Clinical Long-Term Outcomes of Patient-Reported Outcomes in the Prospective Real-World Tofacitinib Response in Ulcerative Colitis Registry.

INTRODUCTION: We previously reported the results of tofacitinib induction therapy in the prospective multisite US real-world Tofacitinib Response in Ulcerative Colitis registry. We now assessed patient-reported outcomes (PROs) and predictors of success during tofacitinib maintenance therapy. METHODS: Tofacitinib Response in Ulcerative Colitis included 103 patients with refractory ulcerative colitis (UC); 67% had failed ≥ 2 biologics. Patients reported the Simple Clinical Colitis Activity Index (SCCAI), Patient-Reported Outcome Measurement Information System measures for anxiety, depression, social satisfaction, and adverse events between weeks 8 and 52 using a web-based system. Paired t test and P for trend were used to compare changes in PRO measures over time. Bivariate analyses and logistic regression models were used to determine factors associated with response (SCCAI <5) or remission (SCCAI <2) at week 52. RESULTS: Of 103 patients, 82.5% entered the maintenance phase and 43.7% remained on tofacitinib at week 52. Tofacitinib de-escalation to 5 mg BID occurred in 15% of patients. At week 52, 42.7% and 31.1% of all patients reported an SCCAI <5 and SCCAI ≤2, respectively. Normalization of bowel frequency, rectal bleeding, and urgency occurred in 79%, 61%, and 48% of patients remaining on maintenance therapy. Social satisfaction improved significantly ( P < 0.001), while anxiety and depression scores only numerically improved. No consistent predictors for tofacitinib long-term treatment efficacy were identified, and safety findings were consistent with the known safety profile of tofacitinib. DISCUSSION: Tofacitinib is an effective maintenance therapy in patients with refractory UC. Dose reductions infrequently occurred during maintenance. Unmet needs in UC maintenance include improvement of urgency and psychosocial factors (NCT03772145).

Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa community acquired pneumonia: Prevalence and locally derived risk factors in a single hospital system.

Objectives: Current American Thoracic Society/Infectious Disease Society of America (ATS/IDSA) community-acquired pneumonia (CAP) guidelines expand the CAP definition to include infections occurring in patients with recent health care exposure. The guidelines now recommend that hospital systems determine their own local prevalence and predictors of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) among patients satisfying this new broader CAP definition. We sought to carry out these recommendations in our system, focusing on the emergency department, where CAP diagnosis and initial empiric antibiotic selection usually ooccur. Methods: We performed a retrospective cohort study of patients admitted with CAP through any of 3 EDs in our hospital system in Northern California between November 2019 and October 2021. Inclusion criteria included an ED admission diagnosis of pneumonia or sepsis, fever or hypothermia, leukocytosis or leukopenia, and consistent chest imaging result. SARS-CoV-2-positive cases were excluded. We abstracted variables historically associated with P. aeruginosa and MRSA. Outcome measures were prevalence of P. aeruginosa and MRSA in the overall clinically defined cohort and among microbiologically confirmed cases and predictors of P. aeruginosa or MRSA isolation, as determined by univariate logistic regression, bootstrapped least absolute shrinkage and selection operator, and random forest analyses. Additionally, we describe the iterative process used and challenges encountered in carrying out the new ATS/IDSA guideline recommendations. Results: There were 1133 unique patients who satisfied our definition of clinically defined CAP, of whom 109 (9.6%) had a bacterial pathogen isolated. There were 24 P. aeruginosa isolates and 11 MRSA isolates in 33 patients. Thus, the prevalence P. aeruginosa and MRSA was 2.9% in the overall CAP cohort, but 30.3% in the microbiologically confirmed cohort. The most important predictors of either P. aeruginosa or MRSA isolation were tracheostomy (odds ratio [OR] 22.08; 95% confidence interval [CI] 10.39-46.96) and gastrostomy tube (OR 14.7; 95% CI 7.14-30.26). Challenges included determining the suspected infection type in patients admitted simply for "sepsis"; interpreting dictated radiology reports; determining functional status, presence of indwelling lines and tubes, and long-term care facility residence from the electronic health record; and correctly attributing culture results to pneumonia. Conclusion: Prevalence of MRSA and P. aeruginosa was low among patients admitted in our medical system with CAP - now broadly defined - but high among those with a microbiologically confirmed bacterial etiology. Our locally derived predictors of MRSA and P. aeruginosa can be used to aid our emergency physicians in empiric antibiotic selection for CAP. Findings from this project might inform efforts at other institutions.

