Impact of G-CSF Prophylaxis on Chemotherapy Dose-Intensity, Link Between Dose-Intensity and Survival in Patients with Metastatic Pancreatic Adenocarcinoma.

BACKGROUND: In metastatic pancreatic adenocarcinoma, few data are available on the use of granulocyte-colony stimulating factor (G-CSF) prophylaxis and its impact on dose-intensity (DI), or the link between DI and progression-free survival (PFS). This study assessed the impact of G-CSF prophylaxis on the DI received by patients and the relationship between full DI and PFS according to chemotherapy regimens. PATIENTS AND METHODS: Patients from three first-line randomized phase II clinical trials were included in this retrospective cohort. G-CSF prophylaxis groups were identified and balanced according to baseline characteristics using a propensity score. Patients were classified into 2 treatment groups (FOLFIRINOX vs FOLFIRI/nab-paclitaxel (NAB)). DI was a binary variable (full/reduced). Adverse events were defined using NCI-CTCAE v4.0. RESULTS: Of the 498 patients, 154 (31%) were in "prophylaxis" group; 179 (36%) were treated by FOLFIRINOX and 319 (64%) by FOLFIRI/NAB. In FOLFIRINOX group, G-CSF prophylaxis was significantly associated with a higher rate of full DI (OR, 5.07; 95% CI, 1.52-16.90; P < .01) while in FOLFIRI/NAB group, it was significantly associated with a lower rate of full DI (OR, 0.23; 95% CI, 0.06-0.83; P = .03). Full DI was associated with a non-significant increase in PFS (FOLFIRINOX group: HR 0.83; 95% CI, 0.59-1.16; P = .27; FOLFIRI/NAB group: HR 0.84; 95% CI, 0.63-1.11; P = .22). CONCLUSION: Granulocyte-colony stimulating factor prophylaxis was associated with a higher rate of full DI with FOLFIRINOX. Full DI was associated with a non-significant increase in PFS. These results need to be confirmed prospectively.

Outcomes following polypectomy for malignant colorectal polyps are similar to those following surgery in the general population.

OBJECTIVE: Population-based studies on colorectal malignant polyps (MPs) are scarce. The aim of this study was to describe time trends in the incidence of colorectal MPs before and after the introduction of a colorectal mass-screening programmein 2003 and to assess outcomes (survival and recurrence) after endoscopic or surgical resection in patients with MPs. DESIGN: We included 411 patients with MPs diagnosed between 1982 and 2011 in a well-defined population. Age-standardised incidence rates were calculated. Univariate and multivariate 5-year recurrence and net survival analyses were performed according to gross morphology. RESULTS: Age-standardised incidence of MPs in patients aged 50-74 years doubled from 5.4 in 1982-2002 to 10.9 per 100 000 in 2003-2011. Pedunculated MPs were more frequently resected endoscopically (38.2%) than were sessile MPs (19.1%; p<0.001). For patients with pedunculated MPs and a pathological margin ≥1 mm, the 5 -year cumulative recurrence rate did not differ significantly between surgical and endoscopic resection (8.2% and 2.4%, respectively). For patients with sessile MPs, it was 3.0% after first-line or second-line surgical resection, 8.6% after endoscopic resection and 17.9% after transanal resection (p=0.016). The recurrence rate decreased dramatically for patients with sessile MPs from 11.3% (1982-2002) to 1.2% (2003-2009) (p=0.010) and remained stable for pedunculated MPs at 4.6% and 6.7%, respectively. Five-year net survival was 81.0% when pathological margins were <1 mm and 95.6% when ≥1 mm (p=0.024). CONCLUSION: Outcomes following polypectomy in patients with a pathological margin ≥1 mm are similar to those following surgery in the general population. Endoscopic resection needs to be completed by surgery if pathological margins are less than 1 mm.

Identification of Endpoints for Development of Antifibrosis Drugs for Treatment of Crohn's Disease.

