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AIM: To conduct a systematic review with meta-analysis to provide a comprehensive synthesis of randomized controlled trials (RCTs) and prospective cohort studies investigating the effects of currently available bolus advisors on glycaemic parameters in adults with diabetes. MATERIALS AND METHODS: An electronic search of PubMed, Embase, CINAHL, Cochrane Library and ClinicalTrials.gov was conducted in December 2022. The risk of bias was assessed using the revised Cochrane Risk of Bias tool. (Standardized) mean difference (MD) was selected to determine the difference in continuous outcomes between the groups. A random-effects model meta-analysis and meta-regression were performed. This systematic review was registered on PROSPERO (CRD42022374588). RESULTS: A total of 18 RCTs involving 1645 adults (50% females) with a median glycated haemoglobin (HbA1c) concentration of 8.45% (7.95%-9.30%) were included. The majority of participants had type 1 diabetes (N = 1510, 92%) and were on multiple daily injections (N = 1173, 71%). Twelve of the 18 trials had low risk of bias. The meta-analysis of 10 studies with available data on HbA1c showed that the use of a bolus advisor modestly reduced HbA1c compared to standard treatment (MD -011%, 95% confidence interval -0.22 to -0.01; I2 = 0%). This effect was accompanied by small improvements in low blood glucose index and treatment satisfaction, but not with reductions in hypoglycaemic events or changes in other secondary outcomes. CONCLUSION: Use of a bolus advisor is associated with slightly better glucose control and treatment satisfaction in people with diabetes on intensive insulin treatment. Future studies should investigate whether personalizing bolus advisors using artificial intelligence technology can enhance these effects.
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Glicemia , Diabetes Mellitus Tipo 1 , Hemoglobinas Glicadas , Hipoglicemiantes , Insulina , Humanos , Insulina/uso terapêutico , Insulina/administração & dosagem , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/administração & dosagem , Glicemia/efeitos dos fármacos , Glicemia/análise , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/efeitos dos fármacos , Adulto , Feminino , Ensaios Clínicos Controlados Aleatórios como Assunto , Controle Glicêmico/métodos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Masculino , Hipoglicemia/prevenção & controle , Hipoglicemia/induzido quimicamenteRESUMO
OBJECTIVE: Perampanel, an antiseizure drug with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist properties, may have a targeted effect in genetic epilepsies with overwhelming glutamate receptor activation. Epilepsies with loss of γ-aminobutyric acid inhibition (e.g., SCN1A), overactive excitatory neurons (e.g., SCN2A, SCN8A), and variants in glutamate receptors (e.g., GRIN2A) hold special interest. We aimed to collect data from a large rare genetic epilepsy cohort treated with perampanel, to detect possible subgroups with high efficacy. METHODS: This multicenter project was based on the framework of NETRE (Network for Therapy in Rare Epilepsies), a web of pediatric neurologists treating rare epilepsies. Retrospective data from patients with genetic epilepsies treated with perampanel were collected. Outcome measures were responder rate (50% seizure reduction), and percentage of seizure reduction after 3 months of treatment. Subgroups of etiologies with high efficacy were identified. RESULTS: A total of 137 patients with 79 different etiologies, aged 2 months to 61 years (mean = 15.48 ± 9.9 years), were enrolled. The mean dosage was 6.45 ± 2.47 mg, and treatment period was 2.0 ± 1.78 years (1.5 months-8 years). Sixty-two patients (44.9%) were treated for >2 years. Ninety-eight patients (71%) were responders, and 93 (67.4%) chose to continue therapy. The mean reduction in seizure frequency was 56.61% ± 34.36%. Sixty patients (43.5%) sustained >75% reduction in seizure frequency, including 38 (27.5%) with >90% reduction in seizure frequency. The following genes showed high treatment efficacy: SCN1A, GNAO1, PIGA, PCDH19, SYNGAP1, POLG1, POLG2, and NEU1. Eleven of 17 (64.7%) patients with Dravet syndrome due to an SCN1A pathogenic variant were responders to perampanel treatment; 35.3% of them had >90% seizure reduction. Other etiologies remarkable for >90% reduction in seizures were GNAO1 and PIGA. Fourteen patients had a continuous spike and wave during sleep electroencephalographic pattern, and in six subjects perampanel reduced epileptiform activity. SIGNIFICANCE: Perampanel demonstrated high safety and efficacy in patients with rare genetic epilepsies, especially in SCN1A, GNAO1, PIGA, PCDH19, SYNGAP1, CDKL5, NEU1, and POLG, suggesting a targeted effect related to glutamate transmission.