Safety and functional outcomes of early antiplatelet therapy within 24 hours following mechanical thrombectomy for secondary prevention in emergent large-vessel occlusion strokes: a registry study.

OBJECTIVE: The aim of this study was to demonstrate the safety and functional outcomes of antiplatelet use within 24 hours following mechanical thrombectomy (MT). METHODS: A retrospective review of prospectively collected data for consecutive patients who underwent MT for acute ischemic stroke (AIS) between 2016 and 2020 was performed. Patient demographics, comorbidities, Alberta Stroke Program Early CT Score (ASPECTS), antiplatelet use, neurological status, and tissue plasminogen activator use were collected. Patients were stratified into two groups, early (< 24 hours) or late (> 24 hours), based on when antiplatelet therapy was initiated post-MT. The primary outcome was safety, determined based on the rate of symptomatic intracranial hemorrhage (sICH) and inpatient mortality. The secondary outcome was functional independence (defined as modified Rankin Scale [mRS] score ≤ 2) at discharge and 30 days and 90 days postoperatively. The two cohorts were compared using univariate analysis. Multiple imputations were used to create complete data sets for missing data. Multivariable analysis was used to identify predictors for sICH and functional outcomes. RESULTS: A total of 190 patients met inclusion criteria (95 per group). Significant differences between the early and late groups included sex, preoperative intravenous thrombolysis, angioplasty, stent placement, and thrombectomy site. ICH (symptomatic and asymptomatic) and inpatient mortality were not significantly different between the groups. The mRS score was significantly lower at discharge (p < 0.001), 30 days (p = 0.011), and 90 days (p = 0.024) following MT in the early group. Functional independence was significantly higher in the early antiplatelet group at discharge (p = 0.015) and at 30 days (p = 0.006). Early antiplatelet use was independently associated with significantly increased odds of achieving functional independence at discharge (OR 3.07, p = 0.007) and 30 days (OR 5.78, p = 0.004). Early antiplatelet therapy was not independently associated with increased odds of sICH. CONCLUSIONS: Early antiplatelet initiation after MT in patients with AIS was independently associated with significantly increased odds of improved postoperative functional outcomes without increased odds of developing sICH.

Preventing Surgical Site Hematoma Using Topical with or Without Intravenous Tranexamic Acid in Lumbosacral Surgery: A Quality Improvement Project.

BACKGROUND: Postoperative surgical site hematoma (SSH) following lumbosacral surgery carries significant morbidity and increased length of stay (LOS). Intravenous tranexamic acid (ivTXA) has been shown to reduce SSH rate. Topical TXA (tTXA) could benefit patients with contraindications to ivTXA. However, this has not been widely studied. We sought to demonstrate that a quality improvement (QI) protocol using tTXA with/without ivTXA in patients undergoing elective open and minimally invasive lumbosacral surgery could decrease the SSH rate and LOS with no increase in associated complications. METHODS: A retrospective chart review for July 2018-June 2019 demonstrated our preimplementation baseline SSH rate. We conducted interdisciplinary meetings to develop standardized institutional measures and perioperative tTXA administration protocol. The primary outcome was SSH necessitating evacuation. The secondary outcome was LOS and TXA-related complications. The postimplementation data were collected prospectively from July 2020-October 2020. Univariate analysis was used to compare preimplementation and postimplementation cohorts. We considered a P-value <0.05 significant. RESULTS: Comparing consecutive lumbosacral surgical patients in pre- (219 patients) and postimplementation (258 patients), the postimplementation group demonstrated a significantly reduced rate of SSH requiring evacuation (0.38% vs. 3.3%, P < 0.001), significantly increased tTXA utilization (86.0% vs. 9.6%, P < 0.001), significantly lower incidence of SSH in tTXA patients (0.45% vs. 4.8%, P = 0.037), and significantly decreased LOS (3.4 ± 2.5 vs. 3.1 ± 2.7, P = 0.003). There were no complications attributable to TXA use. CONCLUSIONS: Our Quality Improvement (QI) project successfully increased compliance with the use of tTXA. Post-implementation rate of SSH requiring evacuation and LOS was significantly lowered with no associated complications.

