Methods: Randomized, parallel-group, open-label clinical trial including 458 adults (mean age, 44.8 years; 49.8% women) with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis (n=81), Crohn disease (n=66), or psoriasis undergoing maintenance therapy with infliximab in 20 Norwegian hospital
Sustained disease control without worsening was evident in 73.9% of pTDM group compared with 55.9% in standard infliximab group
Some limitations of this study:
The open-label study was not powered to detect the difference of pTDM in each of the six diseases
The therapeutic goal for maintenance infliximab was 3 to 8 mg/L, which is a little lower than current goals (ACG expert panel suggests a level of at least 5-10)
My take: This study supports recent expert guidance (see blog post below) on the benefit of pTDM as part of evidence-based care. It is likely that pTDM is even more important in children/teens due to growth.
This retrospective cohort study with 236 subjects (55% received acid blockers) provides a compelling argument that acid suppression is unlikely to be beneficial in infants with laryngomalacia and to consider the possibility of aspiration in them as well. Among all subjects, 27% received H2RA, 11% received PPI, and 17% received both.
Subjects treated with acid suppression had a greater risk of supraglottoplasty (hazard ratio 3.36, 95% CI 1.36-8.29, P = .009), shorter time to supraglottoplasty (5.64 ± 0.92 vs 7.98 ± 1.92 months, P = .006), and increased respiratory hospitalization risk (relative risk 1.97, 95% CI 1.01-3.85, 0.047), even after adjustment for covariates
Subjects receiving thickening had fewer respiratory hospitalization nights and longer time to supraglottoplasty (9.3 ± 1.7 vs 4.56 ± 0.73 months, P = .004), even after adjustment.
Subjects with moderate-to-severe laryngomalacia were more likely to have aspiration on a video fluoroscopic swallow study (VFSS)
Of the 40 patients who had a supraglottoplasty, only 4 (10%) had a VFSS before and afterwards. All repeat VFSS showed improvement at a mean of 4.7 months after supraglottoplasty
It is noted that 36% of subjects underwent a VFSS and 40% had a clinical feeding evaluation. The authors note that other studies have found “a high rate of silent aspiration in laryngomalacia.”
Acid blockers are unlikely to be beneficial in infants with laryngomalacia and are potentially detrimental (findings limited by retrospective design in a tertiary care setting)
Symptoms in children with laryngomalacia may be due to aspiration and evaluation is needed in those with significant symptoms
The following link is the same as the QR code below (from twitter feed) and provides PDF access to ~30 influential articles from the journal, Gastroenterology, this past year (many reviewed on this blog previously):
Using national registries, the authors identified all patients with IBD (>15 years of age) and all cases of urolithiasis in Denmark during 1977-2018. Key findings:
2,549 (3%) of 75,236 IBD patients and 11,258 (2%) of 767,403 non-IBD individuals developed urolithiasis, resulting in a 2-fold increased risk of urolithiasis (HR, 2.27; 95% CI, 2.17-2.38) in patients with IBD
The authors note that a small risk of urolithiasis preceded the diagnosis of IBD: with OR, 1.42; 95% CI: 1.34-1.50 prior to diagnosis
After IBD diagnosis, risk of urolithiasis was associated with anti-TNF therapy and surgery (increased disease severity appears to be associated with increased risk). Anti-TNF therapy had a RR of 2.68 in patients with ulcerative colitis and a RR of 3.56 in patients with Crohn’s disease; for surgery, the RR were 3.14 and 2.74 respectively
One limitation is detection bias as patients with IBD may have more asymptomatic stones identified due to more frequent imaging
My take: This confirms an increased risk of urolithiaiss in patients with IBD and is a good reminder to consider this when patients present with severe abdominal pain/possible flare-up.
