Hirschsprung-associated inflammatory bowel disease: A multicenter study from the APSA Hirschsprung disease interest group

Background/PurposeA small number of Hirschsprung disease (HD) patients develop inflammatory bowel disease (IBD)-like symptoms after pullthrough surgery. The etiology and pathophysiology of Hirschsprung-associated IBD (HD-IBD) remains unknown. This study aims to further characterize HD-IBD, to identify potential risk factors and to evaluate response to treatment in a large group of patients.MethodsRetrospective study of patients diagnosed with IBD after pullthrough surgery between 2000 and 2021 at 17 institutions. Data regarding clinical presentation and course of HD and IBD were reviewed. Effectiveness of medical therapy for IBD was recorded using a Likert scale.ResultsThere were 55 patients (78% male). 50% (n = 28) had long segment disease. Hirschsprung-associated enterocolitis (HAEC) was reported in 68% (n = 36). Ten patients (18%) had Trisomy 21. IBD was diagnosed after age 5 in 63% (n = 34). IBD presentation consisted of colonic or small bowel inflammation resembling IBD in 69% (n = 38), unexplained or persistent fistula in 18% (n = 10) and unexplained HAEC >5 years old or unresponsive to standard treatment in 13% (n = 7). Biological agents were the most effective (80%) medications. A third of patients required a surgical procedure for IBD.ConclusionMore than half of the patients were diagnosed with HD-IBD after 5 years old. Long segment disease, HAEC after pull through operation and trisomy 21 may represent risk factors for this condition. Investigation for possible IBD should be considered in children with unexplained fistulae, HAEC beyond the age of 5 or unresponsive to standard therapy, and symptoms suggestive of IBD. Biological agents were the most effective medical treatment.Level of EvidenceLevel 4     

死亡结构域相关蛋白及其在宫颈病变中的研究进展

宫颈癌对妇女健康构成严重威胁,人乳头瘤病毒感染与宫颈病变及宫颈癌的发生密切相关。关于宫颈癌发生发展的机制仍在研究中。近年研究发现一种多功能核蛋白,即死亡结构域相关蛋白(death domain associated protein,Daxx),其与细胞内蛋白或病毒蛋白相互作用,参与调节细胞凋亡、转录调控、抗病毒等细胞活动,在不同途径中发挥不同的生理或病理作用。通过对Daxx功能及其作用机制的研究有助于进一步阐明宫颈癌发生发展的机制,有助于发现新的预防和治疗方法。综述Daxx的一般特性和研究现况及其在宫颈病变的研究进展。     

Utilization and Complications of Central Venous Access Devices in Oncology Patients

Purpose: To describe how central venous access devices (CVADs) are utilized for ambulatory oncology patients and to evaluate the rate of complications. Method: Single institution retrospective study of oncology patients with CVADs who received systemic treatment at the Walker Family Cancer Centre (WFCC) between 1 January and 31 December 2018. Results: A total of 480 CVADS were placed in 305 patients, of which 408 (85%) were peripherally inserted central catheters (PICCs) and 72 (15%) were implanted vascular access devices (PORTs). The incidence of early and late complications was 9% and 24%, respectively. For the entire cohort, the rate of venous thromboembolism (VTE) was 16%, of which 9% were CVAD-related thrombosis (CRTs) and 7% were distant VTE. The CRT rates were similar for PICCs and PORTs (9% vs. 7%). A total of 6% of CVADs were complicated by infection (i.e., localized infections and bacteremia), with a total infection rate of 0.43 and 0.26 per 1000 indwelling days for PICCs and PORTs, respectively. The incidence of central line associated bloodstream infections (CLABSI) was greater for PICCs than PORTs, at a rate of 0.22 compared with 0.08 per 1000 indwelling days, respectively. The premature catheter removal rate was 26% for PICCs and 18% for PORTs. PORTs required more additional hospital visits. Conclusions: PICCs were utilized more frequently than PORTs and had a higher rate of premature removal. The rates of VTE and CRT were similar for both CVAD types. PORTs had a lower rate of infection per 1000 indwelling days. However, the management of PORT related complications required more visits to the hospital and oncology clinic.     

Immune Checkpoint Inhibitor Toxicities

Immune checkpoint inhibitors are molecules that increase the endogenous immune response against tumors. They have revolutionized the field of oncology. Since their initial approval for the treatment of advanced melanoma, their use has expanded to the treatment of several other advanced cancers. Unfortunately, immune checkpoint inhibitors have also been associated with the emergence of a new subset of autoimmune-like toxicities, known as immune-related adverse events. These toxicities differ depending on the agent, malignancy, and individual susceptibilities. Although the skin and colon are most commonly involved, any organ may be affected, including the liver, lungs, kidneys, and heart. Most of these toxicities are diagnosed by excluding other secondary infectious or inflammatory causes. Corticosteroids are commonly used for treatment of moderate and severe immune-related adverse events, although additional immunosuppressive therapy may occasionally be required. The occurrence of immune-related toxicities may require discontinuation of immunotherapy, depending on the specific toxicity and its severity. In this article, we provide a focused review to familiarize practicing clinicians with this important topic given that the use of immune checkpoint inhibitors continues to increase.     

