Survival rate of odontogenic descending necrotizing mediastinitis. Our experience in last 5 years.

BACKGROUND: Descending necrotising mediastinitis is one of the most lethal and least frequent forms of mediastinitis. It is a life-threatening infection most frequently originating from an oropharyngeal or odontogenic infection. MATERIAL AND METHODS: A retrospective study of 6 patients diagnosed and treated for descending necrotising mediastinitis between 2015 and 2020 is reported. RESULTS: All patients were male, mean age of 34.83 years; 66% were smokers. 83% had an orocervical infection and 34% had initial mediastinal spread. All patients were treated initially with empirical broad-spectrum antibiotics and surgical drainage, with subsequent admission to the Intensive Care Unit; only one of them required tracheostomy. The mean hospital stay was 27.37 days. After a mean follow-up of 6 months, 100% of the cases had a complete recovery. CONCLUSIONS: Early diagnosis and surgical treatment combined with improved life-support treatment in intensive care units and broad-spectrum antibiotic therapy leads to a decrease in associated mortality.

Changes of CD3+CD56+ γδ T cell number and apoptosis during hospital admission are related to mortality in septic patients.

Immunoparalysis and apoptosis of T cells are serious problems for the evolution of septic patients. We aimed to relate changes in the number of αß and γδ T cells during hospital stay to the poor evolution of sepsis. In this prospective study, we recruited a total of 92 septic patients from the Emergency and Intensive Care Departments of two Hospitals, according to the latest criteria for the definition and management of sepsis. According to the severity of the septic process, there was a progressive decrease in T cells, being much more intense in γδ T cells. This decrease recovered in surviving patients, but CD3+CD56+ γδ T cells continued to decreased during hospital stay in non-surviving patients. Apoptosis increased in sepsis. Cell death of CD3+CD56+ γδ T cells progressively increased according to the severity of sepsis, especially in non-surviving patients.

Determination of Anti-Anisakis Simplex Antibodies and Relationship with αß and γδ Lymphocyte Subpopulations in Patients with Crohn's Disease.

BACKGROUND: The etiology of Crohn's disease (CD) is still unknown although new theories are based on defects in innate immunity. We have previously shown a decrease in γδ T cells in CD patients. Previous studies have shown a high prevalence of anti-A. simplex immunoglobulins in CD patients. The diminution of γδ T cells in the peripheral blood and intestinal mucosa of CD patients may create a state of immunosuppression that would facilitate A. simplex infection. AIMS: To study the antibody responses to Anisakis antigens in Crohn's disease patients and its relationship with αß and γδ T cell subsets. METHODS: We recruited 81 CD patients and 81 healthy controls. αß and γδ T cell subsets and anti-A. simplex antibodies were measured. RESULTS: Levels of anti-A. simplex IgG and IgM were significantly increased in CD patients. Almost 20% of CD patients were positive for IgG and IgM anti-A. simplex versus only 3.7 and 2.5%, respectively, in normal subjects. However, lower specific IgA levels were observed in the group of CD patients versus healthy subjects. We found an association between CD3 + CD8 + Î³Î´ subset and IgM anti-A. simplex levels. In ileal cases and stricturing behavior of CD, we observed the highest levels of specific antibodies with the exception of anti-A. simplex IgA. CONCLUSIONS: The relationship of specific antibodies with a γδ T cell deficiency makes these cell candidates to play a role in the immune response against Anisakis. In addition, anti-Anisakis antibodies could be considered as markers of risk of progression in CD.

Allergenicity of vertebrate tropomyosins: Challenging an immunological dogma.

With the exception of tilapia tropomyosin, other anecdotic reports of tropomyosin recognition of vertebrate origin are generally not accompanied by clinical significance and a dogmatic idea is generally accepted about the inexistence of allergenicity of vertebrate tropomyosins, based mainly on sequence similarity evaluations with human tropomyosins. Recently, a specific work-up of a tropomyosin sensitised patient with seafood allergy, demonstrated that the IgE-recognition of tropomyosin from different fish species can be clinically relevant. We hypothesise that some vertebrate tropomyosins could be relevant allergens. The hypothesis is based on the molecular evolution of the proteins and it was tested by in silico methods. Fish, which are primitive vertebrates, could have tropomyosins similar to those of invertebrates. If the hypothesis is confirmed, tropomyosin should be included in different allergy diagnosis tools to improve the medical protocols and management of patients with digestive or cutaneous symptoms after fish intake.

