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BACKGROUND AND OBJECTIVES: Minimally invasive endoscopic approaches in cranial base surgery have been developing in the past decades. The transorbital (TO) route is one promising alternative, yet its adequacy for intracranial vascular lesions remains unclear. The present anatomic work aimed to test the feasibility and to provide a qualitative description of the endoscopic TO approach for the anterior circulation, namely the internal carotid artery and the middle cerebral artery. METHODS: Seven embalmed adult cadaveric specimens (12 sides) were used in the study. Each side was approached in 3 successive steps: (1) Superior-eyelid TO approach, with great and lesser sphenoid wing removal. (2) Removal of anterior clinoid process (ACP). (3) Removal of the lateral orbital rim. All the procedures were performed under endoscopic view. RESULTS: The TO approach without removing the ACP allowed to dissect the sphenoidal and lateral segments of the Sylvian fissure with an adequate identification of the middle cerebral artery bifurcation in all specimens. The removal of the ACP allowed further dissection toward the opticocarotid cistern, with the identification of the ophthalmic, posterior communicating, and the anterior choroidal arteries. The internal carotid artery bifurcation and A1 segment were also readily identified. Finally, removal of the lateral orbital rim provided a wider and more comfortable access to the above-mentioned vascular structures. CONCLUSION: According to our anatomic data, the TO approach can be used to reach the main vascular components of the anterior circulation. This opens the field for exploring its application in the treatment of vascular pathology, particularly aneurysms.
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OBJECTIVE: To characterize and describe clinical experience with childhood-onset non-infectious uveitis. STUDY DESIGN: A multicenter retrospective multidisciplinary national web-based registry of 507 patients from 21 hospitals was analyzed. Cases were grouped as immune disease-associated (IMDu), idiopathic (IDIu) or ophthalmologically distinct. Characteristics of juvenile idiopathic arthritis-associated (non-HLA-B27-related) uveitis (JIAu), IDIu, and pars planitis (PP) were compared. RESULTS: IMDu (62.3%) and JIAu (51.9%) predominated in young females; and IDIu (22.7%) and PP (13.6%) in older children, without sex imbalance. Ocular complications occurred in 45.3% of cases (posterior synechiae [28%], cataracts [16%], band keratopathy [14%], ocular hypertension [11%] and cystoid macular edema [10%]) and were associated with synthetic (86%) and biologic (65%) disease-modifying antirheumatic drug (DMARD) use. Subgroups were significantly associated (p < 0.05) with different characteristics. JIAu was typically anterior (98%), insidious (75%), in ANA-positive (69%), young females (82%) with fewer complications (31%), better visual outcomes, and later use of uveitis-effective biologics. In contrast, IDIu was characteristically anterior (87%) or panuveitic (12.1%), with acute onset (60%) and more complications at onset (59%: synechiae [31%] and cataracts [9.6%]) and less DMARD use, while PP is intermediate, and was mostly bilateral (72.5%), persistent (86.5%) and chronic (86.8%), with more complications (70%; mainly posterior segment and cataracts at last visit), impaired visual acuity at onset, and greater systemic (81.2%), subtenon (29.1%) and intravitreal (10.1%) steroid use. CONCLUSION: Prognosis of childhood uveitis has improved in the "biologic era," particularly in JIAu. Early referral and DMARD therapy may reduce steroid use and improve outcomes, especially in PP and IDIu.
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Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) consisting of a humanised, anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody covalently linked to a topoisomerase I inhibitor cytotoxic payload (DXd). The high drug-to-antibody ratio (8:1) ensures a high DXd concentration is delivered to target tumour cells, following internalisation of T-DXd and subsequent cleavage of its tetrapeptide-based linker. DXd's membrane-permeable nature enables it to cross cell membranes and potentially exert antitumour activity on surrounding tumour cells regardless of HER2 expression. T-DXd's unique mechanism of action is reflected in its efficacy in clinical trials in patients with HER2-positive advanced breast cancer (in heavily pretreated populations and in those previously treated with a taxane and trastuzumab), as well as HER2-low metastatic breast cancer. Thus, ADCs such as T-DXd have the potential to change the treatment paradigm of targeting HER2 in metastatic breast cancer, including eventually within the adjuvant/neoadjuvant setting.
