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Intermittent androgen deprivation therapy for pro... [Can J Urol. 2014] - PubMed - NCBI - 0 views

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    Interesting concept on Androgen deprivation therapy.  ADT has significant negative metabolic effects in men.  Here Intermittent ADT is evaluated and found to be questionable in its outcome.
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Acute myocardial infarction and thyroid function: New pathophysiological and therapeuti... - 0 views

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    Thyroid hormone plays significant role in cardiac remodeling after acute myocardial infarction.  Thyroid hormone, particularly T3 as the vast majority of T3 is produced in heart tissue via D1 enzymatic activity, improves cardiac contractility, reduces systemic vascular resistance, reduces cardiac work load, decreases blood pressure, improves cardiac metabolism, and thus improves outcomes post MI.
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Salivary progesterone and estriol among pregnant w... [Am J Obstet Gynecol. 2008] - Pub... - 1 views

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    saliva testing of progesterone and estriol not questioned, but used to predict outcomes
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A Guide to Perioperative Nutrition - 0 views

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    nutritional therapy before and after surgery improve surgical outcomes
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Perioperative Nutrition and Postoperative Complications in P... : Spine - 0 views

  • Patients with suboptimal nutritional parameters should be supplemented and replenished before elective surgery.
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    Nutrition status should be evaluated before surgery to help improve outcomes
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Thyroid Replacement Therapy and Heart Failure - 0 views

  • A good biomarker of intracardiac TH signaling would be helpful but has not been identified. In the absence of such a marker, a rational, cautious therapeutic approach might be to restore and maintain over time biochemical euthyroidism as documented by normal circulating levels of TSH, FT4, and FT3.
  • a low-T3 state resulting from altered peripheral TH metabolism secondary to caloric restriction is associated with impaired cardiac contractility
  • Low-T3 syndrome is the central finding and defines the illness in a variety of acute and chronic severe nonthyroidal illnesses with cardiac origin, including MI, HF, and surgically treated cardiac disease.1 Low circulating levels of T3 in the absence of primary thyroid hypofunction have been found in 20% to 30% of patients with dilated cardiomyopathy.
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  • FT3 levels were inversely correlated to coronary artery disease
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    Great review of the current understanding of thyroid hormone metabolism in cardiac tissue.  Low T3 and increased rT3 (via increased D3 activity) is CLEARLY associated with poor cardiac performance and post MI and CHF is associated with poor outcomes.  T3 is critical in cardiac remodeling and recovery post MI.  T3 is actually a vasodilatory in the coronary arteries.   Why a endocrinologist would call rT3 useless only points to their ignorance of the literature.
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Association of testosterone with estrogen abolishes the beneficial effects of estrogen ... - 0 views

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    Testosterone reduced the vascular benefits of Estrogen (conjugated equine Estrogen) in female rat model.  Testosterone is seeing widespread use in women with very little positive data.  In fact, the majority of data points to poor metabolic effects and poor outcomes.
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Cancer cells metabolically "fertilize" the tumor microenvironment with hydrogen peroxid... - 0 views

