The precise role of periostin, an extra-cellular matrix protein, in inflammatory bowel disease (IBD) is unclear. Here, we investigated periostin in paediatric IBD including its relationship with ...disease activity, clinical outcomes, genomic variation and expression in the colonic tissue. Plasma periostin was analysed using ELISA in 144 paediatric patients and 38 controls. Plasma levels were assessed against validated disease activity indices in IBD and clinical outcomes. An immuno-fluorescence for periostin and detailed isoform-expression analysis in the colonic tissue was performed in 23 individuals. We integrated a whole-gene based burden metric 'GenePy' to assess the impact of variation in POSTN and 23 other genes functionally connected to periostin. We found that plasma periostin levels were significantly increased during remission compared to active Crohn's disease. The immuno-fluorescence analysis demonstrated enhanced peri-cryptal ring patterns in patients compared to controls, present throughout inflamed, as well as macroscopically non-inflamed colonic tissue. Interestingly, the pattern of isoforms remained unchanged during bowel inflammation compared to healthy controls. In addition to its role during the inflammatory processes in IBD, periostin may have an additional prominent role in mucosal repair. Additional studies will be necessary to understand its role in the pathogenesis, repair and fibrosis in IBD.
Authors' reply to Sabu et al Bajpai, Vijeta; Batra, Akshay; Sarode, Rahul
Cancer research, statistics, and treatment (Online),
04/2023, Letnik:
6, Številka:
2
Journal Article
Neuromyelitis optica (NMO) is an autoimmune demyelinating disease preferentially targeting the optic nerves and spinal cord. Plasmapheresis (PP) is an effective adjunct therapy in severe NMO attacks. ...The recommended minimum plasma volume to be treated per session of PP is equivalent to total plasma volume (TPV) of the patient.
To study the effect of lower plasma volume treated in patients with NMO on clinical efficacy of plasmapheresis in comparison to minimum recommended volume.
This retrospective study was done on acute NMO patients who were managed with PP at our center. Patients who had 5 sessions of PP, spread over 10 days, were included. Clinical outcome was defined as per predefined criteria.
24 patients who underwent PP for acute NMO met our inclusion criteria. Females (age; mean (SD) 33.7 (11.2) years) were more common (
= 18). The minimum recommended plasma volume (PV) that was supposed to be treated per patient during entire acute therapeutic period was 195.5 (14.6) mL per kilogram-body-weight (kg-bw). We treated lower plasma volume (mean (SD) 112.7 (17.0) mL per kg-bw); the difference was significant (
< 0.05). The volume treated was same across the gender (
> 0.05). Significant clinical improvement was observed in 79% of patients (
= 19) after 6 months. There were no significant differences in volume of plasma treated, between patients who had moderate and marked improvement; also, who did, and did not have significant clinical improvement (
> 0.05; for both).
Plasmapheresis is a safe and efficient add-on therapy in NMO, especially in steroid-resistant cases. Although the volumes of plasma treated during acute plasmapheresis were less than recommended minimum volumes, majority of patients had significant clinical improvement.
Background: Bloodstream infections are the major cause of life-threatening complications in febrile neutropenic patients with hematolymphoid malignancies. The prevalence of these bloodstream ...infections is 20-30%. The bacteria that are most frequently isolated belong to Enterobacterales and Pseudomonas species. The overall infection attributable mortality rate is 21.5%.
Objective: The main objective of this study was to evaluate the prevalence of bloodstream infections with multidrug-resistant (MDR) organisms in adult patients with hematolymphoid malignancies and febrile neutropenia at our newly established tertiary cancer center.
Materials and Methods: This was a retrospective observational study conducted between June 2018 and April 2020 in the Departments of Microbiology and Medical Oncology at the Homi Bhabha Cancer Hospital/Mahamana Pandit Madan Mohan Malviya Cancer Center (under the aegis of the Tata Memorial Hospital, Mumbai), a tertiary oncology cancer center in Varanasi, Uttar Pradesh. We analyzed the data of all adult febrile neutropenic patients with hematolymphoid malignancies, specifically the blood culture positivity, isolated bacterial organisms, their antimicrobial resistance spectrum and the overall mortality.
Results: There were 1670 adult patients with hematolymphoid malignancies who visited the outpatient and inpatient departments over a period of 2 years; of them, 307 patients had febrile neutropenia and their blood cultures were sent to the microbiology laboratory. The mean age was 41.8 ± 16.7 (range, 15-82) years, with a male predominance (186, 61%). The most common clinical diagnosis was acute lymphoid leukemia (80, 26.1%), followed by non-Hodgkin's lymphoma (76, 24.8%). Microbiologically confirmed bloodstream infections were present in 74 (24.1%) patients. Forty-seven (64.0%) patients had healthcare-associated infections, whereas 27 (36.4%) had community-acquired infections. Common organisms isolated were Escherichia coli (28, 36.4%), Klebsiella pneumoniae (12, 15.6%), Pseudomonas species (8, 10.8%), coagulase-negative Staphylococcus species (7, 9.4%), Staphylococcus aureus (5, 6.5%), Streptococcus species (4, 5.2%), Enterococcus species (3, 3.9%), Citrobacter koseri (3, 3.9%), Acinetobacter baumannii (2, 2.6%), Aeromonas species, and Shewanella putrefaciens (1, 1.3%). Of the 55 Gram-negative bloodstream infections, 21 (38.2%) were carbapenem-resistant. Of the 19 Gram-positive bloodstream infections, there were a significant proportion of resistant organisms noted as well, including methicillin-resistant Staphylococcus aureus in 15.8% (3/19; 60% 3/5 of the Staphylococcus aureus infections) and vancomycin-resistant Enterococcus (VRE) in 5.3% (1/19; 33.3% 1/3 of all enterococcal infections). Overall, the mortality rate was 32.6% (100/307). The mortality rate was greater in patients with MDR bloodstream infections (20/47, 42.5%) compared to that in patients with non-MDR bloodstream infections (3/27, 11.2%; P = 0.004).
