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Autoimmune encephalidities (AIE) are becoming an increasingly recognized cause of encephalitis. While diagnosis and acute management are well described, information on long-term management and outcomes is limited. Given this, we reviewed 5 years of AIE patients, reporting on chronic management, relapse incidence and possible relapse predictors.
Methods:
We performed a chart review of all patients with non-paraneoplastic AIE presenting to Calgary Neuro-Immunology Clinic and Tom Baker Cancer Centre between 2015 and 2020. Severity of relapse was determined using the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). Variables were assessed with descriptive analysis and/or t-test.
Results:
Patients were followed for a mean of 38.2 months. Outcome data were assessable in 37/38 patients. Relapse rate ranged from 0% (GFAP) to 67% (NMDA), with a mean of 46%. Most relapses (76%) occurred within 3 years. Time to treatment initiation at relapse was significantly shorter than initial presentation (p = 0.0015), and patients had less severe relapses compared to initial presentation (CASE score 5.18 vs 6.53; p = 0.040).
Use of chronic immunotherapy did not appear to impact overall relapse risk, although patients on any immunotherapy at relapse had milder relapses based on ΔCASE (p = 0.0035).
Conclusion:
Relapse was not uncommon (46%) for various AIE subtypes in our cohort, particularly within the first 3 years. Our data enforce the importance of long-term follow-up, which in our study allowed for earlier treatment and less severe relapses compared to initial presentation, as well as the need to further explore which patients would benefit from chronic immunotherapy.
Recurrent respiratory papillomatosis is a benign manifestation of human papillomavirus types 6 and 11 in the respiratory tract. Disease is recurrent, and factors predicting these recurrences and severity of disease are incompletely characterised. This retrospective cohort study examined the relationship of immunosuppression with recurrent respiratory papillomatosis morbidity.
Methods
A retrospective cohort of 97 adult patients with recurrent respiratory papillomatosis treated at a tertiary referral centre from 2005 to 2020 was conducted. Measures assessed included inter-surgical interval, Voice Handicap Index (‘VHI-10’) and anatomical Derkay scores.
Results
Bivariate analyses comparing average inter-surgical interval, Voice Handicap Index and Derkay scores in immunosuppressed and healthy patients were insignificant. When controlling for diabetes mellitus and comparing immunosuppressed to healthy patients, inter-surgical interval and Voice Handicap Index change were insignificant (p = 0.458 and p = 0.465, respectively).
Conclusion
Recurrent respiratory papillomatosis morbidity for immunosuppressed patients did not significantly differ from that of immunocompetent patients.
Necrotising otitis externa is a serious infection with minimal evidence underpinning its management. This review aims to synthesise published evidence of antimicrobial therapies and their outcomes in necrotising otitis externa.
Methods
The review was PROSPERO registered (CRD42022353244) and conducted according to Preferred Reporting Items for Systematic Review and Meta-Analyses (‘PRISMA’) guidelines. A robust search strategy filtered 28 manuscripts into the final review. Antimicrobial therapy and clinical outcome data were extracted and analysed.
Results
Published studies are heterogeneous, with high risk of bias and low certainty. Reporting of outcomes is poor and extremely variable. First-line therapy is most commonly in-patient (95 per cent) empiric fluoroquinolone (68 per cent) delivered intravenously (82 per cent). The lack of granular data and poor outcome reporting mean it is impossible to correlate treatment strategies with clinical outcomes.
Conclusion
Robust, consistent outcome reporting with reference to treatments administered is mandatory, to inform clinical management and optimise future research. Optimal antimicrobial choices and treatment strategies require clarification through prospective clinical trials.
A key clinical feature of necrotising otitis externa is granulation tissue arising from the ear canal, representing epidermal compromise. The aim of this work was to explore the role of epidermal compromise in the aetiology of necrotising otitis externa.
Method
A structured risk factor history was taken from 54 patients diagnosed with necrotising otitis externa between 2017 and 2022. Primary care records were also reviewed.
Results
A total of 94 per cent of patients reported incidents of potential epidermal compromise preceding severe pain onset, including a 35 per cent incidence of ear syringing. A total of 94 per cent of patients were immunosuppressed, including 78 per cent with diabetes. All patients had medical co-morbidities.