BACKGROUND & AIMS: Intestinal fibrosis is a challenge to management of patients with Crohn's disease (CD); there is an urgent need to expedite development of antifibrosis drugs for this disease. The International Organization for the Study of Inflammatory Bowel Disease (IOIBD) aimed to identify a set of endpoints that can be used to determine efficacy of antifibrosis agents tested in clinical trials of patients with CD. METHODS: We conducted a systematic review to identify clinical, radiologic, biochemical, endoscopic, and composite endpoints used in assessing activity of fibrostenosing CD and response to treatment, and determined their operational properties. A panel of IOIBD experts performed a consensus process to identify the best endpoints for inclusion in clinical trials, through a 2-round, Delphi-style online survey. RESULTS: A total of 36 potentially relevant endpoints for intestinal fibrosis were selected and assessed. Forty-eight physicians with expertise in inflammatory bowel disease, from 5 regions (North America, Europe, Middle East, Asia/Pacific, and Latin America), participated in the Delphi consensus process. A core set of 13 endpoints (complete clinical response, long-term efficacy, sustained clinical benefit, treatment failure, radiological remission, normal quality of life, clinical remission without steroids, therapeutic failure, deep remission, complete absence of occlusive symptoms, symptom-free survival, bowel damage progression, and no disability) were rated as critical. Agreement was high among the experts. CONCLUSIONS: Members of the IOIBD reached expert consensus on a set of endpoints that can be used to assess antifibrosis agents in trials of patients with CD. Studies are needed to clarify methods for measuring these outcomes and validate measurement instruments.

The importance of raiding ecology and sex differences in offensive and defensive warfare.

De Dreu and Gross offer a compelling synthesis of a growing literature on the psychology of attack and defense. I argue that human raiding ecology suggests the need to endogenize attacker-defender move order as well as opportunities for tactical mismatch available to defenders. Perhaps most significantly, I draw attention to the surprising lacunae in sex differences across attack and defense.

Physical Layer Cryptographic Key Generation by Exploiting PMD of an Optical Fiber Link.

We present a symmetric physical layer based secret key generation scheme for Point-to-Point Optical Link (PPOL) communication by exploiting Polarization Mode Dispersion (PMD) as a random and inimitable channel characteristic. The randomness and security strength of generated cryptographic keys based on PMD is significantly high. In this paper, we present that random modulation of a probe signal caused by PMD in a high-speed data communication network (40Gb/s and 60Gb/s) is reciprocal with average Pearson correlation coefficient of 0.862, despite the presence of optical nonlinearities, dispersion, and noise in the system. 128-bit symmetric cryptographic key has been successfully generated using the proposed scheme. Moreover, PMD based encryption keys passed the National Institute of Standards and Technology (NIST) tests. We have shown through simulations with a 50km link that, with optimal key generation settings, symmetric keys can be generated with high randomness (high P-values for NIST randomness tests) and with sufficient generation rates (>50%). Furthermore, we considered an attack model of a non-invasive adversary intercepting at 10km into the link and found that the generated keys have high average key bit mismatch rates (>40%).

Microbiota in digestive cancers: our new partner?

Evolution led to an essential symbiotic relationship between the host and commensal microbiota, regulating physiological functions including inflammation and immunity. This equilibrium can be disturbed by environmental factors such as lifestyle, diet or antibiotic pressure, contributing to create a dysbiosis. There is much evidence about the gut microbiota's contribution to carcinogenesis, involving pro-inflammatory and immunosuppressive signals. At the same time, it seems to be increasingly clear that commensal microbes can modulate cancer therapy efficacy and safety, in particular, innovating treatments as immune checkpoint inhibitors. In this review, we discuss how the microbiota can promote digestive tract carcinogenesis, responsiveness to cancer therapeutics and cancer-associated complications.

Iron deficiency anaemia.