  • reducing oxidative stress with powerful antioxidants, is an important strategy for cancer prevention, as it would suppress one of the key early initiating steps where DNA damage and tumor-stroma metabolic-coupling begins. This would prevent cancer cells from acting as metabolic “parasites
  • Oxidative stress in cancer-associated fibroblasts triggers autophagy and mitophagy, resulting in compartmentalized cellular catabolism, loss of mitochondrial function, and the onset of aerobic glycolysis, in the tumor stroma. As such, cancer-associated fibroblasts produce high-energy nutrients (such as lactate and ketones) that fuel mitochondrial biogenesis and oxidative metabolism in cancer cells. We have termed this new energy-transfer mechanism the “reverse Warburg effect.
  • Then, oxidative stress, in cancer-associated fibroblasts, triggers the activation of two main transcription factors, NFκB and HIF-1α, leading to the onset of inflammation, autophagy, mitophagy and aerobic glycolysis in the tumor microenvironment
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  • oxidative stress and ROS, produced in cancer-associated fibroblasts, has a “bystander effect” on adjacent cancer cells, leading to DNA damage, genomic instability and aneuploidy, which appears to be driving tumor-stroma co-evolution
  • tumor cells produce and secrete hydrogen peroxide, thereby “fertilizing” the tumor microenvironment and driving the “reverse Warburg effect.”
  • This type of stromal metabolism then produces high-energy nutrients (lactate, ketones and glutamine), as well as recycled chemical building blocks (nucleotides, amino acids, fatty acids), to literally “feed” cancer cells
  • loss of stromal caveolin (Cav-1) is sufficient to drive mitochondrial dysfunction with increased glucose uptake in fibroblasts, mimicking the glycolytic phenotype of cancer-associated fibroblasts.
  • oxidative stress initiated in tumor cells is transferred to cancer-associated fibroblasts.
  • Then, cancer-associated fibroblasts show quantitative reductions in mitochondrial activity and compensatory increases in glucose uptake, as well as high ROS production
  • These findings may explain the prognostic value of a loss of stromal Cav-1 as a marker of a “lethal” tumor microenvironment
  • aerobic glycolysis takes place in cancer-associated fibroblasts, rather than in tumor cells, as previously suspected.
  • our results may also explain the “field effect” in cancer biology,5 as hydrogen peroxide secreted by cancer cells, and the propagation of ROS production, from cancer cells to fibroblasts, would create an increasing “mutagenic field” of ROS production, due to the resulting DNA damage
  • Interruption of this process, by addition of catalase (an enzyme that detoxifies hydrogen peroxide) to the tissue culture media, blocks ROS activity in cancer cells and leads to apoptotic cell death in cancer cells
  • In this new paradigm, cancer cells induce oxidative stress in neighboring cancer-associated fibroblasts
  • cancer-associated fibroblasts have the largest increases in glucose uptake
  • cancer cells secrete hydrogen peroxide, which induces ROS production in cancer-associated fibroblasts
  • Then, oxidative stress in cancer-associated fibroblast leads to decreases in functional mitochondrial activity, and a corresponding increase in glucose uptake, to fuel aerobic glycolysis
  • cancer cells show significant increases in mitochondrial activity, and decreases in glucose uptake
  • fibroblasts and cancer cells in co-culture become metabolically coupled, resulting in the development of a “symbiotic” or “parasitic” relationship.
  • cancer-associated fibroblasts undergo aerobic glycolysis (producing lactate), while cancer cells use oxidative mitochondrial metabolism.
  • We have previously shown that oxidative stress in cancer-associated fibroblasts drives a loss of stromal Cav-1, due to its destruction via autophagy/lysosomal degradation
  • a loss of stromal Cav-1 is sufficient to induce further oxidative stress, DNA damage and autophagy, essentially mimicking pseudo-hypoxia and driving mitochondrial dysfunction
