Clinical Activity and Quality of Life Indices Are Valid Across Ulcerative Colitis But Not Crohn's Disease Phenotypes.

BACKGROUND: Clinical activity and quality of life (QOL) indices assess disease activity in Crohn's disease (CD) and ulcerative colitis (UC). However, a paucity of data exists on the validity of these indices according to disease characteristics. AIMS: To examine the correlation between QOL and clinical activity indices and endoscopic disease activity according to disease characteristics. METHODS: We used a prospective registry to identify CD and UC patients ≥18 years old with available information on Short Inflammatory Bowel Disease Questionnaire scores (SIBDQ), Harvey-Bradshaw Index (HBI) and simple endoscopic scores for CD (SES-CD), and Simple Clinical Colitis Activity Index (SCCAI) and Mayo endoscopic score for UC. We used Spearman rank correlations to calculate correlations between indices and Fisher transformation to compare correlations across disease characteristics. RESULTS: Among 282 CD patients, we observed poor correlation between clinical activity and QOL indices to SES-CD with no differences in correlation according to disease characteristics. Conversely, among 226 UC patients, clinical activity and QOL had good correlation to Mayo endoscopic score (r = 0.55 and -0.56, respectively) with better correlations observed with left-sided versus extensive colitis (r = 0.73 vs. 0.45, p = 0.005) and shorter duration of disease (r = 0.61 vs. 0.37, p = 0.04). CONCLUSIONS: Our data suggest good correlation between SCCAI and endoscopic disease activity in UC, particularly in left-sided disease. Poor correlations between HBI or SIBDQ and SES-CD appear to be consistent across different disease phenotypes.

Clinical characteristics and patterns and predictors of response to therapy in collagenous and lymphocytic colitis.

BACKGROUND: Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflammatory disorders of the colon. There is a paucity of data on differences in etiology, natural history, and treatment response between CC and LC. METHODS: Between 2002 and 2013, we identified new diagnoses of CC and LC using the Research Patient Data Registry in a tertiary referral center. We used chi square or Fischer's exact test and Wilcoxon rank-sum tests to compare the differences in clinical characteristics, treatment types, and response rates between LC and CC. RESULTS: Through 2013, we confirmed 131 patients with a new diagnosis of microscopic colitis (MC) (55 LC, 76 CC). Compared to cases of LC, patients with a diagnosis of CC were more likely to be women (86% vs. 69%, p = 0.03), have elevated erythrocyte sedimentation rate (mean 28 vs. 13 mm/h, p = 0.04), and less likely to be diabetic (5% vs. 18%, p = 0.02). Budesonide was the most effective treatment for both CC and LC (94% and 80%, respectively). However, there were no statistically significant differences in response to various treatments according to the type of MC (all p > 0.10). Older age at the time of diagnosis was associated with better response to bismuth subsalicylate (odds ratio: 1.76; 95% confidence interval: 1.21-2.56 for every 5-year increase) for both CC and LC. CONCLUSION: Despite differences in the clinical characteristics, response rates to available treatments appeared to be similar in both LC and CC. Older patients may have a better response to bismuth subsalicylate therapy.

The Effect of Retained Hardware on Failure Among Prosthetic Joint Infections of the Knee in the Presence and Absence of Staphylococcus aureus.

Background: The risk of failure associated with different surgical strategies for prosthetic joint infections (PJIs) among patients with and without Staphylococcus aureus is uncertain. The purpose of this study was to assess whether S. aureus modifies the association between retained hardware and failure following revision surgery for PJI of the knee. Methods: This was a single-center retrospective cohort study of 106 first PJIs of the knee between 2016 and 2020 at a rural academic medical center. The exposure was retained hardware following revision surgery for PJI, and the outcomes were recurrent infection, any infection, and a composite outcome including any infection, unplanned revision, failure to undergo reimplantation, amputation, or death within 2 years of revision. We used negative binomial regression to quantify the association between the exposure and outcome and to assess the presence of S. aureus as an effect modifier. Results: Retained hardware was significantly associated with failure when defined as recurrent infection among S. aureus PJI (adjusted risk difference [aRD], 0.38; 95% CI, 0.12-0.64) but not in the absence of S. aureus (aRD, -0.02; 95% CI, -0.17 to 0.13), and S. aureus was an effect modifier (P interaction = .01). Conclusions: We report a significant association between the presence of retained hardware and recurrent infection among S. aureus PJI of the knee, but not for non-S. aureus PJI. This could help inform the surgical management of PJI of the knee in cases where the microbiology is known before surgery.

Predictors of postpandemic preparedness for special pathogens.

In this survey of 31 hospitals, large metropolitan facilities had a 9.5-fold odds of reporting preparedness for special pathogens; hospitals with special pathogens teams had a 14.3-fold odds of reporting preparedness for special pathogens. In the postpandemic world, healthcare institutions must invest in special pathogen responses to maximize patient safety.