Anaemia affects roughly a third of the world's population; half the cases are due to iron deficiency. It is a major and global public health problem that affects maternal and child mortality, physical performance, and referral to health-care professionals. Children aged 0-5 years, women of childbearing age, and pregnant women are particularly at risk. Several chronic diseases are frequently associated with iron deficiency anaemia--notably chronic kidney disease, chronic heart failure, cancer, and inflammatory bowel disease. Measurement of serum ferritin, transferrin saturation, serum soluble transferrin receptors, and the serum soluble transferrin receptors-ferritin index are more accurate than classic red cell indices in the diagnosis of iron deficiency anaemia. In addition to the search for and treatment of the cause of iron deficiency, treatment strategies encompass prevention, including food fortification and iron supplementation. Oral iron is usually recommended as first-line therapy, but the most recent intravenous iron formulations, which have been available for nearly a decade, seem to replenish iron stores safely and effectively. Hepcidin has a key role in iron homoeostasis and could be a future diagnostic and therapeutic target. In this Seminar, we discuss the clinical presentation, epidemiology, pathophysiology, diagnosis, and acute management of iron deficiency anaemia, and outstanding research questions for treatment.

Vaccination recommendations for the adult immunosuppressed patient: A systematic review and comprehensive field synopsis.

BACKGROUND: Immunosuppressed patients are at risk of severe viral infections-related complications. National and international vaccination guidelines have been developed to decrease the mortality risk associated with these infections. However, a summary of these guidelines and the value of immunisation in this population is missing. OBJECTIVES: To summarize specific guidelines regarding vaccination in immunosuppressed patients. METHODS: We performed a literature search based on last update vaccine guidelines in immunosuppressed adult patients published between 1/1/2005-1/31/2016 in English or French language using PubMed, Cochrane and Embase, as well as relevant medical society websites. RESULTS: Of the 389 citations identified, 12 guidelines were selected Three additional guidelines were selected by searching on the websites from medical societies of each specialty. 15 guidelines were included, involving 19 medical societies issued from the US (n = 6), international collaboration (n = 3), UK (n = 2), Canada (n = 1), Australia (n = 1), France (n = 1), and Germany (n = 1). These guidelines provide recommendations on vaccination in asplenic patients (n = 5), cancer patients (n = 4), HIV patients (n = 5), hematopoietic stem cell recipients (n = 4), inflammatory bowel diseases patients (n = 5), psoriasis patients (n = 4), primary immunocompromised patients (n = 3), inflammatory rheumatic diseases patients (n = 6), and solid organ transplant recipients (n = 5). All guidelines recommended pneumococcal and injectable influenza vaccines. Other inactivated vaccines were recommended only in high risk patients. Live vaccines were usually contraindicated in patients under immunosuppressive therapy and/or in HIV patients with a CD4 count under 200/mm3. CONCLUSION: Pneumococcal and injectable influenza are the two essential vaccines recommended in all immunocompromised patients. Other inactivated vaccines are only indicated in high risk patients. Live vaccines are usually contraindicated.

Thiopurines and risk of colorectal neoplasia in patients with inflammatory bowel disease: a meta-analysis.

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) are at increased risk for developing colorectal neoplasia. Researchers have debated whether treatment of IBD with thiopurines reduces cancer risk. We performed a meta-analysis of thiopurine exposure and risk of colorectal dysplasia or cancer in patients with IBD. METHODS: We used MEDLINE, EMBASE, and Cochrane search engines and abstract books from international conferences to identify relevant literature. We included studies on thiopurine exposure and risk of colorectal neoplasia in patients with ulcerative colitis or Crohn's disease. We calculated pooled odds ratios (ORs) with 95% confidence intervals (CIs) and performed a meta-regression analysis of the effect of year of publication. Various sensitivity analyses were conducted. RESULTS: Fifteen studies fulfilled the inclusion criteria. Overall, we did not observe a significant effect of thiopurines on risk for colorectal neoplasia (dysplasia and/or cancer) in patients with IBD (OR, 0.87; 95% CI, 0.71-1.06). The estimate did not change markedly in separate assessments of the 2 population-based studies (OR, 0.87; 95% CI, 0.59-1.29), the 13 clinic-based studies (OR, 0.87; 95% CI, 0.59-1.09), the 7 cohort studies (OR, 0.93; 95% CI, 0.67-1.28), or the 8 case-control studies (OR, 0.83; 95% CI, 0.65-1.08). Studies that used neoplasia (dysplasia or cancer) as outcomes tended to show that thiopurines had protective effects (OR for neoplasia, 0.72; 95% CI, 0.50-1.05); these effects were not observed in studies of colorectal cancer (OR, 0.90; 95% CI, 0.72-1.12) or in studies published in recent years (meta-regression; P = .16). CONCLUSIONS: In a meta-analysis, we did not find a significant protective effect of treatment with thiopurines on the risk of colorectal neoplasia in patients with IBD.

