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BMC Surgery Mar 2023Incisional hernia is a frequent complication after loop-ileostomy closure, rationalizing hernia prevention. Biological meshes have been widely used in contaminated... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Incisional hernia is a frequent complication after loop-ileostomy closure, rationalizing hernia prevention. Biological meshes have been widely used in contaminated surgical sites instead of synthetic meshes in fear of mesh related complications. However, previous studies on meshes does not support this practice. The aim of Preloop trial was to study the safety and efficacy of synthetic mesh compared to a biological mesh in incisional hernia prevention after loop-ileostomy closure.
METHODS
The Preloop randomized, feasibility trial was conducted from April 2018 until November 2021 in four hospitals in Finland. The trial enrolled 102 patients with temporary loop-ileostomy after anterior resection for rectal cancer. The study patients were randomized 1:1 to receive either a light-weight synthetic polypropylene mesh (Parietene Macro™, Medtronic) (SM) or a biological mesh (Permacol™, Medtronic) (BM) to the retrorectus space at ileostomy closure. The primary end points were rate of surgical site infections (SSI) at 30-day follow-up and incisional hernia rate during 10 months' follow-up period.
RESULTS
Of 102 patients randomized, 97 received the intended allocation. At 30-day follow-up, 94 (97%) patients were evaluated. In the SM group, 1/46 (2%) had SSI. Uneventful recovery was reported in 38/46 (86%) in SM group. In the BM group, 2/48 (4%) had SSI (p > 0.90) and in 43/48 (90%) uneventful recovery was reported. The mesh was removed from one patient in both groups (p > 0.90).
CONCLUSIONS
Both a synthetic mesh and biological mesh were safe in terms of SSI after loop-ileostomy closure. Hernia prevention efficacy will be published after the study patients have completed the 10 months' follow-up.
Topics: Humans; Incisional Hernia; Ileostomy; Surgical Mesh; Feasibility Studies; Hernia; Surgical Wound Infection
PubMed: 36973782
DOI: 10.1186/s12893-023-01961-4 -
Journal of Clinical and Translational... Dec 2022The optimal imaging test for gross tumor volume (GTV) delineation in non-spine bone metastases has not been defined. The use of stereotactic body radiotherapy (SBRT)...
BACKGROUND AND AIM
The optimal imaging test for gross tumor volume (GTV) delineation in non-spine bone metastases has not been defined. The use of stereotactic body radiotherapy (SBRT) requires accurate target delineation. Magnetic resonance imaging (MRI) and/or fludesoxyglucose positron emission tomography (18FDG-PET) allow for better visualization of the extent of bone metastases and optimizes the accuracy of tumor delineation for stereotactic radiotherapy compared to computed tomography (CT) alone. We evaluated the interobserver agreement in GTV of non-spine bone metastases in a single center and compared MRI and/or 18FDG-PET and CT in GTV delineation.
METHODS
Anonymous CT and MRI and/or 18FDG-PET obtained from 10 non-spine bone metastases were analyzed by six radiation oncologists at our center. Images acquired by CT and MRI and/or 18FDG-PET were used to delineate 10 GTVs of non-spine bone metastases in the pelvis, extremities, and skull. The cases showed different characteristics: blastic and lytic metastases, and different primary cancers (lung, breast, prostate, rectum, urothelial, and biliary). In both CT and MRI and/or 18FDG-PET, the GTV volumes were compared. The index of agreement was evaluated according to Landis and Koch protocol.
RESULTS
The GTV volume as defined on MRI was in all cases larger or at least as large as the GTV volume on CT (=0.25). The median GTV volume on MRI was 3.15 cc (0.027-70.64 cc) compared to 2.8 cc on CT (0.075-77.95 cc). Interobserver variance and standard deviation were lower in CT than MRI (576.3 vs. 722.2 and 24.0 vs. 26.9, respectively). The level of agreement was fair (kappa=0.36) between CT and MRI. The median GTV volume on 18FDG-PET in five patients was 5.8 cc (0.46-64.17 cc), compared to 4.1 cc on CT (0.99-54.2 cc) (=0.236). Interobserver variance and standard deviation in CT, MRI, and 18FDG-PET were 576.3 versus 722.2 versus 730.5 and 24 versus 26.9 versus 27.0, respectively. The level of agreement was slight (kappa=0.08) between CT and 18FDG-PET.
CONCLUSIONS
Interobserver variance in non-spine bone metastases was equal when MRI and PET were compared to CT. CT was associated with the lowest variance and standard deviation. Compared to CT GTVs, the GTVs rendered from MRI images had fair agreement, while the GTVs rendered from 18FDG-PET had only slight agreement.
