bluuebunny/crossref_metadata_2025 huggingface dataset:
A185 DUAL BIOLOGIC THERAPY IN A PATIENT WITH NIEMANN-PICK TYPE C AND CROHN DISEASE: A CASE REPORT AND LITERATURE REVIEW
Authors: Hudson A , Almeida P , Huynh H Q
Published: February 2022

Background

Since the availability of biologics and biosimilars, inflammatory bowel disease (IBD) therapy has been a rapidly expanding field. Dual biologic therapy has become a new area of interest. This is important given that clinical remission rates from biologic monotherapy are only 40% at one year, and that in Canadian children with IBD, up to 33% will need surgery within ten years. It also holds potential in those who are not likely to respond as well to traditional therapy, such as patients with genetic disorders. Mono-/poly-genic IBD and the role of genetics in IBD is an evolving field. Niemann-Pick disease type C (NPC), a neurodegenerative lysosomal storage disorder, is one such genetic disorder, and its’ associated predisposition to IBD is thought to be related to impaired destruction of intracellular bacteria within macrophages (impaired autophagy). The persistence of bacteria in the gut wall leads to an increased cytokine response.

Aims

We present a case of a teenage patient with NPC and crohn colitis, who sustained clinical remission only after escalating to dual biologic therapy (anti-TNF (infliximab) and anti-IL12/IL23 (ustekinumab)).

Methods

A literature review of dual biologic therapy in Pediatric IBD (all types of patients included) was also completed.

Results

The patient presented with one month of abdominal pain, weight loss, and bloody diarrhea, 9 months after her diagnosis of NPC. Endoscopy revealed mild inflammation in the rectosigmoid junction and rectum, with pathology showing granulomatous pancolitis. Induction therapy was rectal 5-ASA. Subsequent flares resulted in the addition of azathioprine, and then infliximab. She was switched to ustekinumab after a flare 21 months later, which did not lead to adequate improvement, so infliximab was added back on as a dual biologic. With this combination therapy she maintained clinical, biochemical, and endoscopic remission, ongoing two years later. A literature review revealed eight studies (case series/reports only). One Pediatric patient case combined ustekinumab with infliximab, while the remaining combined vedolizumab (gut-specific anti- α 4β 7 integrin) with infliximab.

Conclusions

In Pediatric patients with genetic disorders and IBD who are not responding adequately to biologic therapy, adding a second biologic medication with a different mechanism of action may be efficacious. Targeting both TNFa (which induces pro-inflammatory cytokines, among many other roles), and the proinflammatory cytokines themselves (IL12/23), may be important in genetic disorders with impaired macrophage function and increased cytokine response. This is a potential option even several years into treatment. To date, only case studies are available, with the majority combining vedolizumab with infliximab. Our case adds to the sparse literature on the utility of combining ustekinumab and infliximab.

Funding Agencies

None
A200 CROHN’S-ASSOCIATED E. COLI WORSEN COLITIS SEVERITY IN MICE COLONIZED WITH DEFINED MICROBIOTA
Authors: Jackson K , Hann A , Galipeau H J , Constante M , Coombes B K , Verdu E , Hosseinidoust Z
Published: February 2022

Background

Bacterial infections have been postulated to drive the dysregulated inflammation found in inflammatory bowel disease (IBD). In particular, adherent-invasive Escherichia coli (AIEC) isolated from patients with IBD have pathobiont characteristics and have been implicated in IBD pathogenesis.

Aims

Our aim was to characterize and compare the level of intestinal inflammation and potential microbiota shifts induced by E. coli clinical isolates using a gnotobiotic mouse model of colitis.

Methods

Adult germ-free C57BL/6 mice were transferred to ISO positive cages in a gnotobiotic facility and colonized with altered Schaedler flora-like (ASF) microbiota and one of three clinical E. coli isolates: E. coli C0004 (n = 5), E. coli LF82 (n = 9), E. coli NRG857c (n = 6), or ASF alone (n = 6). Three weeks later, mice were treated for 5 days with low dose dextran sodium sulphate in drinking water (2%; DSS), followed by 2 days of water. Mice were monitored daily for clinical symptoms (weight, stool consistency, and occult blood). At sacrifice, colon tissue was collected for histological analysis. Cecum contents were cultured to determine bacterial load. Fecal samples were collected for 16S rRNA gene sequencing analysis before and after DSS treatment.

Results

All mice colonized with an E. coli isolate displayed significantly greater clinical and microscopic scores of colitis compared to ASF alone, but the severity was dependent on the colonized E. coli strain. E. coli NRG857c-colonized mice exhibited more severe symptoms (p < 0.001) two days earlier than mice colonized with other E. coli isolates. Mice colonized with E. coli LF82 or E. coli NRG857c had higher histological scores of colitis compared to mice colonized with E. coli C0004, which were also significantly greater than ASF alone (p < 0.0001). 16S rRNA gene sequencing revealed that ASF-alone-colonized mice lacked Proteobacteria. All E. coli-colonized mice had comparable bacterial loads, which were verified by 16S rRNA analysis. Following DSS, E. coli LF82 and E. coli NRG857c relative abundance remained stable, whereas the relative abundance of Roseburia/ASF 492 declined significantly in all E. coli colonized mice.

Conclusions

The presence of E. coli pathobionts in mice drive the severity of chemically induced colitis, with AIEC NRG857c inducing the greatest severity. This gnotobiotic mouse model enables us to control the severity of colitis in a well-defined microbiota that is dependent on the colonized E. coli isolate. Using this model, we will be able to assess therapeutic candidates that aim to treat colitis at varying stages of its disease progression.

