Corrigendum: Comparative microbiome analysis of beef cattle, the feedyard environment, and airborne particulate matter as a function of probiotic and antibiotic use, and change in pen environment.

[This corrects the article DOI: 10.3389/fmicb.2024.1348171.].

Comparative microbiome analysis of beef cattle, the feedyard environment, and airborne particulate matter as a function of probiotic and antibiotic use, and change in pen environment.

Introduction: Intensive beef cattle production systems are frequently implicated as a source of bacteria that can be transferred to nearby humans and animals via effluent water, manure used as fertilizer, or airborne particulate matter. It is crucial to understand microbial population dynamics due to manure pack desiccation, antibiotic usage, and antibiotic alternatives within beef cattle and their associated feedyard environment. Understanding how bacterial communities change in the presence of antibiotics can also improve management practices for reducing the spread of foodborne bacteria. Methods: In this study, we aimed to compare the microbiomes within cattle feces, the feedyard environment and artificially produced airborne particulate matter as a function of pen change and treatment with tylosin or probiotics. We utilized 16S rRNA sequencing to compare bacterial communities among sample types, study days, and treatment groups. Results: Bacterial community diversity varied as a function of sampling day and pen change (old or new) within fecal and manure pack samples. Manure pack samples from old pens and new pens contained diverse communities of bacteria on days 0 and 84; however, by day 119 of the study these taxonomic differences were less evident. Particulate matter samples exhibited significant differences in community diversity and predominant bacterial taxa compared to the manure pack they originated from. Treatment with tylosin did not meaningfully impact bacterial communities among fecal, environmental, or particulate matter samples; however, minor differences in bacterial community structure were observed in feces from cattle treated with probiotics. Discussion: This study was the first to characterize and compare microbial communities within feces, manure pack, and airborne particulate matter from the same location and as a function of tylosin and probiotic treatment, and pen change. Although fecal and environmental samples are commonly used in research studies and other monitoring programs to infer public health risk of bacteria and antimicrobial resistance determinants from feedyard environments, our study suggests that these samples may not be appropriate to infer public health risk associated with airborne particulate matter.

Nitric oxide-releasing polyacrylonitrile disperses biofilms formed by wound-relevant pathogenic bacteria.

AIMS: To test the antimicrobial and antibiofilm properties of a nitric oxide (NO)-releasing polymer against wound-relevant bacterial pathogens. METHODS AND RESULTS: Using a variety of 96-well plate assay systems that include standard well plates and the minimum biofilm eradication concentration biofilm assay well plate, a NO-releasing polymer based on (poly)acrylonitrile (PAN/NO) was studied for antimicrobial and antibiofilm activity against the common wound pathogens Pseudomonas aeruginosa (PAO1), Staphylococcus aureus (Mu50) and Enterococcus faecalis (V583). The polymer was capable of dispersing single-species biofilms of Ps. aeruginosa as well as a more clinically relevant multispecies biofilm that incorporates Ps. aeruginosa along with Staph. aureus and Ent. faecalis. PAN/NO also synergistically enhanced the susceptibility of the multispecies biofilms to the common broad-spectrum antibiotic, ciprofloxacin. Multiple in vitro biocompatibility assays show that PAN/NO has limited potential for mammalian cytotoxicity. CONCLUSION: This study demonstrates the feasibility of utilizing the NO-releasing polymer, PAN/NO, to manage biofilms formed by wound-relevant pathogens, and provides proof-of-concept for use of this NO-releasing polymer platform across multiple disciplines where bacterial biofilms pose significant problems. SIGNIFICANCE AND IMPACT OF STUDY: In the clinical sector, bacterial biofilms represent a substantial treatment challenge for health care professionals and are widely recognized as a key factor in prolonging patient morbidity. This study highlights the potential role for the ubiquitous signalling molecule nitric oxide (NO) as an antibiofilm therapy.

Comparison of peripherally inserted central venous catheters (PICC) versus subcutaneously implanted port-chamber catheters by complication and cost for patients receiving chemotherapy for non-haematological malignancies.

