The pivotal phase III ASCENT trial demonstrated improved survival outcomes associated with sacituzumab govitecan (SG), an anti-trophoblast cell-surface antigen 2 (anti-Trop-2) antibody-drug conjugate ...linked with the topoisomerase-inhibitor SN-38, over single-agent chemotherapy treatment of physician’s choice (TPC) in previously treated metastatic triple-negative breast cancer (mTNBC). This prespecified, exploratory biomarker analysis from the ASCENT trial evaluates the association between tumor Trop-2 expression and germline BRCA1/2 mutation status with clinical outcomes.
Patients with mTNBC refractory to or progressing after two or more prior chemotherapies, with one or more in the metastatic setting, were randomized to receive SG (10 mg/kg intravenously days 1 and 8, every 21 days) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity. Biopsy or surgical specimens were collected at study entry to determine Trop-2 expression level using a validated immunohistochemistry assay and histochemical scoring. Germline BRCA1/2 mutation status was collected at baseline.
Of 468 assessable patients, 290 had Trop-2 expression data 64% (n = 151 SG) versus 60% (n = 139 TPC) and 292 had known BRCA1/2 mutation status 63% (n = 149 SG) versus 61% (n = 143 TPC). Median progression-free survival in SG- versus TPC-treated patients was 6.9, 5.6, and 2.7 months versus 2.5, 2.2, and 1.6 months for high, medium, and low Trop-2 expression, respectively. Median overall survival (14.2, 14.9, and 9.3 months versus 6.9, 6.9, and 7.6 months) and objective response rates (44%, 38%, and 22% versus 1%, 11%, and 6%) were numerically higher with SG versus TPC in patients with high, medium, and low Trop-2 expression, respectively. Efficacy outcomes were numerically higher with SG versus TPC in patients with and without germline BRCA1/2 mutations.
SG benefits patients with previously treated mTNBC expressing high/medium Trop-2 compared with standard-of-care chemotherapy and regardless of germline BRCA1/2 mutation status. The small number of patients with low Trop-2 expression precludes definitive conclusions on the benefit of SG in this subgroup.
•The majority of patients (80%) with mTNBC in the ASCENT study with available data had high/medium tumor Trop-2 expression.•Survival outcomes and ORRs were numerically higher in SG- versus TPC-treated patients with high/medium Trop-2 expression.•Benefit of SG in patients with high/medium Trop-2 expression was similar to that of overall primary efficacy population.•The small number of patients with low Trop-2 expression prevents definitive conclusions on benefit of SG in this subgroup.•Benefit of SG over TPC was also similar regardless of germline BRCA1/2 mutation status.
The signature of cold-core eddies and their role in altering the biological productivity of the Bay of Bengal was examined using two recent sets of hydrographic data collected along the central and ...western Bay of Bengal during fall (14 September–12 October, 2002) and spring (12 April–7 May, 2003) intermonsoons under the Bay of Bengal process studies (BOBPS) programme. Based on the thermohaline structure and the satellite-derived sea-level anomaly maps nine cyclonic eddies were identified. Out of this, four cyclonic eddies—two each along the central Bay and along the western boundary—occurred during fall intermonsoon 2002, while five occurred—three along the central Bay and two along the western boundary—during spring intermonsoon. The eddy depressed the temperature, which varied from 3
°C to 7
°C at 120
m depth. Maximum depression of temperature was associated with spring-time eddies in the northern Bay, where subsurface stability was low. The reduced water column stability in spring leads to greater eddy-pumping, thereby cooling the water to a greater extent. However, the cyclonic eddies were unable to break the stratification of the top 20
m layer, thereby curtailing their effects below this depth during both seasons. Eddy-pumping not only cooled the water column but also enhanced the nutrient concentrations. This in turn increased the biological productivity of the Bay to
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2
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2
times. In addition, the subsurface chlorophyll maximum (SCM), which is generally located between 40 and 70
m in fall and 60 and 90
m in spring intermonsoons, shallowed under the influence of the eddies and also enhanced the chlorophyll concentration in the SCM to more than double. Thus, eddy-pumping of nutrients controls the biological productivity of the Bay of Bengal during both the seasons. In the fall intermonsoon, however, the riverine input of nutrients and sediments in the northern Bay also plays a role in altering the biological productivity. This has an overall implication to the basin-wide new production and export flux and, at least partly, resolves the reason for the comparable annual fluxes of organic carbon between the high-productivity Arabian Sea and low-productivity Bay of Bengal.
