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Nathan Goodyear

Gleason Score and Lethal Prostate Cancer: Does 3 + 4 = 4 + 3? - 0 views

www.ncbi.nlm.nih.gov/...PMC2717753

prostate cancer cancer prostate Gleason score

shared by Nathan Goodyear on 16 May 18 - No Cached
  • The Gleason system, introduced in 1974
  • is an architectural grading system that ranges from 1 (well differentiated) to 5 (poorly differentiated)
  • The Gleason score (GS) is the sum of the primary and secondary patterns with a range of 2 to 10
  • ...2 more annotations...
  • patients with GS ≥ 7 are at greater risk for extraprostatic extension and biochemical recurrence
  • It is widely accepted that Gleason grade from biopsy is frequently upgraded at prostatectomy, resulting in a reluctance to assign a low GS at diagnosis
  • Nathan Goodyear on 16 May 18
     
    Review of Gleason score in prostate cancer.
Nathan Goodyear

Histamine dihydrochloride and low-dose interleukin-2 as post-consolidation im... - 0 views

www.academia.edu/...rapy_in_acute_myeloid_leukemia

AML leukemia acute myeloid leukemia IL-2 histamine cancer NK cells

shared by Nathan Goodyear on 31 May 18 - No Cached
  • IL-2 is a central T cell-derived cytokine, which induces NK cell and T cell proliferation, differentiation and activation, and also stim-ulates the production of secondary immunostimulatory cytokines
  • combination of histamine and IL-2 thus triggers efficient NK cell-mediated killing of several types of leukemic cells, including freshly recovered human AML blasts
  • histamine improves the effects of IL-2 on T cell activation
  • ...3 more annotations...
  • principal action of histamine is to protect cytotoxic lymphocytes from myeloid-cell-induced inactivation, thus improving the efficiency of the T and NK cell stimulation achieved by IL-2
  • random-ized Phase II study of patients with renal cell carcinoma further support the suggestion that the combination of HDC and IL-2 improves lymphocyte functions
  • HDC improves the effectiveness of IL-2-induced T and NK cell activation in cancer patients, as predicted in preclinical models
  • Nathan Goodyear on 31 May 18
     
    histamine dihydrochloride enhances immune effects of NK cells in IL02 therapy; specifically in this analysis in AML, the histamin prevented inactivation of the IL-2 activated NK cells.
trungtamnamkhoa

Learn About Male Foreskin Disease - Men's Health Clinic - 1 views

menhealth.vn/...bao-quy-dau

hormone Testosterone Men Disease Male cancer health healthy

shared by trungtamnamkhoa on 25 Jun 19 - No Cached
  • trungtamnamkhoa on 25 Jun 19
     
    Long foreskin It was a situation in which he was always so shy when he opened his eyes even though he could easily go out easily, without pain, without tightening. Even when "greeting the flag" he kept hiding the ball under the glans or just poking out. Must have to wait for the hand of "big brother" to slide down to bear the road to see the world around. When you have a clear understanding of the above concepts, the men of the race race to wonder, "Why is the foreskin of my friend not narrowed but why are my and my brother's bad luck?". The doctor asked for the correct answer, partly because of his bad luck, from birth to growing up, the foreskin was like that, "keep loving and protecting the foreskin." But it is not uncommon for other reasons to make men suffer because of foreskin: First, we have to recall the untimely and improper foreskin effects of parents when children are young. It is these overly "anxious" actions of parents that have counterproductive and narrowed down the latter. There are some autoimmune diseases, making the foreskin a fibrous day, loss of elasticity, gradually worsening, called BXO (balanitisxerotica obliterans) - a narrowed glans. This can also be interpreted as a form of glans, which can even cause narrowing of the urinary tract to lead to urinary retention. Some cases of glans and foreskin have been repeatedly infected by microbiological agents (bacteria, viruses, fungi, etc.), which can be re-infected and non-stop treatment is also available. can lead to complications of fibrosis and secondary stenosis
Nathan Goodyear

