Clinical significance of cefazolin inoculum effect in serious MSSA infections: a systematic review.

Background: The cefazolin inoculum effect (CzIE) is a phenomenon whereby some MSSA isolates demonstrate resistance to cefazolin when a high bacterial inoculum is used for susceptibility testing. The clinical significance of this phenotypic phenomenon remains unclear. We conducted a systematic review to answer the following question: In patients with serious MSSA infection treated with cefazolin, does infection due to CzIE-positive MSSA isolates result in worse clinical outcomes than infection due to CzIE-negative MSSA isolates? Methods: Ovid MEDLINE, Embase, Cochrane CENTRAL, medRxiv and bioRxiv were searched from inception until 12 April 2023. Studies were included if they tested for CzIE in clinical isolates from MSSA infections in humans. Two independent reviewers extracted data and conducted risk-of-bias assessment. Main outcomes were treatment failure and mortality. Pooling of study estimates was not performed given the heterogeneity of patient populations and outcome definitions. Results: Twenty-three observational studies were included. CzIE presence amidst MSSA isolates ranged from 0% to 55%. There was no statistically significant mortality difference in two studies that compared MSSA infections with and without CzIE, with ORs ranging from 0.72 to 19.78. Of four studies comparing treatment failure, ORs ranged from 0.26 to 13.00. One study showed a significantly higher treatment failure for the CzIE group, but it did not adjust for potential confounders. Conclusions: The evidence on CzIE is limited by small observational studies. In these studies, CzIE did not predict higher mortality in MSSA infections treated with cefazolin. Our findings do not support CzIE testing in clinical practice currently.

Evaluating in vivo effectiveness of sotrovimab for the treatment of Omicron subvariant BA.2 versus BA.1: a multicentre, retrospective cohort study.

BACKGROUND: In vitro data suggested reduced neutralizing capacity of sotrovimab, a monoclonal antibody, against Omicron BA.2 subvariant. However, limited in vivo data exist regarding clinical effectiveness of sotrovimab for coronavirus disease 2019 (COVID-19) due to Omicron BA.2. METHODS: A multicentre, retrospective cohort study was conducted at three Canadian academic tertiary centres. Electronic medical records were reviewed for patients ≥ 18 years with mild COVID-19 (sequencing-confirmed Omicron BA.1 or BA.2) treated with sotrovimab between February 1 to April 1, 2022. Thirty-day co-primary outcomes included hospitalization due to moderate or severe COVID-19; all-cause intensive care unit (ICU) admission, and all-cause mortality. Risk differences (BA.2 minus BA.1 group) for co-primary outcomes were adjusted with propensity score matching (e.g., age, sex, vaccination, immunocompromised status). RESULTS: Eighty-five patients were included (15 BA.2, 70 BA.1) with similar baseline characteristics between groups. Adjusted risk differences were non-statistically significant between groups for 30-day hospitalization (- 14.3%; 95% confidence interval (CI): - 32.6 to 4.0%), ICU admission (- 7.1%; 95%CI: - 20.6 to 6.3%), and mortality (- 7.1%; 95%CI: - 20.6 to 6.3%). CONCLUSIONS: No differences were demonstrated in hospitalization, ICU admission, or mortality rates within 30 days between sotrovimab-treated patients with BA.1 versus BA.2 infection. More real-world data may be helpful to properly assess sotrovimab's effectiveness against infections due to specific emerging COVID-19 variants.

Plasmodium knowlesi Infection in Traveler Returning to Canada from the Philippines, 2023.

A 55-year-old man sought treatment for an uncomplicated febrile illness after returning to Canada from the Philippines. A suspected diagnosis of Plasmodium knowlesi infection was confirmed by PCR, and treatment with atovaquone/proguanil brought successful recovery. We review the evolving epidemiology of P. knowlesi malaria in the Philippines, specifically within Palawan Island.

Gordonia sputi-associated bloodstream infection in a renal transplant patient with chronic indwelling central venous catheter: a case report and literature review.

