Monkeypox - a description of the clinical progression of skin lesions: a case report from Colorado, USA.

A rapidly emerging global outbreak of monkeypox virus infection (MPXV) in over 50 non-endemic countries was identified in May 2022. We report the case and images of a patient with MPXV presenting with genital lesions later complicated by superimposed cellulitis in Colorado, USA. MPXV lesions are susceptible to bacterial superinfection, and with the advent of new cases, the early identification of skin lesions and their evolution during MPXV are imperative for treating clinicians. Clinicians should consider MPXV in differential diagnoses of sexually transmitted diseases presenting with genital lesions.

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.

Diagnostic Utility of a Ferritin-to-Procalcitonin Ratio to Differentiate Patients With COVID-19 From Those With Bacterial Pneumonia: A Multicenter Study.

BACKGROUND: There is an urgent need for accurate, rapid, inexpensive biomarkers that can differentiate coronavirus disease 2019 (COVID-19) from bacterial pneumonia. We assess the role of the ferritin-to-procalcitonin (F/P) ratio to classify pneumonia cases into those due to COVID-19 vs those due to bacterial pathogens. METHODS: This multicenter case-control study compared patients with COVID-19 with those with bacterial pneumonia, admitted between March 1 and May 31, 2020. Patients with COVID-19 and bacterial pneumonia co-infection were excluded. The F/P in patients with COVID-19 vs with bacterial pneumonia were compared. Receiver operating characteristic curve analysis determined the sensitivity and specificity of various cutoff F/P values for COVID-19 vs bacterial pneumonia. RESULTS: A total of 242 COVID-19 pneumonia cases and 34 bacterial pneumonia controls were included. Patients with COVID-19 pneumonia had a lower mean age (57.1 vs 64.4 years; P = .02) and a higher body mass index (30.74 vs 27.15 kg/m2; P = .02) compared with patients with bacterial pneumonia. Cases and controls had a similar proportion of women (47% vs 53%; P = .5), and COVID-19 patients had a higher prevalence of diabetes mellitus (32.6% vs 12%; P = .01). The median F/P was significantly higher in patients with COVID-19 (4037.5) compared with the F/P in bacterial pneumonia (802; P < .001). An F/P ≥877, used to diagnose COVID-19, resulted in a sensitivity of 85% and a specificity of 56%, with a positive predictive value of 93.2% and a likelihood ratio of 1.92. In multivariable analyses, an F/P ≥877 was associated with greater odds of identifying a COVID-19 case (odds ratio, 11.27; 95% CI, 4-31.2; P < .001). CONCLUSIONS: An F/P ≥877 increases the likelihood of COVID-19 pneumonia compared with bacterial pneumonia.

Increased mortality associated with uncontrolled diabetes mellitus in patients with pulmonary cryptococcosis: a single US cohort study.

BACKGROUND: Diabetes mellitus is an established risk factor for bacterial infections, but its role in cryptococcosis is unclear. The study aimed to determine whether uncontrolled diabetes (HbA1c >7%) was an independent risk factor for mortality in cryptococcosis. METHODS: A retrospective case-control study partially matched by age and gender was performed in patients tested for Cryptococcus infection at the University of Colorado Hospital from 2000 to 2019. A multivariable logistic regression model was used to identify mortality predictors. Cox proportional hazard model was used for survival analysis. RESULTS: We identified 96 cases of cryptococcosis and 125 controls. Among cases, cryptococcal meningitis (49.0%) and pneumonia (36.5%) constituted most infections. Cases with pulmonary cryptococcosis with uncontrolled diabetes had a higher mortality at 10 weeks (50% versus 7%, p = 0.006) and 1 year (66.7% versus 13.8%, p = 0.005) compared to pulmonary cases with controlled or no diabetes. Unadjusted Cox proportional hazard model found an increased rate of death for uncontrolled diabetes at 10 weeks [hazard ratio 8.4, confidence interval (CI): 1.4-50.8, p = 0.02] and 1 year (hazard ratio 7.0, CI: 1.7-28.4, p = 0.007) among pulmonary cryptococcosis cases. Multivariable analysis showed a significantly increased odds of 10 weeks [odds ratio (OR) = 4.3, CI: 1.1-16.5, p = 0.035] and 1 year (OR = 5.0, CI: 1.4-18.3, p = 0.014) mortality for uncontrolled diabetes among pulmonary cryptococcosis cases. After adjustment for gender, age, and case/control, for every 1% increase in HbA1c levels, the odds of pulmonary cryptococcosis mortality at 1 year increased by 11% (OR = 1.6, CI 95%: 1.1-2.3, p = 0.006). CONCLUSION: Uncontrolled diabetes is associated with worse outcomes in pulmonary cryptococcosis, including a 4-fold and 6-fold increased odds of death at 10 weeks and 1 year, respectively. Glucose control interventions should be explored to improve clinical outcomes in patients with pulmonary cryptococcosis.

Diagnostic utility of a Ferritin-to-Procalcitonin Ratio to differentiate patients with COVID-19 from those with Bacterial Pneumonia: A multicenter study.