Conclusion
This study proposed an aetiological triad for necrotising otitis externa: immunosuppression, infection and epidermal compromise. Epidermal compromise is a potentially modifiable risk factor for necrotising otitis externa. Meticulous primary ear care for older adult, diabetic and immunosuppressed patients is recommended. These populations should never undergo ear syringing and should avoid ear canal trauma and prolonged exposure to moisture.
A cross-sectional and retrospective study of patients with Mycobacterium spp. in a Portuguese tertiary hospital, in 2009 and 2019, was performed to understand better the rise in isolations of nontuberculous mycobacteria (NTM). The number of patients with positive samples for Mycobacterium spp. grew from 56 in 2009 to 83 in 2019. The proportion of NTM rose from 39.3% to 49.4% (P = 0.240), with Mycobacterium avium complex being more frequent in 2009 and Mycobacterium gordonae in 2019, and Mycobacterium tuberculosis complex decreased from 60.7% to 50.6%. Higher age was associated with NTM in both years, and pulmonary disease and immunosuppression were associated with NTM in 2019 (P < 0.05), with weak to moderate correlation (V = 0.231–0.343). The overall rise of NTM, allied to their known capacity to resist antimicrobial therapy, alerts clinicians to the importance of recognising potential risk factors for infection and improving future prevention strategies.
The helminth infection caused by Strongyloides stercoralis is widespread in tropical regions, but rare in European countries. Unfamiliarity with the disease and diagnostic obstacles could contribute to its lethal outcome. Frequent use of corticosteroids during the COVID-19 pandemic could increase its significance. The aim of this retrospective descriptive study was to explore disease patterns and discuss clinical dilemmas in patients with S. stercoralis hyperinfection treated at the University Hospital for Infectious Diseases ‘Dr. Fran Mihaljević’ in Zagreb, Croatia, between 2010 and 2021. Five out of 22 (22.7%) immunosuppressed patients treated due to strongyloidiasis developed hyperinfection. All patients were male, median 64 years; four were immunosuppressed by corticosteroids (although ileum resection could have been the trigger in one) and one by rituximab. The diagnosis was established after a median of 1.5 months of symptom duration, accidentally in all patients, by visualizing the parasite in the gastric/duodenal mucosa in four cases, and bronchial aspirate in one. All patients were cachectic, four out of five had severe hypoalbuminemia and all suffered secondary bacterial/fungal infection. Despite combined antibiotic, antifungal and antihelmintic therapy, three out of five of the patients died, after failing to clear living parasites from stool samples. We can conclude that significant delays in diagnosis and lack of clinical suspicion were observed among our patients with the most severe clinical presentations of strongyloidiasis. Although being beyond diagnostic recommendations for strongyloidiasis, an early upper gastrointestinal endoscopy with mucosal sample analysis could expedite diagnosis in severe, immunosuppressed patients. The persistence of viable parasites in the stool despite antihelmintic therapy should be further investigated.
Necrotising otitis externa is a severe, life-threatening infection. Epidemiological data demonstrate a dramatic rise in reported cases in England from 2002 to 2017. The reasons for this remain elusive.
Methods
A quantitative descriptive study was undertaken using epidemiological data from the Hospital Episode Statistics database. Cases from 2002 to 2017 were compiled and analysed. Four potential theories were explored to explain the rise in incidence.
Results
Within the 16-year period, 7327 necrotising otitis externa cases were reported. Annual necrotising otitis externa incidence increased 1142 per cent within the 16-year period, from 123 recorded cases in 2002 to 1405 cases in 2017. This correlates with an increasing prevalence of diabetes, an ageing population and likely increased physician awareness of necrotising otitis externa. There is insufficient evidence to support antibiotic resistance as a significant associated factor.
Conclusion
Correlation does not imply causation. It is likely that a combination of factors is contributing to the rise in necrotising otitis externa incidence, including increased physician recognition, diagnosis and accurate clinical coding.