Introduction: Although rare, human infections caused by Gordonia spp. have been reported, especially within the immunocompromised population and those with long-term indwelling devices. We report a case of Gordonia spp. bacteraemia in a renal transplant patient and present a literature review on microbiological identification methods of this organism. Case Presentation: A 62-year-old female renal transplant recipient admitted to hospital with a 2-month history of dry cough and fevers occurring weekly when receiving electrolyte replacement infusions via a Groshong line. Over 2 weeks, blood cultures repeatedly isolated a Gram-positive bacillus solely in aerobic bottles, and this was initially reported as Rhodococcus spp. by the local microbiology laboratory. Chest computed tomography (CT) showed multiple ground-glass lung opacities suggestive of septic pulmonary emboli. As central line-associated bloodstream infection was suspected, empirical antibiotics were initiated and the Groshong line was removed. The Gram-positive bacillus was later confirmed by the reference laboratory as Gordonia sputi via 16S rRNA sequencing. Vancomycin and ciprofloxacin for a duration of 6 weeks were completed as targeted antimicrobial therapy. After treatment, the patient remained symptom-free with marked improvement on repeat CT chest imaging. Conclusion: This case illustrates the challenges surrounding identification of Gordonia spp. and other aerobic actinomycetes. 16S rRNA gene sequencing may be a preferred identification method, especially when initial workup of a weakly acid-fast organism fails to make an identification or shows discrepant results using traditional diagnostic modalities.

Dynamic de novo heterochromatin assembly and disassembly at replication forks ensures fork stability.

Chromatin is dynamically reorganized when DNA replication forks are challenged. However, the process of epigenetic reorganization and its implication for fork stability is poorly understood. Here we discover a checkpoint-regulated cascade of chromatin signalling that activates the histone methyltransferase EHMT2/G9a to catalyse heterochromatin assembly at stressed replication forks. Using biochemical and single molecule chromatin fibre approaches, we show that G9a together with SUV39h1 induces chromatin compaction by accumulating the repressive modifications, H3K9me1/me2/me3, in the vicinity of stressed replication forks. This closed conformation is also favoured by the G9a-dependent exclusion of the H3K9-demethylase JMJD1A/KDM3A, which facilitates heterochromatin disassembly upon fork restart. Untimely heterochromatin disassembly from stressed forks by KDM3A enables PRIMPOL access, triggering single-stranded DNA gap formation and sensitizing cells towards chemotherapeutic drugs. These findings may help in explaining chemotherapy resistance and poor prognosis observed in patients with cancer displaying elevated levels of G9a/H3K9me3.

Investigation of Play Intervention for Dementia (PID) Activities in Addressing Cognitive Domains Reflected in Hong Kong Montreal Cognitive Assessment (HK-MoCA).

Background/Objectives: Yee Hong Play Intervention for Dementia (PID) is a community program strengthening East Asians >65 years with dementia in their daily functional activities. We analyzed how PID activities align with Hong Kong Montreal Cognitive Assessment. Methods: Utilizing observation sheets procured from documentation notes from the twice-weekly PID sessions, cognitive domains were identified. Mean time duration and activity frequencies were compared between high and low competency client groups. Results: Independent of competency group, activities predominantly targeted attention/concentration (23.8% HC, 16.4% LC), and hand-eye coordination (19.1% HC, 28.7% LC). Less focused domains were delayed recall (3.1-4.7%) and naming (1.3-1.5%). Conclusions: Yee Hong PID tested innovative cognitive domains not currently covered in HK-MoCA screening assessment, emphasizing attention/concentration-oriented activities and none assessing orientation and language domains. Additionally, presence of new domains such as hand-eye coordination and fine motor dexterity suggested that strict adherence with standardized screening tools (e.g., MoCA) may not be ideal. Likely, facilitators have developed innovative measures to assess individual competency to strengthen resilience in our geriatric population.

Mild acoustic processing of Tisochrysis lutea for multiproduct biorefineries.

Cellular agriculture could represent a more sustainable alternative to current food and nutraceutical production processes. Tisochrysis lutea microalgae represents a rich source of antioxidants and omega-3 fatty acids essential for human health. However, current downstream technologies are limiting its use. The present work investigates mild targeted acoustic treatment of Tisochrysis lutea biomass at different growth stages and acoustic frequencies, intensities and treatment times. Significant differences have been observed in terms of the impact of these variables on the cell disruption and energy requirements. Lower frequencies of 20 kHz required a minimum of 4500 J to disrupt 90% of the cells, while only 1000 J at 1146 kHz. Comparing these results with current industry standards such as bead milling, up to six times less energy use has been identified. These mild biomass processing approaches offer a certain tunability which could suit a wide range of microorganisms with only minor adjustments.