Diamine oxidase levels in different chronic urticaria phenotypes.

BACKGROUND: Diamine oxidase (DAO) is a polyamine-degrading enzyme also implicated in histamine metabolism. Chronic urticaria (CU) has a wide spectrum of clinical presentations and causes. Anisakis sensitisation associated chronic urticaria (CU+) has been characterised as a phenotype with different clinical and immunological characteristics and possibly associated with previous acute parasitism. We aimed to analyse serum DAO levels in different CU phenotypes. We further analysed the possible association of DAO with fish eating habits. METHODS: We studied 35 CU+ patients and 39 non-sensitised CU patients (CU-) as well as 19 controls. We analysed fish-eating frequency as well as fish intake associated exacerbation of CU (FIAE) or gastro-intestinal complaints (GI). DAO levels were further analysed with respect to lymphoproliferative responses, cytokine and specific IgE production. RESULTS: DAO levels were not different between CU and controls, but were significantly higher in CU+ than in CU-. CU+ patients with FIAE had lower DAO levels, but no differences were detected in patients with GI. DAO levels correlated positively with oily and canned fish consumption in CU-. In CU+, DAO levels correlated positively with specific Anisakis IgE, percentages of proliferation in Anisakis stimulated peripheral blood lymphocytes, serum IL-2 and IL-6, but correlated negatively with mitogen stimulated TGF-ß in supernatants. CONCLUSIONS: DAO levels in CU depend on fish-eating habits and in CU+ on the amount of specific IgE production. In the CU+ phenotype, lower levels of DAO predispose to urticaria exacerbation after fish intake, probably due to a relative insufficient enteric availability of this enzyme.

Positive associations between infections of Toxoplasma gondii and seropositivity with Anisakis simplex in human patients suffering from chronic urticaria.

Toxoplasma gondii is a food-borne and orofecal microorganism which produces chronic infection, and attempts have been made to prove its negative association with atopy in the context of the hygiene hypothesis. Anisakis simplex is a fish parasite associated with chronic urticaria (CU) in endemic regions. We analysed the relationship between both infectious agents in CU. We included 42 patients with chronic urticaria (18 patients with CU associated with A. simplex sensitization and 24 not sensitized CU patients). Patients were assessed for atopy by a skin prick test (SPT) against common aeroallergens and for respiratory symptoms. Anisakis simplex sensitization was assessed by SPT and specific IgE by CAP fluoro-enzyme immunoassay (CAP-FEIA). Anti-T. gondii IgG levels were measured by enzyme-linked immunosorbent assay (ELISA). CU patients were analysed with respect to T. gondii seropositivity, A. simplex sensitization, atopy and immigrant status. The seroprevalence of T. gondii was 40.5% in CU patients and 42.1% in the control group. Immigrants were more frequently infected by T. gondii (41.2% versus 12%; P =0.036). Anti-T. gondii IgG antibodies were associated with past A. simplex parasitism (odds ratio 6.73; P =0.03) and independently with atopic sensitization (odds ratio 5.85; P =0.04). In CU patients, T. gondii has no protective effect on atopic sensitization or A. simplex sensitization.

Specific IgG4: possible role in the pathogenesis and a new marker in the diagnosis of Anisakis-associated allergic disease.