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Epilepsias Parciais , Epilepsia , Criança , Humanos , Epilepsias Parciais/tratamento farmacológico , Anticonvulsivantes/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Epilepsia/tratamento farmacológico , Epilepsia/genética , Epilepsia/induzido quimicamente , Convulsões/tratamento farmacológico , Piridonas/efeitos adversos , Ácido Glutâmico , Protocaderinas , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTPRESUMO
Obesity prevalence and sleep habit changes are commonplace nowadays, due to modern lifestyle. A bidirectional relationship likely exists between sleep quality and metabolic disruptions, which could impact quality of life. In our study, we investigated the effects of a chronic high-caloric diet on sleep architecture and sleep regulation in mice. We studied the effect of 3 months high-caloric diet (HCD, 45% fat) on sleep and the sleep electroencephalogram (EEG) in C57BL/6J mice during 24-hr baseline (BL) recordings, and after 6-hr sleep deprivation (SD). We examined the effect of HCD on sleep homeostasis, by performing parameter estimation analysis and simulations of the sleep homeostatic Process S, a measure of sleep pressure, which is reflected in the non-rapid-eye-movement (NREM) sleep slow-wave-activity (SWA, EEG power density between 0.5 and 4.0 Hz). Compared to controls (n = 11, 30.7 ± 0.8 g), mice fed with HCD (n = 9, 47.6 ± 0.8 g) showed an increased likelihood of consecutive NREM-REM sleep cycles, increased REM sleep and decreased NREM sleep EEG SWA. After SD, these effects were more pronounced. The simulation resulted in a close fit between the time course of SWA and Process S in both groups. HCD fed mice had a slower time constant (Ti = 15.98 hr) for the increase in homeostatic sleep pressure compared with controls (5.95 hr) indicating a reduced effect of waking on the increase in sleep pressure. Our results suggest that chronic HCD consumption impacts sleep regulation.
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Dieta/efeitos adversos , Ingestão de Energia , Homeostase/fisiologia , Privação do Sono/fisiopatologia , Sono REM/fisiologia , Sono de Ondas Lentas/fisiologia , Vigília/fisiologia , Animais , Eletroencefalografia , Eletromiografia , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
AIMS: The aim of this study was to examine the direct and indirect effect, through organizational identification, of workplace ostracism on nurses' silence towards patient safety. BACKGROUND: Employee silence in nursing has recently received attention in relation to its antecedents. Yet, very little is known about the role of workplace ostracism in generating nurses' silence. DESIGN: A cross-sectional survey was conducted in a public hospital in Cyprus. METHOD: Data were collected from 157 nurses employed in a public hospital of Cyprus between November 2014-January 2015. To examine the present hypotheses bootstrapping analysis and Sobel test were conducted. RESULTS: Results demonstrated that workplace ostracism has an effect on nurses' silence towards patient safety. Moreover, this effect was partially mediated through organizational identification. CONCLUSIONS: Workplace ostracism among nurses significantly affects both nurses' attitude and behaviour namely organizational identification and employee silence.