Heat-induced SIRT1-mediated H4K16ac deacetylation impairs resection and SMARCAD1 recruitment to double strand breaks.

Hyperthermia inhibits DNA double-strand break (DSB) repair that utilizes homologous recombination (HR) pathway by a poorly defined mechanism(s); however, the mechanisms for this inhibition remain unclear. Here we report that hyperthermia decreases H4K16 acetylation (H4K16ac), an epigenetic modification essential for genome stability and transcription. Heat-induced reduction in H4K16ac was detected in humans, Drosophila, and yeast, indicating that this is a highly conserved response. The examination of histone deacetylase recruitment to chromatin after heat-shock identified SIRT1 as the major deacetylase subsequently enriched at gene-rich regions. Heat-induced SIRT1 recruitment was antagonized by chromatin remodeler SMARCAD1 depletion and, like hyperthermia, the depletion of the SMARCAD1 or combination of the two impaired DNA end resection and increased replication stress. Altered repair protein recruitment was associated with heat-shock-induced γ-H2AX chromatin changes and DSB repair processing. These results support a novel mechanism whereby hyperthermia impacts chromatin organization owing to H4K16ac deacetylation, negatively affecting the HR-dependent DSB repair.

A Microfluidic Cancer-on-Chip Platform Predicts Drug Response Using Organotypic Tumor Slice Culture.

Optimal treatment of cancer requires diagnostic methods to facilitate therapy choice and prevent ineffective treatments. Direct assessment of therapy response in viable tumor specimens could fill this diagnostic gap. Therefore, we designed a microfluidic platform for assessment of patient treatment response using tumor tissue slices under precisely controlled growth conditions. The optimized Cancer-on-Chip (CoC) platform maintained viability and sustained proliferation of breast and prostate tumor slices for 7 days. No major changes in tissue morphology or gene expression patterns were observed within this time frame, suggesting that the CoC system provides a reliable and effective way to probe intrinsic chemotherapeutic sensitivity of tumors. The customized CoC platform accurately predicted cisplatin and apalutamide treatment response in breast and prostate tumor xenograft models, respectively. The culture period for breast cancer could be extended up to 14 days without major changes in tissue morphology and viability. These culture characteristics enable assessment of treatment outcomes and open possibilities for detailed mechanistic studies. SIGNIFICANCE: The Cancer-on-Chip platform with a 6-well plate design incorporating silicon-based microfluidics can enable optimal patient-specific treatment strategies through parallel culture of multiple tumor slices and diagnostic assays using primary tumor material.

R-Loops and Its Chro-Mates: The Strange Case of Dr. Jekyll and Mr. Hyde.

Since their discovery, R-loops have been associated with both physiological and pathological functions that are conserved across species. R-loops are a source of replication stress and genome instability, as seen in neurodegenerative disorders and cancer. In response, cells have evolved pathways to prevent R-loop accumulation as well as to resolve them. A growing body of evidence correlates R-loop accumulation with changes in the epigenetic landscape. However, the role of chromatin modification and remodeling in R-loops homeostasis remains unclear. This review covers various mechanisms precluding R-loop accumulation and highlights the role of chromatin modifiers and remodelers in facilitating timely R-loop resolution. We also discuss the enigmatic role of RNA:DNA hybrids in facilitating DNA repair, epigenetic landscape and the potential role of replication fork preservation pathways, active fork stability and stalled fork protection pathways, in avoiding replication-transcription conflicts. Finally, we discuss the potential role of several Chro-Mates (chromatin modifiers and remodelers) in the likely differentiation between persistent/detrimental R-loops and transient/benign R-loops that assist in various physiological processes relevant for therapeutic interventions.

Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instability.

Correct transcription is crucial for life. However, DNA damage severely impedes elongating RNA polymerase II, causing transcription inhibition and transcription-replication conflicts. Cells are equipped with intricate mechanisms to counteract the severe consequence of these transcription-blocking lesions. However, the exact mechanism and factors involved remain largely unknown. Here, using a genome-wide CRISPR-Cas9 screen, we identified the elongation factor ELOF1 as an important factor in the transcription stress response following DNA damage. We show that ELOF1 has an evolutionarily conserved role in transcription-coupled nucleotide excision repair (TC-NER), where it promotes recruitment of the TC-NER factors UVSSA and TFIIH to efficiently repair transcription-blocking lesions and resume transcription. Additionally, ELOF1 modulates transcription to protect cells against transcription-mediated replication stress, thereby preserving genome stability. Thus, ELOF1 protects the transcription machinery from DNA damage via two distinct mechanisms.