RELEVANCE FOR PATIENTS
The delimitation of the treatment volume in non-spine bone metastases with SBRT is important for the results determining its efficacy. It is therefore essential to know the variability and to manage it to achieve the highest quality of treatment.
PubMed: 36452000
DOI: No ID Found -
The European Respiratory Journal Mar 2023GLPG1205 is a selective functional antagonist of G-protein-coupled receptor 84, which plays an important role in fibrotic processes. This study assessed the efficacy,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
GLPG1205 is a selective functional antagonist of G-protein-coupled receptor 84, which plays an important role in fibrotic processes. This study assessed the efficacy, safety and tolerability of GLPG1205 for treatment of idiopathic pulmonary fibrosis (IPF).
METHODS
PINTA (ClinicalTrials.gov: NCT03725852) was a phase 2, randomised, double-blind, placebo-controlled, proof-of-concept trial. Patients with IPF were randomised 2:1 to once-daily oral GLPG1205 100 mg or placebo for 26 weeks and stratified to receive GLPG1205 alone or with local standard of care (nintedanib or pirfenidone). The primary end-point was change from baseline in forced vital capacity (FVC); other end-points were safety and tolerability, and lung volumes measured by imaging (high-resolution computed tomography). The study was not powered for statistical significance.
RESULTS
In total, 68 patients received study medication. Least squares mean change from baseline in FVC at week 26 was -33.68 (95% CI -112.0-44.68) mL with GLPG1205 and -76.00 (95% CI -170.7-18.71) mL with placebo (least squares mean difference 42.33 (95% CI -81.84-166.5) mL; p=0.50). Lung volumes by imaging declined -58.30 -262.72 mL (whole lung) and -33.68 -135.48 mL (lower lobes) with GLPG1205 placebo, respectively. Treatment with GLPG1205 placebo resulted in higher proportions of serious and severe treatment-emergent adverse events and treatment-emergent discontinuations, most apparent with nintedanib.
CONCLUSIONS
Treatment with GLPG1205 did not result in a significant difference in FVC decline placebo. GLPG1205 demonstrated a poorer safety and tolerability profile than placebo.
Topics: Humans; Idiopathic Pulmonary Fibrosis; Lung; Vital Capacity; Double-Blind Method; Treatment Outcome
PubMed: 36328358
DOI: 10.1183/13993003.01794-2022 -
Open Forum Infectious Diseases Oct 2022Approximately 10 years after vaccination with the recombinant zoster vaccine (RZV), an interim analysis of this follow-up study of the ZOE-50/70 trials demonstrated that...
Long-term Protection Against Herpes Zoster by the Adjuvanted Recombinant Zoster Vaccine: Interim Efficacy, Immunogenicity, and Safety Results up to 10 Years After Initial Vaccination.
Approximately 10 years after vaccination with the recombinant zoster vaccine (RZV), an interim analysis of this follow-up study of the ZOE-50/70 trials demonstrated that efficacy against herpes zoster remained high. Moreover, the safety profile remained clinically acceptable, suggesting that the clinical benefit of the RZV in ≥50-year-olds is sustained up to 10 years.
PubMed: 36299530
DOI: 10.1093/ofid/ofac485 -
European Journal of Cancer (Oxford,... Nov 2022Treatment monitoring in metastatic colorectal cancer (mCRC) relies on imaging to evaluate the tumour burden. Response Evaluation Criteria in Solid Tumors provide a...
BACKGROUND
Treatment monitoring in metastatic colorectal cancer (mCRC) relies on imaging to evaluate the tumour burden. Response Evaluation Criteria in Solid Tumors provide a framework on reporting and interpretation of imaging findings yet offer no guidance on a standardised imaging protocol tailored to patients with mCRC. Imaging protocol heterogeneity remains a challenge for the reproducibility of conventional imaging end-points and is an obstacle for research on novel imaging end-points.
PATIENTS AND METHODS
Acknowledging the recently highlighted potential of radiomics and artificial intelligence tools as decision support for patient care in mCRC, a multidisciplinary, international and expert panel of imaging specialists was formed to find consensus on mCRC imaging protocols using the Delphi method.
RESULTS
Under the guidance of the European Organisation for Research and Treatment of Cancer (EORTC) Imaging and Gastrointestinal Tract Cancer Groups, the European Society of Oncologic Imaging (ESOI) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the EORTC-ESOI-ESGAR core imaging protocol was identified.
