Risk factors and outcomes of cytomegalovirus infection in the intensive care unit.

INTRODUCTION: Cytomegalovirus (CMV) infection has long been recognized as an important viral syndrome in the immunocompromised host. The disease is less well described in critically-ill patients. We evaluated the risk factors for the development of CMV infection in patients admitted to the intensive care unit (ICU). We also compared the outcomes of CMV infection in ICU patients to those of patients with hematological malignancies. METHODOLOGY: This is a retrospective study composed of three arms: patients admitted to the ICU with infection (ICU + / CMV + arm), patients admitted to the ICU who did not develop CMV infection (ICU + / CMV- arm, and patients with hematological malignancies on the hematology ward without CMV infection (ICU - / CMV + arm). RESULTS: Patients who were admitted to ICU for surgical causes had a decreased risk of CMV infection. On the other hand, receiving corticosteroids and vasoactive drugs was associated with an increased risk of CMV infection with adjusted odds ratios (aOR) of 2.4 and 25.3, respectively. Mortality was higher in ICU + / CMV + patients compared to ICU - / CMV + patients. In the ICU + /CMV + population, male sex and being on mechanical ventilation after CMV infection were independent predictors of mortality (aOR 4.6 and 5.0, respectively). CONCLUSIONS: CMV infection in ICU patients is a potentially serious disease requiring close attention. The findings from our study help in identifying patients in the ICU at risk for CMV infection, thereby warranting frequent screening. Patients at high risk of death (male, on mechanical ventilation) should receive prompt treatment and intensive follow-up.

Clinical predictors of mortality in patients with pseudomonas aeruginosa infection.

BACKGROUND: Infections caused by Pseudomonas aeruginosa are difficult to treat with a significant cost and burden. In Lebanon, P. aeruginosa is one of the most common organisms in ventilator-associated pneumonia (VAP). P. aeruginosa has developed widespread resistance to multiple antimicrobial agents such as fluoroquinolones and carbapenems. We aimed at identifying risk factors associated for P. aeruginosa infections as well as identifying independent risk factors for developing septic shock and in-hospital mortality. METHODS: We used a cross-sectional study design where we included patients with documented P. aeruginosa cultures who developed an infection after obtaining written consent. Two multivariable regression models were used to determine independent predictors of septic shock and mortality. RESULTS: During the observed period of 30 months 196 patients were recruited. The most common predisposing factor was antibiotic use for more than 48 hours within 30 days (55%). The prevalence of multi-drug resistant (MDR) P. aeruginosa was 10%. The strongest predictors of mortality were steroid use (aOR = 3.4), respiratory failure (aOR = 7.3), identified respiratory cultures (aOR = 6.0), malignancy (aOR = 9.8), septic shock (aOR = 18.6), and hemodialysis (aOR = 30.9). CONCLUSION: Understanding resistance patterns and risk factors associated with mortality is crucial to personalize treatment based on risk level and to decrease the emerging threat of antimicrobial resistance.

Proinflammatory cytokines levels in sepsis and healthy volunteers, and tumor necrosis factor-alpha associated sepsis mortality: A systematic review and meta-analysis.