IgG4 and IgE are immunoglobulin isotypes which are mediated by the same Th2-mediated mechanism. The postulated pathogenic and protective function of IgE or IgG4, respectively, in allergic disease is opposite in parasitic infection. The possible role of IgG4 against recombinant major allergens on the appearance of different forms of Anisakis simplex-associated allergic disease was studied. Gastro-allergic anisakiasis (GAA) and Anisakis-sensitization-associated chronic urticaria (CU+) were compared for specific IgE, IgG4 and the respective recognition of Ani s 1 and Ani s 7. Gastro-allergic anisakiasis showed higher IgE and IgG4 levels against crude extract and both recombinant allergens. Whereas IgE recognition of Ani s 7 did not differ and supports both clinical entities to be associated with previous acute parasitism, the IgE recognition rates of Ani s 1 and IgG4 recognition of both Ani s 1 and Ani s 7 were higher in GAA. IgG4 levels were associated with IgE, but also with age, time to last parasitic episode and frequency of fish intake. Logistic regression analysis showed that the presence of specific IgG4 against Ani s 7 was an independent marker associated with GAA. In the diagnosis of Anisakis-associated allergic disease phenotypes (GAA versus CU+), measurement of specific IgG4 against recombinant allergens could be useful. Further, evaluation of specific IgE and IgG4 facilitates more insight into the protective versus pathogenic potential of IgE and IgG4.

Large-scale real-life analysis of survival and usage of therapies in multiple myeloma.

Survival in multiple myeloma has improved significantly in recent years, especially in young patients. We reviewed the evolution of the survival of patients with MM in three groups based on age at MM diagnosis over three time periods between 1999 and 2020 at our 12 de Octubre Hospital institution (H12O). Then, to confirm our results, we used data from TriNetx, a global health research platform that includes patients from Europe to US. Finally, we analysed differences in the patterns of treatment between networks across the world. Kaplan‒Meier analysis was used to estimate survival probabilities, and between-group differences were tested using the log-rank test and hazard ratio. For patients from H12O, the median OS was 35.61, 55.59 and 68.67 months for the 1999-2009, 2010-2014 and 2015-2020 cohorts, respectively (p = 0.0001). Among all patients included in the EMEA network, the median OS was 20.32 months versus 34.75 months from 1999-2009 versus 2010-2014. The median OS from the 2010-2014 versus 2015-2020 time cohorts was 34.75 months versus 54.43 months, respectively. In relation to the US cohort, the median OS from before 2010 versus 2010-2014 was not reached in either time cohort and neither when comparing the 2010-2014 versus 2015-2019 time cohorts. Bortezomib is the most commonly used drug in the EMEA cohort, while lenalidomide is the most commonly used drug in the US cohort. This large-scale study based on real-world data confirms the previous finding that MM patients have increased their survival in the last two decades.

The effect of anti-Anisakis simplex antibody levels on C3 and C4 complement components in human sera.

Previously, an in vitro effect was observed on the complement system not only of the excretory-secretory products but also of somatic antigens from L3 Anisakis simplex larvae. In the present work the effect of anti-A. simplex specific antibodies on C3 and C4 levels in human sera was investigated. Up to 309 samples of sera were tested to determine levels of C3 and C4 and anti-A. simplex antibodies, including immunoglobulins IgG, IgM, IgA and IgE. Significant differences were observed between levels of C3 and C4 and all immunoglobulins except for IgE. In the case of immunoglobulins, the probability that an anti-A. simplex positive subject has a C3 deficiency was 3.8 times higher than a subject without specific antibodies. In conclusion, an association between elevated levels of anti-A. simplex antibodies and C3 and C4 deficiency was demonstrated.

Large cell neuroendocrine carcinoma on the floor of the mouth: a rare entity in an unusual location.

Neuroendocrine carcinomas (NEC) are a group of malignant neoplasms usually located in the lungs or gastrointestinal tract. Fewer cases are located in the head and neck, and in these rare presentations, the lingual tonsil, larynx, and major salivary glands are the most frequently affected sites. NECs exhibit similar characteristics regardless of where they arise. However, because these neoplasms are rare, a clear understanding of their aetiopathogenesis has yet to be described, and options for treatment have varied and are not unified. A rare NEC of the floor of the mouth is reported here; it appears that this location has not been reported previously. The diagnosis was established through histopathological analysis, and the patient underwent systemic treatment. He had a partial response to treatment in the first 3 months, but died 6 months after the initial diagnosis. This highly uncommon tumour can pose a significant diagnostic challenge for clinicians and pathologists alike and can result in diagnostic delay.