Increased risk of acute myeloid leukemias and myelodysplastic syndromes in patients who received thiopurine treatment for inflammatory bowel disease.

BACKGROUND & AIMS: Treatment with immunosuppressive thiopurines such as azathioprine is associated with an increased risk of leukemogenesis. We assessed the risk of myeloid disorders, such as acute myeloid leukemia and myelodysplastic syndromes, in a large cohort of patients with inflammatory bowel disease (IBD) in France. METHODS: We performed a prospective observational study of 19,486 patients with IBD enrolled in the Cancers Et Surrisque Associé aux Maladies inflammatoires intestinales En France (CESAME) study from May 2004 through June 2005; patients were followed through December 31, 2007. The incidence of myeloid disorders in the general population, which was used for reference, was determined from the French Network of Cancer Registries. RESULTS: During 49,736 patient-years of follow-up, 5 patients were diagnosed with incident myeloid disorders (2 with acute myeloid leukemia and 3 with myelodysplastic syndromes). Four of these patients had been exposed to thiopurines (1 with ongoing treatment and 3 with past exposure). The risk of myeloid disorders was not increased among the overall IBD population, compared with the general population; the standardized incidence ratio (SIR) was 1.80 (95% confidence interval [CI], 0.58-4.20). The risk of myeloid disorders was not increased among patients with IBD and ongoing thiopurine treatment (SIR, 1.54; 95% CI, 0.05-8.54), but patients with past exposures to thiopurines had an increased risk of myeloid disorders (SIR, 6.98; 95% CI, 1.44-20.36). CONCLUSIONS: Past exposure to thiopurines increases the risk of myeloid disorders 7-fold among patients with IBD. This finding should be considered when initiating thiopurine therapy, so risks and benefits can be calculated.

The interplay of future solar energy, land cover change, and their projected impacts on natural lands and croplands in the US.

Projections for deep decarbonization require large amounts of solar energy, which may compete with other land uses such as agriculture, urbanization, and conservation of natural lands. Existing capacity expansion models do not integrate land use land cover change (LULC) dynamics into projections. We explored the interaction between projected LULC, solar photovoltaic (PV) deployment, and solar impacts on natural lands and croplands by integrating projections of LULC with a model that can project future deployment of solar PV with high spatial resolution for the conterminous United States. We used scenarios of LULC projections from the Intergovernmental Panel on Climate Change Special Report on Emission Scenarios from 2010 to 2050 and two electricity grid scenarios to model future PV deployment and compared those results against a baseline that held 2010 land cover constant through 2050. Though solar PV's overall technical potential was minimally impacted by LULC scenarios, deployed PV varied by -16.5 to 11.6 % in 2050 from the baseline scenario. Total land requirements for projected PV were similar to other studies, but measures of PV impacts on natural systems depended on the underlying land change dynamics occurring in a scenario. The solar PV deployed through 2050 resulted in 1.1 %-2.4 % of croplands and 0.3 %-0.7 % of natural lands being converted to PV. However, the deepest understanding of PV impacts and interactions with land cover emerged when the complete net gains and losses from all land cover change dynamics, including PV, were integrated. For example, one of the four LULC projections allows for high solar development and a net gain in natural lands, even though PV drives a larger percentage of natural land conversion. This paper shows that integrating land cover change dynamics with energy expansion models generates new insights into trade offs between decarbonization, impacts of renewables, and ongoing land cover change.

Prediction of Adjuvant Gemcitabine Sensitivity in Resectable Pancreatic Adenocarcinoma Using the GemPred RNA Signature: An Ancillary Study of the PRODIGE-24/CCTG PA6 Clinical Trial.