Tofacitinib Response in Ulcerative Colitis (TOUR): Early Response After Initiation of Tofacitinib Therapy in a Real-world Setting.

BACKGROUND: Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Using a novel electronic reporting tool, we aimed to prospectively describe the onset of tofacitinib efficacy during induction therapy in a real-world study. METHODS: Patient-reported outcome data (PROs) including the simple clinical colitis activity index (SCCAI), PRO Measurement Identification Systems (PROMIS) measures, and adverse events were collected daily for the first 14 days and at day 28 and 56. Paired t tests and P for trend were utilized to compare changes in SCCAI over time. Bivariate analyses and logistic regression models were performed to describe response (SCCAI <5) and remission (SCCAI ≤2) by clinical factors. RESULTS: Of all included patients (n = 96), 67% had failed ≥2 biologics, and 61.5% were on concomitant steroids. Starting at day 3, PROs showed significant and persistent decline of the mean SCCAI (-1.1, P < 000.1) including significantly lower SCCAI subscores for stool frequency (-0.3; P < .003), bleeding (-0.3; P < .0002) and urgency (-0.2; P < .001). Steroid-free remission at day 14, 28, and 56 was achieved in 25%, 30.2%, and 29.2% of patients, respectively. Neither prior biologics nor endoscopic severity were independently predictive of response or remission in multivariate models. Numeric improvements in all PROMIS measures (anxiety, depression, social satisfaction) were seen through day 56. Rates of discontinuation due to adverse events were low. CONCLUSIONS: In this prospective real-world study, tofacitinib resulted in a rapid and persistent improvement in UC disease activity PROs. The safety findings were consistent with the established safety profile of tofacitinib.

The effect of ketorolac on posterior minimally invasive transforaminal lumbar interbody fusion: an interim analysis from a randomized, double-blinded, placebo-controlled trial.