Navigation in surgical arthroscopy of the temporomandibular joint.

Surgical navigation is a technique that has evolved greatly in recent years. It allows surgeons to navigate through the surgical field in real time, and helps to locate anatomical structures or lesions and to place devices in complex anatomical regions with relatively high accuracy. In this article, we describe the application of surgical navigation in temporomandibular joint (TMJ) arthroscopy using an optical surgical navigator for a more precise diagnosis and to accurately place instruments in the desired position, especially in lateral pterygoid myotomy. We believe this technique will extend our understanding of the TMJ anatomy and will improve functional results in TMJ arthroscopy.

Different serum cytokine levels in chronic vs. acute Anisakis simplex sensitization-associated urticaria.

The knowledge on immune mechanisms of chronic urticaria (CU) at the cytokine level is widely scarce. We compared pro- and anti-inflammatory as well as Th1- and Th2-associated serum cytokine levels in two phenotypes of CU: associated with (CU+) and without (CU⁻) sensitization against Anisakis simplex, a ubiquitous fish parasite, that has been associated with acute urticaria in gastro-allergic anisakiasis (GAA) and with CU+. Thirteen CU+ and 19 CU⁻ patients were compared with 13 GAA patients and 15 control subjects for cytokines, measured by cytometric bead array. Urticaria activity score was positively correlated with IL-6 in CU⁻. Serum levels of IL-10 were lower in CU+ and CU⁻ with respect to the control group. Median IFN-γ was lower in all urticaria groups. Patients with previous parasitism by A. simplex displayed higher TGF-ß levels than subjects without previous parasitism. The main finding was lower levels of IL-17 in CU+ with respect to GAA or controls, with a further tendency to even lower levels in CU⁻. Different urticaria phenotypes are associated with distinct serum cytokine levels.

DNA methylation in oral squamous cell carcinoma: molecular mechanisms and clinical implications.

DNA methylation is an important regulator of gene transcription, and its role in carcinogenesis has been a topic of considerable interest in the last few years. Of the all epigenetic modifications, methylation, which represses transcription of the promoter region of tumor suppressor genes leading to gene silencing, has been most extensively studied. Oral squamous cell carcinoma (OSCC) has long been known to be the endpoint of many genetic changes, not only genomic mutations but also abnormal epigenetic modifications, as such, promoter methylation, contribute to development of this tumors. Recent studies have shown that promoter methylation of tumor suppressor genes is an important factor in carcinogenesis of OSCC. Some of the main genes that frequently showed promoter methylation in OSCC are those that participate in diverse processes such as regulation of the cell cycle, DNA repair, proliferation, and apoptosis. The aim of this review is to assess the current state of knowledge regarding promoter methylation of diverse genes in OSCC.

Impact of COVID-19 in patients with multiple myeloma based on a global data network.

The COVID-19 pandemic has represented a major cause of morbidity/mortality worldwide, overstressing health systems. Multiple myeloma (MM) patients show an increased risk for infections and they are expected to be particularly vulnerable to SARS-CoV-2 infection. Here we have obtained a comprehensive picture of the impact of COVID-19 in MM patients on a local and a global scale using a federated data research network (TriNetX) that provided access to Electronic Medical Records (EMR) from Health Care Organizations (HCO) all over the world. Through propensity score matched analyses we found that the number of new diagnoses of MM was reduced in 2020 compared to 2019 (RR 0.86, 95%CI 0.76-0.96) and the survival of newly diagnosed MM cases decreased similarly (HR 0.61, 0.38-0.81). MM patients showed higher risk of SARS-CoV-2 infection (RR 2.09, 1.58-2.76) and a higher excess mortality in 2020 (difference in excess mortality 9%, 4.4-13.2) than non-MM patients. By interrogating large EMR datasets from HCO in Europe and globally, we confirmed that MM patients have been more severely impacted by COVID-19 pandemic than non-MM patients. This study highlights the necessity of extending preventive measures worlwide to protect vulnerable patients from SARS-CoV-2 infection by promoting social distancing and an intensive vaccination strategies.

