A disease-associated gene desert directs macrophage inflammation through ETS2.

Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health1. This is compounded by the limited efficacy of available treatments1 and high failure rates during drug development2, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22-which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu's arteritis3-6-we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures7, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.

A comparison of the efficacy of trastuzumab deruxtecan in advanced HER2-positive breast cancer: active brain metastasis versus progressive extracranial disease alone.

BACKGROUND: Trastuzumab deruxtecan (T-DXd) has demonstrated efficacy in patients with brain metastasis (BM), a group historically with poor outcomes. The prevalence of BMs in patients commencing T-DXd is currently unknown. No direct comparisons have been made of the activity of T-DXd in patients with active BM versus those with extracranial progression alone. This real-world study explored the prevalence of BMs in patients commencing T-DXd, the efficacy of T-DXd in active BM versus extracranial progression alone and the safety of T-DXd. PATIENTS AND METHODS: Patients with human epidermal growth factor receptor 2-positive advanced breast cancer treated with T-DXd between June 2021 and February 2023 at our specialist cancer hospital were identified and notes reviewed. Clinicopathological information, prior treatment, the presence or absence of central nervous system (CNS) disease, outcomes and treatment-emergent adverse events (TEAEs) were recorded. RESULTS: Twenty-nine female patients, with a median age of 52 years (interquartile range 44-62 years), were identified; the prevalence of BM was 41%. Median number of lines of prior therapy was 2 (range 2-6). At a median follow-up of 13.8 months, median progression-free survival (PFS) for the overall population was 13.9 months [95% confidence interval (CI) 12.4 months-not estimable (NE)], 16.1 months (95% CI 15.1 months-NE) for active BMs and 12.4 months (95% CI 8.3 months-NE) for progressive extracranial disease alone. The 12-month overall survival (OS) rate was 74% (95% CI 59% to 95%) in the overall population, and 83% (95% CI 58% to 100%) and 66% (95% CI 45% to 96%) for active BMs and extracranial disease only, respectively. Most common TEAEs were fatigue, alopecia, and constipation. In nine patients (31%, including two deaths), pneumonitis occurred. CONCLUSION: In this real-world population, we demonstrate T-DXd to be effective in patients with active BMs and those with progressive extracranial disease alone. PFS and OS were numerically longer in those with active BMs. These data demonstrate that patients with active BM treated with T-DXd have at least comparable outcomes to those with extracranial disease alone. The high rate of pneumonitis warrants further consideration.

The role of outpatient needle arthroscopy in the diagnosis and management of musculoskeletal complaints: A systematic review of the Arthrex NanoScope.

BACKGROUND: The aim was to review the literature regarding needle arthroscopy using the Arthrex NanoScope system and evaluate: (1) the diagnostic indications, utility, and efficacy compared to conventional methods, and (2) the therapeutic indications, safety, and reported outcomes. METHODS: Searches of three databases (MEDLINE, Embase and PubMed) were conducted in November 2021 using MeSH terms: 'needle arthroscopy', 'human', 'in office arthroscopy', 'needle arthroscope', 'nanoscopic', 'surgery', 'nanoscope' and 'percutaneous arthroscopy'. The included studies were catalogued, quality-assessed using Methodological Index for Non-Randomised Studies (MINORS), and analysed using the Cochrane data collection templates for randomised control trials (RCT) and non-randomised control trials (non-RCT). The majority of studies were non-numerical and were examined using qualitative analysis. RESULTS: The search yielded 314 studies, 22 of which were included for analysis. MINORS assessment was applicable to four studies. Mean MINORS was 10.7/16 with the most frequent limitations being lack of unbiased endpoint or sample size calculation. The level of evidence ranged from level IV-V. Diagnostic and therapeutic indications were described in relation to the: knee (n = 10); shoulder (n = 6); foot/ankle (n = 3); elbow (n = 2), and miscellaneous (n = 1). CONCLUSIONS: Needle arthroscopy can augment the diagnostic process in patients presenting with musculoskeletal complaints, and may provide benefits in terms of diagnostic accuracy, cost efficiency, timeliness of investigation, and a visually impactful patient-centred consultation. Therapeutic interventions are reported by a small number of pioneer groups who report some benefits over conventional arthroscopy. The available literature remains small and of low quality, and more evidence is needed with regards to patient selection, efficacy, safety, and cost. LEVEL OF EVIDENCE: Level V (based on the weakest study included in the Systematic Review).