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Neoplasias de la Mama , Camptotecina , Inmunoconjugados , Trastuzumab , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Trastuzumab/uso terapéutico , Femenino , Inmunoconjugados/uso terapéutico , Inmunoconjugados/farmacología , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inhibidores , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/farmacologíaRESUMEN
INTRODUCTION: The outbreak of monkeypox occurred in 2022 and led to a fast spread of the disease worldwide. The goal of this study is to describe the epidemiological, clinical, virological and evolving characteristics of the disorder. METHODS: We conducted a retrospective, observational and analytical study between July and October, 2022, in a Dermatology Unit. RESULTS: 124 subjects were included. Mean age was 31.5 years, 123 (99.2%) were men and 75 (60.5%) were HIV positive. The main transmission route was sexual and the incubation period was 7 days. The onset of the rash were the genitalia and perianal region in 74.2% of cases, and median time elapsed until the last scab fell off was 16 days. All patients developed a vesicular rash and 86.3% of them had systemic symptoms. Disease was moderate in 68.5% of patients and complications occurred most often when systemic symptoms and/or disseminated skin disease were present. Proctitis was the most frequent complication (59.4%) and its greater incidence was seen in the population with HIV. No significant difference was observed in real-time PCR cycle threshold values with regards to type of sample or duration of disease. Survival rate was 99.2% and other concomitant sexually transmitted infections were detected in 33.8% of patients. DISCUSSION: It is important to suspect the disease in subjects with high-risk sexual practices and a consistent clinical presentation. Swab samples of lesions as well as of scabs have proven useful for the diagnosis.
Introducción: El brote de viruela símica 2022 se extendió rápidamente por todo el mundo. El objetivo del presente trabajo es describir las características epidemiológicas, clínicas, evolutivas y virológicas. Métodos: Estudio retrospectivo, observacional y analítico entre julio-octubre del 2022 en pacientes atendidos en una Unidad de Dermatología. Resultados: Se incluyeron 124 individuos. La mediana de edad fue de 31.5 años, siendo 123 (99.2%) hombres y 70 (60.5%) HIV positivos. La vía principal de contagio fue la transmisión sexual y el período de incubación de 7 días. Las lesiones se iniciaron en la región genital y perianal en el 74.2% de los casos y el tiempo hasta la caída de la última costra presentó una mediana de 16 días. Todos desarrollaron exantema vesiculoso, el 86.3% de los individuos presentó síntomas sistémicos. La enfermedad fue moderada en el 68.5% de los pacientes y las complicaciones se observaron con mayor frecuencia en aquellos con síntomas sistémicos y/o enfermedad diseminada. Proctitis fue la complicación más destacada (59.4%) y su mayor incidencia se observó en la población con HIV. No hubo diferencias significativas en los valores de Ct de la qPCR al evaluar tipo de muestra procesada o tiempo de evolución de la enfermedad. La sobrevida fue del 99.2% y en el 33.8% de los pacientes se detectaron otras infecciones concomitantes de transmisión sexual. Discusión: Se debe sospechar la enfermedad en individuos con cuadro compatible y prácticas sexuales de riesgo. Las muestras de hisopado de lesiones y de costra resultaron útiles para el diagnóstico.
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Exantema , Mpox , Proctitis , Masculino , Humanos , Adulto , Femenino , Estudios Retrospectivos , Brotes de Enfermedades , Exantema/epidemiologíaRESUMEN
Abstract Introduction : The outbreak of monkeypox occurred in 2022 and led to a fast spread of the disease worldwide. The goal of this study is to describe the epidemiologi cal, clinical, virological and evolving characteristics of the disorder. Methods : We conducted a retrospective, observational and analytical study between July and October, 2022, in a Dermatology Unit. Results : 124 subjects were included. Mean age was 31.5 years, 123 (99.2%) were men and 75 (60.5%) were HIV positive. The main transmission route was sexual and the incubation period was 7 days. The onset of the rash were the genitalia and perianal region in 74.2% of cases, and median time elapsed until the last scab fell off was 16 days. All patients developed a vesicular rash and 86.3% of them had systemic symptoms. Disease was moderate in 68.5% of patients and complications occurred most often when systemic symptoms and/or disseminated skin disease were present. Proctitis was the most frequent complication (59.4%) and its greater incidence was seen in the population with HIV. No significant difference was observed in real-time PCR cycle threshold values with regards to type of sample or duration of disease. Survival rate was 99.2% and other concomitant sexually transmitted infections were de tected in 33.8% of patients. Discussion : It is important to suspect the disease in subjects with high-risk sexual practices and a consistent clinical presentation. Swab samples of lesions as well as of scabs have proven useful for the diagnosis.