PURPOSE: Indwelling central venous catheters (CVCs) have been increasingly used to enable delivery of intravenous chemotherapy. We aimed to compare the safety and cost of two commonly used CVCs, peripherally inserted central venous catheter (PICCs) and ports, in the delivery of chemotherapy in patients with non-haematological malignancies. METHODS: Seventy patients were randomly assigned to receive either a PICC or a port. The primary endpoint was occurrence of major complications, which required removal of the CVC and secondary endpoints included occurrence of any complications. RESULTS: Port devices were associated with fewer complications compared with PICC lines (hazard ratio of 0.25, CI, 0.09-0.86, P = 0.038). Major complication rate was lower in the port arm compared to the PICC arm (0.047 versus 0.193 major complications/100 catheter days, P = 0.034) with 6 versus 20 % of patients experiencing major complications, respectively. Thrombosis, the most common complication, was significantly higher in the PICC arm compared to the port arm (25 versus 0 %, P = 0.013). Quality of life and cost estimates did not differ significantly between the two arms. CONCLUSIONS: Port devices are associated with a lower risk of complications, with no difference in cost, compared to PICC lines in patients with non-haematological malignancies receiving intravenous chemotherapy.

Final results from a randomized phase 3 study of FOLFIRI {+/-} panitumumab for second-line treatment of metastatic colorectal cancer.

BACKGROUND: The study 20050181 demonstrated significant improvements in progression-free survival (PFS), objective response, and a nonsignificant trend toward increased overall survival (OS) with panitumumab-FOLFIRI versus FOLFIRI alone for second-line wild-type (WT) KRAS metastatic colorectal cancer (mCRC). Updated long-term data from a prespecified descriptive analysis are reported. PATIENTS AND METHODS: Patients receiving one prior mCRC treatment were randomly assigned (1:1) to panitumumab (6.0 mg/kg)-FOLFIRI versus FOLFIRI every 2 weeks. Co-primary end points (PFS and OS) were prospectively analyzed by tumor KRAS status. RESULTS: One thousand one hundred and eighty-six patients were randomly assigned. In patients with WT KRAS tumors, panitumumab-FOLFIRI significantly improved PFS versus FOLFIRI [median 6.7 versus 4.9 months; hazard ratio (HR) 0.82 [95% confidence interval (CI) 0.69, 0.97]; P = 0.023]. A trend toward longer OS was observed (median 14.5 versus 12.5 months; HR 0.92 [95% CI 0.78, 1.10]; P = 0.37). Response rates improved from 10% to 36% (P < 0.0001). From post hoc analyses in patients receiving prior oxaliplatin-bevacizumab, panitumumab-FOLFIRI improved PFS (median 6.4 versus 3.7 months; HR 0.58 [95% CI 0.37, 0.90]; P = 0.014). PFS and OS appeared longer for worst-grade skin toxicity of 2-4, versus 0-1 or FOLFIRI. Safety results were as previously reported and consistent with the known toxicities with anti-epidermal growth factor receptor therapy. CONCLUSIONS: These data confirm the primary efficacy and safety findings of this trial and support panitumumab-FOLFIRI as a second-line treatment of WT KRAS mCRC.

Hepatobiliary cystadenomas.

INTRODUCTION: Hepatobiliary cystadenomas are rare cystic tumours that can arise from any portion of the biliary tract but most commonly develop intrahepatically. They typically cause non-specific symptoms and are often detected incidentally. Cystadenomas can be mistaken for simple hepatic cysts on radiological imaging, which leads to inadequate treatment. Hepatobiliary cystadenomas have a malignant predisposition and a high recurrence rate. Complete excision including hepatic resection is therefore generally recommended. METHODS: Three cases of hepatobiliary cystadenoma were identified at one unit over a six-month period. Their clinical details and management are reported. RESULTS: Three female patients are described aged 25, 37 and 73 years. One patient presented because of recurrent infection, one presented because of pressure related symptoms and one lesion was identified incidentally. All patients were investigated by ultrasonography and computed tomography (CT), two additionally had magnetic resonance imaging (MRI) and one had a liver biopsy. The tumours were 4-16cm in size and all lesions were excised by non-anatomical, parenchyma sparing resections. Histology revealed mixed epithelium with underlying ovarian-like stroma. CONCLUSIONS: The management of hepatic cystadenomas as well as operative and pathological findings are discussed. Preoperative ultrasonography, CT and MRI is recommended, and early referral for specialist hepatobiliary review is advised. Operative resection is also recommended and complete excision was achieved in these cases. This strategy is supported by the current literature and recurrence has been shown to be unlikely.

Prolonged hypocalcemia following denosumab therapy in metastatic hormone refractory prostate cancer.

Prostate cancer is a leading cause of cancer death, frequently associated with widespread bone metastases. We report two cases of hypocalcemia following the first dose of denosumab in metastatic hormone refractory prostate cancer, the first case requiring 26 days of intravenous calcium therapy. This is the first report of prolonged hypocalcemia following denosumab in a patient with normal renal function.

Docetaxel plus cetuximab as second-line treatment for docetaxel-refractory oesophagogastric cancer: the AGITG ATTAX2 trial.