Conclusion: The high prevalence of MDR Gram-negative and MRSA bloodstream infections in our patients is an alarming situation in a newly established tertiary cancer center. Rigorous infection control policies, patient education, and doctor and support staff education are important components of antibiotic stewardship and constitute important steps to prevent MDR bloodstream infections and reduce sepsis-related mortality.
Monogenic inflammatory bowel disease (IBD) comprises rare Mendelian causes of gut inflammation, often presenting in infants with severe and atypical disease. This study aimed to identify clinically ...relevant variants within 68 monogenic IBD genes in an unselected pediatric IBD cohort.
Whole exome sequencing was performed on patients with pediatric-onset disease. Variants fulfilling the American College of Medical Genetics criteria as "pathogenic" or "likely pathogenic" were assessed against phenotype at diagnosis and follow-up. Individual patient variants were assessed and processed to generate a per-gene, per-individual, deleteriousness score.
Four hundred one patients were included, and the median age of disease-onset was 11.92 years. In total, 11.5% of patients harbored a monogenic variant. TRIM22-related disease was implicated in 5 patients. A pathogenic mutation in the Wiskott-Aldrich syndrome (WAS) gene was confirmed in 2 male children with severe pancolonic inflammation and primary sclerosing cholangitis. In total, 7.3% of patients with Crohn's disease had apparent autosomal recessive, monogenic NOD2-related disease. Compared with non-NOD2 Crohn's disease, these patients had a marked stricturing phenotype (odds ratio 11.52, significant after correction for disease location) and had undergone significantly more intestinal resections (odds ratio 10.75). Variants in ADA, FERMT1, and LRBA did not meet the criteria for monogenic disease in any patients; however, case-control analysis of mutation burden significantly implicated these genes in disease etiology.
Routine whole exome sequencing in pediatric patients with IBD results in a precise molecular diagnosis for a subset of patients with IBD, providing the opportunity to personalize therapy. NOD2 status informs risk of stricturing disease requiring surgery, allowing clinicians to direct prognosis and intervention.
Pediatric inflammatory bowel disease (pIBD) is a chronic heterogeneous disorder. This study looks at the burden of common and rare coding mutations within 41 genes comprising the NOD signaling ...pathway in pIBD patients. 136 pIBD and 106 control samples underwent whole-exome sequencing. We compared the burden of common, rare and private mutation between these two groups using the SKAT-O test. An independent replication cohort of 33 cases and 111 controls was used to validate significant findings. We observed variation in 40 of 41 genes comprising the NOD signaling pathway. Four genes were significantly associated with disease in the discovery cohort (BIRC2 p = 0.004, NFKB1 p = 0.005, NOD2 p = 0.029 and SUGT1 p = 0.047). Statistical significance was replicated for BIRC2 (p = 0.041) and NOD2 (p = 0.045) in an independent validation cohort. A gene based test on the combined discovery and replication cohort confirmed association for BIRC2 (p = 0.030). We successfully applied burden of mutation testing that jointly assesses common and rare variants, identifying two previously implicated genes (NFKB1 and NOD2) and confirmed a possible role in disease risk in a previously unreported gene (BIRC2). The identification of this novel gene provides a wider role for the inhibitor of apoptosis gene family in IBD pathogenesis.
Background
Subcutaneous emphysema is a condition where air becomes trapped under the skin, typically resulting from surgery or skin trauma. It is mostly localized and its occurrence in blood donors ...is exceedingly rare. Phlebotomy poses minimal risk of subcutaneous emphysema, but procedural errors may lead to such complications.
Study Design and Method
This is a case report of 29‐year‐old repeat blood donor who experienced subcutaneous emphysema following blood donation. The donor was vigorously squeezing sponge ball during donation resulting in displacement of the needle which required readjustment. Post‐donation, the donor reported a crackling sensation and mild swelling near phlebotomy site. Non‐contrast computed tomography (NCCT) scans confirmed subcutaneous emphysema, attributing its development to air trapping in subcutaneous plane due to ball valve mechanism.
Results
Computed tomography (CT) imaging revealed subcutaneous emphysematous changes in the right cubital region and no evidence of hematoma. The swelling spontaneously subsided in 10–12 days without any intervention. The case underscores the importance of differentiating subcutaneous emphysema from common complications like hematoma.