SMARCAD1-mediated active replication fork stability maintains genome integrity.

The stalled fork protection pathway mediated by breast cancer 1/2 (BRCA1/2) proteins is critical for replication fork stability. However, it is unclear whether additional mechanisms are required to maintain replication fork stability. We describe a hitherto unknown mechanism, by which the SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily-A containing DEAD/H box-1 (SMARCAD1) stabilizes active replication forks, that is essential to maintaining resistance towards replication poisons. We find that SMARCAD1 prevents accumulation of 53BP1-associated nucleosomes to preclude toxic enrichment of 53BP1 at the forks. In the absence of SMARCAD1, 53BP1 mediates untimely dissociation of PCNA via the PCNA-unloader ATAD5, causing frequent fork stalling, inefficient fork restart, and accumulation of single-stranded DNA. Although loss of 53BP1 in SMARCAD1 mutants rescues these defects and restores genome stability, this rescued stabilization also requires BRCA1-mediated fork protection. Notably, fork protection-challenged BRCA1-deficient naïve- or chemoresistant tumors require SMARCAD1-mediated active fork stabilization to maintain unperturbed fork progression and cellular proliferation.

Association Between Intraoperative Remifentanil Dosage and Postoperative Opioid Consumption in Adolescent Idiopathic Spine Surgery: A Retrospective Cohort Study.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) surgery is associated with significant postoperative pain. Remifentanil is a short-acting opioid that is often used as a component of total intravenous anesthesia. Remifentanil has been implicated in acute opioid tolerance and opioid-induced hyperalgesia, resulting in increased postoperative pain and opioid consumption. This retrospective study sought to investigate the relationship between the dose of intraoperative remifentanil and cumulative postoperative opioid consumption through 72 hours following surgery for pediatric AIS patients. METHODS: We performed a retrospective chart review of adolescent patients undergoing posterior spine instrumentation under total intravenous general anesthesia at a single major pediatric center between January 2015 and October 2017. The relationship between intraoperative cumulative weight-adjusted remifentanil dose and logarithmic transformation of cumulative weight-adjusted opioid consumption through 72 hours following surgery was examined by regression analysis. A priori determined potential confounding variables were collected, including demographic data, perioperative analgesic agents (ie, ketamine, dexmedetomidine, and acetaminophen), surgical duration, vertebrae instrumented, and blood transfusion. Multivariable linear regression analysis was used to adjust for these possible confounding variables. RESULTS: Eighty-nine patients met inclusion criteria, of which 78 had complete data for analysis. Univariable linear regression analysis revealed no association between remifentanil dose and opioid consumption through 72 hours following surgery (slope = 0.79 [95% confidence interval [CI], 0.61-0.98; R2 = 0.0039; P = .588]). After adjustment for possible confounding factors, no relationship between remifentanil dose (regression coefficient (coeff.) -0.08; 95% CI, -1.59 to 1.43; P = .912) and opioid consumption through 72 hours was found (slope =0.90 [95% CI, -0.65 to 2.46]; R2 = 0.1634). Similar results were obtained when the model was repeated for opioid consumption in postanesthesia care unit (PACU). CONCLUSIONS: In this study examining adolescent patients undergoing surgery for idiopathic scoliosis, no association was found between the dose of intraoperative remifentanil and postoperative opioid consumption in the context of a propofol-based total intravenous anesthetic and multimodal analgesia. These results provide direction for future prospective controlled studies to further evaluate this relationship.

Eutectic solvents with tuneable hydrophobicity: lipid dissolution and recovery.