1. Heart transplantation is a successful treatment for selected patients with severe heart failure.
2. Left ventricular assist devices are increasingly commonplace as a bridge to transplant.
3. After heart transplantation, invasive monitoring and careful assessment of the cardiac index are important, noting the differences in donor heart physiology.
4. Right ventricular dysfunction should be diagnosed and managed promptly.
5. Immunosuppression is started perioperatively, and these drugs require expert management.
Treatment of coronavirus disease 2019 infection can result in immunosuppression. Rhino-orbital-cerebral mucormycosis is a frequent co-infection, even after recovery.
Methods
An ambispective interventional study was conducted of 41 coronavirus patients with rhino-orbital-cerebral mucormycosis at a tertiary care centre from March to May 2021.
Results
There were 28 males and 13 females with a mean age of 48.2 years (range, 21–68 years). Twelve had long-standing diabetes mellitus and 28 had been recently diagnosed. Thirty-six had received systemic corticosteroids for coronavirus disease 2019. Nasal signs were present in 95 per cent of patients, ophthalmic symptoms and signs in 87 per cent, palatal necrosis in 46.3 per cent, facial signs in 24.3 per cent, nerve palsies in 60.9 per cent, and intracranial involvement in 21.9 per cent. Treatment with amphotericin B was based on clinical features and co-morbidities. Endonasal debridement was performed in 51.2 per cent of patients, total maxillectomy in 14.6 per cent and orbital exenteration in 9.7 per cent. At the last follow up, 37 patients (90.24 per cent) were on antifungal therapy; 4 (9.75 per cent) did not survive.
Conclusion
Early detection may improve survival. Follow up of high-risk patients after coronavirus disease 2019 infection is paramount.
Bone marrow (BM) trephine biopsy (BMB) is a frequent and routine diagnostic investigation, as nicely described in the previous chapters, and is also widely used for follow-up of haematological disorders to judge the effectiveness of therapeutic interventions [1]. In addition, several drugs applied primarily for the treatment of non-haematological disorders may cause serious haematological side effects, such as pancytopaenia, agranulocytosis or anaemia. On occasion, the causative link between the haematological symptoms and the previous drug exposure is not perceived and it is not uncommon for BMB to be obtained in such circumstances without any information of a history of previous drug exposure being made available to the haematopathologist [2].
The assessment of gastrointestinal (GI) specimens from immunosuppressed patients can be challenging, particularly because of the increased likelihood of multiple diseases and of rarer diseases. This chapter documents and presents the wide range of luminal GI pathologies that can develop in the three main groups of immunosuppressed patients, i.e. HIV/AIDS patients, individuals with primary immunodeficiencies, and patients receiving iatrogenic immunosuppression. These GI pathologies include infections, neoplasms, drug-related injuries, and diseases that are more specific to certain groups of immunosuppressed patients such as graft-versus-host disease in bone marrow transplant recipients.
The recognition of specific oesophageal infections and the distinction between gastro-oesophageal reflux disease and rarer forms of oesophagitis are key tasks for gastrointestinal pathologists reading mucosal biopsies. Infections can involve the oesophagus either primarily or as part of a wider process. This chapter highlights their features, discussing in detail the common infections including herpes simplex, cytomegalovirus, and Candida, and summarises the features of the rarer ones. A few additional types of oesophagitis have emerged recently, including eosinophilic oesophagitis and lymphocytic oesophagitis. This chapter reviews the recent literature and will discuss the controversies surrounding some of these new entities. There is an emphasis on the need for correlation between clinical/endoscopic information and microscopic appearances, and there is discussion of supplementary special studies including immunohistochemistry where relevant.
Parasites inflict many costs on their hosts. Understanding host–parasite relationship eco-evolutionary dynamics needs appreciation of how parasites affect individual fitness, survival and reproductive potential, and how they combine to influence population demography, dynamics and viability; also, how these processes drive microevolutionary processes that define natural and sexual selection. We synthesise work on the relationship between the red grouse and its main parasite, a gastrointestinal nematode. At individual level, we show how parasites impose a physiological cost, measured by immunosuppression and increased oxidative stress, and how their impact varies depending on contexts. We describe how parasite infection constrains expression of sexually selected traits and summarise how relationships between parasite, host and environment shape host population demography and dynamics. Genetic analyses in red grouse suggest nematode burden is moderately heritable, underpinned by a potentially large array of genes involved in the immune system, energy balance and broader homeostatic processes. There is no clear association between allele frequencies among populations and differences in nematode burdens. Possibly, beneficial alleles for parasite resistance cannot spread through the population due to the strong diversifying e?ects of gene ?ow and genetic drift.