Moving orthopaedic procedures out of the operating theatre:Outpatient needle arthroscopy can reduce cost & waste, and increase inpatient capacity compared to conventional knee arthroscopy.

BACKGROUND: Needle arthroscopy (NA) is an emerging technique that could streamline pathways, facilitate timely care, and reduce service burden. The primary aim was to assess the practical and economic viability of an outpatient NA service. Secondary aims were to assess the relative costs and benefits compared to a conventional arthroscopy (CA) service. METHODS: This service feasibility study was conducted between 2021-2022 in a high-volume national treatment centre. A NA pathway was established for patients with chronic soft tissue pathology or early degenerative knee disease. The pathway was evaluated in terms of: i) cost; ii) efficiency, and iii) waste production, and an assessment was conducted of the patient-related and service-related effects. RESULTS: The cost of the NA pathway was £1555.20 per patient, compared to £2,351.53 for CA. Time to management was 45 days for NA versus 180 days for CA. The NA pathway involved two hospital attendances, whereas CA required a minimum of three. NA cases produced 1.4 kg of non-recyclable waste compared to 5.0 kg produced by CA. For every two cases managed by NA instead of CA, capacity for one additional obligate-inpatient procedure was created. CONCLUSIONS: The NA pathway offers a technically and economically viable approach for the management of refractory knee symptoms in the context of chronic soft tissue or early degenerative disease. NA placed less demand on hospital resources, produced two-thirds less non-recyclable waste, and is amenable to a one-stop clinic approach. Clinical studies focused on objective and patient-reported outcome measures are required to assess clinical efficacy.

Surgeon educator perspectives of implementing a national undergraduate curriculum in otolaryngology.

OBJECTIVE: The General Medical Council will be implementing a national medical licensing assessment for all UK medical students by 2024-25. Surgeon educator perceptions on a national undergraduate curriculum in otolaryngology were reviewed accordingly. METHOD: A mixed methods study was undertaken within a UK school of surgery assessing ENT surgeon educators. Perspectives on teaching content, quality and student experience were assessed with degree of agreement assessed (Likert scoring). Associated qualitative focus group sessions underwent detailed thematic analysis according to grounded theory. RESULTS: A response rate of 50 per cent was achieved involving 21 participants working across 14 hospitals. These showed strong agreement that implementation of a national curriculum would improve the standard of teaching delivered at a personal, institutional and national level. Further themes were identified relating to the personal, institutional and specialty related factors influencing practical delivery. CONCLUSION: A series of practical recommendations are made to potentially assist the implementation of a national ENT curriculum.

Probing the self-assembly and anti-glioblastoma efficacy of a cinnamoyl-capped dipeptide hydrogelator.

Herein, we introduce the first diphenylalanine dipeptide hydrogelator capped with the cinnamoyl functional group (Cin-L-F-L-F). We evaluate the effects of the cinnamoyl moiety on molecular self-assembly events and resultant physical properties of the hydrogel formed. In addition, we report our preliminary results of this dipeptide's cytotoxicity against glioblastoma (GBM) cancer cells.

Identification of a branchial cleft anomaly via handheld point-of-care ultrasound.

Aim of the study: Branchial anomalies result from incomplete obliteration of the branchial arch structures during embryogenesis. Second branchial arch anomalies are commonly found on the lower third of the neck, with an opening at the anterior border of the sternocleidomastoid muscle, and may drain secretions or purulent material. This case demonstrates the use of handheld point-of-care ultrasound to aid in the diagnosis of a branchial anomaly. Case description: The patient presented with a "hole" in the neck with intermittent drainage from the site. A 2 mm defect in the skin was noted anterior to the sternocleidomastoid muscle. A handheld ultrasound system was used to identify a well-defined, hypoechoic, cyst-like structure. Given the history, physical findings, and point-of-care ultrasound imaging, the diagnosis of a second branchial cleft sinus was made. Conclusions: The use of point-of-care ultrasound and knowledge of the sonographic characteristics of these lesions can assist the physician in the diagnosis of branchial arch anomalies.

Impact of the utilization of 500 mL IV bags on crystalloid resuscitation volumes administered to trauma patients.