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Hospitais Públicos , Recursos Humanos de Enfermagem Hospitalar , Cultura Organizacional , Segurança do Paciente , Local de Trabalho , Atitude do Pessoal de Saúde , Estudos Transversais , Chipre , Emprego , Humanos , Inquéritos e QuestionáriosRESUMO
The increased prevalence of obesity worldwide has been implicated in the alarming rise of the incidence of gestational diabetes and preeclampsia, which are both considered threatening conditions for both mother and fetus. We studied gene polymorphisms of the proinflammatory cytokine Interleukin 6 (IL-6) and the gene expression levels of VEGF (vascular endothelial growth factor) and VEGF-R (endothelial growth factor receptor), all known to be involved in pregnancy complications, aiming to identify possible predisposing risk factors in pregnancies with obesity. The G allele of IL-6 was found to correspond with an increased risk for gestational diabetes and preeclampsia occurrence. Furthermore, in obese pregnant mothers with either gestational diabetes or pre-existing type 2 diabetes and those who developed preeclampsia, it was confirmed that gene expression levels of VEGF were reduced while they were increased for VEGF receptors. We conclude that the genetic profile of an obese pregnant woman shares a common background with that of a patient with pre-existing type 2 diabetes mellitus, and therefore predisposes them to complications in pregnancy.
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The incidence of thyroid metastases among patients suffering from primary colorectal cancer is rare, and only a few cases have been described in the literature. As these metastases are usually asymptomatic, they most frequently present as incidentalomas on follow-up imaging. Hereby, we present and discuss an interesting case of metastatic sigmoid adenocarcinoma of the thyroid gland, diagnosed and treated at our institution.
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Given that 5-25% of the adult population report child sexual abuse (CSA), most clinicians will care for victims. Data regarding CSA experiences among medical students are limited and the association of medical students' own history of CSA with relevant perceptions has not been previously examined. The aim of this study was to assess CSA perceptions and exposure of medical students, while exploring their associations. For this purpose, a link was created and made available on a site accessed solely by the Athens medical school undergraduates from February 20 to March 20 2019, comprising a 12-item questionnaire to assess the knowledge and past experience of CSA. This was based on a larger published questionnaire, which was translated and adapted. The questionnaire was then transcripted online, and after pilot testing, was disseminated using the Google documents® platform. Out of 261 responses, CSA was reported by 48 participants (18%), of which 39 were women. Thirty five reported contact CSA. Thirty seven victims (77%) reported previous disclosure of the event, but 18 of them were not protected post disclosure. CSA victims were less likely to agree with the perception that most perpetrators are mentally ill or disabled (p = 0.043), and more likely to strongly disagree with the statement that reputable families are protected from sexual abuse (p = 0.019). In agreement with existing data in general populations globally, about one in five medical students had exposure to CSA. In addition, a potential association of their own experiences with shaping perceptions regarding the identity of CSA perpetrators and affected families for medical students is highlighted.
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Abuso Sexual na Infância , Estudantes de Medicina , Adulto , Criança , Feminino , Humanos , Percepção , Faculdades de Medicina , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Acute kidney injury (AKI) has been observed in up to 20% of adult hospital admissions. Sepsis, diarrhea and heart failure, all causing reduced effective volume, are considered risk factors for AKI, especially among patients treated with medications that block the Renin-Angiotensin System (RAS), such as angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB). We aimed to determine the incidence of acute kidney injury (AKI) in emergency medical admissions in relation to the use and dosage of ACEi/ARB. METHODS: A single-center observational study conducted in 577 consecutive medical admissions via the Emergency Room (ER) at a University General Hospital in Athens, Greece, between June and July 2018. Patients with incomplete medical records, discharged within 24 h, maintained on chronic renal replacement therapy, admitted to the Cardiology Department or the ICU were excluded. Thus, a total of 309 patients were finally included in this analysis. RESULTS: We compared 86 (28%) patients who presented in the ER with AKI (AKIGroup) with 223 (72%) patients without AKI (non-AKI Group) at the time of admission. Patients in the AKI Group were more frequently male (58% vs. 46%, p = 0.06), with a higher frequency of diarrhea (16% vs. 6%, p = 0.006), edema (15% vs. 6%, p = 0.014) and lower systolic blood pressure (120 (107-135) vs. 126 (113-140), p = 0.007) at presentation, despite higher prevalence of hypertension (64% vs. 47%, p = 0.006). Overall, ACEi/ARB were more likely to have been prescribed in the AKI Group than in the non-AKI Group (49% vs. 28%, p = 0.001). Interestingly, AKI was more frequently observed in patients treated with the target or above target dosage of ACEi/ARB, but not in those receiving lower than the recommended dosage. CONCLUSION: The risk of AKI in emergency medical admissions is higher among users of ACEIs/ARB at target or above target dosages. Physicians should adjust RAS blockade according to estimated Glomerular Filtration Rate (eGFR) and advise their patients to withhold ACEi/ARB in cases of acute illness.
