AHR canonical pathway: in vivo findings to support novel antihypertensive strategies.

Essential hypertension (HTN) is a disease where genetic and environmental factors interact to produce a high prevalent set of almost indistinguishable phenotypes. The weak definition of what is under the umbrella of HTN is a consequence of the lack of knowledge on the players involved in environment-gene interaction and their impact on blood pressure (BP) and mechanisms. The disclosure of these mechanisms that sense and (mal)adapt to toxic-environmental stimuli might at least determine some phenotypes of essential HTN and will have important therapeutic implications. In the present manuscript, we looked closer to the environmental sensor aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor involved in cardiovascular physiology, but better known by its involvement in biotransformation of xenobiotics through its canonical pathway. This review aims to disclose the contribution of the AHR-canonical pathway to HTN. For better mirror the complexity of the mechanisms involved in BP regulation, we privileged evidence from in vivo studies. Here we ascertained the level of available evidence and a comprehensive characterization of the AHR-related phenotype of HTN. We reviewed clinical and rodent studies on AHR-HTN genetic association and on AHR ligands and their impact on BP. We concluded that AHR is a druggable mechanistic linker of environmental exposure to HTN. We conclude that is worth to investigate the canonical pathway of AHR and the expression/polymorphisms of its related genes and/or other biomarkers (e.g. tryptophan-related ligands), in order to identify patients that may benefit from an AHR-centered antihypertensive treatment.

Fat Embolism: A Rare Complication of Bone Biopsy.

We report a woman who was admitted to the hospital with a sudden onset of extensive maculopapular erythematous rash involving the trunk and extremities, six weeks after initiating antihypertensive medication. She had atypical lymphocytosis with Gumprecht shadows, elevated liver enzymes, and acute kidney injury. The diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome secondary to antihypertensive drugs was suspected and the antihypertensive drugs were suspended. A hypothesis of lymphoproliferative disease was also considered, and consequently, a myelogram and bone biopsy of the iliac crest were performed. After the procedure, the patient developed acute hypoxemia. After the exclusion of pulmonary thromboembolism by CT angiography, we assumed a presumptive diagnosis of iatrogenic fat embolism syndrome (FES) associated with bone biopsy. The patient deteriorated with worsening hypoxemia and ultimately died. This case represented a diagnostic challenge and highlighted iatrogenesis's undesirable and potentially fatal effects. Careful consideration of the risk-benefit ratio of all medical procedures is paramount in daily medical practice and knowledge of the possible risks is necessary for their early recognition and therapeutic approach.

Gabapentin-Induced Cutaneous Leukocytoclastic Vasculitis: A Case Report.

Leukocytoclastic vasculitis (LCV) is a type of small vessel vasculitis, characterized by a perivascular neutrophilic inflammatory infiltrate with fibrinoid necrosis and fragmentation of nuclei ("leukocytoclasia"). Although up to half of the cases of LCV are idiopathic, infections and drugs are the most common secondary triggers for this condition. We present the case of an 88-year-old woman who developed an erythematous maculopapular rash on both thighs three days after starting gabapentin for neuropathic leg pain, without other associated symptoms. Skin biopsy was compatible with cutaneous vasculitis with a leukocytoclastic pattern. The skin lesions resolved within about 10 days after discontinuing gabapentin, supporting the diagnosis. To our knowledge, there are only four published cases of LCV secondary to gabapentin. This case highlights the importance of being alert for diagnosing drug-related cutaneous manifestations, even if the drug is used in our daily practice and vasculitis is not a common side effect, since discontinuing the suspected agent is crucial to resolve skin lesions and to avoid more serious complications.

One Size Does Not Fit All: Medication Reconciliation and Review at the Hospital at Home.

Mistakes in the medication process are frequent and a common cause of morbidity and mortality. Medication reconciliation (MRec) and medication review (MRev) are the processes of creating the most accurate medication list and adapting it to optimize the effectiveness of medicines and minimize adverse effects. This is crucial in all stages of medical care, especially at discharge. The present study aims to evaluate and describe the process of MRec and MRev, with a focus on deprescribing, that we conduct at the Hospital at Home. We performed a retrospective cohort study including adult patients admitted at our Hospital at Home from 1 November 2022 to 30 April 2023. MRec and MRev were applied during hospitalization, according to patients' characteristics and clinical evolution, and then communicated to patients upon discharge. Our study involved 125 patients, with an average age of 67.6±18.0 years, and half of them had polypharmacy. We discovered discrepancies in 43.2% of patient's medication and did deprescribing in one-third of them. In the deprescribing group, patients were significantly older (mean age, 76.1 versus 66.4 years; p=0.044). It is imperative to create mechanisms to identify patients at a greater risk of adverse drug events and to minimize the burden of care and harms associated with treatments. The Hospital at Home could be an opportunity, although further research is essential.

Lymphomatoid Granulomatosis in HIV-2: A Rare Entity.

Lymphomatoid granulomatosis (LYG) is a rare B-cell lymphoproliferative disorder associated with Epstein-Barr virus (EBV) infection and is frequently associated with immunodeficiency. Pulmonary involvement with angiocentric distribution is the most common clinical manifestation. Diagnosis is confirmed by tissue biopsy, usually from lung lesions. Due to the paucity of reported cases, there is no validated treatment for LYG. Therapeutic options include interferon-alpha, systemic corticosteroids, rituximab, chemotherapy, and autologous hematopoietic stem cell transplantation. We report a case of a 49-year-old man, with human immunodeficiency virus type 2 (HIV-2) infection, who was diagnosed with LYG with lung involvement and had a full remission after treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

Gitelman Syndrome: A Rare Case of Hypokalaemia and a Novel Mutation.