A nurse-driven penicillin allergy risk score in the preoperative setting was associated with increased cefazolin use perioperatively.

STUDY OBJECTIVE: To characterize and assess the effects of a preoperative, nurse-driven penicillin allergy risk stratification tool on rates of perioperative cefazolin and second-line antibiotic use. DESIGN: Quasi-experimental quality improvement study of penicillin-allergic surgical patients undergoing procedures for which cefazolin is indicated. SETTING: Outpatient Perioperative Care Clinic (PCC) for preoperative surgical patients at a tertiary care center. PATIENTS: 670 and 1371 adult penicillin-allergic PCC attendants and non-attendants, respectively. INTERVENTION: A paper penicillin allergy risk stratification questionnaire was administered during the PCC visit. Nurses were educated on its use. MEASUREMENTS: Antibiotic (cefazolin, clindamycin, vancomycin) use rates in the 24 months before and 17 months after intervention implementation in November 2020 (November 2018 - April 2022) were assessed in penicillin-allergic PCC attendants with statistical process control charts. Multivariable logistic regression assessed antibiotic use rates pre- and post-intervention adjusting for age, sex, surgical specialty and penicillin allergy history severity. Similar analyses were done in penicillin-allergic PCC non-attendants. MAIN RESULTS: Of 670 penicillin-allergic PCC attendants, 451 (median [IQR] age, 66 (Sousa-Pinto et al., 2021 [14])) were analyzed pre-intervention and 219 (median [IQR] age, 66 (Mine et al., 1970 [13])) post-intervention. One month after implementation, process measures demonstrated an upward shift in cefazolin use for PCC attendants versus no shift or other special cause variation for PCC non-attendants. There were increased odds of cefazolin use (aOR 1.67, 95% CI [1.09-2.57], P = 0.019), decreased odds of clindamycin use (aOR 0.61, 95% CI [0.42-0.89], P = 0.010) and decreased odds of vancomycin use (aOR 0.56, 95% CI [0.35-0.88], P = 0.013) in PCC attendants post-intervention. This effect did not occur in PCC non-attendants. There was no increase in perioperative anaphylaxis post-intervention. CONCLUSIONS: A simple penicillin allergy risk stratification tool implemented in the preoperative setting was associated with increased use of cefazolin and decreased rates of second-line agents post implementation.

A survey study of the association between active utilization of National Healthcare Safety Network resources and central-line-associated bloodstream infection reporting.

In this survey of 41 hospitals, 18 (72%) of 25 respondents reporting utilization of National Healthcare Safety Network resources demonstrated accurate central-line-associated bloodstream infection reporting compared to 6 (38%) of 16 without utilization (adjusted odds ratio, 5.37; 95% confidence interval, 1.16-24.8). Adherence to standard definitions is essential for consistent reporting across healthcare facilities.

Association between in situ steroids and spine surgical site infections among instrumented procedures.

OBJECTIVE: To estimate the association between in situ steroids and spine surgical-site infections (SSIs), assessing spinal instrumentation as an effect modifier and adjusting for confounders. DESIGN: Case-control study. SETTING: Rural academic medical center. PARTICIPANTS: We identified 1,058 adults undergoing posterior fusion and laminectomy procedures as defined by the National Healthcare Safety Network without a pre-existing SSI between January 2020 and December 2021. We identified 26 SSI as cases and randomly selected 104 controls from the remaining patients without SSI. METHODS: The primary exposure was the intraoperative administration of methylprednisolone in situ (ie, either in the wound bed or as an epidural injection). The primary outcome was a clinical diagnosis of SSI within 6 months of a patient's first spine surgery at our facility. We quantified the association between the exposure and outcome using logistic regression, using a product term to assess for effect modification by spinal instrumentation and the change-in-estimate approach to select significant confounders. RESULTS: Adjusting for Charlson comorbidity index and malignancy, in situ steroids were significantly associated with spine SSI relative to no in situ steroids for instrumented procedures (adjusted odds ratio [aOR], 9.93; 95% confidence interval [CI], 1.54-64.0), but they were not associated with spine SSIs among noninstrumented procedures (aOR, 0.86; 95% CI, 0.15-4.93). CONCLUSIONS: In situ steroids were significantly associated with spine SSI among instrumented procedures. The benefits of in situ steroids for pain management following spine surgery should be weighed against the risk of SSI, especially for instrumented procedures.

Investigating potential drivers of increased central line...associated bloodstream infections during the coronavirus disease 2019 (COVID-19) Omicron surge.