INTRODUCTION: Administering large volumes of crystalloids to trauma patients has been shown to exacerbate metabolic complications of hemorrhage including dilutional coagulopathy and worsening acidosis The aim of this study was to evaluate crystalloid administration volumes in trauma patients after replacing 1 L IV containers with 500 mL IV containers in the emergency department trauma resuscitation bay. MATERIALS AND METHODS: This was a single-center, IRB-approved, retrospective cohort evaluation of adult trauma patients conducted at an 864-bed community tertiary referral center located in the southeastern United States. Patterns of crystalloid administration were examined before and after the trauma resuscitation bay began to exclusively stock 500 mL IV containers. The primary outcome was mean total crystalloid volume infused from time of injury to hospital admission. Secondary outcomes included mean total crystalloid volume infused prior to administration of blood products, proportion of patients who received less than 2 L total of crystalloids, time to initiation of blood products, and mortality in both the emergency department and in-hospital. RESULTS: Patient characteristics were largely similar between both groups including age, mechanism of injury, and Injury Severity Score. For the primary outcome, the mean total crystalloid volume infused from time of injury to hospital administration, patients in the 500 mL IV fluid container group were administered 555 mL less crystalloid when compared to the 1 L IV fluid container group, 1048 mL vs 1603 mL (p < 0.01; 95% CI 406 mL - 704 mL), respectively. After conversion to the 500 mL IV container bags, there was a 27.5% increase in the proportion of patients receiving less than 2 L of crystalloid, 90.5% vs 63.0% in the 500 mL IV fluid container and 1 L IV fluid container groups, respectively (p < 0.01). CONCLUSIONS: Due to reduced mortality, expanding literature and guidelines clearly support minimizing IV crystalloid resuscitation. Institutions must now work to minimize use of IV crystalloids to hemorrhaging trauma patients and a simple solution of using smaller IV fluid bags was shown to improve adherence to this practice.

Adenotonsillectomy for the treatment of obstructive sleep apnoea in extreme paediatric obesity.

OBJECTIVE: Adenotonsillectomy is a recognised treatment for paediatric obstructive sleep apnoea. Recent literature highlights the need to assess outcomes in the extremely obese subpopulation. This study reviewed the efficacy of adenotonsillectomy performed in patients with extreme obesity. METHOD: A retrospective analysis of attendees at a tertiary paediatric obesity clinic was performed, identifying patients with a body mass index z-score equal to or more than three who had undergone adenotonsillectomy for obstructive sleep apnoea. Electronic patient records, including respiratory polygraphy, were analysed. RESULTS: Nine patients met the study criteria. All required nocturnal non-invasive ventilation pre-operatively. Mean age at referral was 6.9 years, and average age of non-invasive ventilation commencement was 7.8 years. Post-operatively, 8 patients (89 per cent) required non-invasive ventilation with evidence of post-operative obstructive sleep apnoea. CONCLUSION: In extreme obesity, adenotonsillectomy does not prevent the need for non-invasive ventilation. Management of this patient group requires treatment of obesity alongside potential surgical intervention. Poor efficacy in treating obstructive sleep apnoea may influence the decision to proceed with adenotonsillectomy.

The Capacity to Produce Hydrogen Sulfide (H2S) via Cysteine Degradation Is Ubiquitous in the Human Gut Microbiome.

As one of the three mammalian gasotransmitters, hydrogen sulfide (H2S) plays a major role in maintaining physiological homeostasis. Endogenously produced H2S plays numerous beneficial roles including mediating vasodilation and conferring neuroprotection. Due to its high membrane permeability, exogenously produced H2S originating from the gut microbiota can also influence human physiology and is implicated in reducing intestinal mucosal integrity and potentiating genotoxicity and is therefore a potential target for therapeutic interventions. Gut microbial H2S production is often attributed to dissimilatory sulfate reducers such as Desulfovibrio and Bilophila species. However, an alternative source for H2S production, cysteine degradation, is present in some gut microbes, but the genes responsible for cysteine degradation have not been systematically annotated in all known gut microbes. We classify mechanisms of cysteine degradation into primary, secondary, and erroneous levels of H2S production and perform a comprehensive search for primary, secondary, and erroneous cysteine-degrading enzymes in 4,644 non-redundant bacterial genomes from the Unified Human Gastrointestinal Genome (UHGG) catalog. Of the 4,644 genomes we have putatively identified 2,046 primary, 1,951 secondary, and 5 erroneous cysteine-degrading species. We identified the presence of at least one putative cysteine-degrading bacteria in metagenomic data of 100% of 6,623 healthy subjects and the expression of cysteine-degrading genes in metatranscriptomic data of 100% of 736 samples taken from 318 individuals. Additionally, putative cysteine-degrading bacteria are more abundant than sulfate-reducing bacteria across healthy controls, IBD patients and CRC patients (p < 2.2e-16, Wilcoxon rank sum test). Although we have linked many taxa with the potential for cysteine degradation, experimental validation is required to establish the H2S production potential of the gut microbiome. Overall, this study improves our understanding of the capacity for H2S production by the human gut microbiome and may help to inform interventions to therapeutically modulate gut microbial H2S production.