Resumen Introducción : El brote de viruela símica 2022 se ex tendió rápidamente por todo el mundo. El objetivo del presente trabajo es describir las características epide miológicas, clínicas, evolutivas y virológicas. Métodos : Estudio retrospectivo, observacional y analí tico entre julio-octubre del 2022 en pacientes atendidos en una Unidad de Dermatología. Resultados : Se incluyeron 124 individuos. La mediana de edad fue de 31.5 años, siendo 123 (99.2%) hombres y 70 (60.5%) HIV positivos. La vía principal de contagio fue la transmisión sexual y el período de incubación de 7 días. Las lesiones se iniciaron en la región genital y perianal en el 74.2% de los casos y el tiempo hasta la caída de la última costra presentó una mediana de 16 días. Todos desarrollaron exantema vesiculoso, el 86.3% de los individuos presentó síntomas sistémicos. La en fermedad fue moderada en el 68.5% de los pacientes y las complicaciones se observaron con mayor frecuencia en aquellos con síntomas sistémicos y/o enfermedad 61 diseminada. Proctitis fue la complicación más destacada (59.4%) y su mayor incidencia se observó en la población con HIV. No hubo diferencias significativas en los valores de Ct de la qPCR al evaluar tipo de muestra procesada o tiempo de evolución de la enfermedad. La sobrevida fue del 99.2% y en el 33.8% de los pacientes se detectaron otras infecciones concomitantes de transmisión sexual. Discusión : Se debe sospechar la enfermedad en in dividuos con cuadro compatible y prácticas sexuales de riesgo. Las muestras de hisopado de lesiones y de costra resultaron útiles para el diagnóstico.
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Introduction: The impact of a pandemic on the mental health of the population is to be expected due to risk factors such as social isolation. Prescription drug abuse and misuse could be an indicator of the impact of the COVID-19 pandemic on mental health. Community pharmacists play an important role in addressing prescription drug abuse by detecting signs and behaviors that give a clearer indication that a drug abuse problem exists. Methods: A prospective observational study to observe prescription drug abuse was conducted from March 2020 to December 2021 to compare with data obtained in the previous 2 years, through the Medicine Abuse Observatory, the epidemiological surveillance system set up in Catalonia. Information was obtained through a validated questionnaire attached on a web-based system and data collection software. A total of 75 community pharmacies were enrolled in the program. Results: The number of notifications during the pandemic period (11.8/100.000 inhabitants) does not indicate a significant change compared with those from pre-pandemic period, when it was 12.5/100.000 inhabitants. However, the number of notifications during the first wave when lockdown was in place stood at 6.1/100,000 inhabitants, significantly lower than in both the pre-pandemic and the whole of the pandemic periods. Regarding the patient's profile, it was observed that the proportion of younger patients (<25 and 25-35) rose in contrast to older ones (45-65 and >65). The use of benzodiazepines and fentanyl increased. Conclusions: This study has made it possible to observe the impact of the pandemic caused by COVID-19 on the behavior of patients in terms of use of prescription drugs through analysis of the trends of abuse or misuse and by comparing them with the pre-pandemic period. Overall, the increased detection of benzodiazepines has pointed out stress and anxiety generated by the pandemic.
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COVID-19 , Farmacias , Humanos , COVID-19/epidemiología , Control de Enfermedades Transmisibles , Pandemias , BenzodiazepinasRESUMEN
Os anti-inflamatórios não esteroidais (AINE) estão entre os medicamentos mais utilizados no mundo e são os fármacos mais frequentemente associados à ocorrência de reações de hipersensibilidade na América Latina. As reações têm grande variabilidade de apresentações clínicas e, consequentemente, com abordagem terapêutica difícil. Nesta revisão, abordamos aspectos farmacológicos dos AINE, bem como as definições, epidemiologia e fisiopatologia das reações de hipersensibilidade aos AINE. Por fim, discutimos aspectos genéticos associados à intolerância e alergia a esses fármacos.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used medications worldwide and the drugs most frequently associated with the occurrence of hypersensitivity reactions in Latin America. The clinical presentation of the reactions varies widely, which makes them difficult to treat. In this review, we address pharmacological aspects of NSAIDs, as well as the definitions, epidemiology, and pathophysiology of hypersensitivity reactions to NSAIDs. Finally, we discuss genetic factors associated with intolerance and allergy to these drugs.
