Unmet needs in abnormal uterine bleeding due to ovulatory dysfunction.

Ovulatory disorders are a common cause of abnormal uterine bleeding in women of reproductive age. The International Federation of Gynecology and Obstetrics currently offers a causal classification system for ovulatory disorders but does not provide clear management recommendations. There remains regional disparity in treatment practices, often influenced by institutional and insurance regulations as well as cultural and religious practices. A panel of experts evaluated current gaps in ovulatory disorder management guidelines and discussed potential strategies for addressing these unmet needs. Key gaps included a lack in consensus about the effectiveness of combined estrogen and progestogen versus progestogen alone, a paucity of evidence regarding the relative effectiveness of distinct hormonal molecules, a lack of data regarding optimal treatment duration, and limited guidance on optimal sequencing of treatment. Recommendations included development of a sequential treatment-line approach and development of a clinical guide addressing treatment scenarios common to all countries, which can then be adapted to local practices. It was also agreed that current guidelines do not address the unique clinical challenges of certain patient groups. The panel discussed how the complexity and variety of patient groups made the development of one single disease management algorithm unlikely; however, a simplified, decision-point hierarchy could potentially help direct therapeutic choices. Overall, the panel highlighted that greater advocacy for a tailored approach to the treatment of ovulatory disorders, including wider consideration of non-estrogen therapies, could help to improve care for people living with abnormal uterine bleeding due to ovarian dysfunction.

Gastropod Allergy: A Comprehensive Narrative Review.

Food allergies have increased significantly in recent decades, with shellfish being a leading cause of food allergy and anaphylaxis worldwide, affecting both children and adults. The prevalence of shellfish allergies is estimated to be approximately 0.5-2.5% of the general population, varying significantly by geographical location, age, and consumption habits. Although mollusk consumption has risen, the prevalence of mollusk allergies remains unknown. While extensive research has focused on crustacean allergies, mollusk allergies, particularly those related to gastropods, have received comparatively less attention. Clinical manifestations of shellfish allergy range from localized symptoms to life-threatening systemic reactions, such as anaphylaxis. Notably, severe bronchospasm is a predominant clinical feature in cases involving gastropods. Several allergens have been identified in mollusks, including paramyosin, tropomyosin, and sarcoplasmic calcium-binding protein. In gastropods, documented allergens include tropomyosin, paramyosin, the heavy chain of myosin, and Der p 4 amylase. Diagnosis typically involves a thorough clinical history, skin testing, in vitro quantification of immunoglobulin (Ig) E, and confirmation through an oral challenge, although the latter is reserved for selected cases. This narrative review highlights the limited research on gastropod allergy. It provides a comprehensive list of purified and recombinant allergens and discusses the applications of component-resolved diagnosis as well as current therapeutic developments.

Advocacy of Precision Allergy Molecular Diagnosis in Decision Making for the Eligibility of Customized Allergen Immunotherapy.

Allergen immunotherapy (AIT) with aeroallergens is the only disease-modifying treatment for patients with different allergic conditions. Despite the effectiveness of AIT having been proven in both randomized controlled trials and real-world studies, it remains underused in less than 10% of subjects with allergic rhinitis (AR) and/or asthma (A). We aimed to determine the current eligibility for house dust mite (HDM) AIT by means of a precision allergy molecular diagnosis (PAMD@) model in a selected cohort of youngsters with different allergic phenotypes according to the available evidence. A complex response to both HDM and storage mite allergens was depicted regardless of the subjects' basal atopic condition. No solely specific IgE-binding responses to Der p 1, Der p 2, and/or Der p 23 were found in the studied cohort. Despite the patients with A and atopic dermatitis showing significantly higher serum titers to six mite allergens than subjects with AR, no specific molecular profile was regarded as disease specific. Given the increasing complexity of specific IgE responses to the local prevailing aeroallergens, the identification and presence of such molecules are needed in commercially available AIT in the era of precision medicine.

Femoral canal lipoma presenting as chronic venous insufficiency.

Lower limb venous obstruction secondary to a lipoma is a rare occurrence. Patients with these benign soft tissue tumors can be asymptomatic, or may experience symptoms of pain, parasthesia, paralysis and swelling secondary to compression on adjacent neurovascular structures. Duplex ultrasound examination is the first-line investigation, but has its limitations. We report on a case of venous obstruction syndrome misdiagnosed as chronic venous insufficiency on duplex ultrasound examination, from a deep-seated giant lipoma compressing on the common femoral and distal external iliac vein in a patient with Dercum's disease.

Infarto de miocardio con elevación del segmento ST inferior y anterior: ¿doble lesión culpable?