BACKGROUND CONTEXT: Postoperative pain control following posterior lumbar fusion continues to be challenging and often requires high doses of opioids for pain relief. The use of ketorolac in spinal fusion is limited due to the risk of pseudarthrosis. However, recent literature suggests it may not affect fusion rates with short-term use and low doses. PURPOSE: We sought to demonstrate noninferiority regarding fusion rates in patients who received ketorolac after undergoing minimally invasive (MIS) posterior lumbar interbody fusion. Additionally, we sought to demonstrate ketorolac's opioid-sparing effect on analgesia in the immediate postoperative period. STUDY DESIGN/SETTING: This is a prospective, randomized, double-blinded, placebo-controlled trial. We are reporting our interim analysis. PATIENT SAMPLE: Adults with degenerative spinal conditions eligible to undergo a one to three-level MIS transforaminal lumbar interbody fusion (TLIF). OUTCOME MEASURES: Six-month and 1-year radiographic fusion as determined by Suk criteria, postoperative opioid consumption as measured by intravenous milligram morphine equivalent, length of stay, and drug-related complications. Self-reported and functional measures include validated visual analog scale, short-form 12, and Oswestry Disability Index. METHODS: A double-blinded, randomized placebo-controlled, noninferiority trial of patients undergoing 1- to 3-level MIS TLIF was performed with bone morphogenetic protein (BMP). Patients were randomized to receive a 48-hour scheduled treatment of either intravenous ketorolac (15 mg every 6 hours) or saline in addition to a standardized pain regimen. The primary outcome was fusion. Secondary outcomes included 48-hour and total postoperative opioid use demonstrated as milligram morphine equivalence, pain scores, length of stay (LOS), and quality-of-life outcomes. Univariate analyses were performed. The present study provides results from a planned interim analysis. RESULTS: Two hundred and forty-six patients were analyzed per protocol. Patient characteristics were comparable between the groups. There was no significant difference in 1-year fusion rates between the two treatments (p=.53). The difference in proportion of solid fusion between the ketorolac and placebo groups did not reach inferiority (p=.072, 95% confidence interval, -.07 to .21). There was a significant reduction in total/48-hour mean opioid consumption (p<.001) and LOS (p=.001) for the ketorolac group while demonstrating equivalent mean pain scores in 48 hours postoperative (p=.20). There was no significant difference in rates of perioperative complications. CONCLUSIONS: Short-term use of low-dose ketorolac in patients who have undergone MIS TLIF with BMP demonstrated noninferior fusion rates. Ketorolac safely demonstrated a significant reduction in postoperative opioid use and LOS while maintaining equivalent postoperative pain control.

Using aneurysm clips for repair of cisterna chyli injury during posterior spinal fusion.

BACKGROUND: Injury to the cisterna chyli (CC) is a rare surgical complication with a lack of literature describing its repair. Aneurysm clips have been successfully used to repair durotomies. Its usage in lymphatic injury has never been described. We sought to demonstrate the use of aneurysm clips for the repair of lymphatic vessels. CASE DESCRIPTION: A 60-year-old male retired physician with Parkinson's disease underwent a lumbosacral instrumented fusion with pelvic fixation (L1-pelvis) in 2011. He returned 5 months postoperatively after a fall and was ambulatory with a cane upon admission. CT demonstrated worsening kyphosis with pedicular and superior endplate fracture at the fusion apex. MRI revealed spinal cord compression at the failed level. Extension thoracolumbar fusion was performed (T3-L1) with intraoperative violation of the anterior longitudinal ligament (ALL) during T12/L1 discectomy. CC laceration was suspected. The ALL was dissected from the CC and aorta, allowing visualization of the injury. Three curved aneurysm clips were applied to the lacerated CC, which was visually inspected to ensure a patent lumen. The disk space was filled with poly-methyl-methacrylate cement in place of an interbody cage, preventing migration of the clips. The patient underwent rehabilitation in an inpatient facility with improved ambulation. He has had regular clinic follow-up and was last seen in 2020 with no evidence of lymphedema noted. CONCLUSION: CC injury is rare, and usage of aneurysm clips in its repair has never been described. We demonstrate the safe use of aneurysm clips to repair CC injury with long-term favorable clinical outcomes.

Health Maintenance Consensus for Adults With Inflammatory Bowel Disease.

BACKGROUND: With the management of inflammatory bowel disease (IBD) becoming increasingly complex, incorporating preventive care health maintenance measures can be challenging. The aim of developing these updated recommendations is to provide more specific details to facilitate their use into a busy clinical practice setting. METHOD: Fifteen statements were formulated with recommendations regarding the target, timing, and frequency of the health maintenance interventions in patients with IBD. We used a modified Delphi method and a literature review to establish a consensus among the panel of experts. The appropriateness of each health maintenance statement was rated on a scale of 1 to 5 (1-2 as inappropriate, and 4-5 as appropriate) by each panelist. Interventions were considered appropriate, and statements were accepted if ≥80% of the panelists agreed with a score ≥4. RESULTS: The panel approved 15 health maintenance recommendations for adults with IBD based on the current literature and expert opinion. These recommendations include explicit details regarding specific screening tools, timing of screening, and vaccinations for adults with IBD. CONCLUSIONS: Patients with IBD are at an increased risk for infections, malignancies, and other comorbidities. Given the complexity of caring for patients with IBD, this focused list of recommendations can be easily incorporated in to clinical care to help eliminate the gap in preventative care for patients with IBD.