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Contamination of surfaces has been implicated in transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We tested by real-time PCR for SARS-CoV-2 contamination environmental samples from three hospitals during the peak of the third pandemic wave. Overall, 19 of 463 (4.1%) samples tested positive: 12 of 173 (6.9%) samples from a COVID-19 hospital, 3 of 177 (1.7%) samples from a non-COVID-19 hospital, and 4 of 113 (3.5%) samples from a pediatric hospital with dedicated COVID-19 clinics. Most positive samples originated from emergency departments (EDs) (47.3%) and the intensive care units (ICUs) (26.3%) of the COVID-19 hospital. Positive samples belonged almost exclusively (18/19) to the highly transmissible B.1.1.7 cluster, that might explain environmental contamination at this stage of the pandemic. The frequency and efficiency of disinfection in high-risk patient areas, such as EDs and ICUs, should be reinforced, especially during this period where highly transmissible variants of concern are widespread.
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COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , COVID-19/epidemiologia , Humanos , Pandemias , Centros de Atenção TerciáriaRESUMO
Artificial light, despite its widespread and valuable use, has been associated with deterioration of health and well-being, including altered circadian timing and sleep disturbances, particularly in nocturnal exposure. Recent findings from our lab reveal significant sleep and sleep electroencephalogram (EEG) changes owing to three months exposure to dim-light-at-night (DLAN). Aiming to further explore the detrimental effects of DLAN exposure, in the present study, we continuously recorded sleep EEG and the electromyogram for baseline 24-h and following 6-h sleep deprivation in a varied DLAN duration scheme. C57BL/6J mice were exposed to a 12:12 h light:DLAN cycle (75lux:5lux) vs. a 12:12 h light:dark cycle (75lux:0lux) for one day, one week, and one month. Our results show that sleep was already affected by a mere day of DLAN exposure with additional complications emerging with increasing DLAN exposure duration, such as the gradual delay of the daily 24-h vigilance state rhythms. We conducted detrended fluctuation analysis (DFA) on the locomotor activity data following 1-month and 3-month DLAN exposure, and a significantly less healthy rest-activity pattern, based on the decreased alpha values, was found in both conditions compared to the control light-dark. Taking into account the behavioral, sleep and the sleep EEG parameters, our data suggest that DLAN exposure, even in the shortest duration, induces deleterious effects; nevertheless, potential compensatory mechanisms render the organism partly adjustable and able to cope. We think that, for this reason, our data do not always depict linear divergence among groups, as compared with control conditions. Chronic DLAN exposure impacts the sleep regulatory system, but also brain integrity, diminishing its adaptability and reactivity, especially apparent in the sleep EEG alterations and particular low alpha values following DFA.
