The optimal induction treatment in potentially-resectable stage IIIA-N2 NSCLC remains undefined.
To compare neoadjuvant high-dose chemoradiotherapy (CRT) to neoadjuvant chemotherapy (CHT) in patients ...with resectable, stage IIIA-N2 non-small-cell lung cancer (NSCLC).
Retrospective, multicentre study of 99 patients diagnosed with stage cT1-T3N2M0 NSCLC who underwent neoadjuvant treatment (high-dose CRT or CHT) followed by surgery between January 2005 and December 2014.
47 patients (47.5%) underwent CRT and 52 (52.5%) CHT, with a median follow-up of 41 months. Surgery consisted of lobectomy (87.2% and 82.7%, in the CRT and CHT groups, respectively) or pneumonectomy (12.8% vs. 17.3%). Nodal downstaging (to N1/N0) and Pathologic complete response (pCR; pT0pN0) rates were significantly higher in the CRT group (89.4% vs. 57.7% and 46.8% vs. 7.7%, respectively; p < 0.001)). Locoregional recurrence was significantly lower in the CRT group (8.5% vs. 13.5%; p = 0.047) but distant recurrence rates were similar in the two groups. Median PFS was 45 months (CHT) vs. “not reached” (CRT). Median OS was similar: 61 vs. 56 months (p = 0.803). No differences in grade ≥3 toxicity were observed. On the Cox regression analysis, advanced pT stage was associated with worse OS and PFS (p < 0.001) and persistent N2 disease (p = 0.002) was associated with worse PFS.
Compared to neoadjuvant chemotherapy alone, a higher proportion of patients treated with preoperative CRT achieved nodal downstaging and pCR with better locoregional control. However, there were no differences in survival. More studies are needed to know the optimal treatment of these patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Patients with metastatic renal carcinoma (mRCC) treated with first-line pazopanib were not included in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model. ...SPAZO (NCT02282579) was a nation-wide retrospective observational study designed to assess the effectiveness and validate the IMDC prognostic model in patients treated with first-line pazopanib in clinical practice.
Data of 278 patients, treated with first-line pazopanib for mRCC in 34 centres in Spain, were locally recorded and externally validated. Mean age was 66 years, there were 68.3% male, 93.5% clear-cell type, 74.8% nephrectomized, and 81.3% had ECOG 0-1. Metastatic sites were: lung 70.9%, lymph node 43.9%, bone 26.3%, soft tissue/skin 20.1%, liver 15.1%, CNS 7.2%, adrenal gland 6.5%, pleura/peritoneum 5.8%, pancreas 5%, and kidney 2.2%. After median follow-up of 23 months, 76.4% had discontinued pazopanib (57.2% due to progression), 47.9% had received second-line targeted therapy, and 48.9% had died.
According to IMDC prognostic model, 19.4% had favourable risk (FR), 57.2% intermediate risk (IR), and 23.4% poor risk (PR). No unexpected toxicities were recorded. Response rate was 30.3% (FR: 44%, IR: 30% PR: 17.3%). Median progression-free survival (whole population) was 11 months (32 in FR, 11 in IR, 4 in PR). Median and 2-year overall survival (whole population) were 22 months and 48.1%, respectively (FR: not reached and 81.6%, IR: 22 and 48.7%, PR: 7 and 18.8%). These estimations and their 95% confidence intervals are fully consistent with the outcomes predicted by the IMDC prognostic model.
Our results validate the IMDC model for first-line pazopanib in mRCC and confirm the effectiveness and safety of this treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A non-LTE model for the NO(nu not greater than 2, J, s) state distributions for altitudes from ground to 200 km for nonauroral conditions is presented. The model includes (1) vibrational excitation ...due to collisions of NO with O and O2, (2) excitation due to photolysis of NO2 and due to NO2 + O - NO + O2 in the stratosphere, and (3) excitation due to N(4S, 2D) + O2 - NO + O in the thermosphere. Spontaneous emission, induced emission, and absorption of tropospheric and solar radiation are included. Intravibrational spin and rotational relaxations are included by means of an exponential power gap law approach. This model improves upon previous work mainly through its completeness. It provides non-LTE distributions of the three spin, rotational, and vibrational degrees of freedom covering the whole atmosphere up to the upper thermosphere. The most important results of the model are (1) the stratospheric daytime vibrational distribution departs from LTE due to NO(nu not less than 1) production by NO2 photolysis; (2) the rotational and spin distributions of the NO(nu = 1, 2) are in non-LTE above about 110 km; (3) a 90 percent propensity to conserve the spin orbit state in intravibrational NO + O collisional relaxation was determined by comparison of the model results to cryogenic infrared radiance for shuttle (CIRRIS-1 A) data. The implications of the non-LTE model results to remote sensing of stratospheric NO abundances from spectrally resolved 5.3 micron limb radiances are discussed. (Author)
•The fundamental 5.3 µm band is the source of all cooling by NO in the thermosphere.•The fundamental 5.3 µm band is exceptionally transparent in earth's atmosphere.•The weak line approximation is ...valid for analysis of NO 5.3 µm emission.•Earthshine, solar radiation, and collisions excite the NO 5.3 µm band below 115 km.•SABER derivations of daily global power radiated by NO are 5% to 15% too large.