El dolor torácico es uno de los motivos de consulta más frecuente en un servicio de urgencia. Dentro de las hipótesis diagnósticas se deben descartar las patologías de mayor gravedad: el infarto al miocardio (IM), la disección aórtica, el tromboembolismo pulmonar y el neumotórax. El escenario más frecuente es el IM debido a un accidente de placa, pero existen casos en donde la disección aórtica puede verse acompañada de un déficit de perfusión coronaria (síndrome de malaperfusión) generando un IM. Su diagnóstico es difícil, con una mayor mortalidad y complejidad quirúrgica. Presentamos el caso de un hombre de 59 años que cursó con dolor torácico y electrocardiograma con elevación del segmento ST inferior y anterior, derivado a angioplastia primaria y que en el estudio angiográfico se identifica compromiso ostial de coronarias, se sospecha una disección aórtica, confirmándose por angiotomografía computada de aorta, donde se evidencia una disección de aorta ascendente con compromiso de ambos ostium coronarios que se trató quirúrgicamente.

Chest pain is one of the most frequent reasons for consultation in the emergency department. The most severe pathologies must be quickly ruled out within the diagnostic hypotheses: myocardial infarction (MI), aortic dissection, pulmonary thromboembolism, and pneumothorax. A frequent scenario is ST elevation MI due to a plaque accident. However, there are infrequent cases of aortic dissection associated with a deficit in coronary perfusion (malperfusion syndrome) that triggers a MI. The diagnosis of a double artery is difficult, with higher mortality and surgical complexity. We present the case of a 59-year-old man who presented chest pain and an electrocardiogram with inferior and anterior ST-segment elevation who was referred for primary angioplasty. The angiographic study confirmed the presence of a coronary ostium defect and suggested aortic dissection. Computed tomography angiography confirmed the diagnosis, showing the dissection of the ascending aorta with the compromise of both coronary ostia, which was subjected to surgical treatment.

Molecular Mapping of Allergen Exposome among Different Atopic Phenotypes.

Climate change and exposure to environmental pollutants play a key role in the onset and aggravation of allergic diseases. As different climate-dependent patterns of molecular immunoglobulin E (IgE) reactivity have been regionally described, we sought to investigate the evolving allergen exposome in distinctive allergic phenotypes and subtropical weather conditions through a Precision Allergy Molecular Diagnosis (PAMD@) model. Concurrent sensitization to several house dust mites (HDM) and storage mite molecules were broadly dominant in the investigated cohort, followed by the major cat allergen Fel d 1, and regardless of the basal allergic disease. Although a complex repertoire of allergens was recognized, a steadily increasing number of IgE binding molecules was associated with the complexity of the underlying atopic disease. Besides the highly prevalent IgE responses to major HDM allergens, Der p 21, Der p 5, and Der p 7 also showed up as serodominant molecules, especially in subjects bothered by asthma and atopic dermatitis. The accurate characterization of the external exposome at the molecular level and their putative role as clinically relevant allergens is essential to elucidate the phenotypic diversity of atopic disease in terms of personalized diagnosis and therapy.

Biopsia endomiocárdica en la práctica actual: Aspectos técnicos, indicaciones y complicaciones / Endomyocardial biopsy in current practice: Technical Aspects, Indications and complications

La biopsia endomiocárdica (BEM) es un procedimiento invasivo y una herramienta diagnóstica, que en el pasado se encontraba principalmente enfocado en el seguimiento del rechazo post trasplante cardíaco. Actualmente, juega un rol importante en el diagnostico de las miocardiopatías no isquémicas. Se realiza frecuentemente por un acceso venoso para acceder al ventrículo derecho. El rendimiento diagnóstico ha mejorado con el avance del análisis anatomo-patológico. El riesgo de complicaciones, cercana al 1%, de este procedimiento en centros con experiencia puede justificarse frente al beneficio potencial de un diagnóstico y pronóstico preciso.

Endomyocardial biopsy (EMB) is an invasive procedure and a diagnostic tool used mainly on the follow-up of post-heart transplant rejection in the past years. Currently, it has an important role in the diagnosis of non-ischemic cardiomyopathies. EMB is frequently performed through a venous access to enter the right ventricle. Diagnostic performance has improved with advances in pathology analysis. Its complications risk, close to 1% in high-volume interventional centers, can be justified considering the potential benefit of an accurate diagnosis and prognosis.

Going over Fungal Allergy: Alternaria alternata and Its Allergens.