Encapsulated Intracerebral Hematoma Presenting as Cerebral Abscess.

Chronic encapsulated intracerebral hematoma is a rare pathology which may present after spontaneous intracerebral hemorrhage (ICH) or radiosurgery for arteriovenous malformations. A 66-year-old male presented with recent diagnosis of cerebrovascular accident (CVA) status post-treatment with tissue plasminogen activator and mechanical thrombectomy. His recent diagnoses included infective endocarditis, septic bacteremia, meningitis, and aspiration pneumonia. One month following his CVA, the patient presented with delayed altered mental status. In the setting of increasing lethargy, computed tomography and magnetic resonance imaging of the brain were performed, which suggested a brain abscess, septic emboli, and ventriculitis. The patient was taken to surgery emergently. Intraoperatively, the patient was found to have an encapsulated mass of liquid consistency. Tissue pathology demonstrated ischemic cortical tissue and hemorrhage. Multiple cultures were negative for growth. The patient was ultimately determined to have an encapsulated intracerebral hematoma. Encapsulated intracerebral hematoma should be a part of the differential diagnosis when presented with a brain abscess in the setting of a patient who is at risk of ICH.

Significance of serrated epithelial change in inflammatory bowel disease.

OBJECTIVES: The clinical significance of hyperplastic polyp-like histologic changes in random biopsy samples ('serrated epithelial change' or SEC) from patients with inflammatory bowel disease (IBD) remains uncertain, with some studies suggesting an increased risk of dysplasia and even carcinoma. Controlled studies are few. We studied the significance of SEC on the development of dysplasia in follow-up surveillance of IBD patients in our system. METHODS: We identified 94 IBD patients with SEC and 187 IBD patients without SEC identified in index biopsy samples, and retrospectively collated results of follow-up surveillance samples in each group, with the development of dysplasia and/or adenocarcinoma as study endpoints. RESULTS: IBD patients with SEC had a 12.8% likelihood of developing dysplasia of any type within IBD-affected areas vs a 4.3% likelihood in non-SEC patients (follow-up in the 1-4 year range for each group). This was significant in univariate analysis (p = 0.013) but not in multivariate analysis, likely due to increased frequency of follow-up sampling in the SEC patients. One cancer developed in each group (p = NS). CONCLUSION: Our data, in the context of other studies, neither prove nor conclusively exclude an increased risk of dysplasia in IBD patients with SEC. But cancer risk appears low and continued surveillance at usual intervals seems reasonable.

Adalimumab Concentration Changes After Dose Escalation in Inflammatory Bowel Disease.

BACKGROUND: Dose escalation of adalimumab (ADA) for loss or response in inflammatory bowel disease (IBD) is a common practice. Recent data suggest improved outcomes with an ADA concentration of 12 mcg/mL, but limited data are available on the ability to achieve a target concentration. The aim of this study was to determine the expected change in serum ADA concentration after a dose escalation performed every 7 days in patients with IBD. METHODS: A retrospective cohort of patients with IBD receiving ADA was divided into every fourteen-day dosing, every 7-day dosing, and dose escalation (ie, q14 to q7 day dosing). The primary outcome was the change in ADA concentration. Multiple logistic regression was performed to identify predictors of achieving a target ADA concentration of ≥12 mcg/mL. RESULTS: Overall, 380 patients were identified, of whom 200 underwent dose escalation, 100 remained on q14 days dosing, and 80 were maintained on q7 day dosing. After dose escalation, the mean ADA concentration increased by 5.5 mcg/mL (P < 0.0001). After dose escalation, a significant proportion of patients achieved an ADA concentration ≥12 mcg/mL (P = 0.0019), as well as clinical remission (P = 0.0053). Based on multiple logistic regression, age of <46 years [odds ratio (OR): 2.4; 95% confidence interval (CI): 1.3, 4.6; P < 0.01], body mass index of <29 (OR: 0.21; 95% CI: 0.1, 0.5; P < 0.0001), and initial ADA concentration of ≥3.0 mcg/mL were found to be associated with a target ADA concentration ≥12 mcg/mL (OR: 4.76; 95% CI: 2.3, 9.7; P < 0.0001). CONCLUSIONS: The average expected increase in serum ADA concentration after dose escalation from q14 to q7 days was 5.5 mcg/mL. The initial ADA concentration, age, and body mass index may influence the ability to achieve a target ADA concentration after dose escalation.