Despite the promising advantages of eutectic solvents, the application of these solvents as an extraction solvent is still limited due to the challenging product recovery. Previously, it was reported that lipids could be recovered from a hydrophobic eutectic solvent with the principle of switchable hydrophobicity. However, this method still involves additional chemicals, such as polymeric amines, water, and CO2, which need to be removed later. In this study, we proposed a different approach by shifting the hydrophobicity spectrum of a semi-hydrophobic solvent. Made of hydrophilic imidazole and hydrophobic hexanoic acid, this combination showed tuneable hydrophobicity when the composition was changed, shown by the change of dipolarity (π*) scale from solvatochromic analysis. At low imidazole content, the solvent was able to dissolve sunflower oil and algae oil, whereas, at high imidazole content, the solvent showed high affinity towards water. By adding imidazole to the solution of oil and the solvent, a phase split was induced between the oil-rich upper phase and the solvent-rich lower phase. With this approach, ∼75% of recovery efficiency was achieved for the two oils, with the purity of ∼100% for sunflower oil and 86% for algae oil.

Anesthesia in the modern world of apps and technology: Implications and impact on wellness.

Recent decades have seen an unprecedented leap in digital innovation, with far-reaching implications in healthcare. Anesthesiologists have historically championed the adoption of new technologies. However, the rapid evolution of these technologies has outpaced attempts at studying their potential impact on healthcare providers' well-being. This document introduces several categories of workplace technologies commonly encountered by the anesthesiologist. We examine examples of novel technology and the impact of these digital interventions on the anesthesiologist's well-being. We also review popular personalized technology aimed at improving wellness and the impact on well-being examined. Finally, technology acceptance models are introduced to improve technology adoption, which, when appropriately applied, may minimize the negative impacts of technology on anesthesiologists' well-being. Incorporating quantitative, serial assessments of well-being as part of technology implementation are proposed as a future direction for examining the wellness impact of technology on anesthesiologists.

Video Modeling and Video Feedback to Reduce Time to Perform Intravenous Cannulation in Medical Students: A Randomized-Controlled Mixed-Methods Study.

PURPOSE: Combined video modeling (VM) and video feedback (VF) may be more beneficial than traditional feedback when teaching procedural skills. This study examined whether repeated VM and VF compared with VM alone reduced the time required for medical students to perform peripheral intravenous (IV) cannulation. METHODS: Twenty-five novice medical students were randomly assigned to groups in a one-way blinded embedded mixed-methods study to perform IV cannulation. Participants received standardized instruction and performed IV cannulation on each other while being audio-video recorded. They were assigned to review a video of an expert performing IV cannulation (VM alone), or both the expert video and a video of their own most recent IV cannulation (VM+VF), before returning to perform another IV cannulation. This was repeated for a total of four IV cannulation encounters and three video reviews. A post-test interview was also conducted and analyzed qualitatively using thematic content analysis. RESULTS: The median [interquartile range] time required to perform IV cannulation in the final encounter was significantly different between the VM+VF group vs VM alone group (126 [93-226] sec vs 345 [131-537] sec, respectively; median difference, 111 sec; 95% confidence interval, 8 to 391; P = 0.02). There was no significant difference in IV cannulation success between VM alone and VM+VF in the final encounter (75% vs 85% respectively; P = 0.65). For the VM+VF group, the time to perform IV cannulation was reduced after the final encounter compared with the baseline encounter (P = 0.002), which was not true of the VM alone group (P = 0.35). CONCLUSION: Video modeling and feedback shortened time to IV skill completion, reduced complications, and improved satisfaction in novice medical students.