Fungal allergy is the third most frequent cause of respiratory pathologies and the most related to a poor prognosis of asthma. The genera Alternaria and Cladosporium are the most frequently associated with allergic respiratory diseases, with Alternaria being the one with the highest prevalence of sensitization. Alternaria alternata is an outdoor fungus whose spores disseminate in warm and dry air, reaching peak levels in temperate summers. Alternaria can also be found in damp and insufficiently ventilated houses, causing what is known as sick building syndrome. Thus, exposure to fungal allergens can occur outdoors and indoors. However, not only spores but also fungal fragments contain detectable amounts of allergens and may function as aeroallergenic sources. Allergenic extracts of Alternaria hyphae and spores are still in use for the diagnosis and treatment of allergic diseases but are variable and insufficiently standardised, as they are often a random mixture of allergenic ingredients and casual impurities. Thus, diagnosis of fungal allergy has been difficult, and knowledge about new fungal allergens is stuck. The number of allergens described in Fungi remains almost constant while new allergens are being found in the Plantae and Animalia kingdoms. Given Alt a 1 is not the unique Alternaria allergen eliciting allergy symptoms, component-resolved diagnosis strategies should be applied to diagnose fungal allergy. To date, twelve A. alternata allergens are accepted in the WHO/IUIS Allergen Nomenclature Subcommittee, many of them are enzymes: Alt a 4 (disulfide isomerase), Alt a 6 (enolase), Alt a 8 (mannitol de-hydrogenase), Alt a 10 (aldehyde dehydrogenase), Alt a 13 (glutathione-S-transferase) and Alt a MnSOD (Mn superoxide dismutase), and others have structural and regulatory functions such as Alt a 5 and Alt a 12, Alt a 3, Alt a 7. The function of Alt a 1 and Alt a 9 remains unknown. Other four allergens are included in other medical databases (e.g., Allergome): Alt a NTF2, Alt a TCTP, and Alt a 70 kDa. Despite Alt a 1 being the A. alternata major allergen, other allergens, such as enolase, Alt a 6 or MnSOD, Alt a 14 have been suggested to be included in the diagnosis panel of fungal allergy.

[Myocardial infarction with elevation of the inferior and anterior ST segment: double artery is the culprit?] / Infarto de miocardio con elevación del segmento ST inferior y anterior: ¿doble lesión culpable?

Chest pain is one of the most frequent reasons for consultation in the emergency department. The most severe pathologies must be quickly ruled out within the diagnostic hypotheses: myocardial infarction (MI), aortic dissection, pulmonary thromboembolism, and pneumothorax. A frequent scenario is ST elevation MI due to a plaque accident. However, there are infrequent cases of aortic dissection associated with a deficit in coronary perfusion (malperfusion syndrome) that triggers a MI. The diagnosis of a double artery is difficult, with higher mortality and surgical complexity. We present the case of a 59-year-old man who presented chest pain and an electrocardiogram with inferior and anterior ST-segment elevation who was referred for primary angioplasty. The angiographic study confirmed the presence of a coronary ostium defect and suggested aortic dissection. Computed tomography angiography confirmed the diagnosis, showing the dissection of the ascending aorta with the compromise of both coronary ostia, which was subjected to surgical treatment.

[Endomyocardial biopsy in current practice: Technical Aspects, Indications and complications]. / Biopsia endomiocárdica en la práctica actual: Aspectos técnicos, indicaciones y complicaciones.

Endomyocardial biopsy (EMB) is an invasive procedure and a diagnostic tool used mainly on the follow-up of post-heart transplant rejection in the past years. Currently, it has an important role in the diagnosis of non-ischemic cardiomyopathies. EMB is frequently performed through a venous access to enter the right ventricle. Diagnostic performance has improved with advances in pathology analysis. Its complications risk, close to 1% in high-volume interventional centers, can be justified considering the potential benefit of an accurate diagnosis and prognosis.

Frail patients having vascular surgery during the early COVID-19 pandemic experienced high rates of adverse perioperative events and amputation.