Cows undergoing a negative energy balance (NEB) often experience a state of immunosuppression and are at greater risk of infectious diseases. The present study aimed to evaluate the impact of a folic acid and vitamin B12 supplement and feed restriction on several immune parameters. Sixteen cows at 45 ± 3 days in milk were assigned to 8 blocks of 2 cows each according to each cow’s milk production in the previous week, and within each block, the cows randomly received weekly intramuscular injections of either saline or 320 mg of folic acid and 10 mg of vitamin B12 for 5 weeks. During week 5, the cows were fed 75% of their ad libitum intake for 4 days. Blood samples were taken before the beginning of the experiment, just before feed restriction and after 3 days of feed restriction, in order to evaluate blood cell populations, the phagocytosis capacity and oxidative burst of polymorphonuclear leukocytes (PMNs), the proliferation of peripheral blood mononuclear cells (PBMCs) and concentrations of non-esterified fatty acids (NEFAs) and β-hydroxybutyrate. The vitamin supplement did not affect any of the tested variables except milk fat and lactose content. Feed restriction reduced milk production and increased the concentration of NEFAs. Feed restriction did not affect blood cell populations but did reduce the percentage of PMN positive for oxidative burst after stimulation with phorbol 12-myristate 13-acetate. The proliferation of PBMCs was reduced when the cell culture medium was supplemented with sera collected during the feed restriction. In conclusion, feed restriction affected the functions of PMN and PBMC and this effect was not prevented by the folic acid and vitamin B12 supplement. These results support the hypothesis that the greater risk of infectious diseases in cows experiencing a NEB is related to impaired immune cell functions by high circulating concentration of NEFAs.
The aim of the present study was to evaluate the prevalence of vitamin B12 (B12) deficiency in kidney transplant recipients (KTR) and its possible association with B12 dietary intake, body adiposity and immunosuppressive drugs. In this cross-sectional study, we included 225 KTR, aged 47·50 (sd 12·11) years, and 125 (56 %) were men. Serum levels of B12 were determined by chemiluminescent microparticle intrinsic factor assay and the cut-off of 200 pg/ml was used to stratify KTR into B12-sufficient or B12-deficient group. B12 dietary intake was evaluated by three 24 h dietary recalls and was considered adequate when ≥2·4 μg/d. Body adiposity was estimated after taking anthropometric measures and using the dual-energy X-ray absorptiometry (DXA) method. B12 deficiency was seen in 14 % of the individuals. B12-deficient group, compared with the B12-sufficient group, exhibited lower intake of B12 (median 2·42 (interquartile range (IQR) 1·41–3·23) v. 3·16 (IQR 1·94–4·55) μg/d, P = 0·04) and higher values of waist circumference (median 96·0 (IQR 88·0–102·5) v. 90·0 (IQR 82·0–100·0) cm, P = 0·04). When the analysis included only women, B12 deficiency was associated with higher total and central body adiposity measurements obtained with anthropometry (BMI, body adiposity index, waist and neck circumferences) and DXA (total and trunk body fat). Among individuals with adequate intake of B12, the deficiency of this vitamin was more frequently seen in those using mycophenolate mofetil (MMF) (17 %) v. azathioprine (2 %), P = 0·01. In conclusion, the prevalence of B12 deficiency in KTR was estimated as 14 % and was associated with reduced intake of B12 as well as higher adiposity, especially in women, and with the use of MMF.