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Chronic pain and subfertility are the main symptoms of concern in women with endometriosis. In order to find new therapeutic options to suppress the pain, translational animal models are indispensable. We have developed a new automated, experimental setup, with full consideration for animal wellbeing, to determine whether operant behaviour can reveal abdominal hyperalgesia in rats with surgically-induced endometriosis, in order to assess whether abdominal hyperalgesia affect behavioural parameters. Endometriosis was induced by transplantation of uterine fragments in the abdominal cavity. Control groups consisted of sham-operated rats and non-operated rats. We have developed an operant chamber (Skinnerbox) which includes a barrier. The rat can climb the barrier in order to reach the food pellet, increasing in this way the pressure to the abdomen. We show that endometriosis rats collect significantly less sugar pellets when compared with the control rats after the introduction of the barrier. In the Skinnerbox experiment, we showed that in a positive operant setting, the introduction of a barrier results in a contrast of operant behaviour of endometriosis rats and control groups, perchance as a result of abdominal discomfort/hyperalgesia due to surgically-induced endometriosis. This is a promising start for the further development of a refined animal model to monitor abdominal discomfort/hyperalgesia in rats with surgically-induced endometriosis.
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Abdome/fisiopatologia , Endometriose/complicações , Hiperalgesia/fisiopatologia , Animais , Modelos Animais de Doenças , Endometriose/fisiopatologia , Feminino , Hiperalgesia/diagnóstico , Ratos , Ratos WistarRESUMO
BACKGROUND: Caffeine is one of the most widely consumed psychostimulants, and it impacts sleep and circadian physiology. AIM: Caffeine is generally used chronically on a daily basis. Therefore, in the current study, we investigated the chronic effect of caffeine on sleep in mice. METHODS: We recorded the electroencephalogram and electromyogram on a control day, on the first day of caffeine consumption (acute), and following two weeks of continuous caffeine consumption (chronic). In the latter condition, a period of six-hour sleep deprivation was conducted during the light period. Control mice, which received normal drinking water, were also recorded and sleep deprived. RESULTS: We found that caffeine induced differential effects following acute and chronic consumption. Over 24 h, waking increased following acute caffeine whereas no changes were found in the chronic condition. The daily amplitude of sleep-wake states increased in both acute and chronic conditions, with the highest amplitude in the chronic condition, showing an increase in sleep during the light and an increase in waking during the dark. Furthermore, electroencephalogram slow-wave-activity in non-rapid eye-movement sleep was increased, compared with both control conditions, during the first half of the light period in the chronic condition. It was particularly challenging to keep the animals awake during the sleep deprivation period under chronic caffeine. CONCLUSIONS: Together the data suggest an increased sleep pressure under chronic caffeine. In contrast to the traditional conception on the impact on sleep, chronic caffeine intake seems to increase the daily sleep-wake cycle amplitude and increase sleep pressure in mice.
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Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Sono/efeitos dos fármacos , Animais , Cafeína/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Eletroencefalografia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sono/fisiologia , Privação do Sono , Vigília/efeitos dos fármacosRESUMO
BACKGROUND: In Greece, the heptavalent pneumococcal conjugate vaccine (PCV7) became available in October 2004 and it was incorporated into the national immunization schedule in January 2006. METHODS: In February 2005, a yearly surveillance of the nasopharyngeal colonization with Streptococcus pneumoniae in children attending day-care centers in Central Greece began. RESULTS: Between February 2005 and May 2007, nasopharyngeal cultures were obtained from 1829 children aged 13-76 months (median age, 47 months). The proportion of attendees vaccinated with > or =1 doses of PCV7 increased from 13% (2005) to 33% (2006) and to 70% (2007); 98% had been immunized on toddler catch-up schedules. Among vaccinated carriers, the proportion of PCV7 serotypes decreased from 33% (2005) to 29% (2006) and to 8.6% (2007) (chi for trend, P < 0.001), the proportion of PCV7-related serotypes increased from 13% (2005) to 26% (2006) and to 28% (2007) (P = 0.16), whereas the proportion of non-PCV7 serotypes was 48% in 2005, 31% in 2006, and 55% in 2007 (P = 0.17). The proportion of PCV7 serotypes declined also among unvaccinated carriers. The carriage of serotype 19A did not increase. Among vaccinated carriers, the rate of highly penicillin-resistant isolates decreased from year 1 to year 3, respectively, 11%, 7.7%, and 0.6% (P = 0.001), whereas the proportion of penicillin-intermediate pneumococci was 13% in 2005, 23% in 2006, and 26% in 2007 (P = 0.22). CONCLUSIONS: In Central Greece, widespread PCV vaccination was followed by a significant reduction of carriage of highly penicillin-resistant pneumococci. The frequency of penicillin-intermediate isolates did not change significantly among vaccinated carriers.
