ESMED small

Challenges and Opportunities in Blood Disorders

Challenges and Opportunities in Blood Disorders

Hullender, D. A., Brown, O. R., & Shrotriya, A. (2023)

Abstract

     This paper describes a novel approach designed for non-invasive, routine screening of patients for cardiovascular disorders without the complexities of using an electrocardiogram or invasive probes. Specifically, an oscillographic-view of the brachial artery blood pressure waveform, including the dicrotic notch, is extracted from information in the pressure pulsations from an ordinary blood pressure cuff. The novelty of this approach is that the total continuous shape of the waveform, not just two numbers for pressures, is generated.  A computer algorithm processes the cuff pressure pulsations and provides a near real-time visual estimate of the continuous shape of the blood pressure waveform to be viewed on oscilloscopes commonly used in hospitals and medical clinics. A model-based Extended Kalman Filter (EKF) algorithm is used to process the information and identify the coefficients of a Fourier transform model for the waveform and the coefficients for an empirical model for artery stiffness. By viewing the total waveform, variations or disorders in the waveform during a series of pulse cycles can be observed and easily recognized. Simulations of two-case studies demonstrate successful convergence of the algorithm for a variety of waveform disorders including arrhythmia, variations in the shape of the dicrotic notch, changing systolic and diastolic pressure levels, and stiff arteries. Experimental verification of this proposed procedure will require invasive pressure measurements while simultaneously processing the algorithm for non-invasive waveform comparisons. Once the algorithm is verified experimentally, the end goal is to use the procedure on patients with known cardiovascular diseases in order to easily create a database of waveform disorders correlated with disorders of specific cardiovascular diseases.

Canaud, B., Hornig, C., & Bowry, S. K. (2022)

Abstract

Sodium and water-related disorders are major components of chronic kidney disease (CKD) and contribute significantly to cardiovascular (CV) complications and mortality. Usually, they are marked by gradual accumulation of sodium, water and have hemodynamic consequences (i.e., fluid overload, hypertension and cardiac disorders) along with the progression of kidney failure culminating in end stage kidney disease. Renal replacement therapy which is then required to sustain life is intended to restore sodium, fluid and pressure disorders along with the objective of reducing the uremic toxin load. Unfortunately, the intermittent nature of conventional short hemodialysis relying on a so called ‘dry weight’ probing approach, only partially restores the sodium-water overload related disorders, thereby exposing patients to further multi-organ damage through the resultant dialysis-induced systemic stress (DISS).

Fluid volume management in dialysis patients has emerged as a very challenging condition that requires further attention and more precise tools. Furthermore, recent findings indicate that the physiology of sodium is more complex than that previously summarized by the kidney-centric two-compartment model (volemia and Interstitium) linked to osmotically active sodium (water-bound sodium). A third tissue compartment (skin, muscle) of sodium has now been identified, taking the form of free-water sodium [glycosaminoglycans (GAGs) or gel-like component] with newly-identified pathophysiologic metabolic consequences.

All these findings suggest that restoration of sodium homeostasis in dialysis-dependent chronic kidney disease patients should encompass a more holistic approach to improve cardiac health and reduce cardiovascular burden in this highly vulnerable population.

In this context, new tools for monitoring and managing dialysis patients to ensure a more precise and personalized control of their sodium and water homeostasis, volemic and hemodynamic disorders are needed. Several monitoring and management tools (e.g., bioimpedance, lung ultrasound, blood volume control, thermal balance control) are already available with potential value. The conductivity measurement-based automated sodium control module represents the latest and very appealing addition to this list of innovative tools. Although establishing the clinical value of these tools requires further outcome-based studies, current clinical use of this new tools has shown promising indications towards the goal of reducing CV morbidity and mortality in kidney dialysis patients.

A brief review of these new pathophysiologic findings as well as clinical interests of these new tools is provided in this narrative review.

Bipat, R., Magali, I., Soekhoe, R., & Toelsie, J. R. (2023)

Abstract

Emerging evidence suggests that a high postprandial glucose level in plasma or blood is an important factor for the etiology of non-communicable disorders like the metabolic syndrome, diabetes, obesity and cardiovascular disease. A high sugar content of the food naturally increases the postprandial glucose level. However, quite a few studies provided proof in the past that the physical properties like viscosity, temperature, and water content of the food we consume also may influence the level of this parameter. The aim of this study is to give a narrative review of present findings that showed the physical properties of consumed food influenced the postprandial glucose level.

The online databases Medline, Pubmed, Google Scholar and Hinari have been searched for publications on “plasma glucose” and “temperature” or “viscosity” or “solubility” or “water content”. All articles dealing with the influence on the postprandial glucose level in the blood have been included. Articles written in a language we could not understand or without a proper translation into English have been excluded.