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Humanos , Epidemiología , Fenómenos GenéticosRESUMEN
Traditionally, health sentinel networks have focused on the reporting of data by primary care physicians and hospitals, ignoring the role of the community pharmacist as an expert in drugs. The objective of this study was to describe a method for creating a network of sentinel pharmacies in a region of Southern Europe in order to have a pharmaceutical surveillance system that is representative of the territory to be monitored and that can respond to any events or incidents that can be followed up by the community pharmacy. The creation process was carried out in three phases: a first phase of selection through a cluster and population analysis and a final adjustment, a second phase of voluntariness and random selection, and a third phase of training and implementation of the network. A sentinel network of 75 community pharmacies has been established in Catalonia. The network monitors 2.47% of the total population with a homogeneous proportion of urban (42), rural (30), and mountain-area (3) pharmacies based on the particular characteristics of the territory. This model allows increased surveillance in the territory, objectively and representatively detects problems arising from the use of medicines, and establishes improvement strategies of public health.
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Servicios Comunitarios de Farmacia , Farmacias , Farmacia , Europa (Continente)/epidemiología , Humanos , Farmacéuticos , Vigilancia de GuardiaRESUMEN
Os betalactâmicos são a classe de drogas que mais causam reações de hipersensibilidade envolvendo um mecanismo imunológico específico, e são os principais desencadeantes entre os antimicrobianos. São representados pelas penicilinas, cefalosporinas, carbapenêmicos, monobactâmicos e inibidores da betalactamase. A estrutura química básica destes fármacos consiste na presença dos seguintes componentes: anel betalactâmico, anel adjacente e cadeias laterais, sendo todos potenciais epítopos. Os anticorpos da classe IgE e linfócitos T estão frequentemente envolvidos no reconhecimento desses epítopos. A reatividade cruzada depende da estabilidade dos produtos intermediários (determinantes antigênicos) derivados da degradação dos anéis betalactâmicos, anéis adicionais e da semelhança estrutural das cadeias laterais entre as drogas. Classicamente acreditava-se num grande potencial de reatividade cruzada dentro de cada classe e até entre as classes, mas estudos da última década mostraram que indivíduos alérgicos à penicilina (com testes cutâneos positivos) reagiam às cefalosporinas em aproximadamente 3% dos casos, aos carbapenêmicos em cerca de 1%, e praticamente não reagiam aos monobactâmicos. Essa reatividade ou tolerância parece estar vinculada ao grau de similaridade entre as cadeias laterais desses antibióticos. Nesta revisão, ressaltamos a importância da investigação sistematizada na confirmação ou exclusão de alergia aos betalactâmicos, descrevemos a prevalência da reatividade cruzada entre estes fármacos e sugerimos um algoritmo de abordagem desses pacientes baseados em sua estrutura química e nos dados publicados na literatura.
Beta-lactams are the drugs most commonly involved in hypersensitivity reactions mediated by a specific immune mechanism and are the main triggers among antibiotics. They include penicillins, cephalosporins, carbapenems, monobactams and beta-lactam inhibitors. The basic chemical structure of these drugs consist on the presence of the following components: betalactam ring, an adjacent ring and side chains, all of which are potential epitopes. IgE antibodies and T lymphocytes are often involved in recognizing those epitopes. Cross-reactivity depends on the stability of intermediate products (antigenic determinants) derived from the degradation of the beta-lactam ring, on the adjacent rings, and on the structural similarity of the side chains between drugs. Classically, it was believed that there was a great potential for cross-reactivity within each class and even between classes, but studies from the last decade showed that individuals allergic to penicillin (with positive skin tests) reacted to cephalosporins in approximately 3% of cases, to carbapenems in about 1%, and rarely reacted to monobactams. This reactivity or tolerance seems to be linked to the degree of similarity between the side chains of these antibiotics. In this review, we emphasize the importance of systematic investigation to confirm or exclude allergy to beta-lactams, we describe the prevalence of crossreactivity between these drugs and we suggest an algorithm for approaching these patients based on their chemical structure and on data published in the literature.
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Humanos , Penicilinas , Monobactamas , Inmunoglobulina E , Linfocitos T , Carbapenémicos , Cefalosporinas , beta-Lactamas , Hipersensibilidad , Pacientes , Preparaciones Farmacéuticas , PrevalenciaRESUMEN
The misuse of medicines is a global public health concern that needs to be taken into consideration and requires actions across all government sectors and society. The aim of this study is to identify trends of drug abuse in Catalonia, a region of Spain located in the South of Europe. For this purpose, a questionnaire-based detection tool was created and implemented in 60 community pharmacies. Out of 548 questionnaires (98.4%), 64.2% of participants were men and the highest age proportion was 25-35 years (31.4%). Potential drug abuse was the highest in urban pharmacies (84.9%). The main drug class involved were benzodiazepines (31.8%), codeine (19.3%), tramadol (7.5%), methylphenidate (5.8%), gabapentinoids (5.8%), cycloplegic drops (4.4%), z-drugs (2.6%), piracetam (2.2%), dextromethorphan (1.6%) and clomethiazole (1.1%). The majority of drugs were requested without prescription (58.6%) and through probably forged prescriptions (23.7%). Slightly less than half (49.8%) of the patients request frequently to the pharmacist, especially in rural and mountain pharmacies (73.3% and 88.5%, respectively). A small proportion (10.8%) were requested with intimidation. Pharmacists only supplied in 21.7% of the cases. This study has demonstrated the suitability of the new detection system, being a useful approach to replicate in other locations with similar needs.
