Pathogen infections and primary biliary cholangitis

Primary biliary cholangitis (PBC) is a multi-factorial disease caused by the interaction of both genetic predisposition and environmental triggers. Bacterial infection has been investigated most intensively, both epidemiologically and experimentally, as a prime environmental aetiology in PBC. The association of recurrent history of urinary tract infection (UTI) with PBC has been frequently confirmed by several large-scale, case–control studies, despite variation in geographic area or case-finding methods. Escherichia coli is a predominant pathogen in most cases with UTI. Animal studies and molecular mimicry analysis between the human and E. coli E2 subunit of the 2-oxo-acid dehydrogenase complexes demonstrated that E. coli infection is a key factor in breaking immunological tolerance against the mitochondria, resulting in the production of anti-mitochondrial autoantibodies (AMA), the disease-specific autoantibodies of PBC. Novosphingobium aromaticivorans, a ubiquitous xenobiotic-metabolizing bacterium, is another candidate which may be involved in the aetiology of PBC. Meanwhile, improved environmental hygiene and increased prevalence of PBC, especially in males, may argue against the aetiological role of bacterial infection in PBC. Multiple mechanisms can result in the loss of tolerance to mitochondrial autoantigens in PBC; nonetheless, bacterial infection is probably one of the dominant pathways, especially in female patients. Notably, there is a rising prevalence of male patients with PBC. With increasing exposure to environmental xenobiotics in both genders, studies directed towards identifying the environmental culprit with systematically designed case–control studies are much needed to further determine the environmental factors and role of bacterial infections in PBC.     

Pathogens and autoimmune hepatitis

Autoimmune hepatitis (AIH) is a severe form of hepatitis resulting in the autoimmune-mediated destruction of the liver parenchyma. Whereas many of the immunopathogenic events have been elucidated and some of the drivers of the disease have been identified, little is known about the aetiology of the disease. There are certain risk factors, such as particular human leucocyte antigen (HLA) haplotypes, that enhance the susceptibility for AIH or influence the severity of the disease. However, as for many other autoimmune diseases, the mere presence of such risk factors does not warrant the occurrence of the disease. Not all individuals carrying risk factors develop AIH, and not all patients with AIH are carriers of high-risk alleles. Thus, additional environmental factors need to be considered as triggers for AIH. Environmental factors include diet, sunlight exposure, stress, medication and hygiene, as well as pathogen infections and vaccinations. This review discusses if pathogens should be considered as triggers for the initiation and/or propagation of AIH.     

Emerging Issues With Diagnosis and Management of Fungal Infections in Solid Organ Transplant Recipients

Invasive fungal infections (IFIs) are being increasingly recognized in solid organ transplant (SOT) recipients, and delayed diagnosis can lead to graft loss and death. Therefore, there is a low threshold for prophylaxis and early initiation of empiric antifungal treatment, in this patient population. Meanwhile, the increasing consumption of antifungals is associated with high cost, medication toxicities and the emergence of resistance in Candida species, all of which call for rational use of antifungal agents. The implementation of fungal biomarkers, molecular diagnostic methods and direct detection of volatile fungal metabolites in breath samples could lead to faster diagnosis, early appropriate treatment and improved clinical outcomes, but also aid in the de‐escalation of antifungal treatment. Those novel diagnostic modalities need to be validated specifically in SOT recipients. Infectious diseases consultation can contribute to optimization of care through prompt initiation and appropriate modification of antifungal treatment, management of medication toxicities and drug‐drug interactions, as well as source control. In this review, we conceptually summarize recent advances in the diagnosis and management of IFI in SOT recipients, and highlight the importance of early diagnostic tools and good stewardship of antifungal drugs.     

Pin tract infection of operatively treated supracondylar fractures in children: long-term functional outcomes and anatomical study

Purpose

The purpose of our study was to determine the long-term functional outcomes of pin tract infection after percutaneous pinning of displaced supracondylar humeral fractures in children, and to evaluate the potential for intracapsular pin placement based on pin configuration in cadaveric elbows.

Methods

We conducted a retrospective review of all patients requiring percutaneous pinning in a single institution over a 19-year period. The functional outcome assessment consisted of a telephone interview using the Disabilities of the Arm, Shoulder and Hand (DASH)] Outcome Measure and the Patient-Rated Elbow Evaluation (PREE) questionnaires. The risk of intracapsular pin placement was studied in cadaveric elbows for the three most common pin configurations: divergent lateral, parallel lateral, and medial and lateral crossed pins.

Results

Of 490 children, 21 (4.3 %) developed pin tract infection. There were 15 (3.1 %) superficial and six (1.2 %) deep infections (osteomyelitis and septic arthritis). Both DASH and PREE scores were excellent at a mean of 18 years post-surgery. The risk of intracapsular pin placement using parallel lateral pins was found to be greater (p < 0.05) than either crossed or divergent lateral pinning configurations.

Conclusions

Most infections after pinning of supracondylar humerus fractures are superficial and can be managed with pin removal, oral antibiotics, and local wound care. Septic arthritis and osteomyelitis are rare complications; when they do occur, they seem to be associated with parallel lateral pin configuration, though a causal relationship could not be established from the current study. Satisfactory long-term outcomes of these deep infections can be expected when treated aggressively with surgical debridement and intravenous antibiotics.     

Single tracheal inoculation of Aspergillus fumigatus conidia induced aspergillosis in juvenile falcons (Falco spp.)

Aspergillosis is a common and life-threatening respiratory disease in raptors with acute and chronic courses. Among raptors, gyrfalcons (Falco rusticolus) and their hybrids are often declared to be highly susceptible with juvenile individuals being the most susceptible. However, species- and age-specific experimental studies are lacking and minimal infective doses (IDs) for Aspergillus spp. conidia are unknown.Therefore, 8-week-old, healthy gyr-hybrid falcons (F. rusticolus X F. cherrug) (N?=?18) were experimentally infected with Aspergillus fumigatus using a single intratracheal inoculation with varying dosages of conidia (10² to 10⁷ conidia). Over 28 days, clinical signs were monitored as well as haematological and serological parameters. Following euthanasia, necropsy, histopathology, bacteriology, and mycology were performed. Re-isolated fungi were compared to the inoculum using microsatellite length polymorphisms. During the trial, clinical signs and dyspnoea correlated significantly with the ID. Necropsy revealed fungal lesions in the upper and lower airways of 10/18 inoculated falcons, but not in the control birds. In 9/18 inoculated falcons, fungal granulomas were confirmed in histopathology and A. fumigatus was re-isolated from these granulomas. Except one nasal isolate all re-isolated fungal strains were identical to the inoculum strain. Based on mycology and histopathology a minimal ID of 50% was calculated to be MID_{50% (±S.E.)}?=?10^4.52±0.67 for a single tracheal inoculation of A. fumigatus conidia. This study demonstrates for the first time that a single exposure is able to cause acute aspergillosis in juvenile falcons.