Hepatitis E virus (HEV) is a well-known cause of acute hepatitis. Immunocompromised subjects, including liver transplant recipients, are considered to be at risk for HEV infection, which occasionally follows a chronic course. The diagnosis of HEV infection in these patients must be based on HEV RNA testing, as serology has variable performance. The aim of this study was to assess the prevalence of HEV infection in liver transplant recipients in Greece by means of HEV RNA testing. Liver transplant recipients followed in the sole transplant centre in Greece were prospectively included. HEV RNA was detected by real-time RT-PCR. Positive samples were further analysed using a nested reverse transcription RT-PCR kit, which amplifies a 137-nucleotide sequence within the ORF2/ORF3 overlapping region to detect the HEV genotype and perform phylogenetic analysis. The mean age of the included patients (n = 76) was 54 years. The most common indication for liver transplantation was viral hepatitis (57%). The majority of the patients (75%) received a calcineurin inhibitor as part of their immunosuppressive regimen and had normal liver enzymes. HEV RNA was found positive in only 1/76 (1.3%) patient. Phylogenetic analysis showed that the sequence clustered into the HEV genotype 3 clade. This patient experienced an acute hepatitis flare, which nonetheless did not become chronic. The prevalence of HEV infection in liver transplant recipients in Greece is similar (1.3%) to that reported previously in other countries. Transplant physicians should be aware of this condition and its associated consequences.
During microbial infections, both innate and adaptive immunity are activated. Viruses and bacteria usually induce an acute inflammation in the first setting of infection, which helps the eliciting an effective immune response. In contrast, macroparasites such as helminths are a highly successful group of invaders known to be capable of maintaining a chronic infestation with the minimum instigation. Undoubtedly, generating such an immunoregulatory environment requires the exploitation of various immunosuppressive mechanisms to debilitate host immunity supporting their survival and replication. Several mechanisms have been recognized whereby helminths prolong their infections including an increase of immunoregulatory cells, inhibition of Th1 or Th2 responses, targeting pattern recognition receptors (PRRs) and lowering the immune cells quantity via induction of apoptosis. Apoptosis is a programmed intracellular process involving a series of consecutive downstream signalling event evolved to cell death. It plays a pivotal role in several immunological reactions in particular deletion of autoreactive immune cells. Helminth-triggered apoptosis in immune cells exhausts host immunity, which paves the way for generating a permissive environment and chronic infection. This review provides a compilation of recent investigations discussing the apoptotic mechanisms exploited by different worms and the immunological consequences of immune cell death. Finally, the anti-cancer effects of some worm-derived molecules due to their apoptotic effects are discussed, highlighting as potentially druggable candidates to combat cancer.
Poultry can be exposed to different kinds of immunosuppressive agents that impair health and welfare by destroying innate and acquired immunity leading to diminished genetic potential of poultry for efficient production. Immunosuppression is a condition characterised by humoral and cellular immune dysfunction that leads to increased susceptibility to secondary infections and vaccine failure. Immune dysfunction at the humoral level is largely due to change in soluble factors mediated by complement or chemokines for innate immunity or due to alterations in antibodies or cytokines for adaptive immunity. In contrast, immune dysfunctions at cellular levels include alterations in neutrophils, monocyte/macrophage, and natural killer cells for innate immunity or changes in B or T lymphocytes for adaptive immunity. In poultry, stress-induced immunosuppression is manifested by failure in vaccination, and increased morbidity and mortality of flocks. Immunosuppressive agents can have cytolytic effects on lymphocyte populations leading to atrophied and depleted lymphoid organs. Immunosuppression can be due to infectious agents or non-infectious agents or due to a combination of them. At present, several modern cellular and molecular approaches are being used to determine the status of the immune system during stress and disease. Comprehensive methodologies for the evaluation of immunosuppression by combined non-infectious and infectious aetiologies have not found general application. Currently, investigations are being developed in order to detect genetic expression of immunologic mediators and receptors by microarray technology. It is likely that this new technique will initiate the development of new strategies for the control and prevention of immunosuppression in poultry. A long term immunosuppression preventive approach involves genetic selection for resistance to immunosuppressive diseases. In general, intervention approaches for immunosuppressive diseases largely rely on minimising stress, reducing exposure to infectious agents through biosecurity, and increasing immune responses by vaccination against immunosuppressive agents.