BACKGROUND: Sepsis is a global health challenge associated with significant morbidity and mortality. Detrimental sepsis effects are attributed to excessive inflammation or a "cytokine storm." However, anti-inflammation therapies have failed to lower sepsis mortality. We aim to characterize levels of key inflammatory cytokines in patients with sepsis and compare levels with those in healthy individuals and relate tumor necrosis factor (TNF) α levels to patient characteristics and outcomes. METHODS: We performed a systematic review and meta-analysis. Medline, Embase, Cochrane Library, and Web of Science Core Collection databases were searched between 1985 and May 2020. Analysis was restricted to studies in English. We included randomized controlled trials (RCTs), controlled trials, cohort studies, case series, and cross-sectional studies that reported mean levels of cytokines in the circulation thought to be relevant for sepsis pathogenesis. We also evaluated concentrations of these cytokines in healthy individuals. The Quality in Prognosis Studies tool was used to assess the methodological quality of included studies. We extracted summary data from published reports. Data analyses were performed using a random-effects model to estimate pooled odds ratios (OR) with 95% confidence intervals for cytokine levels and mortality. This systematic review is registered in PROSPERO (CRD42020179800). FINDINGS: We identified 3654 records, and 104 studies were included with a total of 3250 participants. The pooled estimated mean TNFα concentration in sepsis patients was 58.4 pg/ml (95% Confidence Interval or CI 39.8-85.8 pg/ml), and in healthy individuals was 5.5 pg/ml (95% CI 3.8-8.0 pg/ml). Pooled estimate means for IL-1ß and IFN-γ in sepsis patients were 21.8 pg/ml and 63.3 pg/ml, respectively. Elevated TNFα concentrations associated with increased 28-day sepsis mortality (p = 0.001). In subgroup analyses, we did not detect an association between TNFα levels and sepsis source, sepsis severity, or sequential organ failure assessment (SOFA) score. A TNF-α cutoff level ≥14.7 pg/ml separated sepsis patients from healthy individuals with a sensitivity of 82.6%, a specificity of 91.7%, and a likelihood ratio of 9.9. INTERPRETATION: Sepsis mean TNFα concentration is increased approximately 10-fold compared to mean concentration in healthy individuals, and TNFα associated with sepsis mortality but not sepsis severity. The concept that elevated cytokines cause sepsis should be revisited in the context of these data. FUNDING: None.

Chasing the Ghost: Hyperinflammation Does Not Cause Sepsis.

Sepsis is infection sufficient to cause illness in the infected host, and more severe forms of sepsis can result in organ malfunction or death. Severe forms of Coronavirus disease-2019 (COVID-19), or disease following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are examples of sepsis. Following infection, sepsis is thought to result from excessive inflammation generated in the infected host, also referred to as a cytokine storm. Sepsis can result in organ malfunction or death. Since COVID-19 is an example of sepsis, the hyperinflammation concept has influenced scientific investigation and treatment approaches to COVID-19. However, decades of laboratory study and more than 100 clinical trials designed to quell inflammation have failed to reduce sepsis mortality. We examine theoretical support underlying widespread belief that hyperinflammation or cytokine storm causes sepsis. Our analysis shows substantial weakness of the hyperinflammation approach to sepsis that includes conceptual confusion and failure to establish a cause-and-effect relationship between hyperinflammation and sepsis. We conclude that anti-inflammation approaches to sepsis therapy have little chance of future success. Therefore, anti-inflammation approaches to treat COVID-19 are likewise at high risk for failure. We find persistence of the cytokine storm concept in sepsis perplexing. Although treatment approaches based on the hyperinflammation concept of pathogenesis have failed, the concept has shown remarkable resilience and appears to be unfalsifiable. An approach to understanding this resilience is to consider the hyperinflammation or cytokine storm concept an example of a scientific paradigm. Thomas Kuhn developed the idea that paradigms generate rules of investigation that both shape and restrict scientific progress. Intrinsic features of scientific paradigms include resistance to falsification in the face of contradictory data and inability of experimentation to generate alternatives to a failing paradigm. We call for rejection of the concept that hyperinflammation or cytokine storm causes sepsis. Using the hyperinflammation or cytokine storm paradigm to guide COVID-19 treatments is likewise unlikely to provide progress. Resources should be redirected to more promising avenues of investigation and treatment.

Delayed autoimmune haemolytic anaemia after artesunate therapy for severe malaria.

We report the case of a 51-year-old man with severe malaria, who developed delayed autoimmune haemolytic anaemia following artesunate therapy. Delayed autoimmune haemolytic anaemia following artesunate therapy has been previously described. Its diagnosis can be challenging in the setting of possible dengue coinfection. Clinicians should be vigilant of this potential side effect of artesunate therapy, especially in patients who later develop signs and symptoms of haemolytic anaemia.

Association between cytokine levels, sepsis severity and clinical outcomes in sepsis: a quantitative systematic review protocol.