PURPOSE: GemPred, a transcriptomic signature predictive of the efficacy of adjuvant gemcitabine (GEM), was developed from cell lines and organoids and validated retrospectively. The phase III PRODIGE-24/CCTG PA6 trial has demonstrated the superiority of modified folinic acid, fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX) over GEM as adjuvant therapy in patients with resected pancreatic ductal adenocarcinoma at the expense of higher toxicity. We evaluated the potential predictive value of GemPred in this population. PATIENTS AND METHODS: Routine formalin-fixed paraffin-embedded surgical specimens of 350 patients were retrieved for RNA sequencing and GemPred prediction (167 in the GEM arm and 183 in the mFOLFIRINOX [mFFX] arm). Survival analyses were stratified by resection margins, lymph node status, and cancer antigen 19-9 level. RESULTS: Eighty-nine patients' tumors (25.5%) were GemPred+ and were thus predicted to be gemcitabine-sensitive. In the GEM arm, GemPred+ patients (n = 50, 30%) had a significantly longer disease-free survival (DFS) than GemPred- patients (n = 117, 70%; median 27.3 v 10.2 months, hazard ratio [HR], 0.43 [95% CI, 0.29 to 0.65]; P < .001) and cancer-specific survival (CSS; median 68.4 v 28.6 months, HR, 0.42 [95% CI, 0.27 to 0.66]; P < .001). GemPred had no prognostic value in the mFFX arm. DFS and CSS were similar in GemPred+ patients who received adjuvant GEM and mFFX (median 27.3 v 24.0 months, and 68.4 v 51.4 months, respectively). The statistical interaction between GEM and GemPred+ status was significant for DFS (P = .008) and CSS (P = .004). GemPred+ patients had significantly more adverse events of grade ≥3 in the mFFX arm (76%) compared with those in the GEM arm (40%; P = .001). CONCLUSION: This ancillary study of a phase III randomized trial demonstrates that among the quarter of patients with a GemPred-positive transcriptomic signature, survival was comparable with that of mFOLFIRINOX, whereas those receiving adjuvant gemcitabine had fewer adverse events.

Biliary tract cancers: French national clinical practice guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, UNICANCER, GERCOR, SFCD, SFED, AFEF, SFRO, SFP, SFR, ACABi, ACHBPT).

INTRODUCTION: This document is a summary of the French intergroup guidelines of the management of biliary tract cancers (BTC) (intrahepatic, perihilar and distal cholangiocarcinomas, and gallbladder carcinomas) published in September 2023, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS: This collaborative work was conducted under the auspices of French medical and surgical societies involved in the management of BTC. Recommendations were graded in three categories (A, B and C) according to the level of scientific evidence until August 2023. RESULTS: BTC diagnosis and staging is mainly based on enhanced computed tomography, magnetic resonance imaging and (endoscopic) ultrasound-guided biopsy. Treatment strategy depends on BTC subtype and disease stage. Surgery followed by adjuvant capecitabine is recommended for localised disease. No neoadjuvant treatment is validated to date. Cisplatin-gemcitabine chemotherapy combined to the anti-PD-L1 inhibitor durvalumab is the first-line standard of care for advanced disease. Early systematic tumour molecular profiling is recommended to screen for actionable alterations (IDH1 mutations, FGFR2 rearrangements, HER2 amplification, BRAFV600E mutation, MSI/dMMR status, etc.) and guide subsequent lines of treatment. In the absence of actionable alterations, FOLFOX chemotherapy is the only second-line standard-of-care. No third-line chemotherapy standard is validated to date. CONCLUSION: These guidelines are intended to provide a personalised therapeutic strategy for daily clinical practice. Each individual BTC case should be discussed by a multidisciplinary team.

5-Aminosalicylic acid and chemoprevention: does it work?