IMPORTANCE: There is a need to develop tools to differentiate COVID-19 from bacterial pneumonia at the time of clinical presentation before diagnostic testing is available. OBJECTIVE: To determine if the Ferritin-to-Procalcitonin ratio (F/P) can be used to differentiate COVID-19 from bacterial pneumonia. DESIGN: This case-control study compared patients with either COVID-19 or bacterial pneumonia, admitted between March 1 and May 31, 2020. Patients with COVID-19 and bacterial pneumonia co-infection were excluded. SETTING: A multicenter study conducted at three hospitals that included UCHealth and Phoebe Putney Memorial Hospital in the United States, and Yichang Central People's Hospital in China. PARTICIPANTS: A total of 242 cases with COVID-19 infection and 34 controls with bacterial pneumonia. MAIN OUTCOMES AND MEASURES: The F/P in patients with COVID-19 or with bacterial pneumonia were compared. Receiver operating characteristic analysis determined the sensitivity and specificity of various cut-off F/P values for the diagnosis of COVID-19 versus bacterial pneumonia. RESULTS: Patients with COVID-19 pneumonia had a lower mean age (57.11 vs 64.4 years, p=0.02) and a higher BMI (30.74 vs 27.15 kg/m 2 , p=0.02) compared to patients with bacterial pneumonia. Cases and controls had a similar proportion of women (47% vs 53%, p=0.5) and COVID-19 patients had a higher prevalence of diabetes mellitus (32.6% vs 12%, p=0.01). The median F/P was significantly higher in patients with COVID-19 (4037.5) compared to the F/P in bacterial pneumonia (802, p<0.001). An F/P ≥ 877 used to diagnose COVID-19 resulted in a sensitivity of 85% and a specificity of 56%, with a positive predictive value of 93.2%, and a likelihood ratio of 1.92. In multivariable analyses, an F/P ≥ 877 was associated with greater odds of identifying a COVID-19 case (OR: 11.27, CI: 4-31.2, p<0.001). CONCLUSIONS AND RELEVANCE: An F/P ≥ 877 increases the likelihood of COVID-19 pneumonia compared to bacterial pneumonia. Further research is needed to determine if obtaining ferritin and procalcitonin simultaneously at the time of clinical presentation has improved diagnostic value. Additional questions include whether an increased F/P and/or serial F/P associates with COVID-19 disease severity or outcomes.

Beta-Hemolytic Streptococcal Infective Endocarditis: Characteristics and Outcomes From a Large, Multinational Cohort.

BACKGROUND: Beta-hemolytic streptococci (BHS) are an uncommon cause of infective endocarditis (IE). The aim of this study was to describe the clinical features and outcomes of patients with BHS IE in a large multinational cohort and compare them with patients with viridans streptococcal IE. METHODS: The International Collaboration on Endocarditis Prospective Cohort Study (ICE-PCS) is a large multinational database that recruited patients with IE prospectively using a standardized data set. Sixty-four sites in 28 countries reported patients prospectively using a standard case report form developed by ICE collaborators. RESULTS: Among 1336 definite cases of streptococcal IE, 823 were caused by VGS and 147 by BHS. Patients with BHS IE had a lower prevalence of native valve (P < .005) and congenital heart disease predisposition (P = .002), but higher prevalence of implantable cardiac device predisposition (P < .005). Clinically, they were more likely to present acutely (P < .005) and with fever (P = .024). BHS IE was more likely to be complicated by stroke and other systemic emboli (P < .005). The overall in-hospital mortality of BHS IE was significantly higher than that of VGS IE (P = .001). In univariate analysis, variables associated with in-hospital mortality for BHS IE were age (odds ratio [OR], 1.044; P = .004), prosthetic valve IE (OR, 3.029; P = .022), congestive heart failure (OR, 2.513; P = .034), and stroke (OR, 3.198; P = .009). CONCLUSIONS: BHS IE is characterized by an acute presentation and higher rate of stroke, systemic emboli, and in-hospital mortality than VGS IE. Implantable cardiac devices as a predisposing factor were more often found in BHS IE compared with VGS IE.

Recurrent Campylobacter Bacteremia as the First Manifestation of Hypogammaglobulinemia: a Case Report and Literature Review.

A 30-year-old woman with a past medical history of autoimmune hemolytic anemia presented with fever. Blood cultures grew Campylobacter. Her medical history was significant for four prior episodes of Campylobacter gastroenteritis and bacteremia. She received ciprofloxacin for the index presentation, then Meropenem de-escalated to doxycycline 6 months later following recurrence of Campylobacter. This prompted investigation for an immunodeficiency disorder. She was found to have hypogammaglobulinemia. Her Campylobacter infections resolved following the administration of intravenous immunoglobulins every 3 weeks. She did not have recurrence of Campylobacter during 5 years of follow-up. A literature search revealed additional four case reports of six hypogammaglobulinemic adult individuals presenting with recurrent Campylobacter infections. Three patients were already on intravenous immunoglobulin (IVIG) when Campylobacter infection occurred, and two patients achieved clinical cure following therapy with imipenem and IVIG. This case report highlights the importance of suspecting hypogammaglobulinemia in patients with recurrent Campylobacter infections, as this is sometimes the first manifestation of the condition.

Successful treatment of gonococcal osteomyelitis with one week of intravenous antibiotic therapy.

Gonorrhea is one of the most common sexually transmitted infections (STIs). In a minority of cases, a disseminated infection can occur including gonococcal osteoarticular disease. With the steep and sustained increase in STIs in the US, we could see invasive gonococcal disease more often. Most cases of gonococcal osteomyelitis receive prolonged courses of antibiotic therapy. We report here the successful treatment of gonococcal osteomyelitis with one week of antibiotic therapy. Given the emergence of bacterial resistance worldwide and associated side effects, it is crucial to limit antibiotic exposures to the smallest effective dose possible.

Acute Toxoplasma Dissemination With Encephalitis in the Era of Biological Therapies.

We report the case of a 65-year-old patient with pseudolymphoma who developed acute toxoplasmosis following 6 cycles of rituximab and bendamustine therapy. Acute toxoplasmosis in the setting of biological response modifiers, rather than reactivation, is a unique unreported infection. The patient developed severe disease with multi-organ involvement, including retinitis, myocarditis, and myositis. We discuss the clinical findings, epidemiology, and laboratory diagnosis.

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.