BACKGROUND: Cetuximab can reverse chemotherapy resistance in colorectal cancer. This study evaluated the efficacy and safety of the combination of docetaxel and cetuximab as a second-line treatment in docetaxel-refractory oesophagogastric cancer. METHODS: Patients received docetaxel 30 mg m(-2) on days 1 and 8, every 3 weeks and cetuximab 400 mg m(-2) on day 1, then 250 mg m(-2) weekly. Biomarker mutation analysis was performed. RESULTS: A total of 38 patients were enrolled. Response rates were PR 6% (95% CI 2-19%), s.d. 43% (95% CI 28-59%). Main grade 3/4 toxicities were febrile neutropenia, anorexia, nausea, diarrhoea, stomatitis, and acneiform rash. Median progression-free and overall survival were 2.1 and 5.4 months, respectively. A landmark analysis showed a trend to improved survival times with increased grade of acneiform rash. No KRAS, BRAF or PIK3CA mutations were observed. CONCLUSION: Cetuximab and docetaxel achieve modest responses rates, but maintain comparable survival times to other salvage regimens with low rates of toxicity.

A randomised, double-blind, placebo-controlled phase 2 study of trebananib (AMG 386) in combination with FOLFIRI in patients with previously treated metastatic colorectal carcinoma.

BACKGROUND: This phase 2 study evaluated trebananib (AMG 386), an investigational peptide-Fc fusion protein that neutralises the interaction between angiopoietins-1/2 and the Tie2 receptor, plus FOLFIRI as second-line treatment for patients with metastatic colorectal cancer. METHODS: Patients had adenocarcinoma of the colon or rectum with progression within 6 months of receiving only one prior fluoropyrimidine/oxaliplatin-based chemotherapy regimen for metastatic disease. All patients received FOLFIRI and were randomised 2:1 to also receive intravenous trebananib 10 mg kg(-1) once weekly (QW) (Arm A) or placebo QW (Arm B). The primary end point was investigator-assessed progression-free survival (PFS). RESULTS: One hundred and forty-four patients were randomised (Arms A/B, n=95/49). Median PFS in Arms A and B was 3.5 and 5.2 months (hazard ratio (HR) 1.23; 95% CI, 0.81-1.86; P=0.33) and median overall survival (OS) was 11.9 and 8.8 months, respectively (HR 0.90; 95% CI; 0.53-1.54; P=0.70). Objective response rate (ORR) was 14% and 0% in Arms A and B, respectively. Incidence of grade ≥3 adverse events was similar between treatment arms (Arm A, 61%; Arm B, 65%) and included pulmonary embolism (1%/4%), deep vein thrombosis (5%/2%), and hypertension (1%/0%). CONCLUSION: Administration of trebananib plus FOLFIRI did not prolong PFS compared with placebo plus FOLFIRI. Toxicities were manageable and consistent with those known for FOLFIRI and trebananib.

Phase II randomized, double-blind, placebo-controlled study of AMG 386 (trebananib) in combination with cisplatin and capecitabine in patients with metastatic gastro-oesophageal cancer.

BACKGROUND: We evaluated AMG 386, an investigational peptibody that neutralizes the interaction between angiopoietins-1 and -2 and the Tie2 receptor, combined with cisplatin/capecitabine (CX) as first-line treatment for metastatic gastro-oesophageal cancer. PATIENTS AND METHODS: Patients with metastatic gastric, gastro-oesophageal junction, or distal oesophageal adenocarcinoma were randomized 1:1:1 to CX (cisplatin 80 mg/m(2) IV Q3W; capecitabine 1000 mg/m(2) P.O. BID for 14 days Q3W) plus intravenous AMG 386 10 mg/kg QW (Arm A) or 3 mg/kg QW (Arm B), or placebo QW (Arm C). The primary end point was estimated progression-free survival (PFS). RESULTS: A total of 171 patients were enrolled. Median estimated PFS in Arms A, B, and C was 4.2, 4.9, and 5.2 months, respectively (hazard ratio for Arms A+B combined versus Arm C, 0.98; 95% CI 0.67-1.43; P = 0.92). Objective response rates were 27% (Arm A), 43% (Arm B), and 35% (Arm C). Incidence of grade ≥3 adverse events was 80% in Arm A, 84% in Arm B, and 75% in Arm C. There was no evidence of pharmacokinetic interactions. CONCLUSIONS: In this study, PFS and ORR were estimated to be similar with AMG 386 plus CX and placebo plus CX treatment. Compared with placebo, toxicity of AMG 386 plus CX was greater but manageable. PREVIOUS PRESENTATION: The results of this study have not been previously published or submitted for publication elsewhere. The results were presented in part at the Gastrointestinal Cancers Symposium, San Francisco, CA, January 20-22, 2011. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT00583674.