Funding Agencies

CCC, CIHRNSERC
A225 VACCINE-PREVENTABLE DISEASES IN HOSPITALIZED PATIENTS WITH END-STAGE LIVER DISEASE/CIRRHOSIS: A NATIONWIDE COHORT ANALYSIS
Authors: Hudson D , Khanna R , Brahmania M , Qumosani K , Teriaky A
Published: February 2022

Background

Cirrhosis is associated with immune dysfunction, which increases susceptibility to infection and subsequent hospitalization. Vaccination of this high-risk patient population can mitigate the risk of infection.

Aims

Data from the National Inpatient Sample (NIS) was analyzed to compare the prevalence of vaccine-preventable diseases (VPD) among hospitalized patients both with and without cirrhosis.

Methods

The 2013 NIS database was interrogated using ICD-9-CM codes to identify patients with cirrhosis and VPD. Baseline characteristics were compared (see: Table 1). Univariate and multivariate regression models identified risks associated with VPD adjusting for survey procedures.

Results

313,710 patients were hospitalized for VPD, including 13,080 patients (4.1%) with cirrhosis (see: Table 1) Patients with cirrhosis were more likely to be hospitalized with pneumococcal pneumonia (odds ratio [OR] = 1.45 [95% CI 1.29 – 1.63], P <0.001), hepatitis A (OR = 7.04 [95% CI 5.96 – 8.31], P <0.001) and hepatitis B (OR = 14.41 [95% CI 12.53 – 14.36], P <0.001) infections compared to patients without liver cirrhosis. Patients with cirrhosis were less likely to have an infection with influenza (OR = 0.55 [95% CI 0.49 – 0.62], P <0.001), human papillomavirus (HPV) (OR = 0.57 [95% CI 0.43 – 0.75, P < 0.001) and varicella zoster (OR = 0.78 [95% CI 0.69 – 0.89], P <0.001). Minimal differences in hospitalizations for haemophilus influenzae or meningococcal infections were noted between groups.

Odds ratios for VPD adjusting for age, sex, race, patient location, patient income, hospital type and bed-size, mortality risk, type 2 diabetes mellitus, malignancy, human immunodeficiency virus (HIV), organ transplantation and immunodeficiency:

pneumococcal pneumonia (OR = 1.27 [95% CI 1.13 – 1.44], P < 0.001), hepatitis A (OR = 5.99 [95% CI 5.02 – 7.15], P < 0.001); and hepatitis B (OR = 11.07 [95% CI 10.24 – 11.97], P < 0.001).

Conclusions

These results emphasize the importance of vaccinating patients with cirrhosis against pneumococcal pneumonia, hepatitis A and hepatitis B infections to reduce hospitalization

Table 1: Baseline characteristics of patients with cirrhosis and without cirrhosis presenting with a vaccine preventable disease.

Funding Agencies

None
A234 IN VITRO GUT MICROBIOME AND METABOLITE RESPONSES TO RESISTANT STARCH ARE INDIVIDUALIZED
Authors: Dobranowski P , Qin H , Walker K , Butcher J , Gowing A , Singleton R , Mayne J , Mack D R , Figeys D , Stintzi A
Published: February 2022

Background

Gut microbes degrade and ferment resistant starch (RS) into metabolites that help maintain gut homeostasis. Clinical trials have evaluated RS for various health conditions, but individuals respond to RS with profound variability. The reason for this variability is unclear.

Aims

Using in vitro culturing methods and multi-omic analyses, we hypothesize that individuals will elicit variable responses to RS with respect to overall fermentation, bacterial composition, short chain acid production, and metabolite flux.

Methods

As part of an ongoing clinical trial, we have selected 4 pediatric patients with inflammatory bowel disease to better understand microbiome-RS interactions. We cultured stools anaerobically using a high-throughput platform (“RapidAIM”) with 9 different pre-digested RS. After 18-hour incubations, media supernatants were used to measure pH and perform targeted and semi-targeted metabolomic analyses with a panel of 116 compounds. Bacterial pellets were isolated for 16S rRNA gene sequencing analyses to evaluate changes in microbiome compositions. Data were analyzed with generalized linear mixed models, principal component analysis (PCA), random forest (RF) classification with feature selection, and network construction with graphical lasso.

Results

Changes in several microbiome parameters were different across individuals, including the magnitude of pH changes, metabolite signatures, and relative abundances of important bacterial taxa. Bacterial species known to degrade RS were more abundant in individuals showing stronger RS fermentation. Inter-individual discrimination was accomplished with PCA and RF, from which we could identify metabolite signatures. The robustness of microbiome networks corresponded to RS fermentation and butyrate production.

Conclusions

We report a novel perspective on how individuals respond to RS’ differently. Butyrate remains an important hub of the microbiome architecture with respect to RS fermentation. Future work will interrogate the roles of individualized metabolomic responses on host physiology. In vivo responses to RS are being evaluated in an ongoing clinical trial.

Funding Agencies

CCC, CIHRGenome Ontario, Genome Canada
A235 ILEAL MICROBIOME ALPHA DIVERSITY REMAINS LOWER IN ENDOSCOPICALLY AND HISTOLOGICALLY INACTIVE CROHN’S DISEASE COMPARED TO ULCERATIVE COLITIS OR HEALTHY CONTROLS
Authors: Olivera Sendra P A , Borowski K , Nayeri S , Martinez-Lozano H , Leibovitzh H , Lee S , Hernandez-Rocha C , Silverberg M S
Published: February 2022

Background

Crohn’s disease (CD) has been associated with a lower alpha diversity when compared to ulcerative colitis (UC) patients and healthy controls (HC), which also depends on disease location and endoscopic activity. However, it is unclear whether the resolution of histologic inflammation may influence mucosal alpha diversity in the ileum.