Key finding: A post hoc analysis of data from a phase 4 trial (the MOMENTUM trial) found that, even in patients (n=593 at week 8, n=305 at week 52) with complete endoscopic healing of UC, FC concentration can be used to discriminate patients with ongoing microscopic inflammation from patients with histologic remission. The optimal FC cut-off concentrations for identification of patients with histologic remission were 75 μg/g at week 8 and 99 μg/g at week 52.
Key finding: In this prospective study, 57 patients in deep remission stopped azathioprine after a median of 7 years. 26 (46%) relapsed within a median of 15 months. Fecal calprotectin (FC) levels were >50 mcg/g in all patients with relapse (FC specificity 100%) but the sensitivity was only 50%. Thus, having a normal FC does not preclude relapse but elevated FC is associated with relapse.
In this retrospective study, 75 patients, 9.9% of all patients, who had been changed from originator infliximab to a biosimilar had clinical worsening. Key finding: Improvement of reported symptoms was seen in 73.3% of patients after reverse switching back to originator infliximab; alsor 7 out of 9 patients (77.8%) with loss of response regained response
Methods: This was a retrospective case-control study based on a national registry. Cases included children diagnosed with both IBD and Celiac Disease (CeD). Two matched IBD controls without CeD, and 2 matched CeD controls were selected for each case.
Forty-nine (1.75%) patients with IBD and CeD were identified out of 2800 patients with IBD. CeD was diagnosed before IBD in 37 (75.5%)
Compared with patients with IBD alone, patients with IBD and CeD presented more frequently with autoimmune diseases (odds ratio, 2.81; 95% CI, 0.97–8.37; P = 0.04) (mainly thyroiditis 6.1% vs 0%)
Children with ulcerative colitis and CeD had an increased risk of colectomy despite similar medical treatments compared with patients with ulcerative colitis alone (13.0% vs 0%); however, this was based on a small number (3 surgeries out of 23 patients)
Anti-TNF biologics (46.2% vs 69.2%) were less commonly administered in patients with Crohn’s disease and CeD than in patients with Crohn’s disease alone
Pubertal delay was more common in patients with IBD and CeD compared with patients with IBD alone (14.9% vs 3.2%; odds artio, 5.24)
The discussion emphasizes the need to consider the risk of developing IBD in children with CeD and to recognize the increased risk of autoimmune diseases. Children with both UC and CeD may have a more severe phenotype. The authors recognize the possibility of misdiagnosis of CeD as patients with IBD could present with similar upper GI findings; however, this is likely infrequent as most cases of CeD preceded the diagnosis of IBD.
My take: One point that the authors neglect is the need to consider an underlying monogenetic disorder (eg. CTLA4B) in children with multiple immune-mediated diseases. The main message for children with this double whammy, though, is to consider the need for more aggressive treatment (especially with UC) and the need to screen for other autoimmune conditions (especially thyroiditis).
Personal item: If any blog follower has experience using biologics (eg mepolizumab, benralizumab) in a young child (1 yo) with eosinophilic colitis and marked eosinophilia, please send me a personal email: email@example.com.
“Another series of studies from the University of Texas found that four seconds — yes, seconds — of ferocious bicycle pedaling, repeated several times, was enough to raise adults’ strength and endurance, whatever their age or health when they started.”
“As I wrote in July, the familiar goal of 10,000 daily steps, deeply embedded in our activity trackers and collective consciousness, has little scientific validity. It is a myth that grew out of a marketing accident, and a study published this summer further debunked it, finding that people who took between 7,000 and 8,000 steps a day, or a little more than three miles, generally lived longer than those strolling less or accumulating more than 10,000 steps.”
“Exercise also has a disproportionate impact on our odds of enjoying a long, healthy life. According to one of the most inspiring studies this year, overweight people who started working out lowered their risk of premature death by about 30 percent even if they remained overweight, with exercise providing about twice as much benefit as weight loss might…Exercise enhances our brain power, too, according to other, memorable experiments from this year”
“In the study, which I wrote about in May, active people reported a stronger sense of purpose in their lives than inactive people….In effect, the more people felt their lives had meaning, the more they wound up moving, and the more they moved, the more meaningful they found their lives.
