Pedro Palma

Background/Objectives: The timely initiation of antiretroviral therapy (ART) in persons living with HIV (PLWH) improves clinical outcomes. However, ART commencement is often delayed. Portugal, which has one of the highest new HIV diagnosis rates within the European Union, has limited available data. Evidence from 2017-2018 suggests that the average time to ART initiation exceeds the recommendations for optimal benefits. This study aimed to assess the number of days from the first hospital appointment to the commencement of ART among newly diagnosed PLWH in Portugal between 2017 and 2022 at the national level and across different hospitals within the country. Methods: A retrospective analysis of records from Portuguese public tertiary care hospitals, which manage the majority of HIV patients, was conducted. Descriptive statistics (measures of central tendency, dispersion, and frequency) were applied, along with association tests and a binary logistic regression model to examine factors influencing the timing of ART initiation. Results: A total of 2,229 cases from 19 hospitals were considered eligible. The median time interval between the first hospital appointment and ART initiation was 29.00 days, with a decreasing tendency between 2017 and 2022. Patients initiating therapy after 14 days had higher CD4 levels and lower viral loads compared to those starting within 14 days, with statistical significance. Conclusions: Continuous and regular monitoring of key indicators, such as the time to ART initiation, is pivotal for assessing the effectiveness of HIV treatment programs and pinpointing areas in need of improvement.

The emergence of antibiotic resistance poses a global health threat. High-risk patients such as those with neutropenia are particularly vulnerable to opportunistic infections, sepsis, and multidrug-resistant infections, and clinical outcomes remain the primary concern. Antimicrobial stewardship (AMS) programs should mainly focus on optimizing antibiotic use, decreasing adverse effects, and improving patient outcomes. There is a limited number of published studies assessing the impact of AMS programs on patients with neutropenia, where early appropriate antibiotic choice can be the difference between life and death. This narrative review updates the current advances in strategies of AMS for bacterial infections among high-risk patients with neutropenia. Diagnosis, drug, dose, duration, and de-escalation (5D) are the core variables among AMS strategies. Altered volumes of distribution can make standard dose regimens inadequate, and developing skills towards a personalized approach represents a major advance in therapy. Intensivists should partner antibiotic stewardship programs to improve patient care. Assembling multidisciplinary teams with trained and dedicated professionals for AMS is a priority.

Aortic valvular calcium score (AVCS) is useful in patients with aortic stenosis for whom echocardiography was not conclusive in grading its severity. Transcatheter aortic valve implantation (TAVI) is an established procedure of treatment in symptomatic severe AS. The burden of aortic valve calcification has been associated with some TAVI related complications (as perivalvular leaks), but at the same time it is well accepted that some degree of calcification is needed to ensure stable anchoring of the prosthesis to the aortic annulus. To assess if there is a correlation between aortic valve calcium score and mean transvalvular gradient 6 months after TAVI – is a higher AVCS correlated with lower mean transaortic gradient after TAVI? We performed a single-center, retrospective cohort study including patients who underwent TAVI with a preoperative standardized contrast enhanced MSCT with AVCS available. Clinical and echocardiographic data were collected previously to TAVI (pre-TAVI) and at 6 months follow up (6M-FUP). A total of 187 patients were included, with 54% female and a mean age of 79.4±9.0 years old. Most patients had tricuspid aortic valve (95.7%); 5 patients had aortic bicuspidy and 3 had aortic valve bioprothesis. Concerning the valve type, 73.3% had new generation prosthesis and the main valve used was the CoreValve Evolut Pro (33.7%). Also, 38,5% needed balloon pre-dilation before TAVI. The mean pre-TAVI aortic transvalvular maximum and mean gradients were 76.5±23.2 mmHg and 48.3±15.5 mmHg, respectively; mean aortic valve area was 0.75±0.16 cm². The mean AVCS was 2851±1524 AU (Agaston Units); 81.2% of women had AVCS>1300 AU and 74.4% men had AVCS >2000 AU. Comparing transvalvular aortic gradients previously and 6M-FUP after TAVI, there was an average differential of maximum gradient of 61±22 mmHg and of mean gradient of 40±15 mmHg. A negative and weak correlation was found between the AVCS and the maximum gradient (pearson coefficient of −0.181, p=0.02) and between mean gradient at 6M-FUP (pearson coefficient of −0.191, p=0.014). AVCS is a significant predictor for death, stroke and perivalvular leaks after TAVI. On the other hand, high AVCS is associated with better seating in the native annulus during deployment. Nevertheless, high AVCS did not strongly correlated with mean transaortic gradient 6 months after TAVI. Type of funding sources: None.