The spectroscopy of the υ = 1 → υ = 0 fundamental vibration-rotation band of nitric oxide (NO) in Earth's atmosphere is examined in depth in order to further assess the long-running dataset of infrared radiative cooling rates in the thermosphere from the SABER instrument on the NASA TIMED satellite. The fundamental band at 5.3 µm is shown to be almost solely responsible for the cooling by NO. The distribution of line strength in this band and the concentration of NO in the atmosphere are such that NO is remarkably transparent in Earth's atmosphere. Every fundamental band photon emitted in the nadir direction by NO in the thermosphere has a nearly 100% chance of hitting the Earth's surface before being absorbed by another NO molecule. The mean free paths of these photons exceed 5000 km. Vertical optical depths of the strongest NO absorption lines in 2 km thick layers in the thermosphere are less than 10−4 even during geomagnetically disturbed conditions. Consequently, nearly all of the radiation emitted by thermospheric NO escapes to space or to the lower atmosphere. Radiative excitation of thermospheric NO by upwelling infrared radiation (“earthshine”) from the troposphere is accurately assessed using measurements of infrared spectra made by the IASI instruments on the METOP satellites. Earthshine and solar excitation of NO are shown to compete with collisional excitation of NO by atomic oxygen below 110 km in polar regions and below 115 km in tropical regions. Therefore, NO 5.3 µm energy loss rates currently derived below ~ 115 km from measurements made by the SABER instrument on the NASA TIMED satellite are not representative of radiative cooling. Consequently, the current values of SABER-derived daily global power radiated from the thermosphere by NO are 5% to 15% too large. Approaches to further improve the SABER radiative cooling dataset are presented.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Acute esophagic necrosis or black esophagus is an uncommon clinical entity that owes its name to the endoscopic view of the necrotic esophageal mucosa. It is always related with a critical medical ...condition and usually has an ischemic etiology. We report the first case of acute esophageal necrosis after a spinal anesthetic for partial hip joint arthroplasty. We discuss the underlying pathophysiological mechanisms.
Allogeneic donor CCR5 Δ32 homozygous haemopoietic cell transplantation (HCT) provides the only evidence to date of long-term control of HIV infection. However, availability of conventional CCR5 Δ32 ...homozygous donors is insufficient to develop this as a therapeutic strategy further.
We present a 37-year-old patient with HIV-1 infection and aggressive lymphoma who had disease progression after five lines of radiochemotherapy including an autologous HCT, and in the absence of matched sibling donors, received an allogeneic HCT with four of six HLA-matched CCR5 Δ32 homozygous cord blood cells (StemCyte, Covina, CA), supported with purified CD34+ cells from a haploidentical sibling. Blood or tissue samples were obtained before and weekly after HCT to monitor transplant and HIV infection, including chimerism analysis, CCR5 genotyping and viral tropism, viral isolation and sequence, viral reservoir analysis, immune activation and proliferation, and ex-vivo cell infectivity assays. Combined antiretroviral therapy continued during the procedure.
The patient's HIV was CCR5-tropic by genotypic and phenotypic analyses. Baseline latent reservoir tests showed HIV DNA copies in bulk and resting CD4 T cells and in gut-associated lymphoid tissue, CD4 T-cell-associated HIV RNA, replication competent viral size of 2·1 copies per 10(7) CD4 T cells, and single copy assay of 303 copies per mL. After HCT, plasma HIV DNA load was undetectable by ultrasensitive analyses. Upon cord blood full chimerism, the patient's CCR5 Δ32 homozygous CD4 T cells responded to proliferation and activation stimuli and became resistant to infection by the patient's viral isolate and by laboratory-adapted HIV-1 strains. Death related to lymphoma progression regretfully prevented long-term monitoring of the patient's viral reservoir.
CCR5 Δ32 homozygous cord blood reconstitution can successfully eliminate HIV-1 and render the allogeneic graft recipient's T lymphocytes resistant to HIV infection. Thus, they build on the evidence available to strongly support the use of cord blood as a strategic platform for a broader application of non-functional CCR5 transplantation to other infected individuals.
Spanish Secretariat of Research, the American Foundation for AIDS Research (amfAR).
We report here the draft genome sequence of the probiotic Pediococcus parvulus 2.6, a lactic acid bacterial strain isolated from ropy cider. The bacterium produces a prebiotic and immunomodulatory ...exopolysaccharide, and this is the first strain of the P. parvulus species whose genome has been characterized.
We estimated whether previous episodes of influenza and trivalent influenza vaccination prevented laboratory-confirmed influenza in Navarre, Spain, in season 2013/14. Patients with medically-attended ...influenza-like illness (MA-ILI) in hospitals (n = 645) and primary healthcare (n = 525) were included. We compared 589 influenza cases and 581 negative controls. MA-ILI related to a specific virus subtype in the previous five seasons was defined as a laboratory-confirmed influenza infection with the same virus subtype or MA-ILI during weeks when more than 25% of swabs were positive for this subtype. Persons with previous MA-ILI had 30% (95% confidence interval (CI): -7 to 54) lower risk of MA-ILI, and those with previous MA-ILI related to A(H1N1)pdm09 or A(H3N2) virus, had a, respectively, 63% (95% CI: 16-84) and 65% (95% CI: 13-86) lower risk of new laboratory-confirmed influenza by the same subtype. Overall adjusted vaccine effectiveness in preventing laboratory-confirmed influenza was 31% (95% CI: 5-50): 45% (95% CI: 12-65) for A(H1N1)pdm09 and 20% (95% CI: -16 to 44) for A(H3N2). While a previous influenza episode induced high protection only against the same virus subtype, influenza vaccination provided low to moderate protection against all circulating subtypes. Influenza vaccine remains the main preventive option for high-risk populations.
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