In general, most available studies showed that the physical properties temperature, viscosity, and water content of consumed food influenced the postprandial glucose. An increased temperature, increased viscosity and decreased water content of the food is generally associated with a higher postprandial glucose level in blood or plasma after consumption. Further detailed studies in both preclinical as well as clinical trials should be considered to obtain more detailed results regarding this.

Bipat, R., Magali, I., Soekhoe, R., & Toelsie, J. R. (2023b)

Abstract

Emerging evidence suggests that a high postprandial glucose level in plasma or blood is an important factor for the etiology of non-communicable disorders like the metabolic syndrome, diabetes, obesity and cardiovascular disease. A high sugar content of the food naturally increases the postprandial glucose level. However, quite a few studies provided proof in the past that the physical properties like viscosity, temperature, and water content of the food we consume also may influence the level of this parameter. The aim of this study is to give a narrative review of present findings that showed the physical properties of consumed food influenced the postprandial glucose level.

The online databases Medline, Pubmed, Google Scholar and Hinari have been searched for publications on “plasma glucose” and “temperature” or “viscosity” or “solubility” or “water content”. All articles dealing with the influence on the postprandial glucose level in the blood have been included. Articles written in a language we could not understand or without a proper translation into English have been excluded.

In general, most available studies showed that the physical properties temperature, viscosity, and water content of consumed food influenced the postprandial glucose. An increased temperature, increased viscosity and decreased water content of the food is generally associated with a higher postprandial glucose level in blood or plasma after consumption. Further detailed studies in both preclinical as well as clinical trials should be considered to obtain more detailed results regarding this.

Mehdipour, P. (2023)

Abstract

Successful cancer evolution (CE) relies on the sequential molecular and functional events including 1) telomere; 2) sub-telomere; 3) epigenetic; 4-6) hit-episodes; 7) an innovative cell cycle machinery, as the multi-phase, and 8) chromosomal abnormalities. In this regard, eight available, fundamental/evolutionary and strategic key information (Evolutionary- ID) presented.

Telomere length (TL), has the fundamental role in cancer development, with serious challenges in the clinical managements. Breast cancer and brain tumor are an unresolved problem in Science and Medicine. Besides, an early and translatable diagnostic- prognostic-predictive platform, by considering the targets-ID, is required. Diverse TL in two cases affected with astrocytoma with grade IV, revealed to be 12500 and 15000 bp in tumor, and 10000 and 9000 bp at genomic level. Interestingly, TL is declined in the lymph node, i.e., occurrence of evolution.

Sub-telomeres (STs) through the cellular journey, are the neighboring destination at genomic and somatic level. The evolutionary pattern of STs has not been, routinely, decoded to the personalized clinical managements. The STsequences, are diversely predisposed to variety of environmental factors and play influential role in healthy individuals and the patients. An early detection is available by analysis of the ST- hybridized signals in the biopsy of auxiliary lymph nodes (ALN), and/or by circulating tumor cells (CTCs) into the blood stream. Diverse pattern of signal frequency and intensity in individual chromosomes at both somatic (ALN) and genomic (lymphocytes) levels were remarkable. The most common involved targets included chromosomes 5 and 9, 16 and 19; with diverse intensity at p and q chromosomal arms respectively. These findings have the predisposing, and an initial influence through the patients’ course of disease.

ST- signals, by providing the STs-ID, offer periodical and predictive, indices in cancer screening and therapy.

Furthermore, the complementary, cell cycle protein expression (PE) including Ki67, cyclin D1, and cyclin E, accelerates an early clinical management through the period of disease based on the CTCs.

Epigenetics is the next molecular destination by focusing on the genomic/somatic index, as an evolutionary Epigenetics-ID with its impact on the cancer management. The target panel is Ataxia Telangiectasia mutated gene (ATM) as the molecular marker and an initiator of different cancers.

ATM has remarkable roles, including: 1) in DNA double strand break (DSB), 2) to initiate different types of neoplastic disorders, including cancer, and 3), polymorphism, D1853N as a peridisposing marker by initiating the hit process. The influential characteristics include: family history of neoplastic disorders through the pedigree, the key role of ATM promoter methylation, cooperation of ATM/Rb protein expression, D1853N- marker, telomere length (TL) and the clinico-pathological characteristics in different types of brain tumors, and the environmental factors. Interestingly, TL has an independent influence on the progressive cancer evolution. An early detection by CTCs based on the D1853N/Sub-TL/Cell cycle checkpoints based on the PE assay and molecular test facilitate an early detection and therapy, based on the personalized approach.