Effectiveness of the 10-valent pneumococcal conjugate vaccine against radiographic pneumonia among children in rural Bangladesh: A case-control study

BackgroundPneumococcal conjugate vaccine (PCV) effectiveness against radiographic pneumonia in South Asia is unknown. Bangladesh introduced PCV10 in 2015 using a three dose primary series (3 + 0). We sought to measure PCV10 effectiveness for two or more vaccine doses on radiographic pneumonia among vaccine-eligible children in rural Bangladesh.MethodsWe conducted a matched case-control study over two years from 2015 to 2017 using clinic and community controls in three subdistricts of Sylhet, Bangladesh. Cases were vaccine eligible 3–35 month olds at Upazila Health Complex outpatient clinics with World Health Organization-defined radiographic primary endpoint pneumonia (radiographic pneumonia). Clinic controls were matched to cases within a one week time window by age, sex, and clinic and had an illness unlikely to be Streptococcus pneumoniae; community controls were healthy and similarly matched within a one week time window by age and sex, and distance from the clinic. We estimated adjusted vaccine effectiveness (aVE) using conditional logistic regression.ResultsWe matched 1262 cases with 2707 clinic and 2461 community controls. Overall, aVE using clinic controls was 21.4% (95% confidence interval, −0.2%, 38.4%) for ≥2 PCV10 doses and among 3–11 month olds was 47.3% (10.5%, 69.0%) for three doses. aVE increased with higher numbers of doses in clinic control sets (p = 0.007). In contrast, aVE using community controls was 7.6% (95% confidence interval, −22.2%, 30.0%) for ≥2 doses. We found vaccine introduction in the study area faster and less variable than expected with 75% coverage on average, which reduced power. Information bias may also have affected community controls.ConclusionsClinic control analyses show PCV10 prevented radiographic pneumonia in Bangladesh, especially among younger children receiving three doses. While both analyses were underpowered, community control enrollment – compared to clinic controls – was more difficult in a complex, pluralistic healthcare system. Future studies in comparable settings may consider alternative study designs.     

Infecciones de transmisión sexual en hombres internos en prisión: riesgo de desarrollo de nuevas infecciones

ObjectiveTo measure incidence and main risk factors related to sexually transmitted infections (STIs) in Daroca Prison (Zaragoza, Spain).MethodA retrospective cohort study (2005-2013) to measure the incidence of STI and a cross-sectional study to measure risk factors.ResultsOf the 203 inmates, 79 developed an STI, 37 had a previous STI, 55.2% lacked knowledge on STI prevention, and 28.9% showed behaviours unfavourable for STI prevention. The incidence rate was 6.5 STIs per 1,000 inmates-year. The most frequent STIs were hepatitis B (39.7%), Ureaplasma urealyticum (19.1%), herpes simplex (16.2%) and HIV (8.8%). The risk (hazard ratio, HR) of acquiring a new STI was significantly higher in inmates with a history of previous STI (HR = 2.61; 95%CI: 1.01 to 6.69), and was at the limit of significance for non-preventive behaviour (HR = 2.10; 95%CI: 0.98 to 4.53), but not in knowledge related to STIs (HR = 1.33; 95%CI: 0.58 to 3.07).ConclusionThe most important risk factors in prison are behaviours related to STIs and previous history of STIs. Other factors are being a repeat offender, injecting drug use, or being in a methadone programme. Health personnel and peer education can facilitate prevention and control.     

Diffuse skin rash in tropical areas: Dengue fever or COVID-19?

There have been several clinical manifestations associated with SARS-CoV-2 infection since 2019, including dermatological signs and symptoms. In this article, the authors report a case of a previously healthy patient with COVID-19 who was mistakenly diagnosed with dengue fever due to a skin rash. By the time the patient's investigation was initiated, Joinville (Santa Catarina, Brazil) had approximately 5,000 confirmed cases of dengue fever and 1,700 cases of COVID-19 in 2020. Thus, the authors emphasize that in endemic regions such as Brazil, the two diseases must be considered until proven otherwise. Finally, the authors warn of the possibility of co-infection with these two viruses in regions that are facing both epidemics at the same time.     

Photodynamic therapy to control microbial biofilms

Microorganisms thrive in well-organized biofilm ecosystems. Biofilm-associated cells typically show increased resistance to antibiotics and contribute significantly to treatment failure. This has prompted investigations aimed at developing advanced and novel antimicrobial approaches that could effectively overcome the shortcomings associated with conventional antibiotic therapy. Studies are ongoing to develop effective curative strategies ranging from the use of peptides, small molecules, nanoparticles to bacteriophages, sonic waves, and light energy targeting various structural and physiological aspects of biofilms. In photodynamic therapy, a light source of a specific wavelength is used to irradiate non-toxic photosensitizers such as tetrapyrroles, synthetic dyes or, naturally occurring compounds to generate reactive oxygen species that can exert a lethal effect on the microbe especially by disrupting the biofilm. The photosensitizer preferentially binds to and accumulates in the microbial cells without causing any damage to the host tissue. Currently, photodynamic therapy is increasingly being used for the treatment of oral caries and dental plaque, chronic wound infections, infected diabetic foot ulcers, cystic fibrosis, chronic sinusitis, implant device-associated infections, etc. This approach is recognized as safe, as it is non-toxic and minimally invasive, making it a reliable, realistic, and promising therapeutic strategy for reducing the microbial burden and biofilm formation in chronic infections. In this review article, we discuss the current and future potential strategies of utilizing photodynamic therapy to extend our ability to impede and eliminate biofilms in various medical conditions.