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Nathan Goodyear

Metabolic effects of testosterone replacement therapy on hypogonadal men with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials Cai X, Tian Y, Wu T, Cao CX, Li H, Wang KJ - Asian J Androl - 0 views

  • up to 40% of men with T2DM have testosterone deficiency
  • Among diabetic patients, a reduction in sex hormone binding globulin levels induced by insulin resistance leads to a further decline of testosterone levels
  • low bioavailable testosterone concentration was related to decreased lean body mass and muscle strength
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  • Testosterone deficiency has a high prevalence in men with T2DM, and it is also associated with impaired insulin sensitivity, increased percentage body fat, central obesity, dyslipidemia, hypertension and cardiovascular diseases (CVD)
  • A meta-analysis of four randomized controlled trials (RCTs) showed that TRT seemed to improve glycemic control as well as fat mass in T2DM subjects with low testosterone levels and sexual dysfunction.
  • testosterone administration could increase muscle mass and strength
  • Insulin stimulates glucose uptake into muscle and adipose tissue via the Glut4 glucose transporter isoform. When insulin activates signaling via the insulin receptor, Glut4 interacts with insulin receptor substrate 1 to initialize intracellular signaling and facilitate glucose transportation into the cell
  • The benefits of TRT on glucose metabolism can mainly be explained by its influence on the insulin signaling pathway
  • Insulin resistance as assessed by, which is calculated from the equation (If*Gf/22.5, where If is fasting insulin and Gf is fasting glucose), was definitely improved by TRT after testosterone administration in three studies
  • Testosterone was observed to elevate the expression levels and stimulate translocation of Glut4 in cultured skeletal muscle cells and to upregulate Glut4 by activating insulin receptor signaling pathways in neonatal rats
  • These effects were inhibited by a dihydrotestosterone (DHT) blocker, indicating that glucose uptake may correlate with conversion of testosterone to DHT and activation of the androgen receptor.
  • TRT reduced triglyceride levels
  • TRT has been reported to have a positive effect in the decrease of total and LDL cholesterol levels and triglycerides in hypogonadal men
  • a recent meta-analysis showed that statins could significantly lower testosterone concentrations.
  • Epidemiological studies have found a negative relationship between testosterone levels and typical cardiovascular risk markers, such as body mass index, waist circumference, visceral adiposity and carotid intima-media thickness.
  • Testosterone treatment was shown to raise hemoglobin, hematocrit and thromboxane, all of which might give rise to CVD
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    Low Testosterone is a very significant problem in men with type II Diabetes.  Estimated to reach 40%, likely much higher.  They based these estimates only on T levels and sexual symptoms. Testosterone improves glycemic control primarily through Increased transcription and transloction of GLUT4 insulin receptors to the cell surface.  Inflammation reduction is also a mechanism.  Testosteorne lowers Triglycerides in the traditional lipid profile.  Studies are mixed on the other aspects of  lipids.  
Nathan Goodyear

Nature Clinical Practice Endocrinology & Metabolism | Testosterone and ill-health in aging men | Article - 0 views

