Long-term response control in a patient with metastatic squamous cell lung cancer after treatment with nivolumab: a case report.

INTRODUCTION: Nivolumab is a fully human programmed death control immune point 1 immune checkpoint inhibitor antibody which promotes antitumor immunity. Cutaneous toxicity associated with nivolumab, immune system related, could be linked to a more durable response in patients with squamous cell lung cancer. CASE REPORT: We present the case of a 62-year-old male diagnosed with metastatic squamous cell lung cancer, who was treated with nivolumab after cytotoxic chemotherapy. After treatment discontinuation, due to grade 2 cutaneous toxicity, the patient is maintaining with durable partial response for more than one year with close follow-up. MANAGEMENT AND OUTCOME: Cumulative doses of nivolumab could cause immunological toxicities that may prolong survival of these patients even after discontinuation of treatment. DISCUSSION: Nivolumab was approved by European Medicines Agency (EMA), as second-line therapeutic, for the treatment of squamous cell lung cancer, showing a median of 9.23 months of overall survival. The development of immune-related skin toxicities has been associated with greater clinical benefit in patients with lung cancer. When cutaneous toxicity forces to nivolumab suspension, in certain cases, the option of not starting again and closely following up the patient may appear reasonable, even though there are no survival data in this context. Suspension of treatment with close monitoring of these patients until progression may be an alternative, since immune-related skin toxicities could be related to a greater clinical benefit and a durable response to nivolumab.

Impact of the use of antibiotics on the clinical response to immune checkpoint inhibitors in patients with non-small cell lung cancer.

OBJECTIVE: Recent research suggests that the use of antibiotics could reduce the efficacy of checkpoint inhibitors, in addition to other well-known factors. It could be due to gut microbiota modification, which impact over the immune system response. However, the information available so far is contradictory. The objective of this research was to clarify whether antibiotic use influences efficacy of checkpoint inhibitors treatments in non-small cell lung cancer patients in clinical practice. METHODS: Therefore, a retrospective observational study was designed. Use of antibiotics among patients treated with atezolizumab, pembrolizumab or nivolumab was assessed within 2 months of checkpoint inhibitors treatments initiation. RESULTS: A total of 140 patients were included, mostly men, with good performance status (ECOG 0-1), all of them previously treated with chemotherapy. An antibiotic prescription was identified in 31% of these patients, mainly fluoroquinolones or beta-lactams. The most frequent indication was respiratory infection. Both progression-free survival and overall survival were lower for patients treated with anti-infective drugs, although this difference was not statistically significant. CONCLUSIONS: More studies are needed to draw conclusions about the impact of antibiotics on the efficacy of immunotherapy.

[Dosage of presurgical cefazolin in obese and non-obese patients. Does weight matter?] / Dosificación de cefazolina prequirúrgica en pacientes obesos y no obesos. ¿Importa el peso?

OBJECTIVE: Evaluation of the effectiveness of a standard dose of cefalozin 2 grams for surgical site infection (SSI) prevention in obese patients compared to non-obese patients. There is no still controversy surrounding which is the best dosage of this antibiotic in obese patients for surgical prophylaxis. METHODS: Retrospective review of men who received prophylactic cefazolin between January 1st, 2019 and June 30th, 2019 in a traumatology department of a university hospital. Patients were stratified into 2 groups: obese (≥ 100 kg and body mass index (BMI)> 30 kg / m2) and non-obese. Patients without a 90 days follow-up after surgery and/or with an active infection at the time of surgery and/or treated with immunosuppressants were excluded. Demographic data, height, real weight, smoking, diabetes, concomitant use of immunosuppressants, surgery data and presence of infection until day 90 were collected. RESULTS: A total of 57 patients underwent traumatic surgery with prophylactic cefazolin, 26 non-obese and 23 obese, were studied. Both groups presented statistically significant differences in weight, BMI and post-surgery use of cefazolin. No significant differences were observed in the other variables. Two obese (8.7%) and two non-obese (7.7%) patients developed SSIs after 63 days post-surgery on average, following the difference between the groups being statistically non-significant. CONCLUSIONS: This study shows that there is no significant difference in SSI with a standard prophylactic dose of two grams of cefazolin between obese and non-obese patients.

Cloning and expression in Escherichia coli of the gene coding for phytoene synthase from the cyanobacterium Synechocystis sp. PCC6803.

The gene coding for the carotenoid biosynthesis enzyme phytoene synthase (pys) has been cloned from the unicellular cyanobacterium Synechocystis sp. PCC6803. The gene has been functionally expressed in Escherichia coli, where it directs the biosynthesis of phytoene from geranylgeranyl pyrophosphate (GGPP). Analysis of the sequence of the Synechocystis pys protein deduced from the gene sequence shows that it is highly homologous to the tomato and Synechococcus phytoene synthases and shows conserved domains with other bacterial phytoene synthase enzymes. The pys gene starts 60 nucleotides downstream of the pds gene (which codes for phytoene desaturase). However, it seems to be transcribed mainly from its own promoters, because insertions that disrupt the pds gene do not affect significantly the expression of the pys gene.

Characterization of two carotenoid gene promoters in the cyanobacterium Synechocystis sp. PCC 6803.