The taxonomic distribution of histamine-secreting bacteria in the human gut microbiome.

BACKGROUND: Biogenic histamine plays an important role in immune response, neurotransmission, and allergic response. Although endogenous histamine production has been extensively studied, the contributions of histamine produced by the human gut microbiota have not been explored due to the absence of a systematic annotation of histamine-secreting bacteria. RESULTS: To identify the histamine-secreting bacteria from in the human gut microbiome, we conducted a systematic search for putative histamine-secreting bacteria in 36,554 genomes from the Genome Taxonomy Database and Unified Human Gastrointestinal Genome catalog. Using bioinformatic approaches, we identified 117 putative histamine-secreting bacteria species. A new three-component decarboxylation system including two colocalized decarboxylases and one transporter was observed in histamine-secreting bacteria among three different phyla. We found significant enrichment of histamine-secreting bacteria in patients with inflammatory bowel disease but not in patients with colorectal cancer suggesting a possible association between histamine-secreting bacteria and inflammatory bowel disease. CONCLUSIONS: The findings of this study expand our knowledge of the taxonomic distribution of putative histamine-secreting bacteria in the human gut.

Gut microbiome ADP-ribosyltransferases are widespread phage-encoded fitness factors.

Bacterial ADP-ribosyltransferases (ADPRTs) have been described as toxins involved in pathogenesis through the modification of host proteins. Here, we report that ADPRTs are not pathogen restricted but widely prevalent in the human gut microbiome and often associated with phage elements. We validated their biochemical activity in a large clinical isolate collection and further examined Bxa, a highly abundant ADPRT in Bacteroides. Bxa is expressed, secreted, and enzymatically active in Bacteroides and can ADP-ribosylate non-muscle myosin II proteins. Addition of Bxa to epithelial cells remodeled the actin cytoskeleton and induced secretion of inosine. Bxa-encoding B. stercoris can use inosine as a carbon source and colonizes the gut to significantly greater numbers than a bxa-deleted strain in germ-free and altered Schaedler flora (ASF) mice. Colonization correlated with increased inosine concentrations in the feces and tissues. Altogether, our results show that ADPRTs are abundant in the microbiome and act as bacterial fitness factors.

Computed tomography imaging in ventral hernia repair: can we predict the need for myofascial release?

INTRODUCTION: Currently, the need for additional myofascial release (AMR) in addition to retromuscular dissection during open Rives-Stoppa hernia repair is determined intraoperatively based on the discretion of the surgeon. We developed a novel method to objectively predict the need for AMR preoperatively using computed tomography (CT)-measured rectus width to hernia width ratio (RDR). METHODS: A retrospective chart review of all patients who underwent open retro-muscular mesh repair of midline ventral hernia between August 1, 2007 and February 1, 2018, who had a preoperative CT scan within 1 year prior to their operation. The primary endpoint was the ability of the defect ratio to predict the need for AMR in pursuit of fascial closure. The secondary endpoint was the ability of Component Separation Index (CSI) to predict the need for AMR to obtain fascial closure. RESULTS: Of 342 patients, 208 repaired with rectus abdominis release alone (RM group), while 134 required AMR (RM + group). An RDR of > 1.34 on area under the curve analysis predicted the need for AMR with 77.6% accuracy. There was a linear decrease in the need for AMR with increasing RDR: RDR < 1 required AMR in 78.8% of cases, RDR 1.1-1.49 in 52%, RDR 1.5-1.99 in 32.1%, and RDR > 2 in just 10.8%. Similarly, CSI > 0.146 predicted the need for AMR with 76.3% accuracy on area under the curve analysis. CONCLUSION: The RDR is a practical and reliable tool to predict the ability to close the defect during open Rives-Stoppa ventral hernia repair without AMR. An RDR of > 2 portends fascial closure with rectus abdominis myofascial release alone in 90% of cases.