CONCLUSION
This consensus protocol attempts to promote standardisation and to diminish variations in patient preparation, scan acquisition and scan reconstruction. We anticipate that this standardisation will increase reproducibility of radiomics and artificial intelligence studies and serve as a catalyst for future research on imaging end-points. For ongoing and future mCRC trials, we encourage principal investigators to support the dissemination of these imaging standards across recruiting centres.
Topics: Humans; Consensus; Artificial Intelligence; Reproducibility of Results; Rectal Neoplasms; Colonic Neoplasms
PubMed: 36274570
DOI: 10.1016/j.ejca.2022.09.012 -
Oncology 2023Cancer patients are more susceptible to infections, and infection can be more severe than in patients without cancer diagnosis. We conducted this retrospective study in...
INTRODUCTION
Cancer patients are more susceptible to infections, and infection can be more severe than in patients without cancer diagnosis. We conducted this retrospective study in patients admitted for SARS-CoV-2 infection in order to find differences in inflammatory markers and mortality in cancer patients compared to others.
METHODS
We reviewed the electronic records of patients admitted for SARS-CoV-2 infection confirmed by PCR from March to September 2020. Data on socio-demographics, comorbidities, inflammatory makers, and cancer-related features were analyzed.
RESULTS
2,772 patients were admitted for SARS-CoV-2, to the Hospital Universitario Ramón y Cajal in Madrid during this period. Of these, 2,527 (91%) had no history of neoplastic disease, 164 (5.9%) patients had a prior history of cancer but were not undergoing oncological treatment at the time of infection, and 81 (2.9%) were in active treatment. Mortality in patients without a history of cancer was 19.5%, 28.6% for patients with a prior history of cancer, and 34% in patients with active cancer treatment. Patients in active oncology treatment with the highest mortality rate were those diagnosed with lung cancer (OR 5.6 95% CI: 2.2-14.1). In the multivariate study, active oncological treatment (OR 2.259 95% CI: 1.35-3.77) and chemotherapy treatment (OR 3.624 95% CI: 1.17-11.17), were statistically significant factors for the risk of death for the whole group and for the group with active oncological treatment, respectively.
CONCLUSION
Cancer patients on active systemic treatment have an increased risk of mortality after SARS-CoV-2 infection, especially with lung cancer or chemotherapy treatment.
Topics: Humans; COVID-19; Lung Neoplasms; Medical Oncology; Retrospective Studies; SARS-CoV-2
PubMed: 36063800
DOI: 10.1159/000525802 -
BJS Open Jul 2022Older patients are at high risk of experiencing delayed functional recovery after surgical treatment. This study aimed to identify factors that predict changes in the... (Observational Study)
Observational Study
BACKGROUND
Older patients are at high risk of experiencing delayed functional recovery after surgical treatment. This study aimed to identify factors that predict changes in the level of support for activities of daily living and mobility 1 year after colonic cancer surgery.
METHODS
This was a multicentre, observational study conforming to STROBE guidelines. The prospective data included pre-and postoperative mobility and need for support in daily activities, co-morbidities, onco-geriatric screening tool (G8), clinical frailty scale (CFS), operative data, and postoperative surgical outcomes.
RESULTS
A total of 167 patients aged 80 years or more with colonic cancer were recruited. After surgery, 30 per cent and 22 per cent of all patients had increased need for support and decreased motility. Multivariableanalysis with all patients demonstrated that preoperative support in daily activities outside the home (OR 3.23, 95 per cent c.i. 1.06 to 9.80, P = 0.039) was associated with an increased support at follow-up. A history of cognitive impairment (3.15, 1.06 to 9.34, P = 0.038) haemoglobin less than 120 g/l (7.48, 1.97 to 28.4, P = 0.003) and discharge to other medical facilities (4.72, 1.39 to 16.0, P = 0.013) were independently associated with declined mobility. With functionally independent patients, haemoglobin less than 120 g/l (8.31, 1.76 to 39.2, P = 0.008) and discharge to other medical facilities (4.38, 1.20 to 16.0, P = 0.026) were associated with declined mobility.
CONCLUSION
Increased need for support before surgery, cognitive impairment, preoperative anaemia, and discharge to other medical facilities predicts an increased need for support or declined mobility 1 year after colonic cancer surgery. Preoperative assessment and optimization should focus on anaemia correction, nutritional status, and mobility with detailed rehabilitation plan.
Topics: Activities of Daily Living; Aged, 80 and over; Anemia; Colonic Neoplasms; Geriatric Assessment; Hemoglobins; Humans; Physical Functional Performance; Prospective Studies
PubMed: 35973109
DOI: 10.1093/bjsopen/zrac094 -
Toxicology and Applied Pharmacology Sep 2022Resistance to antitumor treatments is one of the most important problems faced by clinicians in the management of colorectal cancer (CRC) patients. Cancer-Associated...