  • Levels of total and bioavailable testosterone and SHBG were reported to be inversely correlated with the prevalence of the metabolic syndrome in men aged 40–80 years
  • as were total testosterone and SHBG in men aged 65–96 years
  • and in a cross-sectional analysis of a large cohort of non-diabetic men aged 70–89 years
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  • In longitudinal studies, decreased levels of total testosterone and SHBG predicted an increased incidence of metabolic syndrome in nonobese men
  • Free testosterone level is not associated with the prevalence of metabolic syndrome in middle-aged and older men
  • Levels of free, bioavailable and total testosterone are lower in men with T2DM than in age-matched controls,34, 35 and decreased total testosterone level predicts incident T2DM in middle-aged men.
  • men with T2DM commonly have low total or free testosterone levels
  • Total, bioavailable and free testosterone levels are inversely correlated with fasting insulin level and insulin resistance in middle-aged men without T2DM
  • total testosterone is positively correlated with insulin sensitivity in men with normal or impaired glucose tolerance or T2DM
  • low SHBG level is more strongly associated with metabolic syndrome than low total testosterone in aging men
  • the recognized association between low SHBG level and insulin resistance
  • Low levels of SHBG are also associated with smaller, denser LDL-cholesterol molecules in nondiabetic men,58 and were found to predict increased cardiovascular disease mortality in one study of older men
  • Low levels of SHBG might reflect obesity, insulin resistance and overall poor health
  • Compared with those who have normal testosterone levels, men aged 40 years or more with total testosterone levels <9.8 nmol/l or elevated LH level have greater CIMT
  • In men aged 73–94 years, total testosterone was inversely correlated with CIMT
  • a prospective analysis of men aged 73–91 years, progression of CIMT was not related to total testosterone level, but it was inversely related to free testosterone level
  • A study of men aged 55 years or more found that those with total and bioavailable testosterone levels in the highest tertile had a lower risk of severe aortic atherosclerosis (detected by radiography as abdominal aortic calcification) than those with the lowest testosterone levels.
  • a large study of men aged 69–80 years, those with total or free testosterone in the lowest quartile had increased odds of lower-extremity peripheral arterial disease
  • the possibility of reverse causation has to be considered, as systemic illness can result in decreased testosterone levels
  • previous case–control studies and longitudinal studies have failed to identify low testosterone levels as strong predictors of clinically significant coronary disease
  • Reviews of trials on testosterone therapy in men with either low or low-to-normal testosterone levels have not shown consistent beneficial effects either on lipid profiles or on actual cardiovascular events.24, 54, 55 These trials, however, have not been designed or powered to detect treatment-related differences in cardiovascular outcome
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    Declining Testosterone or low Testosterone is clearly associated with poor health in men.   Very nice review of the association between low Testosterone and metabolic dysfunction.  Low T is associated with increased metabolic syndrome, Diabetes, weight gain, insulin resistance...
Nathan Goodyear

Curcumin Extract for Prevention of Type 2 Diabetes - 0 views

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    Curcumin, best taken in form from Turmeric, found to significantly prevent diabetes progression and improve Beta islet cell function.  The dosage used in this 9 month trial was 1500 mg taken in divided dosing.  A major point is that turmeric actually improved pancreatic beta islet cell function and prevented Diabetes.  As "health" care providers our focus should be on prevention of disease.
Nathan Goodyear

Association between endogenous sex steroid hormones and inflammatory biomarkers in US men - 0 views

