Association between immune-mediated adverse events and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab and tremelimumab.

Purpose: Immune-mediated adverse events (imAEs) may be associated with response to immune checkpoint inhibitors. We assessed the relationship between imAE development and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab (anti-programmed cell death ligand-1 [PD-L1]) alone or in combination with tremelimumab (anti-cytotoxic T-lymphocyte-associated protein 4).

Methods: The analysis used individual patient-level data from 307 and 310 patients in the monotherapy and combination arms of MYSTIC, respectively.

Durvalumab After Sequential Chemoradiotherapy in Stage III, Unresectable NSCLC: The Phase 2 PACIFIC-6 Trial.

Introduction: On the basis of the findings of the phase 3 PACIFIC trial (NCT02125461), durvalumab is standard of care for patients with stage III, unresectable NSCLC and no disease progression after concurrent chemoradiotherapy (cCRT). Many patients are considered unsuitable for cCRT owing to concerns with tolerability. The phase 2 PACIFIC-6 trial (NCT03693300) evaluates the safety and tolerability of durvalumab after sequential CRT (sCRT).

-paclitaxel/carboplatin induction in squamous NSCLC: longitudinal quality of life while on chemotherapy.

Background: Longitudinal data on the impact of treatment on quality of life (QoL) in advanced non-small cell lung cancer (NSCLC) are limited. In this palliative setting, treatment that does not deteriorate QoL is key. Here we report longitudinal QoL in patients with squamous NSCLC, receiving ≤4 cycles of -paclitaxel/carboplatin combination chemotherapy.

Delay of simian human immunodeficiency virus infection and control of viral replication in vaccinated macaques challenged in the presence of a topical microbicide.

Objective: Development of an effective vaccine or topical compound to prevent HIV transmission remains a major goal for control of the AIDS pandemic. Using a nonhuman primate model of heterosexual HIV-1 transmission, we tested whether a topical microbicide that reduces viral infectivity can potentiate the efficacy of a T-cell-based HIV vaccine.

Design: A DNA prime and rAd5 virus boost vaccination strategy was employed, and a topical microbicide against the HIV nucleocapsid protein was used.

Different mutational pathways to CXCR4 coreceptor switch of CCR5-using simian-human immunodeficiency virus.

We report here a second case of coreceptor switch in R5 simian-human immunodeficiency virus SF162P3N (SHIV(SF162P3N))-infected macaque CA28, supporting the use of this experimental system to examine factors that drive the change in coreceptor preference in vivo. Virus recovered from CA28 plasma (SHIV(CA28NP)) used both CCR5 and CXCR4 for entry, but the virus recovered from lymph node (SHIV(CA28NL)) used CXCR4 almost exclusively. Sequence and functional analyses showed that mutations in the V3 loop that conferred CXCR4 usage in macaque CA28 differed from those described in the previously reported case, demonstrating divergent mutational pathways for change in the coreceptor preference of the R5 SHIV(SF162P3N) isolate in vivo.

Induction of potent local cellular immunity with low dose X4 SHIV(SF33A) vaginal exposure.

Intravaginal inoculation of rhesus macaques with varying doses of the CXCR4 (X4)-tropic SHIV(SF33A) isolate revealed a threshold inoculum for establishment of systemic virus infection and a dose dependency in overall viral burden and CD4+ T cell depletion. While exposure to inoculum size of 1000 or greater 50% tissue infectious dose (TCID(50)) resulted in high viremia and precipitous CD4+ T cell loss, occult infection was observed in seven of eight macaques exposed to 500 TCID(50) of the same virus. The latter was characterized by intermittent detection of low level virus with no evidence of seroconversion or CD4+ T cell decline, but with signs of an ongoing antiviral T cell immune response.

Efficient repeated low-dose intravaginal infection with X4 and R5 SHIVs in rhesus macaque: implications for HIV-1 transmission in humans.

We examined the effect of inoculum dose on SHIV transmission and infection. We found that repeated low-dose intravaginal exposure with either R5-SHIV(SF162P3) or X4-SHIV(SF33A) results in infections that are blunted and rapidly controlled. Interestingly, although the transmission rate after all repeated exposures is comparable for the two viruses, the probability of low-dose vaginal transmission is greater for the X4 than R5 virus.

Progestin-based contraceptive suppresses cellular immune responses in SHIV-infected rhesus macaques.

Nine rhesus macaques in groups of three received a single dose of the injectable progestin-based contraceptive Depo-Provera 5 weeks prior to challenge intravaginally with varying doses of a mixture of the pathogenic CXCR4 (X4)-SHIV(SF33A) and CCR5 (R5)-SHIV(SF162P3) isolates. As controls, seven Depo-naive animals were inoculated once with a high-dose of the mixed inoculum. Irrespective of inoculum dose, acute viremia was higher in the Depo-treated than in the Depo-naive animals.

[Comparative assessment of the doses received by patients during radiodiagnosis of the urinary system].

The authors present some literature data, estimated data and results of phantom measurements in order to give comparative assessment of radiation exposure of patients during radio-contrast and radionuclide investigation of the urinary system. The importance and distribution of doses absorbed by organs and tissues (HT) and effective equivalent doses (HE) in two most commonly used radiodiagnostic methods were studied. In radiocontrast urography (RCUG) the maximum values of tissue doses were noted for the female gonads and the organs adjacent to the kidneys (the liver, pancreas, etc.

[Diagnostic information value and radiation load on the patient of retrograde cholangiopancreatography and computed tomography of the pancreas].

The paper is devoted to a comparative analysis of the diagnostic value of retrograde cholangiopancreatography (ERCP) and computed tomography (CT) in 50 patients with chronic pancreatitis and pancreatic tumors and comparison of radiation exposure of a patient during the use of these methods of x-ray examination. CT was shown to be a more informative method, particularly in the diagnosis of chronic pancreatitis. However, the results obtained with CT, were not specific enough to make convincing differential diagnosis between tumorous and inflammatory processes.