The in vivo promoter activity of the 5'-region of the genes encoding the carotenogenic enzymes phytoene desaturase (crtP) and phytoene synthase (crtB) from the cyanobacterium Synechocystis sp. PCC 6803 has been studied by deletion mapping, primer extension, Northern blot, and using the chloramphenicol acetyltransferase (cat) reporter gene. crtP and crtB are closely linked in the Synechocystis genome, but it is shown that both genes are independently transcribed. The level of transcription in both cases is very low. Their expression is affected in a similar way by light intensity: very little or no expression is observed in the dark compared with expression under illumination conditions. High light intensities induce a transient increase in transcription initiation as detected with the cat probe. DNA fragments containing 81 base pairs upstream of the crtP putative transcription initiation site or 192 base pairs upstream of the crtB putative transcription initiation site are enough to confer light sensitive expression to a reporter gene.

[Contusion and post-traumatic hematoma of the interventricular septum. Report of a case]. / Contusión y hematoma en el septo interventricular postraumático. A propósito de un caso.

Severe thoracic trauma is a common cause of admission in Intensive Care Units; then heart injury is not a rare finding. We present a case of post-traumatic interventricular dissection and ventricular aneurysm secondary to thoracic trauma caused by traffic accident. We think that ventricular septum injury is a rare finding after chest trauma. Two-dimensional echo-cardiography is an essential procedure in the diagnosis of traumatic heart injury.

[The evaluation of unnecessary venous access ports in an emergency service]. / Evaluación de las vías de acceso venoso innecesarias en un servicio de urgencias.

BACKGROUND: To determine the incidence of unnecessary cannulations of peripheral veins in an emergency department (ED). METHODS: We retrospectively analyzed a sample of 1,113 patients from a total of 24,637 who were attended at ED. We reviewed the cannulations of peripheral veins and if they was used or not. RESULTS: In 202 (18.5%) cases, venous access was obtained. In 84 (41.6%) the venous access was not used. CONCLUSION: The unnecessary use of venous cannulations is a common practice and generates a substantial added cost of poor quality.

[Benchmarking in the emergency unit process in 7 hospitals from different autonomous communities]. / Benchmarking en el proceso de urgencias entre siete hospitales de diferentes comunidades autónomas.

OBJECTIVE: To identify and to share the results among hospitals regarding the process of attention at the Emergency Unit, and to detect the practices that explain the differences. SETTING: 7 hospitals of different regions in Spain. PERIOD OF STUDY: 2005-2007. Firstly the comparability criteria were defined assuring the homotecia in the «emergency process¼. In order to fulfil the study objectives, 11 criteria were selected and every center sent the information of each one. 7 indicators were identified to compare hospitals processes'. Data regarding all the attentions provided during the study period was analyzed, establishing the benchmark among the centers. Finally, a questionnaire was elaborated for the process analysis, considering all the stages of the process, the resources and the procedures used in every stage, to be fulfilled in each hospital. RESULTS: The homotecia has been verified in the 7 hospitals, with some differences between centers. 7 indicators have been analyzed in the different hospitals, corresponding to 1,526,890 patients attended in the study period. A benchmark has been identified, with the best results in four of seven indicators: % of admissions from urgencies: 8.3%, emergency pressure: 56.14%, emergency length of stay: 2 hs 20min, and % of patients with length stay > 24h: 0.05%. Differences between the stages of the process, resources and procedures used in every stage in the benchmark center have been analyzed. CONCLUSIONS: A set of indicators to compare Emergency Departments has been identified, letting us establish the benchmark.

A new type of asymmetrically acting beta-carotene ketolase is required for the synthesis of echinenone in the cyanobacterium Synechocystis sp. PCC 6803.

We have isolated, based on the knowledge of the complete genomic sequence of the cyanobacterium Synechocystis sp. PCC 6803, an open reading frame (slr0088) similar to known bacterial carotene desaturases and have analyzed the function of the encoded protein. Surprisingly, this protein has no detectable desaturase activity with phytoene, hydroxyneurosporene, or zeta-carotene as substrates, but is rather a beta-carotene ketolase that acts asymmetrically introducing a keto group on only one of the two beta-ionone rings of beta-carotene to generate echinenone. This is in contrast to the so far characterized beta-carotene ketolases that act symmetrically, producing the di-keto carotenoid canthaxanthin from beta-carotene without significant accumulation of echinenone. We have designated this new gene crtO. The function of the crtO gene product has been demonstrated by 1) the biosynthesis of echinenone when the crtO gene is expressed in an Escherichia coli strain able to accumulate beta-carotene, 2) the in vitro biosynthesis of echinenone from beta-carotene with cell free extracts from E. coli cells that express the crtO gene, and 3) the absence of echinenone in a Synechocystis strain in which the crtO gene has been insertionally inactivated. The primary structure of the Synechocystis asymmetric ketolase bears no similarity with the known beta-carotene ketolases. crtO is not required for normal growth under standard or high light conditions, neither is the photosynthetic activity of the crtO-deficient strain affected.

A higher-plant type zeta-carotene desaturase in the cyanobacterium Synechocystis PCC6803.

The genomic DNA sequence of Synechocystis was analysed for putative zeta-carotene desaturase genes. Two promising candidates slr0940 and slr0033 were found with similarities to the structurally different zeta-carotene desaturase genes from higher plants and Anabaena, respectively. Only the expression product of the analogue to the plant gene, slr0940, was able to mediate the 2-step desaturation of zeta-carotene via neurosporene to lycopene after complementation of this pathway in Escherichia coli. When enzyme reactions were carried out with this protein, activity was obtained with either zeta-carotene or neuroporene as substrates. The in vitro reaction was inhibited by the pyrimidine derivative J852 which is effective as experimental herbicide in plants. The occurrence of two different types of zeta-carotene desaturases among cyanobacteria and the phylogenetic consequences on chloroplast evolution are discussed.