  • modest statistically significant inverse associations for total and calculated free testosterone, and modest positive associations for total and calculated free estradiol with CRP concentration
  • Estradiol concentrations were also weakly positively associated with WBC count
  • SHBG was weakly inversely associated with WBC
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  • An association between testosterone and WBC count was not observed
  • These findings are consistent with the hypothesis that in men higher androgen concentration is anti-inflammatory, and higher estrogen concentration is pro-inflammatory.
  • the probability of elevated CRP concentrations (≥ 3 mg/L) decreased with higher total and calculated free testosterone concentrations, while the probability increased with higher total and calculated free estradiol concentrations
  • there is ample evidence supporting the immunosuppressive effect of androgens
  • The incidence of autoimmune diseases is higher in androgen-deficient men
  • Studies have shown that the induction of hypogonadism in older men is followed by a significant increase in IL-6 concentrations (Khosla et al. 2002), a potent stimulator of inflammation, and that activation of the androgen receptor exerts a direct anti-inflammatory effect
  • It has been suggested that the mechanisms for the immunosuppressive effect of androgens could be either a direct effect on the expression of inflammatory genes (Bellido et al. 1995; Asirvatham et al. 2006), or an indirect effect through inhibition of nuclear factor-kB activation
  • Estradiol is the major biologically active estrogen, and about 80% is formed in adult men from the aromatization of testosterone primarily in the adipose tissue
  • estrogen can stimulate the transcription factor C/EBP-β, which is involved in CRP transcription
  • Most prior cross-sectional studies have observed inverse associations between androgen concentrations and inflammatory biomarkers
  • A recent study in Chinese men showed that lower concentrations of total and calculated free testosterone were associated with higher CRP concentration
  • Data from the Boston Area Community Health Survey also reported inverse associations between testosterone and CRP concentrations
  • Total testosterone was inversely associated with WBC count (Tang et al. 2007; Schneider et al. 2009; Brand et al. 2012), but calculated free testosterone was not associated with WBC
  • The first trial found a decrease in CRP, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNFα) but no changes in IL-6 and IL-10 concentrations between the active treatment and placebo arms
  • the majority of studies in the literature have not observed statistically significant associations between estradiol and inflammatory biomarkers in men, although several of them observed point estimates in the positive direction
  • total testosterone and estradiol compete for binding to SHBG, and seem to have opposite effects on the concentration of inflammatory biomarkers
  • A small randomized controlled trial of estrogen replacement therapy in prostate cancer patients showed an increase in CRP in the active treatment group versus the comparator group
  • Obese men are known to have lower androgen concentrations compared to their normal-weight counterparts
  • The strongest suggestion of an interaction was the inverse association between androstanediol glucuronide and CRP concentrations in obese participants, while the association was positive in the non-obese
  • A recent Chinese cross-sectional study observed stronger inverse associations between total testosterone and CRP concentrations in individuals with a BMI of 27.5 kg/m2 or greater
  • our results suggest that total and calculated free testosterone are modestly inversely associated with CRP concentrations, and that total and calculated free estradiol are modestly positively associated with CRP and WBC
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    Study results suggest that higher Testosterone and lower Estrogen levels provide anti-inflammatory effects in men.  The inflammatory biomarker assessed here was CRP.  Low total and calculated free Testosterone was associated with an increase in CRP.  In contrast, total and free Estrogen was associated with an increase in CRP.  Estradiol increased WBC count and SHBG was inversely related to WBC count in this study.
Nathan Goodyear

Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris. - PubMed - NCBI - 0 views

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    topical nicotinamide statistically improves acne in 8 week trial.  Nicotinamide actually out performed clindamycin in this head to head study.
Nathan Goodyear

Bleeding patterns of the hormone replacement thera... [Obstet Gynecol. 2002] - PubMed result - 0 views

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    Bleeding patterns of the hormone replacement therapies in the postmenopausal estrogen and progestin interventions trial.
Nathan Goodyear

Salivary estriol as risk assessment for preterm labor: A prospective trial - 0 views

  • Detection of an early estriol surge or increased level (≥2.3 ng/ml) may be clinically helpful in identifying women at elevated risk for preterm labor and birth, allowing for evaluation of biologically based interventions in controlled trials.
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    salivary estriol to assess preterm labor
Nathan Goodyear

Randomized, double blind placebo-controlled trial: effects of myo-inositol on ovarian function and metabolic factors in women with PCOS. | Mendeley - 0 views

  • significant weight loss (and leptin reduction) (P < 0.01) was recorded in the myo-inositol group, whereas the placebo group actually increased weight
  • hese data support a beneficial effect of myo-inositol in women with oligomenorrhea and polycystic ovaries in improving ovarian function.
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    myo-inositol improves weight loss and leptin resistance through insulin secondary messenger
Nathan Goodyear

French adults' cognitive performance after daily supplementation with antioxidant vitamins and minerals at nutritional doses: a post hoc analysis of the Supplementation in Vitamins and Mineral Antioxidants (SU.VI.MAX) trial - 0 views

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    antioxidants improve memory in french adults followed over 6 years.
Nathan Goodyear

European Journal of Clinical Nutrition - Effect of maternal n-3 long-chain polyunsaturated fatty acid supplementation during pregnancy and/or lactation on adiposity in childhood: a systematic review and meta-analysis of randomized controlled trials - 0 views