Aims

To characterize the ileal mucosa-associated microbiome diversity in subjects with ileal predominant CD (iCD) in endoscopic (ER) and endo-histologic (EHR) remission, compared to subjects with colonic predominant CD (cCD), UC and HC, respectively.

Methods

Data from a large cohort of subjects recruited at Mount Sinai Hospital Toronto (2009–2016) was analyzed. ER was defined as a segmental Simple Endoscopic Score for CD of <3 in the ileum. EHR was defined as ER with the absence of active histologic inflammation in ileal biopsies. CD patients were divided according to the Montreal classification into iCD (L1 and L3) and cCD (L2) and compared against UC patients without backwash ileitis and HC. Patients with history of ileocecal resection and/or antibiotic use at baseline were excluded. Microbial 16S rRNA gene was sequenced using the Illumina MiSeq and processed using QIIME2. Alpha diversity was measured using the Shannon index and compared using Kruskal-Wallis test and further pairwise Wilcoxon with Holm correction. An adjusted p-value < 0.05 was considered significant.

Results

We included 35 CD patients with ileal ER, 81 UC patients and 32 HC. Among CD patients, 20/35 (57.1%) and 15/35 (42.9%) had iCD and cCD, respectively. Ileal mucosal alpha diversity was significantly lower in iCD patients in ER compared with that of UC patients (q=0.004) and HC (q=0.001). No differences in ileal mucosal alpha-diversity were seen between iCD than cCD patients (q=0.12). When histology was included to classify CD and UC patients as EHR, the ileal alpha diversity of iCD patients remained reduced compared to UC patients and HC (q=0.008 and q=0.002, respectively). Again, ileal mucosal alpha-diversity was not significantly lower in iCD than cCD patients among those in ileal EHR (q=0.24).

Conclusions

Ileal mucosa of CD patients in ER and EHR have lower alpha diversity than UC and HC. These findings suggest that the ileal mucosa of CD patients remains dysbiotic despite achieving endoscopic and histologic remission.

Funding Agencies

IBD Genetics Consortium
A238 ALTERED GUT MICROBIOME COMPOSITION AND FUNCTION ARE ASSOCIATED WITH GUT BARRIER DYSFUNCTION IN HEALTHY RELATIVES OF CROHN’S DISEASE PATIENTS
Authors: Leibovitzh H , Lee S , Xue M , Raygoza Garay J , Hernandez-Rocha C , Madsen K , Meddings J , Guttmen D S , Espin Garcia O , Goethel A , Griffiths A , Moayyedi P , Huynh H Q , Jacobson K , Mack D R , Abreu M , Bernstein C N , Marshall J , Turner D , Xu W , Turpin W , Croitoru K
Published: February 2022

Background

The gut microbiome may play a role in gut barrier homeostasis including epithelial barrier function, but data are scarce and limited to animal studies

Aims

To assess if alterations in gut microbiome are associated with gut barrier function

Methods

We utilized the Genetic Environmental Microbial (CCC GEM) cohort of healthy first-degree relatives (FDRs) of Crohn’s disease (CD) patients. Gut barrier function was assessed using the ratio of urinary fractional excretion of lactulose to mannitol (LMR). Stool bacterial DNA was extracted and sequenced for the V4 hypervariable region of the 16S rRNA gene using MiSeq and processed using QIIME2. Microbial functions were imputed using PICRUSt2. The cohort was divided into a North American discovery cohort (n=2,472) and non-North American external validation cohort (n=655). LMR>0.025 was defined as abnormal. LMR-microbiome associations were assessed using multivariable regression model and Random Forest (RF) classifier algorithm. q<0.05 was considered significant when multiple tests were performed

Results

The median age of the entire cohort was 17.0 years [IQR 12.0; 24.0], 52.6% were females and 25.4% had LMR>0.025. In the discovery cohort, subjects with LMR>0.025 had markedly reduced alpha diversity (Chao1 index, estimate= -0.0037, p=4.0e-04) and altered beta diversity (Bray-Curtis dissimilarity index, PERMANOVA: pseudo-F statistic = 2.99, p=1.0e-03). We identified eight bacterial genera and 52 microbial pathways associated with LMR>0.025 (q<0.05). Four genera (decreased Adlercreutzia [odds ratio(OR)=0.74, 95% confidence interval (CI) 0.6–0.91], Clostridia-UCG-014 [OR=0.71, 95%CI 0.59–0.86], and Clostridium-sensu-stricto-1 [OR=0.75, 95%CI 0.61–0.92] and increased Colidextribacter [OR=1.65, 95%CI 1.2–2.26]) and eight pathways (including decreased biosynthesis of glutamate [OR=0.4, 95%CI 0.21–0.74], tryptophan [OR=0.06, 95%CI 0.01–0.27] and threonine [OR=0.038, 95%CI 0.003–0.41]) were replicated. Bacterial community composition was associated with gut barrier homeostasis as defined by the RF analysis (p= 1.4e-6)

Conclusions

Gut microbiome community and pathways are associated with gut barrier function. These findings may identify potential microbial targets to modulate barrier function

Submitted on behalf of the CCC-GEM Consortium

Funding Agencies

CCC, CIHRCrohn’s and Colitis Canada Genetics Environment Microbial (CCC-GEM) III; The Leona M. and Harry B. Helmsley Charitable Trust; Kenneth Croitoru is the recipient of the Canada Research Chair in Inflammatory Bowel Diseases
A243 HISTAMINE H1-RECEPTOR ANTAGONISTS SUPPRESS THE HYPEREXCITABILITY OF NOCICEPTIVE NEURONS EXPOSED TO IBS-C PATIENT STOOL SUPERNATANTS
Authors: Neary E , Jiménez-Vargas N N , Lomax A E , Reed D E , Vanner S
Published: February 2022

Background

Abdominal pain is the primary cause of morbidity in many chronic GI disorders such as IBS, but the molecular mechanisms contributing to pain signaling are unclear. Stool supernatants from patients with diarrhea-predominant IBS increase the excitability of DRG neurons compared to supernatants from healthy controls, suggesting that mediators in the stool may sensitize nociceptors. Additionally, histamine has been implicated as a mediator of hypersensitivity in IBS patients. However, it is unclear if stool supernatants from constipation-predominant IBS (IBS-C) patients affect the excitability of DRG neurons. Furthermore, it is unknown if specific neuro-mediators in stool such as histamine impact the excitability of nociceptive neurons in this subgroup of IBS patients.