  • loss of stromal Cav-1 is a powerful biomarker for identifying breast cancer patients with early tumor recurrence, lymph-node metastasis, drug-resistance and poor clinical outcome
  • this type of metabolism (aerobic glycolysis and autophagy in the tumor stroma) is characteristic of a lethal tumor micro-environment, as it fuels anabolic growth in cancer cells, via the production of high-energy nutrients (such as lactate, ketones and glutamine) and other chemical building blocks
  • the upstream tumor-initiating event appears to be the secretion of hydrogen peroxide
  • one such enzymatically-active protein anti-oxidant that may be of therapeutic use is catalase, as it detoxifies hydrogen peroxide to water
  • numerous studies show that “catalase therapy” in pre-clinical animal models is indeed sufficient to almost completely block tumor recurrence and metastasis
  • by eliminating oxidative stress in cancer cells and the tumor microenvironment,55 we may be able to effectively cut off the tumor's fuel supply, by blocking stromal autophagy and aerobic glycolysis
  • breast cancer patients show systemic evidence of increased oxidative stress and a decreased anti-oxidant defense, which increases with aging and tumor progression.68–70 Chemotherapy and radiation therapy then promote further oxidative stress.69 Unfortunately, “sub-lethal” doses of oxidative stress during cancer therapy may contribute to tumor recurrence and metastasis, via the activation of myofibroblasts.
  • a loss of stromal Cav-1 is associated with the increased expression of gene profiles associated with normal aging, oxidative stress, DNA damage, HIF1/hypoxia, NFκB/inflammation, glycolysis and mitochondrial dysfunction
  • cancer-associated fibroblasts show the largest increases in glucose uptake, while cancer cells show corresponding decreases in glucose uptake, under identical co-culture conditions
  • Thus, increased PET glucose avidity may actually be a surrogate marker for a loss of stromal Cav-1 in human tumors, allowing the rapid detection of a lethal tumor microenvironment.
  • it appears that astrocytes are actually the cell type responsible for the glucose avidity.
  • In the brain, astrocytes are glycolytic and undergo aerobic glycolysis. Thus, astrocytes take up and metabolically process glucose to lactate.7
  • Then, lactate is secreted via a mono-carboxylate transporter, namely MCT4. As a consequence, neurons use lactate as their preferred energy substrate
  • both astrocytes and cancer-associated fibroblasts express MCT4 (which extrudes lactate) and MCT4 is upregulated by oxidative stress in stromal fibroblasts.34
  • In accordance with the idea that cancer-associated fibroblasts take up the bulk of glucose, PET glucose avidity is also now routinely used to measure the extent of fibrosis in a number of human diseases, including interstitial pulmonary fibrosis, postsurgical scars, keloids, arthritis and a variety of collagen-vascular diseases.
  • PET glucose avidity and elevated serum inflammatory markers both correlate with poor prognosis in breast cancers.
  • PET signal over-estimates the actual anatomical size of the tumor, consistent with the idea that PET glucose avidity is really measuring fibrosis and inflammation in the tumor microenvironment.
  • human breast and lung cancer patients can be positively identified by examining their exhaled breath for the presence of hydrogen peroxide.
  • tumor cell production of hydrogen peroxide drives NFκB-activation in adjacent normal cells in culture6 and during metastasis,103 directly implicating the use of antioxidants, NFκB-inhibitors and anti-inflammatory agents, in the treatment of aggressive human cancers.
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    Good description of the communication between cancer cells and fibroblasts.  This theory is termed the "reverse Warburg effect".
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Serum thymidine kinase 1 correlates to clinical stages and clinical reactions and monit... - 0 views