  • It is estimated that approximately 30% of children and adolescents in the United States and about 15–30% of those in Europe can be classified as overweight or obese
  • An increasing body of evidence now suggests that the nutritional environment encountered in utero and the early postnatal life may elicit permanent alterations in adipose tissue structure or function and, thereby, programme the individual’s propensity to later obesity
  • The composition of fatty acids in the Western diets has shifted toward an increasing dominance of n-6 relative to n-3 LCPUFAs over the past decades.9,10 This shift is also reflected in the fatty acid composition of breast milk
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  • Evidence from animal studies suggests that the n-6 LCPUFA arachidonic acid promotes adipose tissue deposition, whereas the n-3 LCPUFAs eicosapentaenoic acid and docosahexaenoic acid seem to exert an opposite effect
  • Overall, no effect of supplementation was found on BMI in preschool (<5 years) and school-aged (6–12 years) children
  • increased adiposity, once established in childhood, tends to track into adulthood
  • Many studies have shown that even children <2 years with a high BMI are at increased risk of developing obesity later in life
  • The acquisition of fat cells early in life appears to be an irreversible process
  • Evidence from cell culture and animal studies suggests that early exposure to n-3 LCPUFAs has the potential to limit adipose tissue deposition mainly by attenuating the production of the arachidonic acid metabolite prostacyclin, which has been shown to enhance adipogenesis
  • In conclusion, there is currently no evidence to support that maternal n-3 LCPUFA supplementation during pregnancy and/or lactation exerts a favourable programming effect on adiposity status in childhood
  • our systematic review highlights that most of the trials reviewed were prone to methodological limitations
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    Literature review finds limited data (9 studies, only 6 RCTs) of omega-3 during pregnancy.  No data was found that supported reduced obesity in children by mothers taking n-3 during pregnancy.  No harm was found either.  Data was sparse.   Take home: not enough data, no harm to pregnancy, children, thus if indications are present for mother, then recommend n-3.  At this point not studies have pointed to reduced obesity in children.
Nathan Goodyear

Effect of intravenous ascorbic acid in hemod... [Am J Kidney Dis. 2006] - PubMed - NCBI - 0 views

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    High dose IV vitamin C shown to be well tolerated in those on hemodialysis.  Liver enzymes were followed throughout the course of the 6 month trial.  In fact, IV vitamin C was shown to improve the response of the EPO therapy.
Nathan Goodyear

Multicentre study of l-alpha-glyceryl-ph... [Drugs Aging. 1993 Mar-Apr] - PubMed - NCBI - 0 views

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    alpha-GPC and to a lesser degree acetyl-l-carnitine improved dementia in multi-center trial.
Nathan Goodyear

Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial | Blood Journal - 0 views

  • several independent lines of evidence suggest that cytotoxic effector cells such as T cells and natural killer (NK) cells participate in protecting patients with AML against relapse
  • A plethora of mechanisms have been proposed to account for the dysfunctional antileukemic lymphocytes in AML, including the production of T-cell- and NK-cell-inhibitory factors by AML blasts,48 a deficient expression of NK-cell receptors on leukemic cells,49 inhibition of antileukemic lymphocytes by mononuclear phagocytes,4 and an impaired stimulatory interaction between the CD28 antigen expressed by T cells and contact antigens on AML blasts
  • This trial met the primary endpoint and thus showed a significantly improved LFS for patients receiving HDC/IL-2 as compared with the current standard of care
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  • T cells and NK cells with antileukemic activity can be recovered from most patients with AML in remission not receiving a transplant,
  • The present study evaluated an approach to immunotherapy in AML in which IL-2 is supplemented with histamine dihydrochloride (HDC) to enhance the function of cytotoxic antileukemic lymphocytes
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    IL-2 plus histamine in patients with AML complete remission improves leukemia free survival.
Nathan Goodyear