5-Aminosalicylic acid (5-ASA)-containing drugs are the mainstay of therapy in inflammatory bowel disease (IBD). Intestinal inflammation is the main risk factor for colorectal cancer (CRC) in IBD. Hence, all drugs that are able to induce and maintain mucosal healing (MH) may prevent CRC risk in IBD. In patients with mild to moderate ulcerative colitis (UC), a recent systematic review of 5-ASA trials demonstrated that MH was achieved in nearly 50% of patients. A systematic review including 48 studies linked 5-ASA chemopreventive properties to five distinct pathways: cell cycle progression, scavenging of reactive oxygen- or nitrogen-derived metabolites, TNF-α/TGF-ss signaling, WNT/ß-catenin signaling and antibacterial properties. Therefore, in addition to their overall anti-inflammatory activity on the intestinal mucosa, 5-ASA compounds have specific effects on colorectal carcinogenesis at the molecular level. In 2005, a landmark meta-analysis of observational studies found a protective association between 5-ASA and CRC or a combined end point of CRC/dysplasia in UC patients. More recently, a meta-analysis failed to identify a protective effect of 5-ASA on CRC risk in non-referral populations, but in a separate analysis of 9 clinic-based studies, the pooled odds ratio was 0.58 (95% confidence interval: 0.45-0.75), further highlighting the chemopreventive effect of 5-ASA on CRC risk. In conclusion, 5-ASA therapy may reduce CRC risk by healing the mucosa of UC patients and via specific mechanisms of action at the molecular level. Conducting a clinical trial providing the best level of evidence by comparing UC patients receiving 5-ASA treatment versus those included in a placebo arm would be unethical.

Unexpected Differences in the Speed of Non-Malignant versus Malignant Cell Migration Reveal Differential Basal Intracellular ATP Levels.

Cellular locomotion is required for survival, fertility, proper embryonic development, regeneration, and wound healing. Cell migration is a major component of metastasis, which accounts for two-thirds of all solid tumor deaths. While many studies have demonstrated increased energy requirements, metabolic rates, and migration of cancer cells compared with normal cells, few have systematically compared normal and cancer cell migration as well as energy requirements side by side. Thus, we investigated how non-malignant and malignant cells migrate, utilizing several cell lines from the breast and lung. Initial screening was performed in an unbiased high-throughput manner for the ability to migrate/invade on collagen and/or Matrigel. We unexpectedly observed that all the non-malignant lung cells moved significantly faster than cells derived from lung tumors regardless of the growth media used. Given the paradigm-shifting nature of our discovery, we pursued the mechanisms that could be responsible. Neither mass, cell doubling, nor volume accounted for the individual speed and track length of the normal cells. Non-malignant cells had higher levels of intracellular ATP at premigratory-wound induction stages. Meanwhile, cancer cells also increased intracellular ATP at premigratory-wound induction, but not to the levels of the normal cells, indicating the possibility for further therapeutic investigation.

Exploring the evidence of Middle Amazonian aquifer sedimentary outburst residues in a Martian chaotic terrain.

The quest for past Martian life hinges on locating surface formations linked to ancient habitability. While Mars' surface is considered to have become cryogenic ~3.7 Ga, stable subsurface aquifers persisted long after this transition. Their extensive collapse triggered megafloods ~3.4 Ga, and the resulting outflow channel excavation generated voluminous sediment eroded from the highlands. These materials are considered to have extensively covered the northern lowlands. Here, we show evidence that a lacustrine sedimentary residue within Hydraotes Chaos formed due to regional aquifer upwelling and ponding into an interior basin. Unlike the northern lowland counterparts, its sedimentary makeup likely consists of aquifer-expelled materials, offering a potential window into the nature of Mars' subsurface habitability. Furthermore, the lake's residue's estimated age is ~1.1 Ga (~3.2 Ga post-peak aquifer drainage during the Late Hesperian), enhancing the prospects for organic matter preservation. This deposit's inferred fine-grained composition, coupled with the presence of coexisting mud volcanoes and diapirs, suggest that its source aquifer existed within abundant subsurface mudstones, water ice, and evaporites, forming part of the region's extremely ancient (~ 4 Ga) highland stratigraphy. Our numerical models suggest that magmatically induced phase segregation within these materials generated enormous water-filled chambers. The meltwater, originating from varying thermally affected mudstone depths, could have potentially harbored diverse biosignatures, which could have become concentrated within the lake's sedimentary residue. Thus, we propose that Hydraotes Chaos merits priority consideration in future missions aiming to detect Martian biosignatures.