Hyperbaric Oxygen Therapy Can Improve Post Concussion Syndrome Years after Mild Traumat... - 0 views

www.ncbi.nlm.nih.gov/...PMC3829860

hbot hyperbaric therapy hyperbaric brain concussion post concussion syndrome TBI traumatic brain injury

shared by Nathan Goodyear on 17 May 17 - No Cached
  • The changes in SPECT images after treatment indicate that HBOT led to reactivation of neuronal activity in stunned areas that seemed normal under CT and MRI imaging. While SPECT imaging has a limited spatial resolution (compared, for example, to fMRI), the changes in activity were sufficiently robust to be clearly detected by the SPECT images.
  • HBOT might initiate a cellular and vascular repair mechanism and improve cerebral vascular flow
  • HBOT induces regeneration of axonal white matter [61], [62], [63], [64], has positive effect upon the myelinization and maturation of injured neural fibers [65], and can stimulate axonal growth and increase the ability of neurons to function and communicate with each other
  • ...6 more annotations...
  • HBOT was found to have a role in initiation and/or facilitation of angiogenesis and cell proliferation processes needed for axonal regeneration [67].
  • The observed reactivation of neuronal activity in the stunned areas found here, along with similar results in post-stroke patients
  • At the cellular level, HBOT can improve cellular metabolism, reduce apoptosis, alleviate oxidative stress and increase levels of neurotrophins and nitric oxide through enhancement of mitochondrial function (in both neurons and glial cells)
  • HBOT may promote the neurogenesis of endogenous neural stem cells
  • With regard to secondary injury mechanisms in mTBI, HBOT can initiate vascular repair mechanism and improve cerebral vascular flow [58], [59], [68], [69], promote blood brain barrier integrity and reduce inflammatory reactions [28] as well as brain edema
  • It might be possible that HBOT enables the metabolic change simply by supplying the missing energy/oxygen needed for those regeneration processes.
  • Nathan Goodyear on 17 May 17
     
    Hbot therapy, according to study, induces neuroplasticity and improves brain function in post concussion syndrome and those with mTBI.  The important point about this study was that the study was done years after the injury; what if the therapy was employed immediately after...
Nathan Goodyear

The Risk of Fluoroquinolone-induced Tendinopathy and Tendon Rupture - 0 views

www.ncbi.nlm.nih.gov/...PMC2921747

flouroquinolones ciprofloxacin levoquin tendinitis tendinopathy Tendon rupture

shared by Nathan Goodyear on 02 Aug 17 - No Cached
  • Achilles tendinitis or rupture is among the most serious side effects associated with FQ use
  • The large body of data provided by clinical reports, histopathological examination, and experimental studies provides cogent evidence supporting a direct link between FQ use and tendonitis/tendon rupture
  • Risk factors associated with FQ-induced tendon disorders include age greater than 60 years, corticosteroid therapy, renal failure, diabetes mellitus, and a history of musculoskeletal disorders
  • ...17 more annotations...
  • The average age of FQ-induced tendinopathy is 64 years, with a male-to-female ratio of 2:1, and a 27-percent incidence of bilateral involvement
  • Although more than 95 percent of cases of tendinitis/rupture secondary to FQ involve the Achilles tendon, other reported sites of tendon involvement include the quadriceps, peroneus brevis, and rotator cuff
  • FQs demonstrate a 3.8-fold greater risk for development of Achilles tendinitis/rupture
  • a large population-based case control analysis, patients treated with FQs exhibited a substantially increased risk of developing tendon disorders overall (1.7-fold), tendon rupture (1.3-fold), and ATR (4.1-fold)
  • patients taking FQs with concurrent exposure to corticosteroids were found to experience a compounding effect on the risk of tendon rupture, specifically a 46-fold greater predisposition
  • Some authors have recommended that patients with a history of Achilles tendinitis and advanced age should not be prescribed FQ antibiotics
  • Approximately 50 percent of patients will recover within 30 days, with 25 percent of patients having symptoms persistent for longer than two months
  • The mean latency period between the start of FQ treatment and occurrence of tendinopathy has been reported to be a few hours to months, with a median onset of 6 days
  • The exact pathophysiology of FQ-induced tendinopathy remains elusive
  • it is possible that FQs have a direct cytotoxic effect on enzymes found in mammalian musculoskeletal tissue
  • It has been theorized that FQs disproportionately affect human tendons that have a limited capacity for repair, such as in older patients or structural compromise (i.e., pre-existing tendinopathy or trauma)
  • histopathological findings are similar to those observed in overuse conditions in athletes
  • Treatment with a FQ should be discontinued and physical therapy initiated
  • treatment should include rest and decreasing the physical load on the tendon.
  • Approximately 85 percent of patients present in less than one month
  • Because rupture can occur even late in the course of treatment or after discontinuation of FQ use, patients receiving a FQ should be counseled to seek medical attention immediately if symptoms, such as redness, pain, swelling, and stiffness, develop
  • FQs should be used cautiously in patients with risk factors associated with tendinitis, such as advanced age, history of tendon rupture, corticosteroid use, and/or acute or chronic renal dysfunction
  • Nathan Goodyear on 02 Aug 17
     