Repair of Postoperative Cervical Pseudomeningocele with the Use of Bone Morphogenetic Protein.

Recurrent cerebrospinal fluid (CSF) leak carries significant morbidity and mortality. A 25-year-old Caucasian male developed a symptomatic pseudomeningocele eight days after surgical resection of a cervical schwannoma. With no improvement after lumbar drain placement, the dural sleeve defect over the left C3 nerve root was repaired with suturable DuraGen® (Integra LifeSciences, Plainsboro, NJ, USA). Muscle and fat graft were then laid over the repair site and covered by Tisseel® (Baxter Healthcare, Deerfield, IL, USA). Recombinant human bone morphogenetic protein-2 (rhBMP-2) was applied via extra-small sponge laid over the graft. At 15-month clinical and 16-month radiographic follow-up, the patient had complete resolution of symptoms without any evidence of infection, ectopic bone formation, excessive inflammation, neoplasm, or recurrent CSF leak. This case demonstrates the successful use of BMP in the treatment of recurrent symptomatic cervical pseudomeningocele after tumor resection. We believe that the pro-inflammatory effects of rhBMP-2 lead to early scarring of dural defect and resolution of CSF leak.

Treatment outcomes and associations in an adolescent-specific early intervention for psychosis service.

AIM: Compared with adult onset psychosis, adolescent psychosis has been associated with poorer outcomes in terms of social and cognitive functioning and negative symptoms. Young people experiencing first episode psychosis have developmental needs that frequently pre-date and are compounded by psychosis onset (a previous study). There is a lack of published studies of adolescent onset psychosis and further information is needed so that developmentally appropriate interventions can be developed. We report an observational naturalistic cohort study of an adolescent specific service, the Early Psychosis Support service (EPSS). METHOD: We examined baseline demographic and clinical variables, treatments outcomes and predictors of outcome for this population. RESULTS: The mean age of our sample was 16.3 years. Median duration of untreated illness (DUI) was 88 weeks, and median duration of untreated psychosis (DUP) was 16 weeks. We found significant improvements in positive symptoms, negative symptoms, disorganization, excitement, emotional distress and depression from 0 to 12 months. We found that baseline positive symptoms and DUI significantly predicted positive symptoms at 12 months and only negative symptoms at baseline predicted 12-month negative symptoms. CONCLUSION: Our finding that specialist early intervention for adolescents experiencing psychosis is effective suggests that such treatment should be routinely offered in line with existing clinical guidelines. Our finding that DUI is predictive of poorer outcome at 12 months suggests that even earlier intervention from a specialist team may further improve treatment outcomes.

Correction: Anti-TNF and thiopurine therapy in pregnant IBD patients does not significantly alter a panel of B-cell and T-cell subsets in 1-year-old infants.

The original version of this article contained an error in Fig. 2, in which part of the text in the legend was omitted. This has now been corrected in the PDF and HTML versions of the paper.Furthermore, the figure legends were missing for the Supplementary figure files. The HTML has now been updated to include a corrected version of the Supplementary Information.

