of the pancreas pose dilemmas in the clinical practice. The present study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible articles were sought in MEDLINE up to 30th April 2016. A pooled Cox regression analysis was performed to evaluate factors potentially associated with overall survival (OS) and relapse-free survival (RFS). Fifty-four cases of pure squamous cell pancreatic carcinomas were identified in total. The mean age was 61.9 years, and most patients were males (61.1%). The median OS was 7 months. Resectability (p = 0.003) and more recent publication year (p < 0.001) were associated with better OS, as was low/intermediate tumour grade (p = 0.032) with RFS. Despite its poor prognosis, survival rates of pancreatic squamous cell carcinoma seem improved during the recent years; resectability and low/intermediate grade emerged as favourable prognostic factors. Collaborative epidemiological studies are deemed necessary to further validate the results stemming from the published case reports of this rare entity. © 2017 Elsevier Lt

Robust Neutralizing Antibody Responses 6 Months Post Vaccination with BNT162b2: A Prospective Study in 308 Healthy Individuals

Elucidating long-term immunity following COVID-19 vaccination is essential for decision-making regarding booster shots. The aim of this study was to investigate the kinetics of neutralizing antibodies (Nabs) against SARS-CoV-2 up to six months after the second vaccination dose with the BNT162b2 mRNA vaccine. Nabs levels were measured on days 1 (before the first vaccine shot), 8, 22 (before the second shot), 36, 50, and 3 and 6 months after the second vaccination (NCT04743388). Three hundred and eight healthy individuals without malignant disease were included in this study. At six months, 2.59% of the participants had a Nabs value less than 30%, while 11.9% had Nabs values of less than 50%. Importantly, 58% of the subjects had Nabs values of more than 75%. Nabs were initially eliminated at a relatively slow rate, but after three months their elimination was 5.7 times higher. Older age was inversely associated with Nabs levels at all examined timepoints. Interestingly, a population modeling analysis estimated that half of the subjects will have Nabs values less than 73.8% and 64.6% at 9 and 12 months, respectively, post vaccination completion. In conclusion, we found a persistent but declining anti-SARS-CoV-2 humoral immunity at six months following full vaccination with BNT162b2 in healthy individuals, which was more pronounced among older persons. These data may inform the public health policies regarding the prioritization of booster vaccine shots