Microwave ablation of the liver: a description of lesion evolution over time and an investigation of the heat sink effect.

AIM: Microwave ablation has been successfully used to treat unresectable liver tumours for many years. However, despite its widespread use, there seems to be a relative paucity of experimental data regarding lesion evolution and the effects of any surrounding vasculature on ablation morphology. The aim of this study was to investigate the principal pathological changes in the liver following microwave ablation, in particular the heat sink effect. In addition we carefully reviewed the available literature to provide an overview of all relevant pathological studies. METHODS: Microwave ablation was carried out on male rats at various distances from the hilum. Histological (H&E) and immunocytochemical (caspase 3) analyses of the lesion were performed at various time points; 0, 4, 24, 48  hours, 2 weeks and 1 month. A literature review was carried out using Medline, Embase and the Cochrane database to identify all relevant histological studies. RESULTS: The lesion underwent complete coagulative necrosis and was extremely regular at the ablation edge with no evidence of any influence from surrounding blood vessels at all time points. H&E and caspase 3 results were consistent and microwave caused little collateral damage outside the intended ablation zone. CONCLUSION: This study suggests that microwave ablation is extremely concise and is minimally affected by the heat sink effect. Comparative investigations with other treatment modalities are required.

Risk of arterial thromboembolic events in patients with advanced colorectal cancer receiving bevacizumab.

BACKGROUND: Bevacizumab is an antiangiogenic mAb with efficacy against several cancers, but it is associated with risk of arterial thromboembolism (ATE). Further data are needed to determine the safety of bevacizumab. PATIENTS AND METHODS: We recorded grade 3, 4, or 5 ATE events and other data (including age, baseline cardiovascular risk factors, history of ATE, and aspirin use) from 471 patients with metastatic colorectal cancer in the MAX (Mitomycin, Avastin, Xeloda) trial of capecitabine monotherapy versus capecitabine with bevacizumab with or without mitomycin C. RESULTS: Bevacizumab-treated patients had 12 grade 3, 4, or 5 ATEs (3.8% incidence). ATEs occurred in 2.1% of patients >65 years, 5% of those with a history of ATE, and 5% of those with cardiac risk factors. Age, history of ATE, or vascular risk factors did not increase risk. Aspirin users had a higher incidence than nonusers (8.9% versus 2.7%) but had higher rates of vascular risk factors. CONCLUSIONS: Bevacizumab was associated with a modestly higher risk of ATE, but safety was not significantly worse in older patients or patients with a history of ATE or vascular risk factors. The effect of aspirin in preventing ATE in patients receiving bevacizumab could not be determined from this study.

Social Identity and Preferences.

Social identities prescribe behaviors for people. We identify the marginal behavioral effect of these norms on discount rates and risk aversion by measuring how laboratory subjects' choices change when an aspect of social identity is made salient. When we make ethnic identity salient to Asian-American subjects, they make more patient choices. When we make racial identity salient to black subjects, non-immigrant blacks (but not immigrant blacks) make more patient choices. Making gender identity salient has no effect on intertemporal or risk choices.

Cryotherapy of the liver: a histological review.

INTRODUCTION: Cryotherapy has been largely used in the past for palliation of unresectable liver tumors, but high local recurrence rates and peculiar systemic complications have determined its progressive abandonment. This review analyzes the histological changes produced to provide the basis for the local recurrences. MATERIALS AND METHODS: A detailed literature search was performed on studies focusing on liver cryotherapy. Included were only those that described the histological characteristics in detail. RESULTS: A total of 22 studies were found, one clinical and the others in-vivo animal studies. Similar to other ablative techniques, cryotherapy produces a lesion which is composed by a central zone of coagulative necrosis surrounded with a transitional inflammatory zone. The lesion's dimensions and morphology are influenced by numerous factors including the probe temperature, diameter, the duration of freezing time, fast cooling rate, slow thawing rate, the number of freezing cycles and the inflow occlusion (Pringle maneuver). The temporal evolution is consistent across studies and leads to a progressive inflammatory invasion of the necrosis with definitive fibrotic substitution. CONCLUSIONS: Lesions obtained after cryotherapy seem similar and behave as those obtained after other techniques of liver ablation. However, controversial areas still exist and include the optimum number of freeze thaw cycles, the place of inflow occlusion, the potential corrupting effects of intra-lesional or proximal blood vessels on ablation morphology. The influence of these factors on the local recurrences are still not fully understood.