Nutrients | Free Full-Text | Effect of Probiotics on Metabolic Outcomes in Pregnant Women with Gestational Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials | HTML - 0 views

  • The gut microbial composition is altered during pregnancy
  • probiotic supplements may contribute to the maintenance of bacterial diversity and glucose homeostasis in individuals with metabolic disturbances
  • Assessment of four randomized controlled trials in this review involving 288 pregnant women with GDM found that a 6–8 week probiotic intervention did not improve FBG or LDL-cholesterol levels
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  • probiotic supplementation in women with GDM was associated with significant reductions in insulin resistance
  • One proposed method is by the production of short chain fatty acids (SCFAs), generated as a by-product of bacterial fermentation of dietary fibers. SCFAs act as an energy source for intestinal cells and have been found to regulate the production of hormones effecting energy intake and expenditure such as leptin and grehlin
  • Another hypothesized mechanism of SCFA action includes reducing gastrointestinal permeability by upregulating transcription of tight junction proteins, enhancing production of Glucagon-like peptide-2 (GLP-2) which promotes crypt cell proliferation, and reducing inflammation in colonic epithelial cells by increasing PPAR-gamma activation
  • Maintenance of the integrity of the gut barrier minimizes the concentration of lipopolysaccharide (LPS) in circulation
  • LPS is a structural component of gram negative bacterial cell walls, which induces an immune-cell response upon absorption into the human bloodstream, stimulating proinflammatory cytokine production and the onset of insulin resistance and hyperglycemia
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    Review (4 studies) found that 6-8 weeks of probiotic therapy of pregnant women with gestational diabetes improved insulin resistance.
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Nathan Goodyear

Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism - 0 views

  • The levels of LH in the ibuprofen group had increased by 23% after 14 d of administration
  • This increase was even more pronounced at 44 d, at 33%
  • We found an 18% decrease (P = 0.056) in the ibuprofen group compared with the placebo group after 14 d (Fig. 1A) and a 23% decrease (P = 0.02) after 44 d (Fig. 1C). Taken together, these in vivo data suggest that ibuprofen induced a state of compensated hypogonadism during the trial, which occurred as early as 14 d and was maintained until the end of the trial at 44 d
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  • We first investigated testosterone production after 24 and 48 h of ibuprofen exposure to assess its effects on Leydig cell steroidogenesis. Inhibition of testosterone levels was significant and dose-dependent (β = −0.405, P = 0.01 at 24 h and β = −0.664, P < 0.0001 at 48 h) (Fig. 2A) and was augmented over time
  • The AMH data show that the hypogonadism affected not only Leydig cells but also Sertoli cells and also occurred as early as 14 d of administration
  • Sertoli cell activity showed that AMH levels decreased significantly with ibuprofen administration, by 9% (P = 0.02) after 14 d (Fig. 1B) and by 7% (P = 0.05) after 44 d compared with the placebo group
  • Examination of the effect of ibuprofen exposure on both the ∆4 and ∆5 steroid pathways (Fig. 2B) showed that it generally inhibited all steroids from pregnenolone down to testosterone and 17β-estradiol; the production of each steroid measured decreased at doses of 10−5–10−4 M. Under control conditions, production of androstenediol and dehydroepiandrosterone (DHEA) was below the limit of detection except in one experiment with DHEA
  • Measuring the mRNA expression of genes involved in steroidogenesis in vitro showed that ibuprofen had a profound inhibitory effect on the expression of these genes (Fig. 3 B–D), consistent with that seen above in our ex vivo organ model. Taken together, these data examining effects on the endocrine cells confirm that ibuprofen-induced changes in the transcriptional machinery were the likely reason for the inhibition of steroidogenesis.
  • Suppression of gene expression concerned the initial conversion of cholesterol to the final testosterone synthesis. Hence, expression of genes involved in cholesterol transport to the Leydig cell mitochondria was impaired
  • A previous study reported androsterone levels decreased by 63% among men receiving 400 mg of ibuprofen every 6 h for 4 wk
  • We next examined the gene expression involved in testicular steroidogenesis ex vivo and found that levels of expression of every gene that we studied except CYP19A1 decreased after exposure for 48 h compared with controls
  • the changes in gene expression indicate that the transcriptional machinery behind the endocrine action of Leydig cells was most likely impaired by ibuprofen exposure.
  • Together, these data show that ibuprofen also directly impairs Sertoli cell function ex vivo by inhibiting transcription
  • ibuprofen use in men led to (i) elevation of LH; (ii) a decreased testosterone/LH ratio and, to a lesser degree, a decreased inhibin B/FSH ratio; and (iii) a reduction in the levels of the Sertoli cell hormone AMH
  • The decrease in the free testosterone/LH ratio resulted primarily from the increased LH levels, revealing that testicular responsiveness to gonadotropins likely declined during the ibuprofen exposure. Our data from the ex vivo experiments support this notion, indicating that the observed elevation in LH resulted from ibuprofen’s direct antiandrogenic action
  • AMH levels were consistently suppressed by ibuprofen both in vivo and ex vivo, indicating that this hormone is uncoupled from gonadotropins in adult men. The ibuprofen suppression of AMH further demonstrated that the analgesic targeted not only the Leydig cells but also the Sertoli cells, a feature encountered not only in the human adult testis but also in the fetal testis
  • ibuprofen displayed broad transcription-repression abilities involving steroidogenesis, peptide hormones, and prostaglandin synthesis
  • a chemical compound, through its effects on the signaling compounds, can result in changes in the testis at gene level, resulting in perturbations at higher physiological levels in the adult human
  • The analgesics acetaminophen/paracetamol and ibuprofen have previously been shown to inhibit the postexercise response in muscles by repressing transcription
  • Previous ex vivo studies on adult testis have indeed pointed to an antiandrogenicity, only on Leydig cells, of phthalates (41), aspirin, indomethacin (42), and bisphenol A (BPA) and its analogs
  • ibuprofen’s effects were not restricted to Leydig and Sertoli cells, as data showed that the expression of genes in peritubular cells was also affected
  • short-term exposure
  • In the clinical setting, compromised Leydig cell function resulting in increased insensitivity to LH is defined as compensated hypogonadism (4), an entity associated with all-cause mortality
  • compensated hypogonadic men present with an increased likelihood of reproductive, cognitive, and physical symptoms
  • an inverse relationship was recently reported between endurance exercise training and male sexual libido
  • AMH concentrations are lower in seminal plasma from patients with azoospermia than from men with normal sperm levels
  • inhibin B is a key clinical marker of reproductive health (32). The function of AMH, also secreted by Sertoli cells, and its regulation through FSH remain unclear in men
  • the striking dual effect of ibuprofen observed here on both Leydig and Sertoli cells makes this NSAID the chemical compound, of all the chemical classes considered, with the broadest endocrine-disturbing properties identified so far in men.
  • after administration of 600 mg of ibuprofen to healthy volunteers
  • 14 d or at the last day of administration at 44 d
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    ibuprofen alters genetic expression that results in decreased Testosterone production.
Nathan Goodyear

Abstract GS2-06: Phase Ib/II study evaluating safety and efficacy of pembrolizumab and trastuzumab in patients with trastuzumab-resistant HER2-positive metastatic breast cancer: Results from the PANACEA (IBCSG 45-13/BIG 4-13/KEYNOTE-014) study | Cancer Re - 0 views

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    The addition of keytruda to herceptin in herceptin resistant breast cancer shown to b safe and effective in small pilot trial; only abstract available here.
indian-health

Optilume® Urethral Drug Coated Balloon, a Breakthrough in Urethroplasty Surgery - 0 views

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    "As the ROBUST 1 and ROBUST 3 clinical trials established, Optilume significantly reduces the prevalence of stricture recurrence," stated top 10 urethroplasty surgeons of India.
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https://www.sightcare-co.com/ - 0 views

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