C1-inhibitor deficiency and angioedema: molecular mechanisms and clinical progress.

C1 inhibitor (C1-INH, also known as SERPING1) can be deficient in plasma as a result of genetic or acquired conditions, and this causes an episodic, local increase in vascular permeability in the subcutaneous and submucosal layers, identified as angioedema (hereditary or acquired). Bradykinin, the mediator of the increase in vascular permeability, is released on inappropriate activation of the contact system, which is controlled by C1 inhibitor. Therapy aims to reverse or prevent angioedema. Advances in understanding the complex effects of C1-INH deficiency at the molecular level have led to new molecular-targeted approaches. Three new treatments, an inhibitor of kallikrein to prevent bradykinin release, an antagonist of the bradykinin receptor to prevent its action and a recombinant human C1-INH produced in transgenic animals, are under clinical evaluation currently. Here, we review the molecular mechanisms underlying angioedema due to C1-inhibitor deficiency and clinical progress using molecular-targeted interventions.

Derivation and validation of the clinical prediction model for COVID-19.

The epidemic phase of Coronavirus disease 2019 (COVID-19) made the Worldwide health system struggle against a severe interstitial pneumonia requiring high-intensity care settings for respiratory failure. A rationalisation of resources and a specific treatment path were necessary. The study suggests a predictive model drawing on clinical data gathered by 119 consecutive patients with laboratory-confirmed COVID-19 admitted in Busto Arsizio hospital. We derived a score that identifies the risk of clinical evolution and in-hospital mortality clustering patients into four groups. The study outcomes have been compared across the derivation and validation samples. The prediction rule is based on eight simple patient characteristics that were independently associated with study outcomes. It is able to stratify COVID-19 patients into four severity classes, with in-hospital mortality rates of 0% in group 1, 6-12.5% in group 2, 7-20% in group 3 and 60-86% in group 4 across the derivation and validation sample. The prediction model derived in this study identifies COVID-19 patients with low risk of in-hospital mortality and ICU admission. The prediction model that the study presents identifies COVID-19 patients with low risk of in-hospital mortality and admission to ICU. Moreover, it establishes an intermediate portion of patients that should be treated accurately in order to avoid an unfavourable clinical evolution. A further validation of the model is important before its implementation as a decision-making tool to guide the initial management of patients.

Fitz-Hugh-Curtis Syndrome: A Diagnosis to Consider in a Woman with Right Upper Quadrant Abdominal Pain without Gallstones.

A young woman presented with right upper quadrant abdominal pain exacerbated by movement and breathing. Extensive evaluation revealed no gallstones or any other specific cause. Urine polymerase chain reaction results for Chlamydia trachomatis were positive, so the clinical diagnosis of Fitz-Hugh-Curtis syndrome was confirmed. This type of localized peritonitis is thought to be a complication of an ascending genital infection leading to pelvic inflammatory disease. The diagnosis is established on clinical grounds after excluding alternative, more common conditions. Proper antibiotic treatment usually leads to recovery and prevents long-term complications. LEARNING POINTS: Right upper quadrant pain in a sexually active woman may be due to Fitz-Hugh-Curtis syndrome, a type of localized peritonitis also called perihepatitis.This condition is considered to be a complication of an ascending genital infection leading to pelvic inflammatory disease.Sexually active women with right upper quadrant abdominal pain without gallstones should be tested for Chlamydia trachomatis and Neisseria gonorrhoeae.