Central line...associated bloodstream infection rates increased during the Omicron surge at our rural academic medical center. To identify potential drivers of this increase, we investigated period- and patient-specific factors associated with the increase in central line...associated bloodstream infection. Increased central line utilization, decreased central line bundle compliance monitoring, increased proportion of traveling nurses, increased short-term venous catheter use in the internal jugular vein, increased multilumen catheter use, decreased port...associated infection, and increased patient acuity were significantly associated with the surge. Our results helped us target our local infection prevention efforts.

A comparison of National Healthcare Safety Network surveillance definitions to physician review for central-line-associated bloodstream infections.

For 147 hospital-onset bloodstream infections, we assessed the sensitivity, specificity, positive predictive value, and negative predictive value of the National Healthcare Safety Network surveillance definitions of central-line-associated bloodstream infections against the gold standard of physician review, examining the drivers of discrepancies and related implications for reporting and infection prevention.

Effect of Low-dose and Standard-dose Aspirin on PGE2 Biosynthesis Among Individuals with Colorectal Adenomas: A Randomized Clinical Trial.

Low-dose aspirin is recommended by the U.S. Preventive Services Task Force for primary prevention of colorectal cancer in certain individuals. However, broader implementation will require improved precision prevention approaches to identify those most likely to benefit. The major urinary metabolite of PGE2, 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), is a biomarker for colorectal cancer risk, but it is unknown whether PGE-M is modifiable by aspirin in individuals at risk for colorectal cancer. Adults (N = 180) who recently underwent adenoma resection and did not regularly use aspirin or NSAIDs were recruited to a double-blind, placebo-controlled, randomized trial of aspirin at 81 or 325 mg/day for 8-12 weeks. The primary outcome was postintervention change in urinary PGE-M as measured by LC/MS. A total of 169 participants provided paired urine samples for analysis. Baseline PGE-M excretion was 15.9 ± 14.6 (mean ± S.D, ng/mg creatinine). Aspirin significantly reduced PGE-M excretion (-4.7 ± 14.8) compared with no decrease (0.8 ± 11.8) in the placebo group (P = 0.015; mean duration of treatment = 68.9 days). Aspirin significantly reduced PGE-M levels in participants receiving either 81 (-15%; P = 0.018) or 325 mg/day (-28%; P < 0.0001) compared with placebo. In 40% and 50% of the individuals randomized to 81 or 325 mg/day aspirin, respectively, PGE-M reduction reached a threshold expected to prevent recurrence in 10% of individuals. These results support that aspirin significantly reduces elevated levels of PGE-M in those at increased colorectal cancer risk to levels consistent with lower risk for recurrent neoplasia and underscore the potential utility of PGE-M as a precision chemoprevention biomarker. The ASPIRED trial is registered as NCT02394769.

Lymphocytic colitis: pathologic predictors of response to therapy.

Although the presence of intraepithelial lymphocytosis with surface epithelial damage is a unifying feature of lymphocytic colitis, there are nonclassical features that create morphologic heterogeneity between cases. Limited data on the significance of these secondary histologic features are available. Cases of lymphocytic colitis diagnosed between 2002 and 2013 were identified using the Research Patient Data Registry of a tertiary referral center. Diagnostic biopsy slides were reviewed and evaluated for histologic features of lymphocytic colitis. Clinical data including type of therapy and response to treatment were collected. χ2 Test (or Fisher exact test) and logistic regression analysis were used where appropriate. Thirty-two cases of lymphocytic colitis with complete clinical data and slides available for review were identified. The mean age was 56.4 years, and the female-to-male ratio was 3:2. Eleven patients improved with minimal intervention (group 1), 14 patients responded to steroid therapy (group 2), and 7 patients responded to mesalamine, bismuth subsalicylate, and/or cholestyramine therapy (group 3). Histologic differences in the characteristics of the subepithelial collagen table (P = .018), the severity of lamina propria inflammation (P = .042), and the presence of eosinophil clusters (P = .016) were seen between groups 2 and 3. Patients in group 1 were more likely to have mild crypt architectural distortion in their biopsies than patients in groups 2 and 3. Lymphocytic colitis is a heterogeneous disease, and the evaluation of histologic factors may help identify various subtypes and predict therapy response.

Visceral Adiposity, Genetic Susceptibility, and Risk of Complications Among Individuals with Crohn's Disease.