Methotrexate Is Not Superior to Placebo in Maintaining Steroid-Free Response or Remission in Ulcerative Colitis.

BACKGROUND & AIMS: Parenteral methotrexate induces clinical remission but not endoscopic improvement of mucosal inflammation in patients with ulcerative colitis (UC). We performed a randomized, placebo-controlled trial to assess the efficacy of parenteral methotrexate in maintaining steroid-free response or remission in patients with UC after induction therapy with methotrexate and steroids. METHODS: We performed a 48-week trial, from February 2012 through May 2016, of 179 patients with active UC (Mayo score of 6-12 with endoscopy subscore ≥ 2) despite previous conventional or biological therapy. The study comprised a 16-week open label methotrexate induction period followed by a 32-week double-blind, placebo-controlled maintenance period. Patients were given subcutaneous methotrexate (25 mg/wk) and a 12-week steroid taper. At week 16, steroid-free responders were randomly assigned to groups that either continued methotrexate (25 mg/wk, n = 44) or were given placebo (n = 40) until week 48. We compared the efficacy of treatment by analyzing the proportion of patients who remained relapse free and were in remission at week 48 without use of steroids or other medications to control disease activity. RESULTS: Ninety-one patients (51%) achieved response at week 16, and 84 patients were included in the maintenance period study. During this period, 60% of patients in the placebo group (24/40) and 66% in the methotrexate group (29/44) had a relapse of UC (P = .75). At week 48, 30% of patients in the placebo group (12/40) and 27% of patients in the methotrexate group (12/44) were in steroid-free clinical remission without need for additional therapies (P = .86). No new safety signals for methotrexate were detected. CONCLUSIONS: Parenteral methotrexate (25 mg/wk) was not superior to placebo in preventing relapses of UC in patients who achieved steroid-free response during induction therapy. ClinicalTrials.gov, Number: NCT01393405.

Anti-TNF and thiopurine therapy in pregnant IBD patients does not significantly alter a panel of B-cell and T-cell subsets in 1-year-old infants.

OBJECTIVES: Infants exposed to combination therapy with anti-tumor necrosis factor (anti-TNF) agents and thiopurines may exhibit increased infections at 1 year of age compared to unexposed infants. We hypothesized that this increased risk of infection is due to abnormal development of the newborn immune system. METHODS: We immunophenotyped B-cell and T-cell subsets using multiparameter flow cytometry in 1-year-old infants whose mothers were exposed to therapeutic agents for IBD. We analyzed samples from infants exposed to infliximab (IFX) or adalimumab (ADA) monotherapy (IFX/ADA, n = 11), certolizumab pegol (CZP) monotherapy (CZP, n = 4), IFX or ADA plus thiopurine combination therapy (IFX/ADA + IM, n = 4), and CZP plus thiopurine combination therapy (CZP + IM, n = 2). RESULTS: Percentages of B cells, CD4+ T helper cells, T regulatory cells (Tregs), and CD8+ cytotoxic T cells, were similar among the groups. Infants exposed to combination therapy (IFX/ADA + IM) exhibited trends toward fewer CD27+ B cells, switched memory B cells, plasmablasts, interferon gamma (IFNγ)-producing CD4+ and CD8+ T cells, and CCR5+CD4+ T cells, but these did not reach statistical significance. CONCLUSIONS: Multiparameter immunophenotyping of major B-cell and T-cell subsets suggests that the adaptive newborn immune system develops largely unaltered after exposure to combination therapy as compared to anti-TNF monotherapy.

Shear Wave Ultrasound Elastographic Evaluation of the Rotator Cuff Tendon.