By highlighting the preventive insight in Medicine, a brief record on the “Methylation in Chorionic villus samples (CVS)” with aim of an early detective strategy is provided. All nine CVS samples were methylated for the MCPH1 gene. An early detection is possible either through CV sampling or by the circulating CV cells in the maternal blood.

Evolutionary Hit includes: presence of D1853N polymorphism of ATM, as the hit-initiator through an evolutionary and progressive molecular based sequential alterations led to discovery of three-hit hypothesis in a patient affected with astrocytoma. More hits include five, and eight- hit hypotheses in primary breast cancer patients. Such platforms are considered as the individualized model in cancer. The pedigrees and details at the molecular follow-up studies and functional alteration at protein level are available in the provided sections.

Novel strategy of Cell cycle phases in breast cancer is the major intersection for cancer therapy.

The novel cell cycle hypothesis (CCH) highlights the mosaic based of dual and/or multi-phases, as minor clones at single cell level in the breast cancer (BC) -patients, escorted by the normal cell population. Such mosaicism provided an archetypal, unique diagnostic and therapeutic model, by applying different mosaic patterns (MPs) as well as “G1/S, S/G2 and G1/S/G2, and accompanied by normal phases, as a sole including G1, S, and G2 at the single cells level.  

Diagnosis is based on the mode of signal copy numbers (SCN) and the related PE. Interestingly MPs were also unmasked in patients with chronic myelogeneous leukemia and other solid tumors.

Finally, the predisposing/predictive/prognostic/preventive square provides an innovate CDKs inhibitor-based therapy in BC and other cancers.

Personalized base cancer therapy is the confusing procedure and requires the pedigree-based data, personalized, evolutionary based information including molecular and functional at both genomic and somatic, at single cell levelThe target territories comprise cell cycle phases, proteins, Telomere length, telomerase, sub-telomere, and Epigenetics. The aim is directing the cell cycle fundamental forces back to normal, by performing:

1) Applying personalized, single cell-based approach, at molecular, functional level, pedigree analysis, and balancing the micro-/macro-environmental factors, including nutrition.

2) Satisfactory high single cell enumeration based on the FISH and protein expression assays;

3) Decoding the required dosage and combined therapeutic regimens accordingly,

4) Unmasking the cell cycle combined (mosaic) phases including different Cyclins; and

5) Bilateral cooperation between Pharmacology, Medicine, and Cancer Genetics/cell biology.


 Let’s combine the evolutionary based strategy by translating the personalized data at molecular/ Functional/ Informative, and pedigree-based level to the personalized therapy.

Maksimovich, I. V. (2023)

Abstract

Background: Alzheimer’s disease (AD) is the world’s number one cerebral neurodegenerative disease. Up to 80% of all dementia cases are due to this disease. AD occurs not only because of impaired metabolism of amyloid beta (Aβ) and tau protein in cerebral tissue, but also in connection with specific disorders of cerebral blood supply, manifested in dyscirculatory angiopathy of Alzheimer’s type (DAAT).

Aims: The present research focuses on the clinical discovery of the sequence of development of dyscirculatory angiopathy of Alzheimer’s type, cerebral atrophy, and dementia in patients with AD and their immediate family members.

Methods: 99 patients were selected for the research, of whom:

Test Group 1

93 (93.94%) suffered from various stages of AD and severity of dementia (age 34-79 (mean age 67): 32 (34.40%) men, 61 (65.59%) women).

Test Group 2

6 (6.06%) children aged 8-12 with a high probability of inheriting AD. Each of them had a parent diagnosed with AD with mild dementia (TDR-1), and a grandparent diagnosed with AD with moderate (TDR-2) or severe dementia (TDR-3). Each child complained of fatigue, memory loss, difficulty in remembering, difficulty in concentrating, and frequent headaches.

Results:

Test Group 1. According to the severity of dementia and atrophic changes in the temporal lobes, the patients were subdivided: preclinical stage TDR-0 – 10 (10.75%) people, mild stage AD TDR-1 – 26 (27.96%) people, moderately severe stage AD TDR-2-40 (43.01%) people, severe AD TDR-3 – 17 (18.28%) people. We identified dyscirculatory angiopathy of Alzheimer’s type in all patients, regardless of their AD stage.

Test Group 2. There were no signs of dementia of cognitive disorders in any case. Initial involutive cerebral changes were detected in all 6 (100%) patients. Phenomena similar to DAAT were detected in all 6 (100%) patients.

Conclusion: Cerebrovascular changes manifested by dyscirculatory angiopathy of Alzheimer’s type, regardless of the stage of the disease, are observed in all patients with AD, as well as in all their young offspring.