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Portador Sadio/epidemiologia , Portador Sadio/microbiologia , Vacinas Meningocócicas/imunologia , Resistência às Penicilinas , Faringe/microbiologia , Vacinas Pneumocócicas/imunologia , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/isolamento & purificação , Criança , Creches , Pré-Escolar , Feminino , Grécia/epidemiologia , Vacina Pneumocócica Conjugada Heptavalente , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Prevalência , Sorotipagem , Streptococcus pneumoniae/classificaçãoRESUMO
Physical activity is beneficial for health. It has been shown to improve brain functioning and cognition, reduce severity of mood disorders, as well as facilitate healthy sleep and healthy aging. Sleep has been studied in healthy aged mice and absolute slow-wave-activity levels (SWA, electroencephalogram power between 0.75 and 4.0 Hz) in non-rapid-eye-movement sleep (NREM) were elevated, suggesting changes in brain connectivity. To investigate whether physical activity can diminish this aging-induced effect, mice of three age groups were provided with a running wheel (RW) for 1-3 months (6-months-old, n = 9; 18-months-old, n = 9; 24-months-old, n = 8) and were compared with control sedentary mice (n = 11, n = 8 and n = 9 respectively). Two weeks before the sleep-wake recordings the running wheels were removed. The electroencephalogram (EEG) and electromyogram were continuously recorded during undisturbed 24 h baseline (BL) and a sleep-deprivation was conducted during the first 6 h of the second day. Increased waking and decreased NREM sleep was found in the young RW mice, compared to young controls. These effects were not evident in the 18 and 24 months old mice. Unlike sleep architecture, we found that SWA was altered throughout the whole age spectrum. Notably, SWA was increased with aging and attenuated with exercise, exhibiting the lowest levels in the young RW mice. To utilize the cross-age revealing features of SWA, we applied machine learning techniques and found that characteristic information regarding age and exercise was enclosed in SWA. In addition, with cluster analysis, we could classify and accurately distinguish the different groups based solely on their SWA. Therefore, our study comprises a three-fold contribution: (a) effects of exercise on sleep are sustained following 2 weeks after removal of the wheel, (b) we show that EEG SWA can be used as a physiological marker of brain age in the mouse,
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Changes in sleep pattern are typical for the normal aging process. However, aged mice show an increase in the amount of sleep, whereas humans show a decrease when aging. Mice are considered an important model in aging studies, and this divergence warrants further investigation. Recently, insights into the network dynamics of cortical activity during sleep were obtained by investigating characteristics of individual electroencephalogram (EEG) slow waves in young and elderly humans. In this study, we investigated, for the first time, the parameters of EEG slow waves, including their incidence, amplitude, duration and slopes, in young (6 months) and older (18-24 months) C57BL/6J mice during undisturbed 24 h, and after a 6-h sleep deprivation (SD). As expected, older mice slept more but, in contrast to humans, absolute NREM sleep EEG slow-wave activity (SWA, spectral power density between 0.5-4 Hz) was higher in the older mice, as compared to the young controls. Furthermore, slow waves in the older mice were characterized by increased amplitude, steeper slopes and fewer multipeak waves, indicating increased synchronization of cortical neurons in aging, opposite to what was found in humans. Our results suggest that older mice, in contrast to elderly humans, live under a high sleep pressure.