Resistance to antitumor treatments is one of the most important problems faced by clinicians in the management of colorectal cancer (CRC) patients. Cancer-Associated Fibroblasts (CAFs) are the main producers and remodelers of the extracellular matrix (ECM), which is directly involved in drug resistance mechanisms. Primary Normal Fibroblasts (NFs) and CAFs and cell lines (fibroblasts and tumor cells), were used to generate ECM and to identify its role in the oxaliplatin and cetuximab chemoresistance processes of CRC cells mediated by SNAI1-expressing fibroblasts. Matrices generated by Snai1 KO MEFs (Knockout Mouse Embryonic Fibroblasts) confer less resistance on oxaliplatin and cetuximab than wild-type MEF-derived matrices. Similarly, matrices derived from CAFs cause greater survival of colorectal cancer cells than NF-derived matrices, in a similar way to Snai1 expression levels. In addition, Snail1 expression in fibroblasts regulates drug resistance and metabolism gene expression in tumor cells mediated by ECM. Finally, a series of 531 patients (TCGA) with CRC was used to assess the role of SNAI1 expression in patients' prognosis indicating an association between tumor SNAI1 expression and overall survival in colon cancer patients but not in rectal cancer patients. SNAI1 expression in CRC cancer patients, together with in vitro experimentation, suggests the possible use of SNAI1 expression in tumor-associated fibroblasts as a predictive biomarker of response to oxaliplatin and cetuximab treatments in patients with CRC.
Topics: Animals; Cell Line, Tumor; Cetuximab; Colorectal Neoplasms; Drug Resistance; Extracellular Matrix; Fibroblasts; Mice; Mice, Knockout; Oxaliplatin
PubMed: 35878797
DOI: 10.1016/j.taap.2022.116171 -
Frontiers in Genetics 2022Pinnipeds found across islands provide an ideal opportunity to examine the evolutionary process of population subdivision affected by several mechanisms. Here, we report...
Pinnipeds found across islands provide an ideal opportunity to examine the evolutionary process of population subdivision affected by several mechanisms. Here, we report the genetic consequences of the geographic distribution of rookeries in Galapagos fur seals (GFS: ) in creating population structure. We show that rookeries across four islands (nine rookeries) are genetically structured into the following major groups: 1) a western cluster of individuals from Fernandina; 2) a central group from north and east Isabela, Santiago, and Pinta; and possibly, 3) a third cluster in the northeast from Pinta. Furthermore, asymmetric levels of gene flow obtained from eight microsatellites found migration from west Isabela to Fernandina islands (number of migrants = 1), with imperceptible in any other direction. Our findings suggest that the marked structuring of populations recovered in GFS is likely related to an interplay between long-term site fidelity and long-distance migration in both male and female individuals, probably influenced by varying degrees of marine productivity.
PubMed: 35664327
DOI: 10.3389/fgene.2022.725772 -
Heredity Apr 2022The Galapagos Archipelago is recognized as a natural laboratory for studying evolutionary processes. San Cristóbal was one of the first islands colonized by tortoises,...
The Galapagos Archipelago is recognized as a natural laboratory for studying evolutionary processes. San Cristóbal was one of the first islands colonized by tortoises, which radiated from there across the archipelago to inhabit 10 islands. Here, we sequenced the mitochondrial control region from six historical giant tortoises from San Cristóbal (five long deceased individuals found in a cave and one found alive during an expedition in 1906) and discovered that the five from the cave are from a clade that is distinct among known Galapagos giant tortoises but closely related to the species from Española and Pinta Islands. The haplotype of the individual collected alive in 1906 is in the same clade as the haplotype in the contemporary population. To search for traces of a second lineage in the contemporary population on San Cristóbal, we closely examined the population by sequencing the mitochondrial control region for 129 individuals and genotyping 70 of these for both 21 microsatellite loci and >12,000 genome-wide single nucleotide polymorphisms [SNPs]. Only a single mitochondrial haplotype was found, with no evidence to suggest substructure based on the nuclear markers. Given the geographic and temporal proximity of the two deeply divergent mitochondrial lineages in the historical samples, they were likely sympatric, raising the possibility that the lineages coexisted. Without the museum samples, this important discovery of an additional lineage of Galapagos giant tortoise would not have been possible, underscoring the value of such collections and providing insights into the early evolution of this iconic radiation.
Topics: Animals; DNA, Mitochondrial; Ecuador; Genome; Haplotypes; Humans; Microsatellite Repeats; Museums; Phylogeny; Turtles
PubMed: 35217806
DOI: 10.1038/s41437-022-00510-8