RéSUMé: OBJECTIF: La combinaison d'une vidéo de démonstration (VD) et d'une vidéo de rétroaction (VR) pourrait être plus efficace que la rétroaction traditionnelle pour l'enseignement des habiletés nécessaires pour des procédures. Cette étude a cherché à savoir si la répétition d'une VD et d'une VR réduisait davantage le temps nécessaire à des étudiants en médecine pour effectuer une canulation intraveineuse périphérique (IV) par rapport à la seule VD. MéTHODES: Vingt-cinq étudiants en médecine novices ont été assignés par randomisation à des groupes d'une étude utilisant différentes méthodes intégrées d'apprentissage avec insu unilatéral pour la réalisation d'une canulation IV. Les participants ont reçu un enseignement standardisé et ont réalisé une canulation IV sur un autre participant tout en étant filmés (audio-vidéo). Selon leur groupe, ils devaient visionner la vidéo d'un expert effectuant une canulation IV (groupe VD uniquement) ou voir la vidéo de l'expert et une vidéo de leur plus récente canulation IV (groupe VD + VR) avant d'effectuer une autre canulation IV. La procédure a été répétée (total de 4 tentatives de canulations et 3 séances de vidéos). Un entretien post test a été également mené et analysé du point de vue qualitatif au moyen d'une analyse thématique du contenu. RéSULTATS: Le temps médian [plage interquartile] nécessaire pour effectuer la canulation IV au cours de la dernière tentative a été significativement différent entre le groupe VD+VR et le groupe VD seule (respectivement, 126 secondes [93 à 226 s] contre 345 s [131 à 537 s]; différence des médianes, 111 s; intervalle de confiance à 95 % : 8 à 391; P = 0,02). Il n'y a pas eu de différence significative entre le taux de réussite des canulations entre le groupe VD seule et le groupe VD+VR (respectivement, 75 % contre 85 %; P = 0,65). Pour le groupe VD+VR, le temps nécessaire à la canulation IV au moment de la dernière tentative a été plus court par rapport au temps mis au cours de la première tentative (P = 0,002), ce qui n'a pas été le cas pour le groupe VD seule (P = 0,35). CONCLUSION: La vidéo de démonstration et la vidéo de rétroaction ont permis de raccourcir le temps de réalisation des habiletés d'une canulation IV, ont réduit les complications et amélioré la satisfaction des étudiants en médecine novices.

Assessing impact of MALDI mass spectroscopy on reducing directed antibiotic coverage time for Gram-negative organisms.

The objective of this study was to assess whether use of matrix assisted laser desorption ionization-time of flight (MALDI-TOF), through improvements in identification time, reduces time to directed antibiotic coverage. We therefore conducted a retrospective review of 377 blood cultures from hospitalized patients with gram negative bacteremia that underwent testing by MALDI-TOF compared to standard identification methods (VITEK 2) for blood cultures from January 2016 to December 2017. We found that MALDI significantly reduced time between blood culture collection to reach pathogen identification and was associated with a significantly reduced time to initiate more specific therapy, with a mean difference of 16.37 hours, 95% CI 10.05 to 22.69 (mean time 50.34 hours (+/- 21.21) vs VITEK: 66.71 hrs (+/- 27.12), p<0.001 as well as a reduced time to discontinue previous therapy (p = 0.004). In conclusion, in reducing time to identification of gram negative bacteremia, MALDI-TOF led to improvements in antibiotic coverage.

Red and Processed Meat Consumption and Risk for All-Cause Mortality and Cardiometabolic Outcomes: A Systematic Review and Meta-analysis of Cohort Studies.

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Dietary guidelines generally recommend limiting intake of red and processed meat. However, the quality of evidence implicating red and processed meat in adverse health outcomes remains unclear. Purpose: To evaluate the association between red and processed meat consumption and all-cause mortality, cardiometabolic outcomes, quality of life, and satisfaction with diet among adults. Data Sources: EMBASE (Elsevier), Cochrane Central Register of Controlled Trials (Wiley), Web of Science (Clarivate Analytics), CINAHL (EBSCO), and ProQuest from inception until July 2018 and MEDLINE from inception until April 2019, without language restrictions, as well as bibliographies of relevant articles. Study Selection: Cohort studies with at least 1000 participants that reported an association between unprocessed red or processed meat intake and outcomes of interest. Data Extraction: Teams of 2 reviewers independently extracted data and assessed risk of bias. One investigator assessed certainty of evidence, and the senior investigator confirmed the assessments. Data Synthesis: Of 61 articles reporting on 55 cohorts with more than 4 million participants, none addressed quality of life or satisfaction with diet. Low-certainty evidence was found that a reduction in unprocessed red meat intake of 3 servings per week is associated with a very small reduction in risk for cardiovascular mortality, stroke, myocardial infarction (MI), and type 2 diabetes. Likewise, low-certainty evidence was found that a reduction in processed meat intake of 3 servings per week is associated with a very small decrease in risk for all-cause mortality, cardiovascular mortality, stroke, MI, and type 2 diabetes. Limitation: Inadequate adjustment for known confounders, residual confounding due to observational design, and recall bias associated with dietary measurement. Conclusion: The magnitude of association between red and processed meat consumption and all-cause mortality and adverse cardiometabolic outcomes is very small, and the evidence is of low certainty. Primary Funding Source: None. (PROSPERO: CRD42017074074).