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Eletroencefalografia , Fases do Sono/fisiologia , Fatores Etários , Animais , Fenômenos Eletrofisiológicos , Camundongos , Sono/fisiologia , Sono REM/fisiologiaRESUMO
BACKGROUND: Multiple sclerosis (MS) patients have a low general cancer risk and cases of neoplastic comorbidity are attributed by many researchers in chance, or therapeutical side-effects. Human leucocyte antigen (HLA) class II allele DRB1 15:01 is considered the main genetic factor independently associated with increased susceptibility for MS in Caucasians. Epstein-Barr virus (EBV) has also been proven to be a core triggering factor in MS initiation and progress, mainly in HLA-DRB1 15:01 positive MS patients. CASE REPORT: We present an exceptional case of a Greek-origin woman, carrying a distinct immunogenetic profile (HLA-A 26:01-Cw 06:02-DRB1 15:01), which gradually developed psoriasis, nasopharyngeal carcinoma (NPC), MS, breast cancer, uterine leiomyoma and other neoplasms. DISCUSSION: EBV plays a fundamental role in the pathogenesis of both autoimmunity (i.e. MS) and cancer (i.e. NPC). Our patient's immunogenetic profile included HLA alleles which are associated with psoriasis (Cw 06:02), NPC (A 26:01), MS (DRB1 15:01) and increased risk of MS, in patients carrying EBV (DRB1 15:01). We made a targeted review of the literature finding data supporting an EBV-HLA interaction mechanism behind our patient's unique combination of disorders, suggesting that beyond the standard role of each factor, their combination could act as the hidden link, in initiation or/and comorbidity of autoimmunity and cancer.
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Neoplasias da Mama/sangue , Cadeias HLA-DRB1/sangue , Herpesvirus Humano 4/metabolismo , Esclerose Múltipla/sangue , Neoplasias Nasofaríngeas/sangue , Psoríase/sangue , Autoimunidade/imunologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/imunologia , Carcinoma , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/imunologia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/imunologia , Psoríase/diagnóstico , Psoríase/imunologiaRESUMO
BACKGROUND: An experimental 26-valent M protein Group A streptococcal (GAS) vaccine has entered clinical studies. Pharyngeal GAS emm type surveillances in different areas and time-periods enhance the understanding of the epidemiology of GAS pharyngitis. Moreover, these surveillances, combined with the data on GAS invasive disease, can play a significant role in the formulation of multivalent type-specific vaccines. METHODS: During a 7-year period (1999-2005), 2408 GAS isolates were recovered from consecutive children with pharyngitis in Western Greece. The overall macrolide resistance rate was 22.8%. Along the study period we noted a tendency towards significantly decreased rates of resistance, with the lowest rates occurring in 2002 (15.3%), 2003 (15%) and 2004 (16.7%). A random sample of isolates from each year, 338 (61.7%) of the 548 macrolide-resistant and 205 (11%) of the macrolide-susceptible, underwent molecular analysis, including emm typing. RESULTS: The 543 typed isolates had 28 different emm types. A statistically significant association was found between macrolide resistance and emm4, emm22 and emm77, whereas emm1, emm3, emm6, emm12, emm87 and emm89 were associated with macrolide susceptibility. A significant yearly fluctuation was observed in emm4, emm28 and emm77. The most common macrolide-resistant GAS were emm77 isolates harboring erm(A), either alone or in combination with mef(A), emm4 carrying mef(A), emm28 possessing erm(B), emm75 carrying mef(A), emm12 harboring mef(A) and emm22 carrying erm(A). We estimated that 82.8% of the isolates belonged to emm types included in the novel 26-valent M protein vaccine. The vaccine coverage rate was determined mainly by the increased frequency of nonvaccine emm4 isolates. CONCLUSIONS: A limited number of emm types dominated among macrolide-susceptible and macrolide-resistant GAS isolates. We observed seasonal fluctuations, which were significant for emm4, emm28 and emm77. This type of data can serve as baseline information if the novel 26-valent M protein GAS vaccine is introduced into practice.