Gitelman syndrome (GS) is a hereditary renal tubulopathy caused by mutations in the SLC12A3 gene which encodes the thiazide-sensitive apical sodium-chloride cotransporter. GS is characterized by hypokalaemia, hypomagnesaemia and metabolic alkalosis. Treatment is based on potassium and magnesium replacement ad eternum. We present the case of a young man with palpitations and persistent hypokalaemia, who was diagnosed with GS. Genetic testing revealed 2 mutations in the gene SLC12A3 of combined heterozygosity, both considered pathological. Interestingly, 1 of these mutations was not yet described in the literature or in the reviewed databases. We also discuss the clinical approach and the specificities of managing this rare hereditary renal tubulopathy.. LEARNING POINTS: Gitelman syndrome is a rare cause of persistent hypokalaemia.A definitive diagnosis is determined by the identification of mutations in the SLC12A3 gene.Management consists of chronic potassium and magnesium supplementation aimed at symptom control.

Osler-Weber-Rendu Syndrome with Severe Hepatic Manifestations: A Rare Clinical Case.

Rendu-Osler-Weber syndrome is a rare inherited syndrome with autosomal dominant transmission characterized by systemic arteriovenous malformations (AVMs) with multi-organ involvement. Its incidence is 1-2/100,000 and it is predominant in females (the male/female ratio varies from 1:2 to 1:4.5). Clinical manifestations and complications are related to recurrent bleeding and, in some cases, the development of end-organ failure. Management is mostly supportive care and it is essential to promote control of the disease as much as possible and screen eventual complications. We describe the case of a 67-year-old male patient with Rendu-Osler-Weber syndrome admitted to the emergency department with decompensated heart failure due to acute anaemia because of severe epistaxis. During hospitalization, the patient progressed to acute-on-chronic liver failure with hepatic encephalopathy and an abdominal computed tomography scan showed multiple hepatic AVMs considered to be the cause of the chronic liver disease. LEARNING POINTS: Rendu-Osler-Weber syndrome is a rare autosomal dominant syndrome characterized by systemic arteriovenous malformations (AVMs) with multi-organ involvement, in which the most common manifestation is recurrent epistaxis.In more severe cases the prognosis is determined by organ dysfunction caused by AVMs, including hepatic involvement, which happens in 74-79% of cases, leading to poor outcomes.The treatment is mainly supportive care so early recognition of major organ involvement is fundamental to prevent severe complications.

Derivation and external validation of the SHIeLD score for predicting outcome in normotensive pulmonary embolism.

BACKGROUND: Identifying patients with normotensive pulmonary embolism (PE) who may benefit from thrombolysis remains challenging. We sought to develop and validate a score to predict 30-days PE-related mortality and/or rescue thrombolysis. METHODS: We retrospectively assessed 554 patients with normotensive PE. Independent predictors of the studied endpoint were identified from variables available at admission in the emergency department and were used to create a score. The model was validated in 308 patients from a separate hospital. RESULTS: A total of 64 patients died or needed rescue thrombolysis (44 in the derivation cohort). Four independent prognostic factors were identified: Shock index ≥ 1.0 (OR 3.33; 95% CI 1.40-7.93; P = 0.006), HypoxaemIa by the PaO2/FiO2 ratio (OR 0.92 per 10 units; 95% CI 0.88-0.97; P < 0.001), Lactate (OR 1.38 per mmol/L; 95% CI 1.09-1.75; P = 0.008) and cardiovascular Dysfunction (OR 5.67; 95% CI 2.60-12.33; P < 0.001) - SHIeLD score. In the development cohort, event rates for each risk tercile were 0.0%, 2.2%, and 21.6%. In the validation cohort, corresponding rates were 0.0%, 1.9%, and 14.3%. The C-statistic was 0.90 (95% CI 0.86-0.94, P < 0.001) in the derivation cohort and 0.82 (95% CI 0.75-0.89, P < 0.001) in the validation cohort. Decision curve analysis showed that the SHIeLD score is able to accurately identify more true positive cases than the European Society of Cardiology decision criteria. CONCLUSIONS: A risk score to predict 30-days PE-related mortality and/or rescue thrombolysis in patients with normotensive PE was developed and validated. This score may assist physicians in selecting patients for closer monitoring or aggressive treatment strategy.

Presentación de un paciente con regeneración de defectos óseos periodontales y con plasma rico en plaquetas / Presentation of a Patient with Regeneration of Periodontal Bone Defects and Platelet-Rich Plasma

Las periodontitis implican pérdida de inserción clínica y destrucción ósea visible en las radiografías. Se consideran las enfermedades más comunes entre las que afectan al periodonto de inserción. Su prevalencia aumenta con la edad hasta alcanzar alrededor del 80% a los 50 años. Con el objetivo de demostrar la regeneración ósea periodontal con plasma rico en plaquetas, se presentó este caso clínico, paciente de 19 años de edad que acudió en búsqueda de atención estomatológica, la cual fue diagnosticada con una periodontitis juvenil. Como conclusión se comprobó que el plasma rico en plaquetas es una posibilidad válida para regenerar o reconstruir el tejido óseo.

Periodontitis involve clinical attachment loss and bone destruction visible on radiographs. They are considered the most common diseases among those affecting the periodontal insertion. Its prevalence increases with age up to about 80% at 50 years. In order to demonstrate the periodontal bone regeneration with platelet-rich plasma, a patient of 19 years old who came for dental care, which was diagnosed as a periodontitis in young people. The author concluded that the platelet-rich plasma is a valid possibility to regenerate or reconstruct the bone tissue