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    TK-1 to screen for cancer, as well as to follow therapy and recurrence.
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Stuck at the bench: Potential natural neuroprotective compounds for concussion - 0 views

  • Long-chain polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are highly enriched in neuronal synaptosomal plasma membranes and vesicles
  • The predominant CNS polyunsaturated fatty acid is DHA
  • effective supplementation and/or increased ingestion of dietary sources rich in EPA and DHA, such as cold-water fish species and fish oil, may help improve a multitude of neuronal functions, including long-term potentiation and cognition.
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  • multiple preclinical studies have suggested that DHA and/or EPA supplementation may have potential benefit through a multitude of diverse, but complementary mechanisms
  • pre-injury dietary supplementation with fish oil effectively reduces post-traumatic elevations in protein oxidation
  • The benefits of pre-traumatic DHA supplementation have not only been independently confirmed,[150] but DHA supplementation has been shown to significantly reduce the number of swollen, disconnected and injured axons when administered following traumatic brain injury.
  • DHA has provided neuroprotection in experimental models of both focal and diffuse traumatic brain injury
  • potential mechanisms of neuroprotection, in addition to DHA and EPA's well-established anti-oxidant and anti-inflammatory properties
  • Despite abundant laboratory evidence supporting its neuroprotective effects in experimental models, the role of dietary DHA and/or EPA supplementation in human neurological diseases remains uncertain
  • Several population-based, observational studies have suggested that increased dietary fish and/or omega-3 polyunsaturated fatty acid consumption may reduce risk for ischemic stroke in several populations
  • Randomized control trials have also demonstrated significant reductions in ischemic stroke recurrence,[217] relative risk for ischemic stroke,[2] and reduced incidence of both symptomatic vasospasm and mortality following subarachnoid hemorrhage
  • Clinical trials in Alzheimer's disease have also been largely ineffective
  • The clinical evidence thus far appears equivocal
  • curcumin has gained much attention from Western researchers for its potential therapeutic benefits in large part due to its potent anti-oxidant[128,194,236] and anti-inflammatory properties
  • Curcumin is highly lipophilic and crosses the blood-brain barrier enabling it to exert a multitude of different established neuroprotective effects
  • in the context of TBI, a series of preclinical studies have suggested that pre-traumatic and post-traumatic curcumin supplementation may bolster the brain's resilience to injury and serve as a valuable therapeutic option
  • Curcumin may confer significant neuroprotection because of its ability to act on multiple deleterious post-traumatic, molecular cascades
  • studies demonstrated that both pre- and post-traumatic curcumin administration resulted in a significant reduction of neuroinflammation via inhibition of the pro-inflammatory molecules interleukin 1β and nuclear factor kappa B (NFκB)
  • no human studies have been conducted with respect to the effects of curcumin administration on the treatment of TBI, subarachnoid or intracranial hemorrhage, epilepsy or stroke
  • studies have demonstrated that resveratrol treatment reduces brain edema and lesion volume, as well as improves neurobehavioral functional performance following TBI
  • green tea consumption or supplementation with its derivatives may bolster cognitive function acutely and may slow cognitive decline
  • At least one population based study, though, did demonstrate that increased green tea consumption was associated with a reduced risk for Parkinson's disease independent of total caffeine intake
  • a randomized, placebo-controlled trial demonstrated that administration of green tea extract and L-theanine, over 16 weeks of treatment, improved indices of memory and brain theta wave activity on electroencephalography, suggesting greater cognitive alertness
  • Other animal studies have also demonstrated that theanine, another important component of green tea extract, exerts a multitude of neuroprotective benefits in experimental models of ischemic stroke,[63,97] Alzheimer's disease,[109] and Parkinson's disease
  • Theanine, like EGCG, contains multiple mechanisms of neuroprotective action including protection from excitotoxic injury[97] and inhibition of inflammation
  • potent anti-oxidant EGCG which is capable of crossing the blood-nerve and blood-brain barrier,
  • Epigallocatechin-3-gallate also displays neuroprotective properties
  • More recent research has suggested that vitamin D supplementation and the prevention of vitamin D deficiency may serve valuable roles in the treatment of TBI and may represents an important and necessary neuroprotective adjuvant for post-TBI progesterone therapy
  • Progesterone is one of the few agents to demonstrate significant reductions in mortality following TBI in human patients in preliminary trials
  • in vitro and in vivo studies have suggested that vitamin D supplementation with progesterone administration may significantly enhance neuroprotection
  • Vitamin D deficiency may increase inflammatory damage and behavioral impairment following experimental injury and attenuate the protective effects of post-traumatic progesterone treatment.[37]
  • emerging evidence has suggested that daily intravenous administration of vitamin E following TBI significantly decreases mortality and improves patient outcomes
  • high dose vitamin C administration following injury stabilized or reduced peri-lesional edema and infarction in the majority of patients receiving post-injury treatment
  • it has been speculated that combined vitamin C and E therapy may potentiate CNS anti-oxidation and act synergistically with regards to neuroprotection
  • one prospective human study has found that combined intake of vitamin C and E displays significant treatment interaction and reduces the risk of stroke
  • Pycnogenol has demonstrated the ability to slow or reduce the pathological processes associated with Alzheimer's disease
  • Pcynogenol administration, in a clinical study of elderly patients, led to improved cognition and reductions in markers of lipid peroxidase
  • One other point of consideration is that in neurodegenerative disease states like Alzheimer's disease and Parkinson's disease, where there are high levels of reactive oxygen species generation, vitamin E can tend to become oxidized itself. For maximal effectiveness and to maintain its anti-oxidant capacity, vitamin E must be given in conjunction with other anti-oxidants like vitamin C or flavonoids
  • These various factors might account for the null effects of alpha-tocopherol supplementation in patients with MCI and Alzheimer's disease
  • preliminary results obtained in a pediatric population have suggested that post-traumatic oral creatine administration (0.4 g/kg) given within four hours of traumatic brain injury and then daily thereafter, may improve both acute and long-term outcomes
  • Acutely, post-traumatic creatine administration seemed to reduce duration of post-traumatic amnesia, length of time spent in the intensive care unit, and duration of intubation
  • At three and six months post-injury, subjects in the creatine treatment group demonstrated improvement on indices of self care, communication abilities, locomotion, sociability, personality or behavior and cognitive function when compared to untreated controls
  • patients in the creatine-treatment group were less likely to experience headaches, dizziness and fatigue over six months of follow-up
  • CNS creatine is derived from both its local biosynthesis from the essential amino acids methionine, glycine and arginine
  • Studies of patients with CNS creatine deficiency and/or murine models with genetic ablation of creatine kinase have consistently demonstrated significant neurological impairment in the absence of proper creatine, phosphocreatine, or creatine kinase function; thus highlighting its functional importance
  • chronic dosing may partially reverse neurological impairments in human CNS creatine deficiency syndromes
  • Several studies have suggested that creatine supplementation may also reduce oxidative DNA damage and brain glutamate levels in Huntington disease patients
  • Another study highlighted that creatine supplementation marginally improved indices of mood and reduced the need for increased dopaminergic therapy in patients with Parkinson's disease
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    great review of natural therapies in the treatment of concussions
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Adapted ECHO-7 virus Rigvir immunotherapy (oncolytic virotherapy) prolongs survival in ... - 0 views