BACKGROUND: Frailty predicts adverse perioperative outcomes and increased mortality in patients having vascular surgery. Frailty assessment is a potential tool to inform resource allocation, and shared decision-making about vascular surgery in the resource constrained COVID-19 pandemic environment. This cohort study describes the prevalence of frailty in patients having vascular surgery and the association between frailty, mortality and perioperative outcomes. METHODS: The COVID-19 Vascular Service in Australia (COVER-AU) prospective cohort study evaluates 30-day and six-month outcomes for consecutive patients having vascular surgery in 11 Australian vascular units, March-July 2020. The primary outcome was mortality, with secondary outcomes procedure-related outcomes and hospital utilization. Frailty was assessed using the nine-point visual Clinical Frailty Score, scores of 5 or more considered frail. RESULTS: Of the 917 patients enrolled, 203 were frail (22.1%). The 30 day and 6 month mortality was 2.0% (n = 20) and 5.9% (n = 35) respectively with no significant difference between frail and non-frail patients (OR 1.68, 95%CI 0.79-3.54). However, frail patients stayed longer in hospital, had more perioperative complications, and were more likely to be readmitted or have a reoperation when compared to non-frail patients. At 6 months, frail patients had twice the odds of major amputation compared to non-frail patients, after adjustment (OR 2.01; 95% CI 1.17-3.78), driven by a high rate of amputation during the period of reduced surgical activity. CONCLUSION: Our findings highlight that older, frail patients, experience potentially preventable adverse outcomes and there is a need for targeted interventions to optimize care, especially in times of healthcare stress.

Storage Mite Precision Allergy Molecular Diagnosis in the Moderate-to-Severe T2-High Asthma Phenotype.

Storage mites (SM) may induce allergic respiratory symptoms in sensitized individuals, in both rural and urban settings. The relationship among specific IgE reactions to determined groups of SM allergens in the coincident asthma pheno-endotypes has not yet been investigated. We aimed to study a Precision Allergy Molecular Diagnosis (PAMD@) model to depict the SM molecular profile in individuals presenting with Type-2 inflammation, in two different (moderate and severe) asthma phenotypes. A customized PAMD@ panel, including SM allergens and their concurrent protein allergenic characterization was investigated. Mite group 2 allergens were most frequently recognized, including Lep d 2 (83.45%), followed by Gly d 2 (69.17%) and Tyr p 2 (47,37%), in 133/164 asthmatic subjects. Blo t 5 and Blo t 21 exhibited significant higher titres in both asthma groups. Although relevant mite group 2 allergens cross-reactivity is suggested, individualized sensitization patterns were relevantly identified. The present PAMD@ panel confirmed the dominance of mite group 2 allergens in moderate-to-severe T2 asthmatics. A broadly heterogeneous molecular repertoire of SM allergens was found in all subjects, regardless of their asthma severity. Blomia tropicalis deserves special attention in certain territories, as diagnostic and/or therapeutic approaches merely based on Pyroglyphidae mites may be insufficient.

Serodominance Profile in a Dust Mite Complex Region.

BACKGROUND/OBJECTIVE: The objective of this study was to describe the molecular sensitization profile of mite allergy in an area with a high environmental exposure of house dust mites (HDM) and storage mites. METHODS: Skin prick tests were performed with standardized extracts (DIATER, Madrid, Spain). A specific commercial molecular panel (MADx) for Dermatophagoides pteronyssinus (Dpt), Dermatophagoides farinae (Dfar), Lepidoglyphus destructor (Ldt), Tyrophagus putrescentiae (Tput), and Blomia tropicalis (Blot) was correlated with clinical parameters in Galician (northwestern of Spain) HDM allergic patients. RESULTS: Fifty patients (60% female) met the inclusion and exclusion criteria. All of the patient's present rhinitis (50), 28% (14) rhinitis and asthma, and 18% (9) atopic dermatitis (AD). Hundred patients had a positive prick test for Dpt, followed by Dfar (92%), Ldt and Tput (74%), and Blot (68%). More than 50% recognized specific IgE for Der p 1, Der p 2, reaching 86% in the case of Der p 23. No statistically significant differences in IgE levels were found between patients with/without asthma and those with mild or moderate-severe rhinitis. Der p 7 was higher among rhinitis patients (p value 0.05). AD relative risk (RR) was increased in patients sensitized to Der f 2, Der p 2, and Der p 23. Der p 10 decreases the risk to have AD (RR 0.80). CONCLUSION: The evaluation of IgE results in a comprehensive panel of allergens allows differentiation of serological reactivity profiles with their clinical expression, to perform an optimal management. Improvements in component resolved diagnosis and more research on the clinical relevance of mite allergens are needed to achieve a genuine diagnosis leading to specific immunotherapy.

Yeast cell death pathway requiring AP-3 vesicle trafficking leads to vacuole/lysosome membrane permeabilization.

Unicellular eukaryotes have been suggested as undergoing self-inflicted destruction. However, molecular details are sparse compared with the mechanisms of programmed/regulated cell death known for human cells and animal models. Here, we report a molecular cell death pathway in Saccharomyces cerevisiae leading to vacuole/lysosome membrane permeabilization. Following a transient cell death stimulus, yeast cells die slowly over several hours, consistent with an ongoing molecular dying process. A genome-wide screen for death-promoting factors identified all subunits of the AP-3 complex, a vesicle trafficking adapter known to transport and install newly synthesized proteins on the vacuole/lysosome membrane. To promote cell death, AP-3 requires its Arf1-GTPase-dependent vesicle trafficking function and the kinase Yck3, which is selectively transported to the vacuole membrane by AP-3. Video microscopy revealed a sequence of events where vacuole permeability precedes the loss of plasma membrane integrity. AP-3-dependent death appears to be conserved in the human pathogenic yeast Cryptococcus neoformans.