Percutaneous valve commissurotomy (PMC) is a viable alternative to mitral valve (MV) surgery in the treatment of patients with clinically significant mitral stenosis (MS). About 40% of patients treated with PMC will require at least one reintervention (either PMC or MVS) along time. To evaluate the long-term results of PMC in patients with rheumatic MS. We retrospectively analysed all consecutive patients between 1991 and 2008 with clinically significant rheumatic MS undergoing PMC. Clinical and echocardiographic data were collected at baseline and during early and long-term follow-up. MACE was a composite of adverse events defined as all-cause mortality, MV re-intervention or cardiovascular hospitalization. A total of 124 patients were enrolled: 108 (87%) were female, with a mean age at the time of PMC of 46±11 years. At baseline, 34% patients were in NYHA class ≥ III and 81% had a Wilkins score ≤8; all patients had preserved biventricular systolic function and 83% presented pulmonary hypertension. Regarding associated valve disease, 46 patients had mild tricuspid regurgitation (TR), 19 mild aortic regurgitation (AR), 14 moderate IT and 5 moderated AR. Most of the procedures were successful (91%) and without complications (94%), with median improvement in MV area of 0.9 cm² (IQR 0.5) and median reductions in mean transmitral gradient (MTG) of 6 mmHg (IQR 6) and in pulmonary artery systolic pressure (PASP) of 8 mmHg (IQR 10) early after PMC. During the mean follow-up of 20±6 years, 52 (42%) of patients had MV re-intervention (86% surgery and 14% re-PMC), 37 (30%) were hospitalized and 30 (24%) died. Concerning time-to-event analysis, approximately 80% of patients kept MACE-free after 10 years; after 30 years, more than 20% continued MACE-uneventful, approximately 50% were alive and about 45% were free from re-intervention. Considering patients submitted to surgical re-intervention, 9 underwent MV valvuloplasty and the others MV replacement with mechanical (32) or biological prothesis (11). At the same procedure, 23 patients were submitted to tricuspid annuloplasty, 9 to other valve replacement and one to coronary artery bypass graft. Using Cox regression, we found that the presence of moderate disease of other valves at PMC time was associated with a 2.3-fold greater rate of re-intervention compared to patients with none or mid disease of other valves (HRcrude 2.3; 95% IC 1.221–4.331, p=0.017). After adjusting for the success of the PMC and for mitral regurgitation after PMC, the observed effect remained significant (HRadjusted = 2.7; 95% CI 1.417–5.233, p=0.003). PMC was safe and effective in clinically significant rheumatic MS. Most of the patients were free from adverse events after 10 years and half were alive after 30 years. Still, about 40% required re-intervention, with moderate disease of other valves as its independent predictor. Type of funding sources: None. Figure 1 Figure 2

A few molecularly proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases of symptomatic reinfection are currently known worldwide, with a resolved first infection followed by a second infection after a 48 to 142-day intervening period. We report a multiple-component study of a clinically severe and prolonged viral shedding coronavirus disease 2019 (COVID-19) case in a 17-year-old Portuguese female. She had two hospitalizations, a total of 19 RT-PCR tests, mostly positive, and criteria for releasing from home isolation at the end of 97 days. The viral genome was sequenced in seven serial samples and in the diagnostic sample from her infected mother. A human genome-wide array (>900 K) was screened on the seven samples, and in vitro culture was conducted on isolates from three late samples. The patient had co-infection by two SARS-CoV-2 lineages, which were affiliated in distinct clades and diverging by six variants. The 20A lineage was absolute at the diagnosis (shared with the patient’s mother), but nine days later, the 20B lineage had 3% frequency, and two months later, the 20B lineage had 100% frequency. The 900 K profiles confirmed the identity of the patient in the serial samples, and they allowed us to infer that she had polygenic risk scores for hospitalization and severe respiratory disease within the normal distributions for a Portuguese population cohort. The early-on dynamic co-infection may have contributed to the severity of COVID-19 in this otherwise healthy young patient, and to her prolonged SARS-CoV-2 shedding profile.

Purpose of review: Overview of influenza infection, focusing on outcome and complications in critically ill patients. We also discuss relevant elements in immunopathogenesis and their role as predictors of severity. Recent findings: Pandemic influenza A (H1N1) virus circulates seasonally and remains the predominant subtype among intensive care patients. Mortality in acute respiratory failure (ARF) is around 20%, independent of influenza subtypes. During severe infection, the imbalance between pro-inflammatory and anti-inflammatory molecules, such as Th1 and Th17 cytokines, is associated with complicated infections and mortality. Primary viral pneumonia presents in more than 70% of ICU influenza patients and more than 50% develop acute respiratory distress syndrome. Bacterial secondary infection occurs in 20% of severe cases and Streptococcus pneumoniae and Staphylococcus aureus remain the prevalent pathogens. Myocarditis and late-onset cardiovascular complications are associated with mortality. Antiviral therapy within 48 h after onset, avoidance of corticosteroids and rescue therapies for ARF or myocarditis, such as extracorporeal membrane oxygenation, improve survival. Summary: The present review summarizes current knowledge on pathogenesis and clinical manifestations of severe influenza. Immunological dysfunction during viral infection correlates with severity and mortality among ICU patients. A theranostics strategy should be implemented to improve outcomes.