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Servicios Comunitarios de Farmacia , Farmacias , Trastornos Relacionados con Sustancias , Adulto , Codeína , Europa (Continente) , Humanos , Masculino , Farmacéuticos , Trastornos Relacionados con Sustancias/epidemiologíaRESUMEN
Betalactams are the most frequent cause of hypersensitivity reactions to drugs mediated by a specific immune mechanism. Immediate reactions occur within 1 to 6 hours after betalactam administration, and are generally IgE-mediated. They clinically translate into urticaria, angioedema and anaphylaxis. Non-immediate or delayed reactions occur after 1 hour of administration. These are the most common reactions and are usually mediated by T cells. The most frequent type is the maculopapular or morbilliform exanthematous eruption. Most individuals who report allergies to penicillin and betalactams can tolerate this group of antibiotics. To make diagnosis, a detailed medical history is essential to verify whether it was an immediate or non-immediate reaction. Thereafter, in vivo and/or in vitro tests for investigation may be performed. The challenging test is considered the gold standard method for diagnosis of betalactam hypersensitivity. The first approach when suspecting a reaction to betalactam is to discontinue exposure to the drug, and the only specific treatment is desensitization, which has very precise indications. The misdiagnosis of penicillin allergy affects the health system, since the "penicillin allergy" label is associated with increased bacterial resistance, higher rate of therapeutic failure, prolonged hospitalizations, readmissions, and increased costs. Thus, it is essential to develop strategies to assist the prescription of antibiotics in patients identified with a label of "betalactam allergy" at hospitals, and to enhance education of patients and their caregivers, as well as of non-specialist physicians.
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Anafilaxia , Hipersensibilidad a las Drogas , Antibacterianos/efectos adversos , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/etiología , Humanos , Penicilinas/efectos adversos , beta-Lactamas/efectos adversosRESUMEN
INTRODUCTION: The sixth World Symposium of Pulmonary Hypertension (sixth WSPH) brought to the forefront for the first time the value of earlier, aggressive management with an upfront oral combination in patients with pulmonary arterial hypertension (PAH) of low or intermediate risk. This was prompted by results from the AMBITION study (ambrisentan + tadalafil). A literature search was conducted to collect all evidence provided by upfront treatment with this combination, as well as other combinations under investigation at the time the manuscript was prepared. AREAS COVERED: The value of an upfront oral combination with ambrisentan and tadalafil is reviewed on the basis of topics discussed at the sixth WSPH, such as evidence in different PAH etiologies, according to risk stratification and in so-called 'atypical' patients where monotherapy is still recommended. Evidence in clinical practice is also reviewed. New evidence about the value of the upfront oral combination is also commented. Finally, tendencies in primary endpoints to assess the effect of PAH-targeted therapies (time to clinical worsening and hemodynamics) and their value are also reviewed. EXPERT OPINION: All above-mentioned aspects are put into perspective with regard to the impact of new advances on improving PAH management in clinical practice.