The Bay of Bengal is traditionally considered to be a less productive basin compared to the Arabian Sea. We explore the reasons for this in the central Bay during summer. Copious rainfall and river ...water freshen the upper layers of the Bay by 3–7 psu during summer, and SST was warmer by 1.5–2°C than in the central Arabian Sea. This leads to a strongly stratified surface layer. The weaker winds over the Bay are unable to erode the strongly stratified surface layer, thereby restricting the turbulent wind‐driven vertical mixing to a shallow depth of <20 m. This inhibits introduction of nutrients from below, situated close to the mixed layer bottom, into the upper layers. While advection of nutrients rich water into the euphotic zone makes the Arabian Sea highly productive, this process is unlikely in the Bay of Bengal.
The Bay of Bengal is traditionally considered to be a less productive basin compared to the Arabian Sea. Despite the contrasting chlorophyll and primary productivity pattern, sediment trap data shows ...that annual fluxes of organic carbon reach comparable rates in both the basins. The traditional mechanisms of nutrient supply to the upper ocean waters cannot account for this. We propose eddy pumping as a possible mechanism of vertical transfer of nutrients across the halocline to the oligotrophic euphotic zone during summer monsoon when upper ocean is highly stratified. This would induce rapid biological uptake and in turn significantly increase biological production. In the northern Bay, riverine input acts as an additional source of nutrients and augments the subsurface nutrient injection to the euphotic zone by eddy pumping. Notwithstanding this, the lower than expected primary production in the north suggests the possible role of riverine sediment in limiting the sunlight for photosynthesis.
To describe the accuracy of noninvasive hemoglobin (Hb) obtained with pulse co-oximeter (SpHb) compared with total Hb (tHb) from laboratory co-oximeter in neonates.
Neonates with birth weight (BW) ...<3000 g admitted to LAC+USC Medical Center neonatal intensive care unit were included. SpHb was recorded using Masimo Radical-7 and compared with tHb. A total of three data sets were obtained for each patient. Regression analysis and Bland-Altman analysis were performed.
Sixty-one patients (mean±s.d., BW 1177±610 g and gestational age 28.7±3.9 weeks) were enrolled. The mean tHb value was 13.9±2.0 g dl(-1) and the mean SpHb was 14.0±2.0 g dl(-1). There was a moderately positive correlation between SpHb and tHb (r=0.66, P<0.001) with a bias and precision of -0.09±1.67 g dl(-1). Data from a subgroup of infants with gestational age ⩽32 weeks (52/61 patients) were analyzed, and the correlation coefficient was moderately positive (r=0.69, P<0.001) with a bias and precision of -0.23±1.60 g dl(-1).
Our results suggest that noninvasive SpHb may be considered as an adjunct to invasive tHb measurements in newborn infants <3000 g especially in preterm infants ⩽32 weeks of gestation.