House Dust Mite Precision Allergy Molecular Diagnosis (PAMD@) in the Th2-prone Atopic Dermatitis Endotype.

Atopic dermatitis (AD) endotyping might be important for developing personalized diagnostic and therapeutic strategies to the different phenotypes. The current study investigated the IgE molecular profile to Dermatophagoides pteronyssinus (D. pteronyssinus) in a subset of patients afflicted with varying severity stages of atopic dermatitis in a subtropical region subjected to a high perennial house dust mite (HDM) exposure. We selected patients showing a clinically relevant sensitization to HDM with mild-to-moderate and severe AD according to their basal Severity Scoring Atopic Dermatitis (SCORAD) index. Skin prick test (SPT) with standardized mite extracts, as well as a Precision Allergy Molecular Diagnosis (PAMD@) panel including nine different D. pteronyssinus allergens and the related protein allergenic characterization, were assessed in all serum samples. A total of 80 European American AD patients with the marked T2 endotype confirmed their eligibility for the study. Major allergens (Der p 23, Der p 2, and Der p 1) were present in more than 86% of all subjects, with mid-tier allergens (Der p 5, Der p 7, and Der p 21) reaching up to 65%. A serodominant role for Der p 11 could not be quantitatively confirmed in the present cohort. The proposed component resolved diagnosis (CRD) panel appeared to be sufficient to obtain a precise D. pteronyssinus molecular diagnosis in AD patients subjected to a climate-dependent high-mite allergen exposure. The raised seroprevalence of IgE response to Der p 23 confirmed this constituent as a major D. pteronyssinus allergen in severe stages of atopic dermatitis. A clinically driven molecular approach appears to be essential to frame a more precise diagnosis and therapy of this heterogeneous allergic condition.

Consequences of COVID-19 pandemic on myocardial infarction reperfusion therapy and prognosis.

Background The coronavirus disease (COVID-19) pandemic affected the prompt diagnosis and treatment of Acute myocardial infarction (AMI). AIM: To characterize the clinical profile of patients with AMI during the COVID-19 pandemic, comparing them with a historical cohort. MATERIAL AND METHODS: A case-control study of 96 patients with AMI transferred to a high-volume percutaneous coronary intervention (PCI) hospital between March and July 2020, and a historical cohort of 269 patients transferred during the same period in 2019. RESULTS: When comparing patients transferred during the pandemic with those of the historical cohort, the former were younger (63 ± 12 vs 68 ± 12 years, p < 0.01), had a higher frequency of hypertension (66 vs 45%, p < 0.01) and of smoking (40% vs 25%, p < 0.01). Also, during COVID-19 outbreak a higher proportion of patients had ST-elevation AMI consulting > 12 hours from the onset of symptoms (44 vs 0%, p < 0.01), a higher median door-to-device time (4 vs 3 hours, p < 0.01), a higher use of primary percutaneous coronary intervention (97 vs 71%, p < 0.01), and higher frequencies of cardiogenic shock (20 vs 4%, p < 0.01) and mechanical complications (10% vs 2%, p < 0.01). Patients during COVID pandemic had a higher thirty-day overall (20 vs 1.4%, p < 0.01) and cardiovascular mortality (13 vs 1%, p < 0.01). During the outbreak, 40% of patients had positive COVID-19 status, which was a predictor for thirty-day overall mortality (Risk ratio 2.90; 95% confidence intervals 1.14-7.36). CONCLUSIONS: During the pandemic patients with AMI exhibited delays in consultations and treatment, higher morbidity, and increased mortality. COVID-19 positivity was associated to worse thirty-day overall survival.

El infarto oculto: las claves para el diagnóstico precoz de infarto posterior / True posterior infarction diagnosis: report of three cases

Acute Coronary Syndrome with ST segment elevation requires rapid reperfusion, which is why the timely identification of these conditions, based on the patient's symptoms and the correct interpretation of the EKG, is essential for therapeutic decisions. We report three patients with True Posterior Infarction and their difficult EKG diagnosis. The classic 12-lead EKG method is often not capable of supporting the diagnosis, so we recommend the use of posterior leads and mirror images observing inverted V1-V2-V3 leads on the classic EKG.