These changes affect amyloid beta metabolism in the brain and contribute to its deposition and accumulation in cerebral tissue, which leads to neurodegeneration and AD development.

The data obtained indicate that dyscirculatory angiopathy of Alzheimer’s type is primary and, moreover, possibly congenital in AD development.

De Moraes Salles Salles, M. L., García, N., Laurindo, L. F., Scanavacca, A., Ezídio, K., Tofano, R. J., Detregiachi, C. R. P., Haber, J. F. D. S., Marconatto, M., Barbalho, S. M., & Quesada, K. (2022)

Abstract

Poor sleep quality can affect cardiovascular health and is considered a significant risk factor for the development of risk factors for Metabolic syndrome (MetS). This study aimed to investigate possible associations between sleep quality measured by the Pittsburgh Sleep Quality Index and the MetS. This was a cross-sectional that comprised data from 208 patients. Biochemical and anthropometric parameters were assessed. The identification of MetS was performed according to the International Diabetes Federation guidelines. The quantitative variables were described with the support of the BioEstat 5.3 software. To assess the association of the studied variables with the diagnosis of MetS, the Mann-Whitney and Chi-square (n x n) statistical tests were used. The level of significance considered was 5%. According to the International Diabetes Federation criteria, 111 (53,36%) men and women presented MetS. There were no statically significant differences between the groups with or without sleep disorders and the values of waist circumference (p=0.6996), high-density lipoprotein cholesterol levels (p=0.7940), triglycerides levels (p=0.8703), blood pressure values (p= 0.9851, and p=0.9795 for systolic and diastolic blood pressure, respectively), and glycemia (p=0.5351). Eighty-eight volunteers (42%) presented sleep quality dysfunction, with the highest proportion observed among individuals affected by MetS (p=0.0019). Our results indicate an association between sleep quality and the prevalence of MetS . Therefore, sleep quality could be evaluated in patients with MetS so that the therapeutic strategy would not be limited to the intervention in biochemical and anthropometric factors.

Maksimovich, I. V. (2022)

Abstract

Background: Alzheimer’s disease (AD) and Binswanger’s disease (BD) are among the most common neurodegenerative disorders associated with cognitive impairment and dementia. Using energy of lasers with low output power of the red or near-infrared spectrum region called Photobiomodulation Therapy (PBMT), is an achievement in the development of methods for the treatment of these diseases.

Aims: The present study investigates the impact of Transcatheter Intracerebral Laser Photobiomodulation Therapy (PBMT) on the reduction of cognitive, mental impairment and dementia in patients with various Alzheimer’s Disease and Binswanger’s Disease stages.

Methods: For the research, we selected 62 patients suffering from dementia, aged 34-81 (mean age 72.75), 25 men (40.32%), 37 women (59.68%).

Test Group 1 – 48 patients previously diagnosed with Alzheimer’s Disease. According to dementia severity, patients were subdivided: preclinical stage (dementia level TDR-0) – 4, mild stage (dementia level TDR-1) – 16, moderately severe stage (dementia level TDR-2) – 21, severe stage (dementia level TDR-3) – 7.

Test Group 2 – 14 patients with previously diagnosed Binswanger’s Disease. According to dementia severity, the patients were subdivided: mild stage (dementia level CDR-1) – 9, moderately severe stage (dementia level CDR-2) – 5.

All patients underwent Transcatheter Intracerebral Laser Photobiomodulation Therapy (PBMT).

Results:

Test Group 1. Thanks to angiogenesis and neurogenesis stimulation using Transcatheter Intracerebral Laser Photobiomodulation Therapy (PBMT), in all 48 (100%) cases, cerebral blood supply and microcirculation improved, cerebral involutive and atrophic changes decreased. Patients showed persistently decreasing dementia, cognitive and mental abilities improvement. The vast majority began to correspond to the group with a milder disease stage.

Test Group 2. Due to angiogenesis and neurogenesis stimulation, all 14 (100%) cases demonstrated stable dementia reduction, restoration of cognitive, mental functions and daily life activities.

Conclusion: Transcatheter Intracerebral Laser Photobiomodulation Therapy (PBMT) is an effective, physiologically based method of stimulating cerebral angiogenesis and neurogenesis for Alzheimer’s Disease and Binswanger’s Disease patients. Due to complex laser exposure, patients show cerebral collateral and capillary revascularization, tissue metabolism improvement and cerebral regenerative processes development. Clinically, this leads to stable dementia level decrease, cognitive functions restoration and improvement in patients’ quality of life. The resulting clinical effect lasts for many years.