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Hipertensión Arterial Pulmonar , Antihipertensivos/efectos adversos , Quimioterapia Combinada , Humanos , Fenilpropionatos , Piridazinas , Tadalafilo/uso terapéuticoRESUMEN
Childhood obesity is a strong risk factor for adult obesity, type 2 diabetes, and cardiovascular disease. The mechanisms that link early adiposity with late-onset chronic diseases are poorly characterised. We developed a mouse model of early adiposity through litter size reduction. Mice reared in small litters (SLs) developed obesity, insulin resistance, and hepatic steatosis during adulthood. The liver played a major role in the development of the disease. OBJECTIVE: To gain insight into the molecular mechanisms that link early development and childhood obesity with adult hepatic steatosis and insulin resistance. METHODS: We analysed the hepatic transcriptome (Affymetrix) of control and SL mice to uncover potential pathways involved in the long-term programming of disease in our model. RESULTS: The circadian rhythm was the most significantly deregulated Gene Ontology term in the liver of adult SL mice. Several core clock genes, such as period 1-3 and cryptochrome 1-2, were altered in two-week-old SL mice and remained altered throughout their life course until they reached 4-6 months of age. Defective circadian rhythm was restricted to the periphery since the expression of clock genes in the hypothalamus, the central pacemaker, was normal. The period-cryptochrome genes were primarily entrained by dietary signals. Hence, restricting food availability during the light cycle only uncoupled the central rhythm from the peripheral and completely normalised hepatic triglyceride content in adult SL mice. This effect was accompanied by better re-alignment of the hepatic period genes, suggesting that they might have played a causal role in mediating hepatic steatosis in the adult SL mice. Functional downregulation of Per2 in hepatocytes in vitro confirmed that the period genes regulated lipid-related genes in part through peroxisome proliferator-activated receptor alpha (Ppara). CONCLUSIONS: The hepatic circadian rhythm matures during early development, from birth to postnatal day 30. Hence, nutritional challenges during early life may misalign the hepatic circadian rhythm and secondarily lead to metabolic derangements. Specific time-restricted feeding interventions improve metabolic health in the context of childhood obesity by partially re-aligning the peripheral circadian rhythm.
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Ritmo Circadiano/fisiología , Lactancia , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Adiposidad , Adulto , Animales , Ritmo Circadiano/genética , Diabetes Mellitus Tipo 2/metabolismo , Ayuno , Femenino , Humanos , Hipotálamo/metabolismo , Recién Nacido , Resistencia a la Insulina/fisiología , Enfermedades Metabólicas/metabolismo , Ratones , Ratones Endogámicos ICR , Enfermedad del Hígado Graso no Alcohólico/genética , Obesidad/metabolismo , Obesidad InfantilRESUMEN
ABSTRACT Betalactams are the most frequent cause of hypersensitivity reactions to drugs mediated by a specific immune mechanism. Immediate reactions occur within 1 to 6 hours after betalactam administration, and are generally IgE-mediated. They clinically translate into urticaria, angioedema and anaphylaxis. Non-immediate or delayed reactions occur after 1 hour of administration. These are the most common reactions and are usually mediated by T cells. The most frequent type is the maculopapular or morbilliform exanthematous eruption. Most individuals who report allergies to penicillin and betalactams can tolerate this group of antibiotics. To make diagnosis, a detailed medical history is essential to verify whether it was an immediate or non-immediate reaction. Thereafter, in vivo and/or in vitro tests for investigation may be performed. The challenging test is considered the gold standard method for diagnosis of betalactam hypersensitivity. The first approach when suspecting a reaction to betalactam is to discontinue exposure to the drug, and the only specific treatment is desensitization, which has very precise indications. The misdiagnosis of penicillin allergy affects the health system, since the "penicillin allergy" label is associated with increased bacterial resistance, higher rate of therapeutic failure, prolonged hospitalizations, readmissions, and increased costs. Thus, it is essential to develop strategies to assist the prescription of antibiotics in patients identified with a label of "betalactam allergy" at hospitals, and to enhance education of patients and their caregivers, as well as of non-specialist physicians.
RESUMO Os beta-lactâmicos constituem a causa mais frequente de reações de hipersensibilidade a fármacos mediadas por mecanismo imunológico específico. As reações imediatas ocorrem em 1 até 6 horas após a administração do beta-lactâmico, sendo geralmente IgE-mediadas. Elas se traduzem clinicamente por urticária, angioedema e anafilaxia. As reações não imediatas ou tardias ocorrem após 1 hora da administração. São as reações mais comuns, sendo geralmente mediadas por células T. O tipo mais frequente é o exantema maculopapular ou morbiliforme. A maioria dos indivíduos que refere alergia aos beta-lactâmicos pode tolerar esse grupo de antibióticos. No diagnóstico, uma história clínica detalhada é fundamental para verificar se a reação foi do tipo imediato ou não imediato. A partir daí, podem ser realizados testes in vivo e/ou in vitro para investigação. O teste de provocação é considerado o método padrão-ouro no diagnóstico de hipersensibilidade aos beta-lactâmicos. A primeira conduta diante da suspeita de uma reação ao beta-lactâmico é suspender a exposição ao medicamento, e o único tratamento específico é a dessensibilização, que possui indicações bem precisas. O diagnóstico equivocado de alergia à penicilina afeta o sistema de saúde, pois o rótulo de "alergia à penicilina" está associado a aumento da resistência bacteriana, maior índice de falha terapêutica, hospitalizações prolongadas, readmissões e aumento dos custos. Assim, torna-se fundamental elaborar estratégias com o objetivo de auxiliar na prescrição de antibióticos em pacientes com rótulo de "alergia aos beta-lactâmicos" nos hospitais e melhorar a educação dos pacientes e seus responsáveis, além de médicos não especialistas.