Human placenta is rich in mesenchymal stem/stromal cells (MSC), with their origin widely presumed fetal. Cultured placental MSCs are confounded by a high frequency of maternal cell contamination. Our ...recent systematic review concluded that only a small minority of placental MSC publications report fetal/maternal origin, and failed to discern a specific methodology for isolation of fetal MSC from term villi. We determined isolation conditions to yield fetal and separately maternal MSC during ex vivo expansion from human term placenta. MSCs were isolated via a range of methods in combination; selection from various chorionic regions, different commercial media, mononuclear cell digest and/or explant culture. Fetal and maternal cell identities were quantitated in gender‐discordant pregnancies by XY chromosome fluorescence in situ hybridization. We first demonstrated reproducible maternal cell contamination in MSC cultures from all chorionic anatomical locations tested. Cultures in standard media rapidly became composed entirely of maternal cells despite isolation from fetal villi. To isolate pure fetal cells, we validated a novel isolation procedure comprising focal dissection from the cotyledonary core, collagenase/dispase digestion and explant culture in endothelial growth media that selected, and provided a proliferative environment, for fetal MSC. Comparison of MSC populations within the same placenta confirmed fetal to be smaller, more osteogenic and proliferative than maternal MSC. We conclude that in standard media, fetal chorionic villi‐derived MSC (CV‐MSC) do not grow readily, whereas maternal MSC proliferate to result in maternal overgrowth during culture. Instead, fetal CV‐MSCs require isolation under specific conditions, which has implications for clinical trials using placental MSC. Stem Cells Translational Medicine 2017;6:1070–1084
Respiratory distress syndrome (RDS) is the most common respiratory diagnosis in preterm infants. Surfactant therapy and mechanical ventilation using conventional or high-frequency ventilation have ...been the standard of care in the management of RDS. Bronchopulmonary dysplasia (BPD) continues to remain as a major morbidity in very low birth weight infants despite these treatments. There is no significant difference in pulmonary outcome when an optimal lung volume strategy is used with conventional or high-frequency ventilation. Lung injury is directly related to the duration of invasive ventilation via the endotracheal tube. Studies using noninvasive ventilation, such as nasal continuous positive airway pressure and noninvasive positive pressure ventilation, have shown to decrease postextubation failures as well as a trend toward reduced risk of BPD. Lung protective ventilatory strategy may involve noninvasive ventilation as a primary therapy or following surfactant administration in very preterm infants with RDS. Initial steps in the management of preterm infants may also include sustained inflation to establish functional residual capacity, followed by noninvasive ventilation to minimize lung injury and subsequent development of BPD.
Up to 1.5 billion people worldwide suffer from various forms of hearing loss, with an additional 1.1 billion people at risk from various insults such as increased consumption of recreational ...noise-emitting devices and ageing. The most common type of hearing impairment is sensorineural hearing loss caused by the degeneration or malfunction of cochlear hair cells or spiral ganglion nerves in the inner ear. There is currently no cure for hearing loss. However, emerging frontier technologies such as gene, drug or cell-based therapies offer hope for an effective cure. In this review, we discuss the current therapeutic progress for the treatment of hearing loss. We describe and evaluate the major therapeutic approaches being applied to hearing loss and summarize the key trials and studies.
We report the first measurements of new production (15N tracer technique), the component of primary production that sustains on extraneous nutrient inputs to the euphotic zone, in the Bay of Bengal. ...Experiments done in two different seasons consistently show high new production (averaging around 4 mmol N m−2 d−1 during post monsoon and 5.4 mmol N m−2 d−1 during pre monsoon), validating the earlier conjecture of high new production, based on pCO2 measurements, in the Bay. Averaged over annual time scales, higher new production could cause higher rate of removal of organic carbon. This could also be one of the reasons for comparable organic carbon fluxes observed in the sediment traps of the Bay of Bengal and the eastern Arabian Sea. Thus, oceanic regions like Bay of Bengal may play a more significant role in removing the excess CO2 from the atmosphere than hitherto believed.
Recent measurements of chlorophyll, primary productivity (PP) and nutrients along the central Bay of Bengal (BOB) during summer, fall and spring intermonsoons showed that the northern bay becomes ...less productive compared to the south in summer and fall intermonsoon, in spite of the nutrient input to the upper ocean by way of river influx as well as eddypumping. Along the western boundary also, highest PP in the northern bay did not occur during summer or in the fall intermonsoon, but occurred in the spring intermonsoon. The reason for this was explored using diffuse attenuation (Kd(490)) and photosynthetically active radiation (PAR) which indicates the influence of the river flux in curtailing the downward penetration of solar radiation and cloud cover respectively. During summer and fall intermonsoon, biological productivity in the northern BOB is severely limited by the reduced downward penetration of solar radiation due to the large quantities of sediment brought by the adjoining rivers. Though the cloud cover reduces PAR in the northern BOB, this has only a secondary effect in comparison to the light limitation due to turbidity, which showed an order of magnitude increase in the northern Bay.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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