Gammadelta T cells as a predictor of surgical relapse of Crohn's disease.

BACKGROUND: We recently demonstrated a decrease in the overall lymphocyte population in the peripheral blood of patients with CD compared to healthy controls and this decrease is more evident in γδ T lymphocytes. The percentages of T cell subsets could reflect the risk of surgical relapse in CD patients. The aim of this study is to study the correlation between αß and γδ T cell subsets in the peripheral blood of patients with CD and the risk for surgery during follow up. METHODS: A prospective study of 102 patients with CD compared with 102 healthy subjects (control group) matched by age and sex was conducted. Lymphocytic populations of CD3+, CD4+, CD8+, CD56+, and αß and γδ T cell subsets were measured in the peripheral blood of all participants. RESULTS: We found evidence of a relationship between lower γδ T cell levels and risk of surgical relapse in CD. The lowest subsets observed in CD patients with surgical relapse were CD3+γδ, CD3+CD8+γδ and CD3+CD56+γδT cells. We observed a relationship between a decrease in γδ T cells and the most severe forms of the disease. The lowest levels of CD3+γδ and CD3+CD8+γδT cells were observed in the fistulizing phenotype. CONCLUSIONS: The deficit of γδ T cells was related with the severity and the risk for surgical relapse in CD patients. Patients with CD3+γδ deficit were more prone to surgery than patients without this deficit. These results suggest that γδ T cells could be used as markers of poor prognosis of CD following the diagnosis of the disease.

[Exposure to second-hand smoke in school adolescents from Tunja (Colombia), 2017]. / Exposición al humo de segunda mano en adolescentes escolarizados de Tunja, Colombia, 2017.

INTRODUCTION: Adolescents exposed to second-hand smoke have a higher risk of morbidity. This is one of the main preventable public health problems in Latin America. OBJECTIVE: To determine the prevalence and sociodemographic factors associated with exposure to second-hand tobacco smoke at home and out-of-home, in school adolescents from Tunja-Colombia. METHODOLOGY: This cross-sectional study included 1100 school students, aged between 11 and 19 years. The information was obtained using a self-administered and totally anonymous questionnaire. For the analysis, the proportions of everyday exposure and the mean number of days of exposure to second-hand smoke during a regular week were estimated. For the associations, ordinal logistic regression and negative binomial regression models were performed. RESULTS: The average age of the participants was 14.5 years, with the majority (59%) being female. As regards second-hand tobacco smoke exposure at home, an everyday prevalence of 4.9% was found, from 1 to 6 days of 14.7%, with a mean exposure of 0.7 days (SD 1.7). Additionally, there was a higher prevalence of exposure to second-hand smoke out-of-home: every day 8%, from 1 to 6 days of 34.1%, with a mean exposure of 1.5 days (SD 2.2). CONCLUSION: The prevalence of exposure to second-hand smoke in adolescents of Tunja was high. Interventions at school and family level are recommended to counteract this problem.

The Anisakis simplex Ani s 7 major allergen as an indicator of true Anisakis infections.

Ani s 7 is currently the most important excretory/secretory (ES) Anisakis simplex allergen, as it is the only one recognized by 100% of infected patients. The allergenicity of this molecule is due mainly to the presence of a novel CX(17-25)CX(9-22)CX(8)CX(6) tandem repeat motif not seen in any previously reported protein. In this study we used this allergen as a model to investigate how ES allergens are recognized during Anisakis infections, and the usefulness of a recombinant fragment of Ani s 7 allergen (t-Ani s 7) as a marker of true Anisakis infections. The possible antigenic relationship between native Ani s 7 (nAni s 7) from Anisakis and Pseudoterranova decipens antigens was also investigated. Our results demonstrate that nAni s 7 is secreted and recognized by the immune system of rats only when the larvae are alive (i.e. during the acute phase of infection), and that this molecule is not present in, or is antigenically different from, Pseudoterranova allergens. The t-Ani s 7 polypeptide is a useful target for differentiating immunoglobulin E antibodies induced by true Anisakis infections from those induced by other antigens that may cross-react with Anisakis allergens, including P. decipiens. The results also support the hypothesis that the Ani s 7 major allergen does not participate in maintaining the antigenic stimulus during chronic infections.