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Humanos , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/etiología , Anafilaxia , Penicilinas/efectos adversos , beta-Lactamas/efectos adversos , Antibacterianos/efectos adversosRESUMEN
OBJECTIVE: The purpose of the study was to develop an easily applicable predictive model to predict deep infiltrating endometriosis in patients with ovarian endometrioma. STUDY DESIGN: We performed a retrospective analysis of 178 consecutive women with ovarian endometrioma who underwent surgery, with histological confirmation and complete removal of endometriosis in the Hospital Clinic of Barcelona. Several markers were prospectively obtained and compared between the group of patients presenting deep infiltrating endometriosis associated with ovarian endometrioma and women with only ovarian endometrioma. Multiple logistic regression analysis was performed to create a model to predict the presence of deep infiltrating endometriosis and internal validation was later performed. RESULTS: Of the 178 patients studied, 80 (45%) were classified in the ovarian endometrioma group and 98 (55%) in the group of patients presenting deep infiltrating endometriosis associated with ovarian endometrioma. The independent variables to predict deep infiltrating endometriosis were: at least one previous pregnancy, a past history of surgery for endometriosis and the mean endometriosis-associated pelvic pain score. The area under the ROC curve was 0.91 (95% confidence interval: 0.86-0.94), with an optimal cut-off of the predicted probability of 0.54. The sensitivity of the model was 80% and the specificity 84%. CONCLUSIONS: This model predicts the development of deep infiltrating endometriosis in patients with ovarian endometriomas allowing prioritization of women for referral to specialized centers.
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Endometriosis/diagnóstico , Enfermedades del Ovario/diagnóstico , Enfermedades Peritoneales/diagnóstico , Endometriosis/cirugía , Femenino , Humanos , Modelos Teóricos , Enfermedades del Ovario/cirugía , Enfermedades Peritoneales/cirugía , Sensibilidad y EspecificidadRESUMEN
INTRODUCTION: Recent reports consider endometriosis to be an immunological disorder, thus suggesting potential efficacy of immunomodulators for its treatment. The aim of this study was to assess the effects of oral administration of pentoxifylline on endometriosis-like lesions in a heterologous mice model. STUDY DESIGN: Human endometrial tissue obtained from women (n = 5) undergoing surgery for benign conditions was implanted in nude female mice (n = 30). The animals were distributed into 3 experimental groups receiving: saline 0.1 mL/d (control, group 1); pentoxifylline 100 mg/kg/d (group 2), and pentoxifylline 200 mg/kg/d (group 3). After 28 days, the number of implants and the total volume of surgically extracted tissue were recorded. Immunohistochemical analysis was performed to assess the area of endometriosis and vascularization of endometriosis-like lesions. Cytokine levels in peritoneal fluid samples were measured. RESULTS: Macroscopic quantification showed a trend to dose-dependent reduction in the number of the endometriosis-like lesions after 28 days. The volume was significantly reduced in group 3 versus group 2 and controls (399.10 ± 120.68 mm3 vs 276.75 ± 94.30 mm3 and 145.33 ± 38.20 mm3, respectively; P = .04). Similarly, the mean area of endometriosis was significantly lower in group 3 (0.12 ± 0.08 mm2) versus group 2 (1.35 ± 0.43 mm2) and control (2.84 ± 0.60 mm2; P = .001). Vascularization and cytokine levels were also reduced posttreatment. CONCLUSION: Our results suggest that the oral administration of pentoxifylline may be an alternative to current therapies for endometriosis. Nonetheless, further studies are required.
