mSep: investigating physiological and immune-metabolic biomarkers in septic and healthy pregnant women to predict feto-maternal immune health - a prospective observational cohort study protocol.

INTRODUCTION: Maternal sepsis remains a leading cause of death in pregnancy. Physiological adaptations to pregnancy obscure early signs of sepsis and can result in delays in recognition and treatment. Identifying biomarkers that can reliably diagnose sepsis will reduce morbidity and mortality and antibiotic overuse. We have previously identified an immune-metabolic biomarker network comprising three pathways with a >99% accuracy for detecting bacterial neonatal sepsis. In this prospective study, we will describe physiological parameters and novel biomarkers in two cohorts-healthy pregnant women and pregnant women with suspected sepsis-with the aim of mapping pathophysiological drivers and evaluating predictive biomarkers for diagnosing maternal sepsis. METHODS AND ANALYSIS: Women aged over 18 with an ultrasound-confirmed pregnancy will be recruited to a pilot and two main study cohorts. The pilot will involve blood sample collection from 30 pregnant women undergoing an elective caesarean section. Cohort A will follow 100 healthy pregnant women throughout their pregnancy journey, with collection of blood samples from participants at routine time points in their pregnancy: week 12 'booking', week 28 and during labour. Cohort B will follow 100 pregnant women who present with suspected sepsis in pregnancy or labour and will have at least two blood samples taken during their care pathway. Study blood samples will be collected during routine clinical blood sampling. Detailed medical history and physiological parameters at the time of blood sampling will be recorded, along with the results of routine biochemical tests, including C reactive protein, lactate and white blood cell count. In addition, study blood samples will be processed and analysed for transcriptomic, lipidomic and metabolomic analyses and both qualitative and functional immunophenotyping. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Wales Research Ethics Committee 2 (SPON1752-19, 30 October 2019). TRIAL REGISTRATION NUMBER: NCT05023954.

A National Strategy to Diagnose Coronavirus Disease 2019-Associated Invasive Fungal Disease in the Intensive Care Unit.

BACKGROUND: Fungal coinfection is a recognized complication of respiratory virus infections, increasing morbidity and mortality, but can be readily treated if diagnosed early. An increasing number of small studies describing aspergillosis in coronavirus disease 2019 (COVID-19) patients with severe respiratory distress are being reported, but comprehensive data are lacking. The aim of this study was to determine the incidence, risk factors, and impact of invasive fungal disease in adult COVID-19 patients with severe respiratory distress. METHODS: An evaluation of a national, multicenter, prospective cohort evaluation of an enhanced testing strategy to diagnose invasive fungal disease in COVID-19 intensive care patients. Results were used to generate a mechanism to define aspergillosis in future COVID-19 patients. RESULTS: One-hundred and thirty-five adults (median age: 57, M/F: 2.2/1) were screened. The incidence was 26.7% (14.1% aspergillosis, 12.6% yeast infections). The overall mortality rate was 38%; 53% and 31% in patients with and without fungal disease, respectively (P = .0387). The mortality rate was reduced by the use of antifungal therapy (mortality: 38.5% in patients receiving therapy vs 90% in patients not receiving therapy (P = .008). The use of corticosteroids (P = .007) and history of chronic respiratory disease (P = .05) increased the likelihood of aspergillosis. CONCLUSIONS: Fungal disease occurs frequently in critically ill, mechanically ventilated COVID-19 patients. The survival benefit observed in patients receiving antifungal therapy implies that the proposed diagnostic and defining criteria are appropriate. Screening using a strategic diagnostic approach and antifungal prophylaxis of patients with risk factors will likely enhance the management of COVID-19 patients.

Case report: Eastern equine encephalitis virus imported to the UK.

Eastern equine encephalitis (EEE) is rare, but the most severe of the mosquito-borne encephalitides in the United States with a high case fatality rate of 30%. Here, we present a patient with EEE. EEE virus causes sporadic human disease in the Eastern parts of the United States, but the case we describe was a Scottish tourist who acquired the disease from mosquito bites while in holiday in the United States. This is a first report of an imported case to Europe.