Infective endocarditis is a growing problem with many shifts due to ever-increasing comorbid illnesses, invasive procedures, and increase in the elderly. We performed this multinational study to depict definite infective endocarditis. Adult patients with definite endocarditis hospitalized between January 1, 2015, and October 1, 2018, were included from 41 hospitals in 13 countries. We included microbiological features, types and severity of the disease, complications, but excluded therapeutic parameters. A total of 867 patients were included. A total of 631 (72.8%) patients had native valve endocarditis (NVE), 214 (24.7%) patients had prosthetic valve endocarditis (PVE), 21 (2.4%) patients had pacemaker lead endocarditis, and 1 patient had catheter port endocarditis. Eighteen percent of NVE patients were hospital-acquired. PVE patients were classified as early-onset in 24.9%. A total of 385 (44.4%) patients had major embolic events, most frequently to the brain (n = 227, 26.3%). Blood cultures yielded pathogens in 766 (88.4%). In 101 (11.6%) patients, blood cultures were negative. Molecular testing of vegetations disclosed pathogens in 65 cases. Overall, 795 (91.7%) endocarditis patients had any identified pathogen. Leading pathogens (Staphylococcus aureus (n = 267, 33.6%), Streptococcus viridans (n = 149, 18.7%), enterococci (n = 128, 16.1%), coagulase-negative staphylococci (n = 92, 11.6%)) displayed substantial resistance profiles. A total of 132 (15.2%) patients had cardiac abscesses; 693 (79.9%) patients had left-sided endocarditis. Aortic (n = 394, 45.4%) and mitral valves (n = 369, 42.5%) were most frequently involved. Mortality was more common in PVE than NVE (NVE (n = 101, 16%), PVE (n = 49, 22.9%), p = 0.042).

Introduction: Sepsis is the leading cause of mortality in critically ill patients and, despite the improvements in patient care, in-hospital mortality remains unchanged. The role of the dysregulated immune response in the pathophysiology of sepsis, coupled with the diversity of phenotypes it encompasses, highlights the need for a precision medicine approach. Areas covered: This paper is a narrative review of the current evidence on precision medicine in sepsis. The main recent advances are in the field of Omics-based technologies and big data analytics. Expert opinion: Different clusters of patients based on gene-expression profiles have been identified and showed potential diagnostic and prognostic utility. Prediction models based on electronic medical records (EMR) and developed with artificial intelligence algorithms are being applied in clinical practice. Integration of Omics-based technologies and EMR data through artificial intelligence algorithms provides the landscape to identify endotypes and biomarkers predicting response to therapies. This opens the door to a theranostic approach in sepsis and to an improvement in outcomes.

Cytomegalovirus (CMV) reactivation with neurological involvement in patients with acquired immunodeficiency syndrome (AIDS) is increasingly rare since the introduction of antiretroviral therapy (ART). Manifestations include encephalitis, myelitis, polyradiculopathy and, less commonly, mononeuritis multiplex (MNM). We report a case of disseminated CMV disease with gastrointestinal and peripheral and central nervous system involvement in a patient with AIDS, manifesting primarily as MNM. A 31-year old woman with AIDS presented with a clinical picture of MNM. Electromyography confirmed the clinical findings. CMV DNA was detected in cerebrospinal fluid (CSF) and blood. Gastrointestinal involvement was histologically documented. HIV RNA was also detected in CSF and brain MRI was consistent with HIV encephalopathy. A diagnosis of disseminated CMV disease (with esophagitis, colitis, encephalitis and MNM) and HIV encephalopathy was made. Treatment consisted of ganciclovir and foscarnet, followed by maintenance therapy with valganciclovir. Evolution was favorable and valganciclovir was stopped after sustained immune recovery following ART initiation. We discuss the diagnostic approach to CMV neurological disease, with a focus on MNM and CMV encephalitis. Combination therapy with ganciclovir and foscarnet should be considered for all forms of neurological involvement, although available data are scarce. Since there is significant overlap between CMV encephalitis and HIV encephalopathy, ART drugs with higher CSF penetration may have to be considered. ART and immune recovery are essential to improve outcomes.