Aims

To evaluate whether IBS-C stool supernatants induce nociceptive signaling in DRG neurons compared to healthy control (HC) stool supernatants.

If so, to evaluate the role of histamine 1 (H1) receptors in DRG neuron nociceptive signaling initiated by mediators in IBS-C stool supernatants.

Methods

IBS-C (n=5) and HC (n=2) patient stool was collected, filtered, and dissolved with Krebs solution in a 1:8 (g/v) dilution. Dorsal root ganglion (DRG) neurons from C57BL/6 mice were incubated with HC or IBS-C stool supernatant for 30 minutes. To evaluate whether histamine in stool supernatants can sensitize H1 receptors on nociceptors, DRG neurons were pre-incubated with the H1-receptor antagonist pyrilamine (1μM, 30 min) before stool supernatants. Changes in DRG neuronal excitability were recorded using perforated patch-clamp techniques to measure the rheobase (minimum input current needed to elicit an action potential) and the resting membrane potential (RMP).

Results

In neurons incubated with IBS-C stool supernatants (n=28) the rheobase decreased (63%) compared to healthy controls (78 ± 13.7 pA; n=6). This effect was reversed in DRG neurons pre-incubated with the H1 receptor antagonist, pyrilamine, (n=26) (77 ± 5.9 pA, p<0.001) compared to neurons incubated with IBS-C supernatant alone (50 ± 5.13 pA; n=28). No changes were found in the RMP. The data were analyzed with the non-parametric Kruskal-Wallis test.

Conclusions

IBS-C stool supernatants increase the excitability of DRG neurons compared to HC. Furthermore, the H1-receptor antagonist pyrilamine inhibits the neuronal hyperexcitability evoked by mediators in IBS-C patient stool. These findings suggest that the neuroactive metabolite histamine may contribute to visceral pain experienced by patients with IBS-C. Further studies are needed to examine whether similar signaling to nociceptive neurons by stool supernatants occurs in other subtypes of IBS.

Funding Agencies

CAG, CIHR
A247 MEDITATION AND YOGA FOR IRRITABLE BOWEL SYNDROME (MY-IBS): A RANDOMIZED CONTROLLED TRIAL
Authors: D’Silva A , Marshall D , Rajagopalan V , Nasser Y , Vallance J , Raman M
Published: February 2022

Background

When delivered in person, yoga is effective in managing Irritable Bowel Syndrome (IBS) symptoms. However, research is needed to determine the feasibility and effectiveness of yoga as a therapeutic option when delivered virtually.

Aims

The aim was to explore the feasibility and effectiveness of a yoga program, delivered virtually, for patients with IBS. We hypothesized the program would be feasible and effective in improving outcomes in the intervention group compared to the control group.

Methods

Adults diagnosed with IBS were randomized to receive either a Hatha yoga intervention or to an advice-only control group. The intervention consisted of facilitator-led weekly online classes for eight weeks delivered using Microsoft Office Teams and daily home practice. Yoga sessions included sequential delivery of postures, chanting, breathing exercises, and meditation over four weeks, with integrated practice over the final four weeks. Feasibility was evaluated with recruitment and attrition rates, adherence, and safety. The primary outcome was severity of IBS symptoms (IBS-Symptom Severity Score, IBS-SSS). Secondary outcomes included anxiety (General Anxiety Disorder-7), depression (Patient Health Questionnaire-9), and stress (Perceived Stress Scale) assessed at baseline and eight weeks. Unadjusted and adjusted analysis of variance (and covariance) models compared baseline and post-intervention data between groups using intent to treat analysis.

Results

Sixty-five participants participated (32 treatment, 33 control). The mean age was 44.2±14.1 years and 91% identified as female. Participants had been living with IBS for 11.7±11 years. Fifteen participants were lost to follow-up (20% attrition rate). Participants attended on average 5.9±1.7 out of a possible 8 sessions (74% adherence) and accumulated 1,187±545 minutes in daily practice over eight weeks. No adverse events were reported. The groups did not differ at baseline (P>0.05). From baseline to post intervention, unadjusted ANOVA models indicated the yoga program was not statistically superior to the control group for IBS-symptoms (-17.5 points; 95% CI -62.6 to 27.6; P = 0.440), anxiety (-0.91 points; 95% CI -2.47 to 0.64; P = 0.245) and stress (-0.65 points; 95% CI -1.73 to 0.44; P = 0.239). Significant differences between groups were seen for depression (-1.82 points; 95% CI -3.49 to -0.15; P = 0.033). A second model considered relevant covariates including age, comorbidities, and years since diagnosis (i.e., ANCOVA), and the results were similar to the unadjusted model.

Conclusions

Our virtual Hatha yoga and mediation program was feasible, and participants showed improvement in their depression scores. However, they did not experience a significant improvement in their IBS symptoms, anxiety, or stress, perhaps due to the short timeframe of the intervention.