Prophylactic mesh augmentation using permanent synthetic mesh: outcomes of keyhole and Stapled Ostomy Reinforcement with Retromuscular Mesh techniques.

INTRODUCTION: Parastomal hernias (PSH) are the most common complication of stoma creation and can cause significant morbidity. We present a consecutive series of patients receiving prophylactic mesh augmentation (PMA) for prevention of PSH. METHODS: This retrospective review evaluates the efficacy and outcomes of PMA for PSH prevention, and retrospectively compares traditional keyhole PMA (tPMA) (n = 28) with a prophylactic Stapled Ostomy Reinforcement with Retromuscular Mesh technique (pSTORRM) (n = 24). RESULTS: PMA was performed in 52 cases between January 2015 and July 2018. All cases used a large-pore, non-coated, mid-weight polypropylene mesh placed in the retrorectus space. With a median follow-up of 16 mos, parastomal hernia was confirmed in 11.5% (n = 6), 5 of whom were symptomatic. patient-reported outcomes (PRO) indicated 6 additional patients with symptoms associated with PSH without clinical or radiographic confirmation. Patients had similar comorbidities and operative characteristics between tPMA and pSTORRM techniques, and no difference in a median follow-up. pSTORRM patients had fewer surgical site infections (8.3 vs 32.1%; p = 0.046) and occurrences (12.5 vs 46.4%; p = 0.015), and lower rate of PSH, though not statistically significant (4.2 vs 17.9%; p = 0.195). CONCLUSION: Permanent synthetic mesh placed as a sublay in the retromuscular space is safe and appears to decrease the risk of PSH formation after the creation of permanent stomas. A stapled technique may provide advantages over a traditional keyhole technique.

Primary thoracoabdominal hernias.

BACKGROUND: Primary thoracoabdominal hernias involve the triad of an intercostal hernia, abdominal wall hernia, and diaphragmatic hernia. We report a case series of this rare entity and describe the evolution and outcomes. METHODS: We completed a retrospective analysis of thoracoabdominal hernia repairs performed January 2010-April 2019 at Prisma Health-Upstate and Carolinas Medical Center. This includes all patients with spontaneous defects, excluding incisional hernias or those resulting from external trauma. RESULTS: Of 16 patients with thoracoabdominal hernias, 15 patients developed hernias after forceful coughing and one patient developed a hernia after strenuous physical activity. Seven patients required at least one additional intervention; two for recurrence; two for recurrence of original intercostal repairs done elsewhere; two for wound complications; and one had a missed abdominal wall component. CONCLUSIONS: Primary thoracoabdominal hernias require a high index of suspicion. Durable repair involves complex reconstruction of the thoracoabdominal wall including the diaphragm, intercostal space, rib fracture fixation, and mesh reinforcement of the abdominal wall with permanent fixation constructs.

Multisite Analysis of Lesions in the Respiratory Tract of the Rat and Nonhuman Primate (Cynomolgus Monkey) Exposed to Air, Vehicle, and Inhaled Small Molecule Compounds.

This paper presents a review of the nature, range, and incidences of background pathology findings in the respiratory tract of cynomolgus monkeys and rats. Data were collected from 81 inhalation studies and 133 non-inhalation studies evaluated at 3 geographically distinct contract research organization facilities. The inhalation studies were comprised of 44 different small molecule pharmaceuticals or chemicals which were also analyzed in order to understand the patterns of induced changes within the respiratory tract. The lung was the most frequently affected organ in both species, with increased alveolar macrophages being the most common background and test article-related finding. In the upper respiratory tract (URT), inflammatory cell infiltrates were the most common background findings in the nasal cavity in monkeys. Induced URT findings were more frequent in rats than monkeys, with squamous metaplasia in the larynx, and goblet cell hyperplasia in the nasal cavity being the most common. Overall, the data revealed a limited pattern of response to inhaled molecules in the respiratory tract, with background and test article-related findings often occurring in the same regions. It is hoped that these data will assist in the interpretation of findings in the respiratory tract induced by novel inhaled small molecule entities.