  • Rigvir is a 2 ml frozen solution
  • ECHO-7 virus strain, Picornaviridae family, Enterovirus genus, Enteric Cytopathic Human Orphan (ECHO) type 7, group IV, positive-sense single-stranded RNA virus
  • a few side effects were reported, for example subfebrile temperature (37.5°C for a couple of days), pain in the tumour area, sleepiness and diarrhoea
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  • In this retrospective study, however, there was no record of any untoward side effect from Rigvir treatment or its discontinuation
  • Early observations of tumour regressions after virus infections have been published starting from the late 19th century
  • The present results show that in substage IB, IIA, IIB and IIC melanoma patients, Rigvir administration after surgery significantly (P<0.05) prolongs survival compared with patients who were managed according to current published guidelines
  • no value higher than grade 2 was recorded in Rigvir-treated patients. This is in contrast to most other cancer therapies, where grades 3 and 4 are frequently observed
  • Administration of virus induces the formation of neutralising antibodies that might potentially influence the efficiency of Rigvir
  • In 94 healthy adult participants tested, the titres were found to be low (1 : 20 to 1 : 62) 39,40. When tested in 155 adult cancer patients who had not been treated with Rigvir, neutralising antibodies against ECHO-7 were detected in ∼50% of the patients
  • the presence of ECHO-7 antibodies was shown to increase with age in children and level off to a plateau of around 75% in adults
  • Rigvir is an immunomodulator that affects both the humoral, antibody-mediated, and the cellular immune systems
  • neutralising antibodies do not affect efficacy when local or regional administration is used
  • it reduces the viability of melanoma, as well as pulmonary, gastric, pancreatic, bone, and breast cancer cell cultures
  • It is oncolytic in melanoma and rectum cancer patients
  • shown to improve the 5-year survival in rectum cancer patients
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    RIGVIR shown to improve survival against standard therapy in stage IB, IIA, IIB, and IIC in malignant melanoma patients in retrospective study. Side effects are minimal. Neutralizing antibodies are an area to watch that likely effects individual outcome beyond that of the type of cancer
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Prostate-specific antigen flare induced by cabazitaxel-based chemotherapy in patients w... - 0 views

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    Taxanes associated with PSA flare. The authors concluded that the flar within 12 weeks of therapy was not associated with any change in outcomes and could be ignored. The Taxanes as a whole group appears to be associated with this PSA flare pheonomenon.
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Oncolytic virotherapy promotes intratumoral T cell infiltration and improves Anti-PD-1... - 0 views

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    Study found that viral oncolytic therapy improved efficacy of PD-1 check point inhibitors by 62%. Increased CD8 expression, interferon-gamma...Interesting, starting CD8 levels played no role in predicting outcome.
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Utility of MYD88 in the Differential Diagnosis and Choice of Second-Line Therapy in a C... - 0 views