Prevalence and clinical significance of Ureaplasma urealyticum and Mycoplasma hominis in the lower genital tract of HIV-1-infected women.

Mycoplasma hominis and Ureaplasma urealyticum are frequently isolated from the cervical and vaginal tracts of HIV-negative asymptomatic women. Published data lack indisputable conclusions and doubts still exist as to whether these mycoplasmas are pathogens or mere co-factors associated with genital infections. We therefore conducted a surveillance study to investigate the prevalence of genital mycoplasmas in HIV-1 positive women (110 patients), attending the outpatient Infectious Diseases Clinic of our tertiary referral Hospital, by speculum examination, PAP test, endocervical and vaginal swabs obtained by gynaecologists. Ureaplasma urealyticum was isolated from the cervix of 45 women (41%). Mycoplasma hominis was recovered from 12 women (11%), in four of whom it was isolated at the same time from the vagina. PAP test results ruled out subclinical cervicitis in all women. Bacterial vaginosis, assessed by Amsel criteria and the Nugent score, was absent in all women. Our data show that the mycoplasmas in question are found in the lower genital tract of asymptomatic HIV-1-positive women at a frequency similar to that reported in the HIV-negative female population, and make a role for these microorganisms unlikely in the aetiology of cervico-vaginal infections also in this particular patient population.

Painful neuropathy vasculitis in 2 patients with long-standing human immunodeficiency virus-1 infection.

We describe 2 most unusual cases of distal symmetrical painful polyneuropathy in patients with long-standing HIV-1 infection well controlled by HAART. Sural nerve biopsies revealed vasculitis in both cases and steroid therapy led to resolution of symptoms not influenced by analgesics and anti-inflammatory drugs. These unusual cases outline the importance of nerve biopsies in order to reach a diagnosis.

[No improvement of lipodystrophy syndrome in an HIV-infected patient]. / Sindrome lipodistrofica in un paziente con infezione da HIV, trattato con pentoxifillina.

Lipodystrophy in patients with HIV-infection has been studied intensively to understand its epidemiology and pathophysiology. Recently its development was attributed to a dysregulation of TNF-alpha synthesis' homeostasis by HAART. A few years ago it was found that pentoxifylline decreases TNF-alpha production. We describe one HIV-infected patient, with lipodystrophy syndrome, treated with pentoxifylline without any improvement of lipodystrophic symptoms.

Histoplasmosis in two human immunodeficiency virus-positive immigrants to Italy: clinical features and management in the highly active antiretroviral therapy era.

We report two cases of histoplasmosis occurring in human immunodeficiency virus-positive patients who immigrated to Italy, and focus our attention on the clinical features and therapeutic aspects, with particular emphasis on secondary prophylaxis. The patients had comparable human immunodeficiency virus baseline parameters, but had a completely different compliance over therapeutic regimens. The two patients were followed in two different city hospitals of our region, Padua and Verona, and the diagnosis was made on the basis of instrumental, histologic, and microbiologic findings. One of them was treated with corticosteroids because of nephrotic syndrome.

Enanthema as the first clinical manifestation of abacavir hypersensitivity reaction: a case report.

Abacavir is a nucleoside analogue reverse transcriptase inhibitor used in combination with other antiretroviral drugs for the treatment of HIV 1-infection. Approximately 3% of patients who receive abacavir develop an idiosyncratic hypersensitivity reaction. The most common symptoms are fever, skin rash and gastrointestinal disorders. Respiratory symptoms occurred in approximately 20% of patients who have hypersensitivity reaction. We describe the first case, to our knowledge, of hypesensitivity reaction characterized by enanthema and fever without skin rash promptly resolved after discontinuation of abacavir

Acute mediastinitis: a severe complication of transdermal therapy in a patient with ischaemic heart disease. A case report.

Acute mediastinitis is an uncommon and potentially devastating infection. Generally, mediastinitis occurs as a postoperative infection following median sternotomy. We describe a case of acute mediastinitis in a patient with ischaemic heart disease, secondary to the spread of cutaneous infection of the chest wall in the application site of transdermal nitroglycerine patches.