Tacrolimus as a Promising Drug for Epistaxis and Gastrointestinal Bleeding in HHT.

BACKGROUND: Hereditary Hemorrhagic Telangiectasia (HHT) is a vascular autosomically inherited rare disease. Epistaxis (nose bleeds) is the most common symptom in HHT, leading to anemia and affecting the patient's quality of life. In addition to epistaxis, gastrointestinal bleeding (GI), more often at older ages, may lead to severe anemia and the need for blood transfusions. Thus, finding drugs to control both types of bleeding is a primary necessity in HHT. METHODS: A cross-sectional observational study was conducted in a series of 11 HHT patients treated with low tacrolimus doses (0.5-2 mg/day) on an off-label prescription basis. Patients showed refractory bleeding to previous treatments. The epistaxis severity score (ESS) and hemoglobin levels were the parameters used to evaluate the impact of tacrolimus. The occurrence of side effects was also recorded. RESULTS: Tacrolimus was well tolerated in all of the patients except 2 (who stopped the treatment). The remaining patients tolerated the treatment, with a general improvement in their health condition. Epistaxis was significantly reduced when comparing the ESS before and after the treatment. Hemoglobin levels significantly increased, overcoming the anemia, during the course of the treatment. CONCLUSION: Tacrolimus at low doses should be considered as a promising treatment for epistaxis and gastrointestinal bleeding in HHT.

Hereditary Hemorrhagic Telangiectasia: Genetics, Pathophysiology, Diagnosis, and Management.

Hereditary hemorrhagic telangiectasia is an inherited disease related to an alteration in angiogenesis, manifesting as cutaneous telangiectasias and epistaxis. As complications, it presents vascular malformations in organs such as the lung, liver, digestive tract, and brain. Currently, diagnosis can be made using the Curaçao criteria or by identifying the affected gene. In recent years, there has been an advance in the understanding of the pathophysiology of the disease, which has allowed the use of new therapeutic strategies to improve the quality of life of patients. This article reviews some of the main and most current evidence on the pathophysiology, clinical manifestations, diagnostic approach, screening for complications, and therapeutic options, both pharmacological and surgical.

Lactic Acidosis as an Unusual Finding in Undifferentiated Carcinoma.

Lactic acidosis associated with solid neoplasms is a rare complication; its occurrence is poorly described, and it is associated with a poor prognosis. We present the case of an 84-year-old woman who was admitted to the internal medicine department with a diagnosis of urinary tract infection accompanied by a blood gas analysis showing lactic acidosis. During her admission, an abdominal mass was evidenced and finally diagnosed as undifferentiated carcinoma. We wanted to emphasize the importance of correlating clinical and laboratory data at the time of making a diagnostic approach and also highlight other possible explanations of lactic acidosis that should be considered in addition to hypoperfusion due to sepsis, especially in the elderly who are at increased risk of malignancy.

Predicting critical illness on initial diagnosis of COVID-19 based on easily obtained clinical variables: development and validation of the PRIORITY model.

OBJECTIVES: We aimed to develop and validate a prediction model, based on clinical history and examination findings on initial diagnosis of coronavirus disease 2019 (COVID-19), to identify patients at risk of critical outcomes. METHODS: We used data from the SEMI-COVID-19 Registry, a cohort of consecutive patients hospitalized for COVID-19 from 132 centres in Spain (23rd March to 21st May 2020). For the development cohort, tertiary referral hospitals were selected, while the validation cohort included smaller hospitals. The primary outcome was a composite of in-hospital death, mechanical ventilation, or admission to intensive care unit. Clinical signs and symptoms, demographics, and medical history ascertained at presentation were screened using least absolute shrinkage and selection operator, and logistic regression was used to construct the predictive model. RESULTS: There were 10 433 patients, 7850 in the development cohort (primary outcome 25.1%, 1967/7850) and 2583 in the validation cohort (outcome 27.0%, 698/2583). The PRIORITY model included: age, dependency, cardiovascular disease, chronic kidney disease, dyspnoea, tachypnoea, confusion, systolic blood pressure, and SpO2 ≤93% or oxygen requirement. The model showed high discrimination for critical illness in both the development (C-statistic 0.823; 95% confidence interval (CI) 0.813, 0.834) and validation (C-statistic 0.794; 95%CI 0.775, 0.813) cohorts. A freely available web-based calculator was developed based on this model (https://www.evidencio.com/models/show/2344). CONCLUSIONS: The PRIORITY model, based on easily obtained clinical information, had good discrimination and generalizability for identifying COVID-19 patients at risk of critical outcomes.

Usefulness of Fecal Calprotectin in the Management of Patients with Toxigenic Clostridioides difficile.

The availability of highly sensitive molecular tests for the detection of Clostridioides difficile in feces leads to overtreatment of patients who are probably only colonized. In this prospective study, the usefulness of fecal calprotectin (fCP) is evaluated in a cohort of patients with detection of toxigenic C. difficile in feces. Patients were classified by an infectious diseases consultant blinded to fCP results into three groups-group I, presumed Clostridioides difficile infection (CDI); group II, doubtful but treated CDI; and group III, presumed C. difficile colonization or self-limited CDI not needing treatment. One hundred and thirty-four patients were included. The median fCP concentrations were 410 (138-815) µg/g in group I, 188 (57-524) µg/g in group II, and 51 (26-97) µg/g in group III (26 cases); p < 0.05 for all comparisons. In forty-five out of 134 cases (33.5%), the fCP concentrations were below 100 µg/g. In conclusion, fCP is low in most patients who do not need treatment against C. difficile, and should be investigated as a potentially useful test in the management of patients with detected toxigenic C. difficile.