Study of the effect of Anisakis simplex larval products on the early and late components in the classical complement pathway.

In previous studies, we have reported that the larval products (crude extract [CE] and excretory-secretory [ES]) of Anisakis simplex showed a dose-dependent inhibition of the lysis mediated by classical (CP) and alternative pathways (AP) of the human complement system, with the major inhibition on the CP rather than on AP. This inhibition of hemolysis is due to the consumption of complement factors because the assays performed shortening the preincubation period result in a significant decrease of the inhibitory effect on the lysis of the larval products compared with the standard time. Likewise, we found that the larval products reduce the inhibitory percentages in the CP using C3-deficient sera, but not in the AP, which could indicate that other complement components are implicated in the inhibitory effect in the CP. Hence, we have studied the activity of the larval products of A. simplex on individual components in the CP, using different complement-deficient sera. The investigated complement molecules were C1q, C2, C4, C5, C6, C7, C8, and C9. The larval products showed activity at the C2 level but failed to have a significant effect on the other components. Therefore, CE and ES products from A. simplex interact with C3 and C2 complement proteins, which are early components of the complement system, but not with the late complement components.

Towards a differential definition of atopy: Anisakis simplex and the relationship between parasites and arthropods in respiratory allergy.

Protective as well as enhancing effects of parasite infections on allergic disease have been postulated. Previous studies on this relationship focused frequently on skin test reactivity against aeroallergens, being house dust mites (HDM) the main agents responsible for a positive atopy outcome. We aimed to analyse the possible relationship between human parasite infection induced Anisakis simplex urticaria and respiratory allergy. A total of 86 patients with gastro-allergic Anisakiasis and 203 patients with chronic urticaria sensitized against A. simplex were studied for sensitization against aeroallergens and evaluated for rhinoconjunctivitis or bronchial asthma (RCBA). We compared the results with a control group of 250 consecutive patients referred for evaluation of allergic RCBA and atopy prevalence data of our region. Whereas no effect of A. simplex related disease on the overall allergic respiratory disease could be detected, a highly significant higher prevalence of RCBA associated HDM sensitization, but diminished allergy against other common aeroallergens (pollen, mould or dander) was observed in these groups. The relationship between A. simplex parasitism-associated acute or chronic urticaria on one side and allergic respiratory disease on the other side depends on the definition of atopy. We propose a differential definition of atopy, with a special emphasis on arthropod related sensitization.

Follow-up of antibody avidity in BALB/c mice infected with Toxocara canis.

In human Toxocara canis infection, an association has been shown between high IgG avidity in the chronic phase and low IgG avidity in recently acquired toxocarosis. The evolution of the antibody response in terms of avidity has been carried out through a T. canis infection in BALB/c mice. Infection with T. canis embryonated eggs (EE) was carried out with single doses (SD) of 6, 12, 50, 100, 200 or 1000 EE/mouse and with multiple doses (MD) of 200 and 1000 EE. Specific antibodies against T. canis (IgM+G, IgG, IgG1 and IgM) were detected by ELISA and Western Blot (WB) techniques in the presence and absence of urea. With the ELISA method, an increase in the avidity index (AI) of around 50% was detected from days 40-80 p.i. to the end of the study, with all the doses studied. The WB method showed the presence of high avidity antibodies bound to 100 kDa and 75 kDa T. canis proteins in all the cases when the IgM+G and the IgG1 antibodies were investigated. Antibodies of variable avidity were observed in those sera that recognized the group of low molecular weight proteins, between 37 kDa and 25 kDa.