INTRODUCTION: Adipose tissue in mesenteric fat plays a key role in systemic and luminal inflammation. However, little is known about the role of visceral adipose tissue (VAT) and its interaction with genetic predisposition in Crohn's disease (CD) progression. METHODS: Our study population included patients with CD enrolled in Prospective Registry in Inflammatory Bowel Disease Study at Massachusetts General Hospital (PRISM). VAT volume was measured from computed tomography using Aquarius 3D. We used logistic regression models to estimate the multivariable-adjusted odds ratio and 95% CI. We tested for effect modification by genetic predisposition using the log likelihood ratio test. RESULTS: Among 482 patients with CD with available data on VAT, 174 developed penetrating disease, 132 developed stricturing disease, 147 developed perianal disease, and 252 required surgery. Compared with individuals in the lowest quartile of VAT volume, the multivariable-adjusted odds ratio of surgery among individuals in the highest quartile was 2.02 (95% CI, 1.09-3.76; Ptrend = 0.006). Similarly, the risk of penetrating disease seemed to increase with greater VAT volume (Ptrend = 0.022) but not stricturing or perianal disease (all Ptrend > 0.23). The associations between VAT volume and CD complications were not modified by genetic predisposition (all Pinteraction > 0.12). CONCLUSIONS: Visceral adiposity as measured by VAT volume may be associated with a significant increase in the risk of penetrating disease and surgery in CD. Our data suggest that visceral adiposity as measured by VAT may negatively impact long-term progression of CD regardless of genetic predisposition.

Identification and Characterization of a Novel Association between Dietary Potassium and Risk of Crohn's Disease and Ulcerative Colitis.

BACKGROUND: Recent animal studies have identified that dietary salt intake may modify the risk and progression of autoimmune disorders through modulation of the IL-23/TH17 pathway, which is critical in the pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD). METHODS: We conducted a prospective study of U.S. women enrolled in the Nurses' Health Study (NHS) and NHSII who provided detailed and validated information on diet and lifestyle beginning in 1984 in NHS and 1991 in NHSII. We confirmed incident cases of UC and CD reported through 2010 in NHS and 2011 in NHSII. We used Cox proportional hazards models to calculate hazard ratios and 95% confidence intervals. In a case-control study nested within these cohorts, we evaluated the interaction between single nucleotide polymorphisms (SNPs) in genes involved in TH17 pathway and dietary potassium on risk of CD and UC. In a cohort of healthy volunteers, we also assessed the effect of supplemental potassium on development of naïve and memory T cells, differentiated with TGFß1 or TH17 conditions. RESULTS: Among a total of 194,711 women over a follow-up of 3,220,247 person-years, we documented 273 cases of CD and 335 cases of UC. Dietary intake of potassium (Ptrend = 0.005) but not sodium (Ptrend = 0.44) was inversely associated with risk of CD. Although, both dietary potassium and sodium were not significantly associated with risk of UC, there was a suggestion of an inverse association with dietary potassium (Ptrend = 0.08). The association of potassium with risk of CD and UC appeared to be modified by loci involved in the TH17 pathway that have previously been associated with susceptibility to CD, particularly SNP rs7657746 (IL21) (Pinteraction = 0.004 and 0.01, respectively). In vitro, potassium enhanced the expression of Foxp3 in both naïve and memory CD4+ T cells via activating Smad2/3 and inhibiting Smad7 in TH17 cells. CONCLUSION: Dietary potassium is inversely associated with risk of CD with both in vitro and gene-environment interaction data suggesting a potential role for potassium in regulating immune tolerance through its effect on Tregs and TH17 pathway.

Body Mass Index, Genetic Susceptibility, and Risk of Complications Among Individuals with Crohn's Disease.

BACKGROUND: Obesity is associated with systemic and intestine-specific inflammation and alterations in gut microbiota, which in turn impact mucosal immunity. Nonetheless, a specific role of obesity and its interaction with genetics in the progression of Crohn's disease (CD) is unclear. METHODS: We conducted a cross-sectional study of patients with CD enrolled in Prospective Registry in Inflammatory Bowel Disease Study at Massachusetts General Hospital (PRISM). Information on diagnosis of CD and its complications were collected and confirmed through review of medical records. A genetic risk score was calculated using previously reported single-nucleotide polymorphisms-associated genome-wide with CD susceptibility. We used logistic regression to estimate the effect of body mass index (BMI) and its interaction with genetic risk on risk of CD complications. RESULTS: Among 846 patients with CD, 350 required surgery, 242 with penetrating disease, 182 with stricturing disease, and 226 with perianal disease. There were no associations between obesity (BMI ≥ 30 kg/m2) and risk of perianal disease, stricturing disease, or surgery. Compared with normal-weight individuals with BMI < 25 kg/m2, obesity was associated with lower risk of penetrating disease (odds ratio [OR = 0.56; 95% confidence interval [CI], 0.31-0.99). This association persists among a subgroup of participants with available BMI before development of penetrating disease (OR = 0.40; 95% CI, 0.16-0.88). There were no interactions between BMI and genetic risk score on risk of CD complications (all P interaction > 0.28). CONCLUSIONS: Our data suggest that obesity does not negatively impact long-term progression of CD, even after accounting for genetic predisposition.