Factors associated with the development of paediatric chronic otitis media by age nine: a prospective longitudinal cohort study of 6560 children.

OBJECTIVE: This study aimed to analyse social, health and environmental factors associated with the development of chronic otitis media by age nine. METHOD: This was a prospective, longitudinal, birth cohort study of 6560 children, reviewed at age nine. Chronic otitis media defined as previous surgical history or video-otoscopic changes of tympanic membrane retraction, perforation or cholesteatoma. Non-affected children were used as the control group. RESULTS: Univariate analysis demonstrated an association between chronic otitis media and otorrhoea, snoring, grommet insertion, adenoidectomy, tonsillectomy, hearing loss, abnormal tympanograms and preterm birth. Multivariate analysis suggests many of these factors may be interrelated. CONCLUSION: The association between chronic otitis media and otorrhoea, abnormal tympanograms and grommets supports the role of the Eustachian tube and otitis media (with effusion or acute) in the pathogenesis of chronic otitis media. The role of snoring, adenoidectomy and tonsillectomy is unclear. Associations suggested by previous studies (sex, socioeconomic group, parental smoking, maternal education, childcare, crowding and siblings) were not found to be significant predictors in this analysis.

What is the role of surgical simulation on operative opportunity for the trainee ENT surgeon?

OBJECTIVE: This study sought to assess the impact of simulation training in influencing trainees' initial surgical participation as perceived by experienced surgeon trainers. METHODS: Twenty ENT surgeons assessed how much of a given procedure they would expect to allow a trainee to perform for their first time. Responses were provided for trainees who had undergone a relevant simulation course and those who had not, and scored according to the eLogbook levels of involvement in surgery. This was completed for simulated procedures with validated models, across four grades of junior doctors. RESULTS: A total of 1120 judgements on the trainees' intended level of involvement were made. The median involvement score was higher in the simulation group versus the non-simulation group (Mann-Whitney U, p = 0.0001), corresponding to a translation in surgical opportunity from a primarily assisting role to an active role. CONCLUSION: Trainer perception of a relevant ENT simulation course appears to positively impact on the initial surgical opportunities afforded to the trainee.

Association Between Sulfur-Metabolizing Bacterial Communities in Stool and Risk of Distal Colorectal Cancer in Men.

BACKGROUND & AIMS: Sulfur-metabolizing microbes, which convert dietary sources of sulfur into genotoxic hydrogen sulfide (H2S), have been associated with development of colorectal cancer (CRC). We identified a dietary pattern associated with sulfur-metabolizing bacteria in stool and then investigated its association with risk of incident CRC using data from a large prospective study of men. METHODS: We collected data from 51,529 men enrolled in the Health Professionals Follow-up Study since 1986 to determine the association between sulfur-metabolizing bacteria in stool and risk of CRC over 26 years of follow-up. First, in a subcohort of 307 healthy men, we profiled serial stool metagenomes and metatranscriptomes and assessed diet using semiquantitative food frequency questionnaires to identify food groups associated with 43 bacterial species involved in sulfur metabolism. We used these data to develop a sulfur microbial dietary score. We then used Cox proportional hazards modeling to evaluate adherence to this pattern among eligible individuals (n = 48,246) from 1986 through 2012 with risk for incident CRC. RESULTS: Foods associated with higher sulfur microbial diet scores included increased consumption of processed meats and low-calorie drinks and lower consumption of vegetables and legumes. Increased sulfur microbial diet scores were associated with risk of distal colon and rectal cancers, after adjusting for other risk factors (multivariable relative risk, highest vs lowest quartile, 1.43; 95% confidence interval 1.14-1.81; P-trend = .002). In contrast, sulfur microbial diet scores were not associated with risk of proximal colon cancer (multivariable relative risk 0.86; 95% CI 0.65-1.14; P-trend = .31). CONCLUSIONS: In an analysis of participants in the Health Professionals Follow-up Study, we found that long-term adherence to a dietary pattern associated with sulfur-metabolizing bacteria in stool was associated with an increased risk of distal CRC. Further studies are needed to determine how sulfur-metabolizing bacteria might contribute to CRC pathogenesis.