Funding Agencies

None
A251 USE OF INDIRECT CALORIMETRY TESTING TO DIRECT NUTRITION SUPPORT IN CRITICALLY ILL PATIENTS WITH GASTROINTESTINAL CONDITIONS
Authors: Russell L , Janisse N , Jones G , Karachi T , Serrano P E , ApSimon M , Armstrong D , Pinto-Sanchez M I
Published: February 2022

Background

Indirect calorimetry (IC), which measures oxygen uptake and carbon dioxide output, determines energy expenditure (EE) more precisely than predictive equations in critically ill patients. It is unknown whether the use of IC affects energy provision in critically ill patients with gastrointestinal (GI) conditions that affect absorption and digestion

Aims

To (1) compare IC and predictive equations for determining energy needs and (2) evaluate whether IC results affect changes in nutrition support in critically ill patients with GI conditions.

Methods

In a prospective, observational study, IC was performed for 25 to 55 mins in critically ill patients admitted to intensive care or clinical wards at 2 tertiary-care hospitals in Hamilton, Ontario between Feb 2018 to Sept 2021. EE measured by IC was compared to EE determined by a predictive equation (25 kcal/kg) or the Harris-Benedict (HB) formula. A change in energy provision was defined as a change of >10% directed by IC. Continuous data are expressed as means and standard deviation (SD), and categorical data as a proportion of patients. The Mann Whitney U Test (SPSSv26) was used to compare GI and non-GI populations.

Results

Of 296 IC tests in 229 patients, 39 of them were in 30 GI patients (11 female; mean age 62 yrs; SD 19). Admission GI diagnoses were pancreatitis (33%), liver disease (20%), Crohn’s disease/ autoimmune enteropathy (20%), post-bowel resection (10%), chronic abdominal pain (10%), and cholangitis (7%). The predictive formula underestimated EE in 67% of GI patients (mean deficit 503 kcal/day) compared to IC, corresponding to a mean deficit of 25% of patients’ energy needs. The HB formula underestimated EE in 73% of patients (mean deficit 652 kcal/day), a mean deficit of 28% of patients’ energy needs compared to IC. Pancreatitis was the majority diagnosis (75% of the predictive equation; 50% HB) among patients with the highest deficit (>30%) in energy needs when compared to IC. There were no significant differences in the rates of underestimation of energy needs based on predictive and HB formulas between the GI and non-GI patients or between luminal GI and non-luminal GI conditions. After IC, 63% of tests led to changes in energy provisions in GI patients; most requiring an increase in energy provisions (53%).

Conclusions

The use of IC to accurately measure EE led to changes in energy provisions in critically ill GI patients. Preventing over- and underfeeding with the implementation of IC to guide nutrition has the potential to improve outcomes in critically ill patients with gastrointestinal conditions.

Funding Agencies

None
A257 PANCREATIC CANCER TREATMENT AND END OF LIFE OUTCOMES: A POPULATION BASED COHORT STUDY
Authors: Khan R , Salim M , Tanuseputro P , Hsu A , Coburn N , Talarico R , James P
Published: February 2022

Background

Patients with pancreatic cancer face challenging decisions regarding treatment choices following their diagnosis and often lack data on end-of-life (EOL) outcomes. Without the available information, older patients may be undertreated, dying earlier than they would have with treatment, while others may be overtreated and exposed to aggressive measures with harmful side effects.

Aims

To describe survival and EOL outcomes among pancreatic cancer patients based on index cancer treatment, disease stage, and patient characteristics.

Methods

We conducted a population based cohort study in Ontario, Canada of patients who died from April 2010 to December 2017 and were diagnosed with pancreatic cancer prior to death. We used administrative databases to collect data on demographics, baseline health status, treatments, and outcomes. The primary exposure was index cancer treatment (no treatment, radiation, chemotherapy alone, surgery alone, and surgery with chemotherapy). The primary outcomes were mortality, health care encounters per 30 days in the last six months of life, and palliative care visits per 30 days within the last six months of life. Secondary outcomes were location of death (institution vs. community), hospitalization within the last 30 days of life, and receipt of chemotherapy within the last 30 days of life. We estimated the association between the exposure and outcomes using multivariable models, adjusting for demographics, comorbidities, and cancer stage. Hazard ratios, adjusted mean differences, and odds ratios were reported with 95% confidence intervals.

Results

Our cohort included 9950 adults with a median age at diagnosis of 78. 56% received no index treatment, 5% underwent radiation, 27% underwent chemotherapy alone, 7% underwent surgery alone, and 6% underwent surgery and chemotherapy. In the multivariable regression (Table and Figure), radiation, chemotherapy alone, surgery alone, and surgery with chemotherapy were all associated with decreased mortality and fewer healthcare encounters. All groups except radiation were associated with fewer palliative care visits. All treatment groups were associated with lower odds of institutional death and hospitalization within the last 30 days of life, and higher odds of chemotherapy within the last 30 days of life.

Conclusions

Our data, the first to provide EOL outcome estimates based on index cancer treatment, can help patients make initial treatment decisions after a diagnosis of pancreatic cancer.

Multivariable regression analyses predicting primary and secondary outcomes

Association between index cancer treatment and primary outcomes.

Funding Agencies

CIHR
A258 ROSAI-DORFMAN0-DESTOMBES DISEASE: A RARE CAUSE OF OBSTRUCTIVE JAUNDICE
Authors: Akhtar D , Donaldson M A , Akhtar N H , Owen D , Gan S
Published: February 2022

Background

Rosai-Dorfman-Destombes Disease (RDD) is rare histiocytic disorder that is most frequently seen in children and young adults. Gastrointestinal involvement is reported in <1% of cases and typically involves the small bowel and colon. Pancreatic and hepatic involvement has been previously reported but is extremely rare.