    Great review of the link between flouroquinolones and Tendinitis and Tendon rupture.  Yes, there is a direct link.
Nathan Goodyear

Availability of evidence of benefits on overall survival and quality of life of cancer ... - 0 views

www.bmj.com/bmj.j4530

cancer cancer treatment survival quality of life

shared by Nathan Goodyear on 20 Dec 17 - No Cached
  • Although the goal of cancer treatment is to improve the quantity and quality of life,123 clinical trials designed to gain regulatory approval for new drugs often evaluate indirect or “surrogate” measures of drug efficacy. These endpoints show that an agent has biological activity, but they are not reliable surrogates for improved survival4567891011 or quality of life46111213
  • two recent systematic reviews suggest that the strength of association between surrogates in cancer clinical trials and life extension is generally low
  • Available data from the US show that only a small proportion of cancer treatments approved by the US Food and Drug Administration (FDA) unequivocally show benefits on survival or quality of life.30
  • ...16 more annotations...
  • We sought to systematically evaluate the evidence base for all new drugs and new indications for the treatment of solid tumours and haematological malignancies approved by the EMA in the five year period 2009-13
  • Three investigators (AP, EP, and EG) independently extracted data on and descriptively analysed the following trial features: characteristics of the participant population, study design (randomisation, crossover from experimental to control group, and blinding of investigators and participants), experimental and control groups, enrolment, primary and secondary endpoints, magnitude of benefit on survival and quality of life, and narrative interpretation of the findings
  • Only 18 of the 68 (26%) were supported by a pivotal study powered to evaluate overall survival as the primary outcome
  • From 2009 to 2013, the EMA approved use of 48 oncology drugs
  • Seventeen drugs were approved for treatment of haematological malignancies and 51 for treatment of solid tumours
  • Overall, 72 clinical trials supported the approval of 68 novel drug uses
  • Our scoring was limited to drugs for solid tumours
  • Among 68 cancer drug indications approved by the EMA in the period 2009-13, and with a median of 5.4 years’ follow-up, only 35 (51%) were associated with a significant improvement in survival (26/35) or quality of life (9/35) over existing treatment options, placebo, or as add on treatment
  • Only two of the 26 drugs shown to extend life also showed benefits on quality of life
  • 33 (49%) had not shown any improvement on survival or quality of life
  • This systematic evaluation of oncology drug approvals by the EMA in 2009-13 shows that most of the drugs (39/68, 57%) entered the market without evidence of improved survival or quality of life
  • At a minimum 3.3 years after market entry, there was still no conclusive evidence that 33 of these 39 cancer drugs either extended or improved life
  • What are potential reasons for the paucity of drug approvals with demonstrable survival advantages over existing treatments?
  • Firstly, only 18 (26%) indications for use in our cohort were supported by trials in which extension of life was the primary outcome
  • None of the pivotal studies supporting oncology drug approvals from 2009 to 2013 included quality of life as a primary outcome measure
  • Most new oncology drugs authorised by the EMA in 2009-13 came onto the market without clear evidence that they improved the quality or quantity of patients’ lives
  • Nathan Goodyear on 20 Dec 17
     
    New study from European Medicines Agency questions alot of the new cancer drugs brought to the market 2009-2013.  57% of the new drugs (39/68) were brought to the market without evidence of improved survival or quality of life.
Nathan Goodyear

NETosis and Neutrophil Extracellular Traps in COVID-19: Immunothrombosis and Beyond - PMC - 0 views