Asunto(s)
Endometriosis/tratamiento farmacológico , Endometrio/efectos de los fármacos , Pentoxifilina/uso terapéutico , Vasodilatadores/uso terapéutico , Administración Oral , Animales , Modelos Animales de Enfermedad , Endometriosis/patología , Endometrio/patología , Femenino , Ratones , Ratones Desnudos , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/patología , Pentoxifilina/administración & dosificación , Resultado del Tratamiento , Vasodilatadores/administración & dosificaciónRESUMEN
BACKGROUND: The identification of presurgical clinical markers may be helpful to allow the staging of endometriosis severity. It has been suggested that pain characteristics orientate the gynecologist about the anatomical involvement of endometriosis. The study was performed to analyze the correlation between pain symptoms and the anatomical location of endometriosis. METHODS: One hundred fifty-five consecutive patients with a complete removal of deep infiltrating endometriosis (DIE) were included. Prior to surgery, data on patient and disease characteristics were obtained. The intensity of the pain symptoms was registered using a Visual Analogue Scale. The endometriotic lesions were categorized according to the Enzian morphological classification. Correlation and multivariate analysis were performed to assess the potential associations between pain characteristics (dysmenorrhea, pelvic pain, dyschezia, dyspareunia or dysuria) and the location of endometriosis or other disease-related characteristics (hematuria, rectal bleeding or adenomyosis). RESULTS: Pelvic pain was significantly associated with the presence of adenomyosis. Dyschezia was correlated with rectal bleeding and dysuria with the presence of hematuria. No relationship was found between other kinds of pain and the morphological location of endometriosis or other disease-related characteristics. CONCLUSION: Our data suggest that pelvic pain is correlated with the presence of adenomyosis in women with DIE. Further studies are required.
Asunto(s)
Adenomiosis/fisiopatología , Endometriosis/patología , Endometriosis/fisiopatología , Dimensión del Dolor , Adulto , Estreñimiento/fisiopatología , Dismenorrea/complicaciones , Dismenorrea/fisiopatología , Dispareunia/fisiopatología , Disuria/fisiopatología , Endometriosis/cirugía , Femenino , Humanos , Persona de Mediana Edad , Dolor Pélvico/fisiopatología , Enfermedades PeritonealesRESUMEN
AIMS: The primary outcome was to evaluate the subjective success rates of two laparoscopic POP operation techniques: uterine-sparing surgery versus a subtotal hysterectomy plus cervicopexy. METHODS: Prospective cohort of 45 women with symptomatic POP recruited between January and December 2010 who self-selected surgery group: group A (n = 15), sacral laparoscopic hysteropexy was performed and group B (n = 30), laparoscopically conducted subtotal hysterectomy plus cervicopexy. All patients had a positive answer in the "Epidemiology of prolapse and incontinence" questionnaire (EPIQ, question number 35) and also had a POPQ ≥2nd degree. The primary outcome was the subjective success rate, measured by a negative answer to the Q35 of EPIQ: "Do you have a sensation that there is bulge in vagina or that something is falling out from your vagina" and also by rating their symptoms improvement by the "Patient Global Impression of Improvement". The secondary outcome was the objective success rate assessed by pelvic examination: cure was considered when POPQ <2nd degree in all vaginal compartments at 6 and 12 months. RESULTS: Baseline demographic characteristics were similar between groups. Subjective success rate was significantly superior in group B both after 6 and 12 months (P = 0.001). Similarly, objective pelvic examination led to a significantly higher rate of successful apical outcome in group B after 6 and 12 months (P = 0.009 and P = 0.002, respectively). Neither major complications nor vaginal mesh erosions were registered. CONCLUSIONS: The overall success rate was significantly higher in the laparoscopic subtotal hysterectomy plus cervicopexy group, compared with the laparoscopic sacral hysteropexy group.
Asunto(s)
Procedimientos Quirúrgicos Ginecológicos/métodos , Histerectomía/métodos , Laparoscopía , Prolapso de Órgano Pélvico/cirugía , Adulto , Femenino , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Humanos , Histerectomía/efectos adversos , Laparoscopía/efectos adversos , Persona de Mediana Edad , Satisfacción del Paciente , Prolapso de Órgano Pélvico/diagnóstico , Proyectos Piloto , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The purpose of this study was to investigate if the concentration of lactate can provide additional information for pathologies that need examination of the cerebrospinal fluid (CSF) in their diagnostic controls or protocols. METHODS: A prospective study carried out in the year 2001 at the University Hospital of Bellvitge (Barcelona), on 92 samples of CSF from patients who needed this examination. The concentration of lactate, glucose, and the cell count was determined. One year later, the diagnosis revealed from the previous analyzed samples were sorted into groups according to the diagnosis. RESULTS: In the group with multiple sclerosis (MS) (n = 30), there was a significant decrease in lactate concentration (1.52 +/- 0.19 mmol/L) compared to the control group (1.89 +/- 0.11 mmol/L) (p < 0.001). The glucose concentration remained within the normal range and the cell count was < 4 cell/microL even in the relapses. CONCLUSIONS: In the early stages of MS, the lactate concentration in CSF is decreased and this could be related to alterations in sensitivity observed in those patients. Further studies are needed to evaluate if this lactate concentration is a prognostic indicator of the disease.