Aims

To describe a case of obstructive jaundice in the setting of a very rare histiocytic disorder known as RDD.

Methods

Case Report

Results

A 59-year old previously healthy male of Asian descent presented with obstructive jaundice. Initial imaging demonstrated intra and extrahepatic biliary duct dilation with concurrent diffuse enlargement of the pancreas compatible with autoimmune pancreatitis. Endoscopic retrograde cholangiopancreatography (ERCP) was performed with stenting and biopsy. ERCP demonstrated a distal common bile duct stricture with biopsies suggestive of low grade reactive changes and inflammation. Subsequent endoscopic ultrasound (EUS) guided biopsy of the pancreas showed active and chronic inflammation, necrosis, and atrophic pancreatic tissue, with no definitive evidence of autoimmune pancreatitis (Figure 1). Ca-19-9 and IgG4 were normal. He was treated with a course of prednisone and responded well, with repeat CT imaging showing almost complete resolution of the previously demonstrated pancreatic changes. A diagnosis of autoimmune pancreatitis was made. He re-presented 6-months later, however, with fatigue and repeat imaging now displayed lymphadenopathy in the neck, chest, and abdomen, and a bulky pancreatic head with associated hepatomegaly. Lymph node excisional biopsy confirmed the diagnosis of RDD with the presence of scattered histiocytic cells showing emperipolesis with a low number of IgG4 positive cells (Figure 1). The patient was promptly initiated on prednisone and rituximab and has since then had excellent clinical response.

Conclusions

RDD is a rare non-Langerhans cell histiocytosis of unknown etiology that has a prevalence of 1:200 000. RDD clinically presents with painless bilateral cervical lymphadenopathy and can manifest with both nodal and extra nodal involvement. The most common sites of extra nodal disease are the skin and central nervous system, but rarely, can also present with pancreatic involvement. The use of fine needle guided biopsy in diagnosing RDD with extra nodal disease can be limited by low yield, sclerotic tissue, or non-diagnostic findings. For this reason, RDD with pancreatic involvement can masquerade as autoimmune pancreatitis, pancreatic malignancy and IgG4-related disease.This case report raises awareness about RDD with pancreatic and biliary involvement, a rare entity, that can present with obstructive jaundice.

Figure 1: Histological sections of lymph node(left) with hystiocytic cells showing emperipolesis(arrow) and pancreas(right) showing active and chronic inflamation, necrosis and atrophy

Funding Agencies

None
A three-stage hybrid clustering system for diagnosing children with primary headache disorder
Authors: Simić Svetlana , Sakač Slađana , Banković Zorana , Villar José R , Calvo-Rolle José Luis , Simić Svetislav D , Simić Dragan
Published: February 2022

Headache disorders can be considered as the predominant neurological condition. In the field of neurological diseases, migraine was estimated to cost a total of €27 billion per year for the loss through reduced work productivity in the European Community. Medical data and information in turn provide knowledge based on which physicians make scientific decisions for diagnosis and treatments. It is, therefore, very useful to create diagnostic tools to help physicians make better decisions. This paper is focused on a new hybrid clustering system combining analytic hierarchy process and weighted fuzzy c-means clustering method for diagnosing children with primary headache disorder. The proposed three-stage hybrid diagnosing system is tested on data set collected from hospitalized children in the Clinical Centre of Vojvodina, Novi Sad, Serbia.
Two-stage treatment of idiopathic scoliosis using the LSZ growing system with a 10-year follow-up: a case report
Authors: Sampiev M T , Zagorodniy N V , Lysenko I S , Dubinin I P , CHemurzieva K H M
Published: February 2022

A clinical case of an 11-year-old patient with idiopathic scoliosis treatment using the LSZ growing system. The main thoracic curve was 88°, with a lumbar curve of 52°. The patient was at Risser stage 3. At the first stage, posterior correction and instrumentation (T1-L5) of the deformity using the LSZ growing system were performed. Residual deformity of the spine was 15°. At a follow-up, the spine grew by 5 cm. As the second stage of surgical treatment, this system was removed and replaced with selective instrumentation at T4-T12. The patient was followed up for 10 years. On the control radiographs of the spine in the standing position in 2021, adequate correction is preserved. That described technique allowed to ultimately perform selective definitive instrumentation, preserving near full range of movement in the lumbar spine. Further studies are needed to determine the effectiveness of the described approach.
Spectroscopic observations of V455 Andromedae superoutburst in 2007: The most exotic spectral features in dwarf nova outbursts
Authors: Tampo Yusuke , Nogami Daisaku , Kato Taichi , Ayani Kazuya , Naito Hiroyuki , Narita Norio , Fujii Mitsugu , Hashimoto Osamu , Kinugasa Kenzo , Honda Satoshi , Takahashi Hidenori , Narusawa Shin-ya , Sakamoto Makoto , Imada Akira
Published: February 2022