For successful aging, recognize one’s issues and adapt accordingly. “Sooner or later, we all must recognize what is no longer possible and find alternatives,” says Jane Brody (Personal Health columnist) –“Inspired by Steven Petrow’s book, “Stupid Things I Won’t Do When I Get Old.”
Learning from ‘Super-Agers’ — “past research has revealed lifestyle factors that contribute to resilience such as obtaining a high level of quality education; holding occupations that deal with complex facts and data; consuming a Mediterranean-style diet; engaging in leisure activities; socializing with other people; and exercising regularly”
The sweet spot for longevity lies around 7,000 steps a day (or 30 minutes of exercise).
Methods: A retrospective cohort study using anonymized UK primary care records (2002-2016). All adults without a baseline diagnosis of AILD (autoimmune liver disease) were included and followed up until the first occurrence of an AILD diagnosis, death, or they left the database.
1314 incident cases of PBC, 396 of PSC, and 1034 of AIH. Crude incidences were as follows: PBC, 2.47 (95% CI, 2.34–2.60); PSC, 0.74 (95% CI, 0.67–0.82); and AIH, 1.94 (95% CI, 1.83–2.06) per 100,000 per year.
A more northerly latitude was associated strongly with incidence of PBC: 2.16 to 4.86 from 50°N to 57°N (P = .002) and incidence of AIH: 2.00 to 3.28 (P = .003), but not incidence of PSC: 0.82 to 1.02 (P = .473)
After adjustments, PBC was more frequent in smokers than those who had never smoked at 3.40 (3.03–3.77) per 100,000/y and 1.96 (1.80–2.12) cases per 100,000/y; there was a lower incidence of PSC in smokers 0.47 (0.33–0.61) per 100,000/y compared with those who had never smoked 0.95 (0.83–1.07) per 100,000/y. For AIH, there was no difference between current smokers and those who had never smoked
The authors speculate in the discussion about potential reasons why latitude could correlate with disease incidence. Some potential explanations include sunlight/vitamin D metabolism (though this is at odds with the fact that those with increased skin pigmentation are NOT at increased risk), environmental exposures (related to geology, diet, air quality) or unrecognized genetic tendency based on geography.
My take: In the UK, there is an association between a more northernly latitude and both PBC and AIH.
This data from NY Times shows that deaths due to COVID-19 are following a familiar pattern and spiking about 3 weeks after a spike in cases; this time the spike is being driven by omicron cases. However, this wave may in fact have lower severity per case; with this current wave, the number of reported cases is probably undercounted by a greater degree than in previous spikes due to widespread availability of home testing and the likelihood of more asymptomatic cases. Thus, it could be that the death rate per case would/will be significantly lower if/when all cases are accounted for.
In this nationwide population-based cohort study in Sweden from 1969-2017 of 6,016 adults with histologically-confirmed AIH (all 18 years or older) and 28,146 matched general population, key findings:
3,185 individuals with AIH died (41.4/1000 person-years) compared with 10,477 reference individuals (21.9/1000 person-years)
The 10-year cumulative incidence of death was 32.3% (95%CI [ 31.1-33.6) for AIH individuals and 14.1% (95%CI [ 13.7-14.5) for reference individuals
AIH individuals with cirrhosis on biopsy had a high risk of death (HR [ 4.55; 95%CI [ 3.95-5.25), while mortality risks for patients with noncirrhotic fibrosis (HR, 2.68) and inflammation without fibrosis (HR, 2.18) were similar to overall risk
In this cohort, 13.7% had cirrhosis at diagnosis (lower than other studies)
My take: In this study over nearly 50 years, AIH was associated with “a 2-fold increased risk of death. Risks were particularly high in individuals with cirrhosis, portal hypertension (HR, 7.55), and overlap with cholestatic liver disease.”