www.ncbi.nlm.nih.gov/...PMC8924116

cancer NETosis SARS-CoV-2 COVID COVID-19 COVID19 platelets

shared by Nathan Goodyear on 18 Apr 23 - No Cached
  • Pneumonia is a typical symptom of COVID-19 infection, while acute respiratory distress syndrome (ARDS) and multiple organ failure are common in severe COVID-19 patients
  • NETs are important for preventing pathogen invasion, their excessive formation can result in a slew of negative consequences, such as autoimmune inflammation and tissue damage
  • SARS-CoV-2 infection has also been linked to increased neutrophil-to-lymphocyte ratios, which is associated with disease severity and clinical prognosis
  • ...40 more annotations...
  • NETosis is a special form of programmed cell death in neutrophils, which is characterized by the extrusion of DNA, histones, and antimicrobial proteins in a web-like structure known as neutrophil extracellular traps (NETs)
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      Definition
  • increased generation of reactive oxygen species (ROS) is a crucial intracellular process that causes NETosis
  • Another indirect route of SARS-CoV-2-induced NET production is platelet activation
  • When NETs are activated in the circulation, they can also induce hypercoagulability and thrombosis
  • In COVID-19, major NET protein cargos of NETs (i.e., NE, MPO, and histones) are significantly elevated.
  • SARS-CoV-2 can also infect host cells through noncanonical receptors such as C-type lectin receptors
  • Immunopathological manifestations, including cytokine storms and impaired adaptive immunity, are the primary drivers behind COVID-19, with neutrophil infiltration being suggested as a significant cause
  • NETosis and NETs are increasingly recognized as causes of vascular injury
  • SARS-CoV-2 and its components (e.g., spike proteins and viral RNA) attach to platelets and increase their activation and aggregation in COVID-19, resulting in vascular injury and thrombosis, both of which are linked to NET formation
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      Connects SARS-CoV-2 to TLR on Platelets to NETosis to metastasis.
  • NET formation may be caused by activated platelets rather than SARS-CoV-2 itself
  • NETosis, leading to aberrant immunity such as cytokine storms, autoimmune disorders, and immunosuppression.
  • early bacterial coinfections were more prevalent in COVID-19 patients than those infected with other viruses
  • NETosis and NETs may also have a role in the development of post COVID-19 syndromes, including lung fibrosis, neurological disorders, tumor growth, and worsening of concomitant disease
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      NETosis-> tumor growth
  • NETs and other by-products of NETosis have been shown to act as direct inflammation amplifiers. Hyperinflammation
  • “cytokine storm”
  • SARS-CoV-2 drives NETosis and NET formation to allow for the release of free DNA and by-products (e.g., elastases and histones). This may trigger surrounding macrophages and endothelial cells to secrete excessive proinflammatory cytokines and chemokines, which, in turn, enhance NET formation and form a positive feedback of cytokine storms in COVID-19
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      Cycle of hyperinflammation
  • NET release enables self-antigen exposure and autoantibody production, thereby increasing the autoinflammatory response
  • patients with COVID-19 who have higher anti-NET antibodies are more likely to be detected with positive autoantibodies [e.g., antinuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA)]
  • COVID-19 NETs may act as potential inducers for autoimmune responses
  • have weakened adaptive immunity as well as a high level of inflammation
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      Immunomodulation
  • tumor-associated NETosis and NETs promote an immunosuppressive environment in which anti-tumor immunity is compromised
  • NETs have also been shown to enhance macrophage pyroptosis in sepsis
  • facilitating an immunosuppressive microenvironment
  • persistent immunosuppression may result in bacterial co-infection or secondary infection
  • can enhance this process by interacting with neutrophils through toll-like receptor 4 (TLR4), platelet factor 4 (PF4), and extracellular vesicle-dependent processes
  • NET-induced immunosuppression in COVID-19 in the context of co-existing bacterial infection
  • Following initial onset of COVID-19, an estimated 50% or more of COVID-19 survivors may develop multi-organ problems (e.g., pulmonary dysfunction and neurologic impairment) or have worsening concomitant chronic illness
  • NETs in the bronchoalveolar lavage fluid of severe COVID-19 patients cause EMT in lung epithelial cells
  • decreased E-cadherin (an epithelial marker) expression
    • Nathan Goodyear
      Nathan Goodyear on 23 Apr 23
       
      Leads to emt
  • COVID-19 also has a long-term influence on tumor progression
  • Patients with tumors have been shown to be more vulnerable to SARS-CoV-2 infection and subsequent development of severe COVID-19
  • patients who have recovered from COVID-19 may have an increased risk of developing cancer or of cancer progression and metastasis
  • awaken cancer cells
  • NETs have been shown to change the tumor microenvironment
  • enhance tumor progression and metastasis
  • vitamin C has been tested in phase 2 clinical trials aimed at reducing COVID-19-associated mortality by reducing excessive activation of the inflammatory response
  • vitamin C is an antioxidant that significantly attenuates PMA-induced NETosis in healthy neutrophils by scavenging ROS
  • vitamin C may also inhibit NETosis and NET production in COVID-19
  • Metformin
  • Vitamin C
  • Nathan Goodyear on 18 Apr 23
     
    NETosis intimately involved in progressive COVID, long COVID, autoimmunity, and cancer
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