Atezolizumab plus bevacizumab in advanced hepatocellular carcinoma after treatment failure with multikinase inhibitors.

BACKGROUND AND AIMS: Data on the effectiveness of atezolizumab plus bevacizumab (atezo-bev) after failure of multikinase inhibitor (MKI) therapy in patients with advanced hepatocellular carcinoma are scarce. METHODS: This retrospective multicentre study included all consecutive patients treated with atezo-bev after failing one or more MKI treatments in the setting of an early access program. The primary endpoint was the objective response rate (ORR) by investigator assessment (using Response Evaluation Criteria in Solid Tumors v1.1). Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan‒Meier method. RESULTS: Fifty patients were included in this analysis. Atezo-bev was started between April 2020 and November 2021 (median follow-up, 18.21 months). The investigator-assessed ORR was 14% (95% CI 5.37-22.63%), with 7 patients displaying a tumour response, and the disease control rate was 56% (95% CI 51.21-60.8%). After starting atezo-bev, the median OS was 17.1 months (95% CI 10.58-22.01), and the median PFS was 7.99 months (95% CI 4.78-10.50). Treatment-related adverse events led to treatment discontinuation in 7 patients. CONCLUSIONS: Atezo-bev every three weeks showed clinical benefit for a proportion of patients previously treated with one or multiple lines of MKIs.

Triggering Receptors Expressed on Myeloid Cells 1 : Our New Partner in Human Oncology?

Inflammation is recognized as one of the hallmarks of cancer. Indeed, strong evidence indicates that chronic inflammation plays a major role in oncogenesis, promoting genome instability, epigenetic alterations, proliferation and dissemination of cancer cells. Mononuclear phagocytes (MPs) have been identified as key contributors of the inflammatory infiltrate in several solid human neoplasia, promoting angiogenesis and cancer progression. One of the most described amplifiers of MPs pro-inflammatory innate immune response is the triggering receptors expressed on myeloid cells 1 (TREM-1). Growing evidence suggests TREM-1 involvement in oncogenesis through cancer related inflammation and the surrounding tumor microenvironment. In human oncology, high levels of TREM-1 and/or its soluble form have been associated with poorer survival data in several solid malignancies, especially in hepatocellular carcinoma and lung cancer. TREM-1 should be considered as a potential biomarker in human oncology and could be used as a new therapeutic target of interest in human oncology (TREM-1 inhibitors, TREM-1 agonists). More clinical studies are urgently needed to confirm TREM-1 (and TREM family) roles in the prognosis and the treatment of human solid cancers.

Testing for SARS-CoV-2 in Symptomatic Vaccinated and Unvaccinated Health Care Workers During the Delta Variant Surge.

BACKGROUND: Infection with SARS- CoV- 2 in health care workers (HCWs) challenges employee health services. METHODS: We analyzed telephone Coronavirus Disease 2019 (COVID-19) hotline data over 8 weeks in 2021 during SARS- CoV- 2 Delta variant surge. We calculated COVID-19 case rates among persons-under-investigation (PUIs) for illness at two health care centers (HCs). RESULTS: There were 41 COVID-19 cases among the 285 PUIs (14.4%) at the study HC and 549 (16.9%) of 3244 at the comparison HC. At the study HC, 11.7% of vaccinated PUIs versus 36.6% of unvaccinated PUIs were COVID-19 positive. The COVID-19 positivity rates among vaccinated and unvaccinated PUIs at the comparison HC were 16.1% and 33.3%, respectively. DISCUSSION: In the SARS-CoV-2 Delta variant surge, COVID-19 test positivity rates among unvaccinated symptomatic HCWs are dramatically elevated. Aggressive testing of HCW PUIs is particularly critical during periods of disease upsurge.