Discussion
Subcutaneous emphysema in blood donors is exceptionally rare but should be managed with clear communication. Donors should be reassured that the condition, although rare, is benign and self‐resolving. Healthcare providers should be equipped to handle such rare complications, offering appropriate care and documenting incidents for future prevention.
Abstract Introduction Childhood cancers are a significant global health concern, particularly in low‐ and middle‐income countries (LMICs), where over 80% of childhood cancer patients reside. In ...India, acute myeloid leukemia (AML) constitutes a significant portion of childhood cancers; however, the data on the cost‐effectiveness of childhood AML treatment in India and other LMICs remain limited. Methods The study focused on children (<15 years of age) diagnosed with AML at a tertiary care cancer center in North India. Data, including treatment outcome, treatment‐related morbidity, mortality, and costs were retrospectively collected from the electronic medical record and hospital database. Cost‐effectiveness was assessed using disability‐adjusted life years (DALY) averted in relation to the country‐specific cost‐effectiveness threshold. Results Among 59 AML patients, treatment‐related high mortality rates, abandonment, and limited access to bone marrow transplantation were notable challenges. Intensive chemotherapy resulted in substantial sepsis‐related complications, with treatment‐related mortality reaching 30%. The 3‐year event‐free survival and overall survival of the 43 patients who received intensive therapy were 24.5% ± 7.6% and 27.9% ± 8.3%, respectively. Despite these challenges, treating childhood AML was still found to be cost‐effective. The total cost per newly diagnosed patient treated with curative intent was $4454. Cost per DALY averted accounted for 24% of the gross domestic product (GDP) per capita, rendering the treatment to be cost‐effective with a stringent cost‐effectiveness threshold utilized. Conclusion The study underscores the challenges faced while treating childhood AML in LMICs, including treatment‐induced high sepsis‐related mortality and abandonment. Despite these challenges, it remains cost‐effective to treat childhood AML in India. Future efforts should focus on reducing treatment‐related morbidity and mortality to further improve outcomes and cost‐effectiveness.
Ultrashort bowel syndrome (USBS) is a group of heterogeneous disorders where the length of small bowel is less than 10 cm or 10% of expected for the age. It is caused by massive loss of the gut which ...in the neonatal period can be a result of vanishing gastroschisis or surgical resection following mid-gut volvulus, jejunoileal atresia and/or extensive necrotising enterocolitis. The exact prevalence of USBS is not known although there is a clear trend towards increasing numbers because of increased incidence and improved survival. Long-term parenteral nutrition (PN) is the mainstay of treatment and is best delivered by a multidisciplinary intestinal rehabilitation team. Promoting adaptation is vital to improving long-term survival and can be achieved by optimising feeds, reducing intestinal failure liver disease and catheter-related bloodstream infections. Surgical techniques that can promote enteral tolerance and hence improve outcome include establishing intestinal continuity and bowel lengthening procedures. The outcome for USBS is similar to patients with intestinal failure due to other causes and only a small proportion of children who develop irreversible complications of PN and will need intestinal transplantation. In this review, we will summarise the available evidence focusing particularly on the epidemiology, management strategies and outcome.
The Pediatric Crohn Disease Morbidity Index (PCD‐MI) Ashton, James J.; Gurung, Abhilasha; Davis, Cai ...
Journal of pediatric gastroenterology and nutrition,
July 2023, Letnik:
77, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Background/Objective:
Heterogeneity and chronicity of Crohn disease (CD) make prediction of outcomes difficult. To date, no longitudinal measure can quantify burden over a patient’s disease course, ...preventing assessment and integration into predictive modeling. Here, we aimed to demonstrate the feasibility of constructing a data driven, longitudinal disease burden score.
Methods:
Literature was reviewed for tools used in assessment of CD activity. Themes were identified to construct a pediatric CD morbidity index (PCD‐MI). Scores were assigned to variables. Data were extracted automatically from the electronic patient records at Southampton Children’s Hospital, diagnosed from 2012 to 2019 (inclusive). PCD‐MI scores were calculated, adjusted for duration of follow up and assessed for variation (ANOVA) and distribution (Kolmogorov‐Smirnov).
Results:
Nineteen clinical/biological features across five themes were included in the PCD‐MI including blood/fecal/radiological/endoscopic results, medication usage, surgery, growth parameters, and extraintestinal manifestations. Maximal score was 100 after accounting for follow‐up duration. PCD‐MI was assessed in 66 patients, mean age 12.5 years. Following quality filtering, 9528 blood/fecal test results and 1309 growth measures were included. Mean PCD‐MI score was 14.95 (range 2.2–32.5); data were normally distributed (P = 0.2) with 25% of patients having a PCD‐MI < 10. There was no difference in the mean PCD‐MI when split by year of diagnosis, F‐statistic 1.625, P = 0.147.
Conclusions:
PCD‐MI is a calculatable measure for a cohort of patients diagnosed over an 8‐year period, integrating a wide‐range of data with potential to determine high or low disease burden. Future iterations of the PCD‐MI require refinement of included features, optimized scores, and validation on external cohorts.
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