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    Interesting study that highlights the complexities between Waldenstrom's Macroglobulinemia and other B-cell lymphoma's. These authors concluded that sFLC's correlated better with treatment outcomes than IgM levels.
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Role of maximum standardized uptake value in fluorodeoxyglucose positron emission tomog... - 0 views

  • 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is an effective and popular technique for evaluating patients before and after breast cancer surgery.
  • Quantitative FDG-PET/CT imaging is becoming prevalent in cancer treatment as it measures glucose metabolism that reflects the growth potential and metabolic activity of malignant tumors
  • The FDG-PET/CT findings of primary lesions in colorectal and lung cancers correlate with metastasis and prognosis because FDG reflects tumor viability
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  • The technique is valuable for predicting the prognosis of patients with recurrent breast cancer and for determining and predicting the outcomes of neoadjuvant chemotherapy
  • FDG-PET/CT is useful not only for evaluating metastasis but also for predicting the prognosis of recurrent breast cancer and measuring treatment effects
  • reports remain limited to small-scale clinical trials of about 100 patients.
  • MaxSUV, which is the most popular FDG-PET/CT value, can vary up to 30 % because of differences among PET/CT devices and among the operators who create the images
  • the degree of malignancy would increase with an increase in maxSUV when ER or HER-2 signaling is involved.
  • Factors that determine the rate of cancer progression include T-factor (tumor diameter) and N-factor (presence or absence/number of lymph node metastasis)
  • The prognostic factors applied in breast cancer can be broadly divided into those that determine staging and those that determine biological tumor characteristics
  • Prognosis was previously predicted based on T, N, and M staging, which indicates the degree of progression. However, prognosis is now predicted and treatment regimes are presently selected by also considering ER and HER-2 levels, which determine the nature of the tumor
  • maxSUV presently serves as an indicator of metabolic activity during cancer therapy. For instance, the maxSUV of primary lung and hematological cancer lesions correlates with metastasis and prognosis, whereas maxSUV also seems useful for predicting the prognosis of recurrent breast cancer and in determining and predicting the outcome of neoadjuvant chemotherapy
  • The maxSUV cut-off calculated from ROC curves for recurrence was 3.0
  • Factors that determine the nature of tumors also include ER, HER-2, Ki-67 labeling index, and nuclear grade
  • both ER status and maxSUV as independent prognostic factors
  • maxSUV has a closer correlation with prognosis
  • maxSUV, clinical T-factor and ER were significant prognostic factors
  • Our results showed that maxSUV has the potential to be a novel prognostic factor and that it can be used to determine future therapies
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    Retrospective, multi-facility finds maxSUV can be used in prognosis in cancer.  Others have shown benefit in recurrence risk.  MaxSUV was found to be an independent factor.
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Immunonutrition in Surgical Patients: Ingenta Connect - 0 views

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    Malnutrition is associated with increased surgical risk and poor outcomes. The authors support IV preoperative nutrition at least 10 days prior to surgery and for 7 days post surgery.  This therapy reduced inflammation and oxidative stress.
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Perioperative Nutrition and Nutritional Supplements : Plastic Surgical Nursing - 0 views

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    Optimize nutrition to decrease complications and optimize surgical outcomes in plastic surgery or any surgery for that matter as poor nutrition will negatively effect both.
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A CLINICAL-STUDY OF IMMUNOTHERAPY VERSUS ENDOCRINE THERAPY VERSUS CHEMOTHERAPY IN THE T... - 0 views

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    Head to head study of IL-2 + melatonin versus chemotherapy in advanced pancreatic cancer found slightly better outcomes in the immunotherapy arm versus standard chemotherapy.  This difference was statistically significant.
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Supplemental ascorbate in the supportive treatment of cancer: Reevaluation of prolongat... - 0 views

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    This is the republication of the original Pauling and Cameron study. This re-analysis actually revealed better outcomes than the original. Also, they found that vitamin C likely is responsible for the release of Fe from ferritin required for the cytotoxicity with vitamin C.
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Prognostic value of RDW in cancers: a systematic review and meta-analysis - 0 views

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    Elevated RDW associated with poor outcomes and poor prognosis in patients with cancer.
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