AYA testis cancer: The unmet challenge

Testis cancer is considered a rare‐incidence cancer but comprises the third most common cancer diagnosed within the adolescent and young adult (AYA) years (15–39 years). Most testis cancer patients can anticipate a survival outcome in excess of 95%. However, there are subgroups of AYA patients where outcomes are considerably worse, including younger adolescents, patients with certain histological subtypes, or from certain ethnic backgrounds. For those cured with chemotherapy, the toxicity of treatment and burden of late effects is significant. Newer germ cell tumor–specific biomarkers may identify patients who do not require further treatment interventions or may detect early recurrence, potentially reducing the burden of treatment required for cure. An international collaboration for this rare tumor is creating the forum for trial design, where these biomarker research questions are embedded. Going forward, AYA testis cancer patients could benefit from having a more personalized treatment plan, tailored to risk, that minimizes the overall burden of late effects.     

Circulating tumor DNA predicts efficacy of a dual AKT/p70S6K inhibitor (LY2780301) plus paclitaxel in metastatic breast cancer: plasma analysis of the TAKTIC phase IB/II study

The phosphatidylinositol‐3‐kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is frequently activated in HER2‐negative breast cancer and may play a role in taxane resistance. The phase IB/II TAKTIC trial ({"type":"clinical-trial","attrs":{"text":"NCT01980277","term_id":"NCT01980277"}}NCT01980277) has shown that combining a dual AKT and p70 ribosomal protein S6 kinase (p70S6K) inhibitor (LY2780301) taken orally with weekly paclitaxel in HER2‐negative advanced breast cancer is feasible, with preliminary evidence of efficacy. We wanted to explore whether circulating tumor DNA (ctDNA) may be a surrogate marker of treatment efficacy in this setting. Serial plasma samples were collected and cell‐free DNA was sequenced using low‐coverage whole‐genome sequencing, and analysis was completed with droplet digital polymerase chain reaction (PCR) for some patients with driver mutations. Baseline tumor fraction (TF) and TF after 7 weeks on treatment were compared to progression‐free survival (PFS) and the overall response rate. We also explored circulating copy number alterations associated with treatment failure. Of the 51 patients enrolled in the TAKTIC trial, at least one plasma sample was available for 44 cases (96 timepoints). All patients with tumor TP53, PI3KCA, or AKT1 mutations harbored at least one of these alterations in plasma. TF at inclusion was correlated with PFS (6m‐PFS was 92% for ctDNAneg patients vs 68% for ctDNApos cases; hazard ratio [HR] = 3.45, 95% confidence interval [CI] [1.34–8.90], P = 0.007). ctDNA status at week 7 was not correlated with prognosis. Even though most circulating copy number alterations were conserved at disease progression, some genomic regions of interest were altered in post‐progression samples. In conclusion, ctDNA detection at baseline was associated with shorter PFS in patients included in the TAKTIC trial. Plasma‐based copy number analysis may help to identify alterations involved in resistance to treatment.     

Self-administered measurement of symphysis-fundus heights

BACKGROUND: Antenatal identification of infants small for gestational age (SGA) improves their perinatal outcome. Repeated measurement of symphysis-fundus (SF) heights performed by midwives is the most widespread screening method for detection of SGA. However, the inefficiency of this method necessitates improved practices. Earlier start and more frequent SF measurements, which could be accomplished by self-administered measurements, might improve the ability to detect deviant growth. The present study was set up to evaluate whether pregnant women can reliably perform SF measurements by themselves. METHOD: Forty healthy women with singleton and ultrasound-dated pregnancies from 2 antenatal clinics in Uppsala, Sweden, were asked to perform 4 consecutive SF measurements once every week, from 20 to 25 weeks of gestation until delivery. The self-administered SF measurements were recorded and systematically compared with midwives' SF measurements. RESULTS: Thirty-three pregnant women performed self-administered SF measurements over a 14-week period (range: 1-21). The SF curves constructed from self-administered SF measurements had the same shape as previously constructed population-based reference curves. The variance for self-administered SF measurements was higher than that of the midwives. CONCLUSIONS: Pregnant women are capable of measuring SF heights by themselves, but with higher individual variance than midwives. Repeated measurements at each occasion can compensate for the higher variance. The main advantage of self-administered SF measurements is the opportunity to follow fetal growth earlier and more frequently.     

Ergebnisse allergologischer Untersuchungen bei den Säuglings-Ernährungsstörungen und verwandten Syndromen

Journal of Molecular Medicine -     

STUDIES ON THE MECHANISM OF IMMUNITY IN TUBERCULOSIS : THE R?LE OF EXTRACELLULAR FACTORS AND LOCAL IMMUNITY IN THE FIXATION AND INHIBITION OF GROWTH OF TUBERCLE BACILLI

1. The fate of bacilli of reinfection at the portal of entry and in metastatic foci, and also the associated host responses, are essentially similar in rabbits and guinea pigs. 2. However, in the guinea pig tubercle bacilli of reinfection are more effectively fixed at the portal of entry than in the rabbit. 3. The guinea pig fixes at the site of reinfection unrelated substances, such as trypan blue and agar particles, more effectively than the rabbit. 4. At the site of a local non-specific inflammation precipitins from the circulating blood accumulate in higher concentration in tuberculous guinea pigs than in tuberculous rabbits. 5. These differing fixing capacities of the two species are associated with differences of extracellular character in the inflammation resulting from reinfection. (a) In the guinea pig, whose tissues are highly sensitized and greatly injured by the tubercle bacillus, the lymphatics adjoining the site of reinfection become thrombosed. In the rabbit whose tissues are moderately sensitized and less injured by the tubercle bacillus the corresponding lymphatics remain open. (b) In the guinea pig the fibrinous network at the site of inflammation forms a fine sieve-like structure. In the rabbit this network forms a coarse sieve-like barrier. 6. In rabbits and guinea pigs primarily infected, the destruction of tubercle bacilli takes place first and most extensively at the portal of entry. At this time they are less effectively destroyed in the nearest metastatic foci. Simultaneously they are still growing without hinderance in such foci in remote internal organs. 7. The cell-free body fluids of normal animals support the growth of tubercle bacilli in vivo. The body fluids of tuberculous animals under the same conditions are bacteriostatic for this microorganism. 8. Tubercle bacilli often multiply by preliminary subdivision into non-acid-fast granules, from which the acid-fast rods sprout. This confirms the work of Kahn.     

Metastasen

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Gehirn,Nerven

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