We present our spectroscopic observations of V455 Andromedae during the 2007 superoutburst. Our observations cover this superoutburst from around the optical peak of the outburst to the post-superoutburst stage. During the early superhump phase, the emission lines of the Balmer series, He i, He ii, Bowen blend, and C iv/N iv blend were detected. The He ii 4686 line exhibited a double-peaked emission profile, where Balmer emission lines were single-peaked, which is unexpected from its high inclination. In the ordinary superhump phase, the Balmer series transitioned to double-peaked emission profiles, and high-ionization lines were significantly weakened. These transitions of the line profiles should be related to the structural transformation of the accretion disk, as expected between the early and ordinary superhump transition in the thermal–tidal instability model. The Doppler map of Hα during the early superhump phase exhibits a compact blob centered at the primary white dwarf. In analogy to SW Sex-type cataclysmic variables, this feature could emerge from the disk wind and/or the mass accretion column on to the magnetized white dwarf. The Doppler map of He ii 4686 Å is dominated by the ring-like structure and imposed two flaring regions with the velocity of ∼300 km s−1, which is too slow for a Keplerian accretion disk. The phase of the flaring regions was coincident with the inner spiral arm structure identified during the early superhump phase. Our disk wind model with the enhanced emission from the wind component launched from the inner arm structure successfully reproduced the observed properties of He ii 4686 Å. Therefore, V455 And is the first case in dwarf nova outbursts where the presence of the disk wind is inferred from an optical spectrum.
Detection of nitrogen and oxygen in a galaxy at the end of reionization
Authors: Tadaki Ken-ichi , Tsujita Akiyoshi , Tamura Yoichi , Kohno Kotaro , Hatsukade Bunyo , Iono Daisuke , Lee Minju M , Matsuda Yuichi , Michiyama Tomonari , Nagao Tohru , Nakanishi Kouichiro , Nishimura Yuri , Saito Toshiki , Umehata Hideki , Zavala Jorge
Published: February 2022

We present observations of [N ii] 205 μm, [O iii] 88 μm, and dust emission in a strongly-lensed, submillimeter galaxy (SMG) at z = 6.0, G09.83808, with the Atacama Large Millimeter/submillimeter Array (ALMA). Both [N ii] and [O iii] line emissions are detected at >12σ in the ${0{^{\prime \prime}_{.}}8}$-resolution maps. Lens modeling indicates that the spatial distribution of the dust continuum emission is well characterized by a compact disk with an effective radius of 0.64 ± 0.02 kpc and a high infrared surface brightness of ΣIR = (1.8 ± 0.3) × 1012 L⊙ kpc−2. This result supports that G09.83808 is the progenitor of compact quiescent galaxies at z ∼ 4, where the majority of its stars are expected to be formed through a strong and short burst of star formation. G09.83808 and other lensed SMGs show a decreasing trend in the [N ii] line to infrared luminosity ratio with increasing continuum flux density ratio between 63 and 158 μm, as seen in local luminous infrared galaxies (LIRGs). The decreasing trend can be reproduced by photoionization models with increasing ionization parameters. Furthermore, by combining the [N ii]/[O iii] luminosity ratio with far-infrared continuum flux density ratio in G09.83808, we infer that the gas phase metallicity is already Z ≈ 0.5–0.7 Z⊙. G09.83808 is likely one of the earliest galaxies that has been chemically enriched at the end of reionization.
Transparency in a “Post-Fact” World
Authors: Schnell Sabina
Published: February 2022

What role can government transparency play in a democratic polity in a post-fact and a post-truth world? If the problem is not that citizens lack information about what the government does, but that they filter existing information through pre-existing ideological biases and world views, can government transparency still contribute to better informed citizens and more accountable government? To answer these questions, the article first reviews the critiques of transparency that are particularly salient in a post-fact world: that it reduces trust in government and increases polarization in deliberation. It then discusses three possible solutions: less transparency, tailored transparency, and reasoned transparency. Drawing on deliberative democracy theory, the article concludes that to reclaim the value of transparency, public administration scholars and practitioners need to move from a narrow interpretation of transparency as access to information to a broader, more holistic one, that considers more explicitly the communicative aspects of transparency and its normative foundations.
Mastering Prognostic Tools: An Opportunity to Enhance Personalized Care and to Optimize Clinical Outcomes in Physical Therapy
Authors: Tousignant-Laflamme Yannick , Houle Catherine , Cook Chad , Naye Florian , LeBlanc Annie , Décary Simon
Published: February 2022

In health care, clinical decision making is typically based on diagnostic findings. Rehabilitation clinicians commonly rely on pathoanatomical diagnoses to guide treatment and define prognosis. Targeting prognostic factors is a promising way for rehabilitation clinicians to enhance treatment decision-making processes, personalize rehabilitation approaches, and ultimately improve patient outcomes. This can be achieved by using prognostic tools that provide accurate estimates of the probability of future outcomes for a patient in clinical practice. Most literature reviews of prognostic tools in rehabilitation have focused on prescriptive clinical prediction rules. These studies highlight notable methodological issues and conclude that these tools are neither valid nor useful for clinical practice. This has raised the need to open the scope of research to understand what makes a quality prognostic tool that can be used in clinical practice. Methodological guidance in prognosis research has emerged in the last decade, encompassing exploratory studies on the development of prognosis and prognostic models. Methodological rigor is essential to develop prognostic tools, because only prognostic models developed and validated through a rigorous methodological process should guide clinical decision making. This Perspective argues that rehabilitation clinicians need to master the identification and use of prognostic tools to enhance their capacity to provide personalized rehabilitation. It is time for prognosis research to look for prognostic models that were developed and validated following a comprehensive process before being simplified into suitable tools for clinical practice. New models, or rigorous validation of current models, are needed. The approach discussed in this Perspective offers a promising way to overcome the limitations of most models and provide clinicians with quality tools for personalized rehabilitation approaches.

Impact

Prognostic research can be applied to clinical rehabilitation; this Perspective proposes solutions to develop high-quality prognostic models to optimize patient outcomes.
The impact of COVID-19 on rheumatology training—results from the COVID-19 Global Rheumatology Alliance trainee survey
Authors: Young Kristen , Yeoh Su-Ann , Putman Michael , Sattui Sebastian , Conway Richard , Graef Elizabeth , Kilian Adam , Konig Maximilian , Sparks Jeffrey , Ugarte-Gil Manuel , Upton Laura , Berenbaum Francis , Bhana Suleman , Costello Wendy , Hausmann Jonathan , Machado Pedro , Robinson Philip , Sirotich Emily , Sufka Paul , Yazdany Jinoos , Liew Jean , Grainger Rebecca , Wallace Zachary , Jayatilleke Arundathi
Published: February 2022

Objective

The aim was to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on the clinical experiences, research opportunities and well-being of rheumatology trainees.