OBJECTIVES: (1) Assess the association between the B-mode morphologic appearance and elasticity in the rotator cuff tendon using shear wave elastography (SWE). (2) Assess the association between SWE and symptoms. METHODS: Institutional Review Board approval and informed consent were obtained. A retrospective review identified 21 studies in 19 eligible patients for whom SWE was performed during routine sonographic evaluations for shoulder pain. Evaluations were compared with 55 studies from 16 asymptomatic volunteers and 6 patients with asymptomatic contralateral shoulders. Repeated studies were accounted for by resampling. Proximal and distal tendon morphologic characteristics were graded from 1 to 4 (normal to full-thickness tear), and average shear wave velocity (SWV) measurements were obtained at both locations. In 68 examinations, deltoid muscle SWV measurements were available for post hoc analysis. RESULTS: The morphologic grade and SWV showed weak-to-moderate negative correlations in the proximal (P < .001) and distal (P = .002) rotator cuff tendon. A weakly significant SWV decrease was found in the proximal tendon in symptomatic patients (P = .049); no significant difference was seen in the distal tendon. The deltoid muscle SWV showed weak-to-moderate negative correlations with the morphologic grade in the proximal (P = .004) and distal (P = .007) tendon; the deltoid SWV was also significantly lower in symptomatic shoulders (P = .001). CONCLUSIONS: Shear wave elastography shows tendon softening in rotator cuff disease. It captures information not obtained by a morphologic evaluation alone; however, a poor correlation with symptoms suggests that SWE will be less useful in workups for shoulder pain than for preoperative assessments of tendon quality. Deltoid muscle softening seen in morphologically abnormal and symptomatic patients requires further exploration.

Not the usual suspect: a case of erythema induration of Bazin in an urban primary care clinic.

Frontline clinicians in the United States, especially those working in safety net hospitals or with immigrant populations, will likely see cutaneous tuberculosis given the tremendous burden of tuberculosis infection worldwide. The tuberculid is a subtype of cutaneous tuberculosis that poses a diagnostic challenge because organisms are not found in smears or cultures taken from the lesions. Tuberculid lesions can mimic erythema nodosum, thrombophlebitis, and cellulitis. We describe the case of a 57-year-old woman immigrant from China who presented with tender, subcutaneous nodules on her ankle and thigh in the setting of prior exposure to tuberculosis. We describe the clinical, pathophysiologic, and histopathologic features of tuberculids in order to raise awareness among primary care clinicians about this difficult to diagnose but readily treatable manifestation of tuberculosis.

Mesalamine dose escalation reduces fecal calprotectin in patients with quiescent ulcerative colitis.

BACKGROUND & AIMS: Among patients with quiescent ulcerative colitis (UC), lower fecal concentrations of calprotectin are associated with lower rates of relapse. We performed an open-label, randomized controlled trial to investigate whether increasing doses of mesalamine reduce concentrations of fecal calprotectin (FC) in patients with quiescent UC. METHODS: We screened 119 patients with UC in remission on the basis of Simple Clinical Colitis Activity Index scores, FC >50 µg/g, and intake of no more than 3 g/day mesalamine. Participants taking mesalamine formulations other than multimatrix mesalamine were switched to multimatrix mesalamine (2.4 g/day) for 6 weeks; 52 participants were then randomly assigned (1:1) to a group that continued its current dose of mesalamine (controls, n = 26) or a group that increased its dose by 2.4 g/day for 6 weeks (n = 26). The primary outcome was continued remission with FC <50 µg/g. Secondary outcomes were continued remission with FC <100 µg/g or <200 µg/g (among patients with pre-randomization values above these levels). RESULTS: The primary outcome was achieved by 3.8% of controls and 26.9% of the dose escalation group (P = .0496). More patients in the dose escalation group reduced FC to below 100 µg/g (P = .04) and 200 µg/g (P = .005). Among the patients who were still in remission after the randomization phase, clinical relapse occurred sooner in patients with FC >200 µg/g compared with those with FC <200 µg/g (P = .01). CONCLUSIONS: Among patients with quiescent UC and increased levels of FC, increasing the dose of mesalamine by 2.4 g/day reduced fecal concentrations of calprotectin to those associated with lower rates of relapse. Clinicaltrials.gov number: NCT00652145.