INTRODUCTION: It is widely assumed that sepsis is a life-threatening systemic inflammation caused by a dysregulated host response to infection mediated by an increase in multiple proinflammatory cytokines. The levels of key proinflammatory cytokines tumour necrosis factor, interleukin-1ß and interferon γ are poorly characterised during sepsis. We believe this project will produce a 'gold-standard' document to which other reports on cytokine levels will be compared. The objective of this systematic review will be to identify key cytokine circulating levels in patients with sepsis and assess the association between these levels and morbidity and mortality outcomes related to sepsis. METHODS AND ANALYSIS: We would include reports of any design except for case reports. Sepsis patients will comprise those with a diagnosis of sepsis, severe sepsis or septic shock. The primary exposure is levels of three proinflammatory cytokines. The primary outcome is mortality at 28 or 30 days. Study subjects can be of any age, sex or ethnicity. Studies will be restricted to the English language. Medline, Embase, Cochrane Library and Web of Science Core Collection will be searched for eligible studies. A database search will include studies from 1985 to May 2020. Two reviewers will independently screen and select studies, assess methodological quality and extract data. A meta-analysis will be performed, if possible, and the Grading of Recommendations Assessment Development and Evaluation Summary of Findings presented. ETHICS AND DISSEMINATION: Formal ethical approval is not required as data will be extracted from existing literature. This systematic review will be disseminated through a peer-reviewed publication and at conference meetings. PROSPERO REGISTRATION NUMBER: CRD42020179800.

Palliative Care via Telemedicine: A Qualitative Study of Caregiver and Provider Perceptions.

Background: Telemedicine has been proposed as a means to improve access to palliative care. There is limited information about how health care workers feel about providing this kind of care and how families feel about receiving it. Objective: This study assesses provider and caregiver perceptions of the safety and efficacy of the Distance Support Program (DSP) of a home-based palliative care provider in Beirut, Lebanon. Design: Interviews were conducted with 8 physicians and nurses who provided that care through the DSP as well as 49 caregivers of patients who received care between January 2015 and December 2017. Interviews were analyzed thematically. Results: Although they would have preferred having access to home visits, caregivers reported that they valued the information, guidance, and emotional support they received through the DSP and they appreciated having telephone access to providers. Health providers reported the DSP was more efficient than home visits. They felt it was safest when delivered by an experienced provider, they had access to a reliable caregiver, and the patient was assessed at least once. They felt it was important to communicate clear expectations to patients and caregivers when delivering care by telephone. Conclusions: Telemedicine can be a useful tool to provide palliative care services in settings where they would otherwise not be available.

Vascular Graft Infections: An update.

Vascular graft infection is a devastating complication of vascular reconstructive surgery. The infection can occur early in the postoperative period and is largely due to intraoperative contamination or by contiguous extension from a nearby infection. It can also occur years after implantation. Staphylococci remain the most common organisms and biofilm production makes eradication difficult. Factors commonly reported to predispose to vascular graft infection are periodontal disease, nasal colonization with Staphylococcus aureus, bacteremia, certain graft characteristics, diabetes mellitus, postoperative hyperglycemia, location of the incision, wound infection, and emergency procedure. Management consists of antibiotic and surgical therapy. Preventive methods are described.

Cutibacterium (formerly Propionibacterium) acnes infections associated with implantable devices.

INTRODUCTION: Cutibacterium acnes (C. acnes), a Gram-positive biofilm-forming rod implicated in acne vulgaris, is increasingly recognized for its role in implant-associated infections. The diagnosis of C. acnes implant-associated infections remains challenging. The optimal treatment is a combination of both surgical intervention and antibiotic therapy. Areas covered: In this review, we discuss the different types of implant-associated infections caused by C. acnes. We also highlight the clinical manifestations pertaining to the various sites of infection, and identify several risk factors previously reported in the literature. We then cover the diagnostic laboratory markers, such as IL-6 and AD-1, optimizing C. acnes recovery in culture, and the specific molecular techniques. Finally, we examine the various effective antibiotic regimens and identify some preventive methods against C. acnes infections. Expert commentary: Biomarkers such as IL-6 and AD-1 should be further investigated for the diagnosis of C. acnes implant-associated infections. The use of 16S rRNA gene sequencing and other molecular techniques should be further explored in this setting. Longer incubation periods should be requested whenever C. acnes infection is suspected. If the clinical suspicion is high, sonication of the excised implant should be encouraged. Research should focus on developing effective anti-biofilm agents. Finally, preventive methods such as hair removal prior to surgery should be further explored.