Methods

A voluntary, anonymous, Web-based survey was administered in English, Spanish or French from 19 August 2020 to 5 October 2020. Adult and paediatric rheumatology trainees were invited to participate via social media and email. Using multiple-choice questions and Likert scales, the perceptions of trainees regarding the impact of the COVID-19 pandemic on patient care and redeployment, learning and supervision, research and well-being were assessed.

Results

There were 302 respondents from 33 countries, with 83% in adult rheumatology training. An increase in non-rheumatology clinical work was reported by 45%, with 68% of these having been redeployed to COVID-19. Overall, trainees reported a negative impact on their learning opportunities during rheumatology training, including outpatient clinics (79%), inpatient consultations (59%), didactic teaching (55%), procedures (53%), teaching opportunities (52%) and ultrasonography (36%). Impacts on research experiences were reported by 46% of respondents, with 39% of these reporting that COVID-19 negatively affected their ability to continue their pre-pandemic research. Burnout and increases in stress were reported by 50% and 68%, respectively. Physical health was negatively impacted by training programme changes in 25% of respondents.

Conclusion

The COVID-19 pandemic has had a substantial impact on rheumatology training and trainee well-being. Our study highlights the extent of this impact on research opportunities and clinical care, which are highly relevant to future curriculum planning and the clinical learning environment.
Who is Doctor Bauer?: Rematriating a Censored Story on Internment, Wardship, and Sexual Violence in Wartime Alaska, 1941 - 1944
Authors: Guise Holly Miowak
Published: February 2022

This article unites Indigenous women’s voices from oral histories and the archives to connect sexual violence and colonialism and to advance historical discourse on rematriation. Sexual violence, rape, and internment intersected in the Alaskan territory during the Second World War. From 1941 to 1944, the Bureau of Indian Affairs (BIA) employed the physician H.O.K. Bauer to work for the Alaska Indian Service. This physician’s power to enact sexual violence came from his position as an employee for the BIA—an institution that had a history of intimate colonial ties with Indigenous communities. Utilizing Native American and Indigenous Studies methods and ethics, making transparent the relationship between a scholar and elders in the community, and purposefully uncovering some silences while maintaining others allows this analysis of historical sexual violence to prioritize an Indigenous woman elder who advocated for the telling of a story of sexual violence. In doing so, it identifies rematriation as a process that unravels colonial power and restores power to Indigenous women.
Neurocranial bones are key to untangling the sea cow evolutionary tree: osteology of the skull of Sobrarbesiren cardieli (Mammalia: Pan-Sirenia)
Authors: Díaz-Berenguer Ester , Moreno-Azanza Miguel , Badiola Ainara , Canudo José Ignacio
Published: February 2022

The pan-sirenian Bauplan is conservative, probably owing to the constraints of adaptation to an aquatic lifestyle. Gathering morphological data from extinct forms is complex, resulting in poorly resolved phylogenies for stem pan-sirenians. Extant sirenians ossify the falx cerebri and the tentorium cerebelli, membranes of the dura mater of the brain attached to the parietal bone. Nevertheless, these ossifications are not present in some pan-sirenians. The basioccipital bone has received little attention in the literature except for establishing the relative age of individuals. Here, we present new cranial elements and a detailed description of the skull of Sobrarbesiren cardieli, a stem pan-sirenian from the Lutetian of Spain represented by eight individuals; we study its intraspecific variation and palaeoecological implications and explore the evolution of the endocranial structures and the basioccipital bone in pan-sirenians. Six new phylogenetic characters are added to the latest pan-sirenian dataset, resulting in a well-resolved topology where Sobrarbesiren is recovered close to the root, in a clade with Prototherium and Eotheroides aegyptiacum. The basioccipital bone and the ossified endocranial membranes have a phylogenetic signal, and the absence of such endocranial structures represents the plesiomorphic condition for pan-sirenians and is not diagnostic for the family Protosirenidae as previously believed.
Biodiversity and phylogeny of Cocculinidae (Gastropoda: Cocculinida) in the Indo-West Pacific
Authors: Lee Hsin , Puillandre Nicolas , Kano Yasunori , Chen Wei-Jen , Samadi Sarah
Published: February 2022

The family Cocculinidae (Gastropoda: Cocculinida) consists of small, usually colourless benthic limpets living primarily at depths below 100 m, and on decaying plant or animal remains. These habitats are difficult to sample and the knowledge about Cocculinidae species diversity, biogeography, ecology and evolution is therefore poor. To explore the species diversity of the Cocculinidae, we examined 499 specimens collected from 196 sites, mainly explored during expeditions of the ‘Tropical Deep-Sea Benthos’ programme in the Indo-West Pacific (IWP). To propose a species hypotheses, we used an integrated approach to taxonomy in which we combined DNA-based methods, with morphological, geographical and ecological considerations. To classify the species hypotheses into genera, we used a combination of one mitochondrial and two nuclear gene fragments to reconstruct a phylogenetic tree. We then used six morphological characters to diagnose the identified genera. Our results revealed an exceptionally high diversity of IWP Cocculinidae, with 51 species hypotheses that were mostly not assigned to available species names. We also discovered a previously unknown type of copulatory structure in the group. At a higher taxonomic level, we identified ten main clades in the family. Although six of them matched existing genera, four others should be regarded as new genera awaiting formal description.