The Contribution of 18F FDG PET-CT for the Investigation of Fever of Unknown Origin and Inflammation of Unknown Origin.

BACKGROUND: Fever of unknown origin and inflammation of unknown origin are highly challenging diagnostic conditions. The current practice for evaluating patients is to conduct a positron emission tomography-computed tomography (PET-CT) scan as either a first- or a second-line modality. We aimed to assess the contributory effect of PET-CT to the diagnosis and compare it with the contributory effect of CT alone. METHODS: We performed a systematic review and meta-analysis. We included all cohorts that examined the contribution of PET-CT to the investigation of classical fever of unknown origin and inflammation of unknown origin. The primary outcome was the contribution of PET-CT to the final diagnosis. Secondary outcomes were sensitivity and specificity of PET-CT and CT scans, and contribution of a CT scan. We pooled the results of all studies and calculated the pooled contributory effect of PET-CT. RESULT: Thirty-six studies (3516 patients) were included in the systematic review. The pooled contribution of PET-CT was 75.4%. The compiled sensitivity and specificity values for all studies were 85.9% and 59.5%, respectively. Five studies (405 patients) compared between the PET-CT component and the total body CT component. The pooled contribution of a CT scan was 68%. The summed sensitivity and specificity values of a CT scan for all studies were 63.1% and 84.4%, respectively. CONCLUSIONS: PET-CT has a contributory effect of 75% for the diagnosis of fever of unknown origin and inflammation of unknown origin. PET-CT had superior sensitivity and inferior specificity vs the CT scan.

Ceftriaxone 1 g versus 2 g per day, for the treatment of community-acquired pneumonia: a retrospective cohort study.

Guidelines recommend intravenous (IV) ceftriaxone at a dose of 1-2 g/d as empirical treatment in adults hospitalized with community acquired pneumonia (CAP), with the addition of macrolide. We examined whether 1 g/d of IV ceftriaxone is associated with similar clinical outcomes to those of 2 g/d. This is a single-center, retrospective, cohort study of all adult patients hospitalized at Rabin Medical Center between 2015 and 2018 with CAP. The primary outcome was 30-day all-cause mortality. Risk factors for 30-day all-cause mortality were identified by univariable and multivariable analyses, using logistic regression analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A total of 2045 patients were treated with IV ceftriaxone 1 g/d and were and compared to 1944 patients who were treated with 2 g/d. The groups were comparable in their baseline characteristics and their clinical presentation. The 30-day all-cause mortality rate was similar between the groups (301/2045 (14.7%) for 1 g/d vs. 312/1944 (16.0%) for 2 g/d, p = 0.24). The rate of C. difficile infection (CDI) was significantly decreased with 1 g/d compared to 2 g/d (4/2045 (0.2%) vs. 12/1944 (0.6%), p = 0.03) and the length of stay was significantly shorter (median 4 days interquartile range (IQR) 3-7 vs. 5 days IQR 3-8, p = 0.02). None of the blood isolates of Streptococcus pneumoniae were penicillin or ceftriaxone resistant. For hospitalized patients with CAP, IV ceftriaxone 1 g/d was associated with similar mortality rates as IV ceftriaxone 2 g/d, with a decreased rate of CDI and shorter length of stay. Ceftriaxone 1 g/d may be sufficient to treat patients with CAP in countries with low prevalence of drug resistant Streptococcus pneumoniae.

Ceftriaxone versus ampicillin for the treatment of community-acquired pneumonia. A propensity matched cohort study.

OBJECTIVES: Ceftriaxone is recommended as first-line antibiotic treatment (with the addition of macrolide) for hospitalised adults with community acquired pneumonia (CAP). Narrower-spectrum ß-lactam as ampicillin, may be associated with comparable clinical outcomes, with less emergence of resistant pathogens or Clostridioides difficile infection (CDI). We aimed to examine whether ampicillin and ceftriaxone (with the addition of macrolides for both arms) are comparable for the treatment of hospitalized adults due to CAP. METHODS: This was a single center, observational cohort study. We included adult patients who were hospitalized in internal medicine wards due to CAP and were treated with either ceftriaxone or ampicillin with the addition of macrolide. A propensity-score model was used. The primary outcome was 30-day all-cause mortality. A multivariable logistic regression analysis and Kaplan-Meier survival analysis was performed. We performed subgroup analyses for the main outcome based on CURB-65 score and age. RESULTS: A total of 1586 patients fulfilled the inclusion criteria. There was no difference in 30-day mortality rate in the total cohort (28/233 vs. 208/1353 in ampicillin and ceftriaxone arm, respectively; p = 0.184). In the propensity matched cohort (197 in ampicillin and 394 in ceftriaxone arm), there was no significant difference in 30-day all-cause mortality between treatment groups in multivariable analysis of the main model (OR 0.67, 95% CI, 0.37-1.2; p = 0.189) and Kaplan-Meier survival analysis (p = 0.108). Thirty-day mortality rate was (19/197 vs. 57/394, in ampicillin and ceftriaxone arms, respectively; p = 0.108) Patients who were treated with ampicillin experienced significantly lower rates of CDI (0/197, 0% vs. 8/394, 2%; p = 0.044). DISCUSSION: Ampicillin was associated with comparable clinical outcomes in comparison to ceftriaxone for patients who were hospitalized due to CAP. Ampicillin was associated with significantly lower rate of CDI. Results need to be confirmed by more robust study designs.

Tocilizumab Treatment Effect on Iron Homeostasis in Severe COVID-19 Patients.

BACKGROUND: Tocilizumab has been proposed as an effective treatment for severe COVID-19. We aimed to investigate whether tocilizumab administration is associated with increased availability of serum iron which may possibly be associated with adverse effects on clinical outcomes. METHODS: We performed an observational, retrospective cohort study. We included adults, who were hospitalized in ICU with the diagnosis of severe COVID-19 infection eligible for tocilizumab treatment. Laboratory data including serum iron, ferritin, transferrin saturation, hemoglobin, and C-reactive protein levels of all patients were collected shortly before and 24 h, 48 h, and 72 h after tocilizumab administration. RESULTS: During the study period, 15 patients fulfilled the inclusion criteria and were eligible to receive tocilizumab treatment. Tocilizumab therapy was associated with a prominent increase in serum iron and transferrin saturation levels (26 ± 13 µg/dL and 15 ± 8% before treatment and 79 ± 32 µg/dL and 41 ± 15% 72 h after treatment, respectively, p < 0.001) and decrease in serum ferritin levels (1,921 ± 2,071 ng/mL before and 1,258 ± 1,140 ng/mL 72 h after treatment, p = 0.027). CONCLUSION: Treatment of severe COVID-19 patients with tocilizumab is associated with a profound increase in serum iron and ferritin saturation levels along with a decrease in ferritin levels. This may represent an undesirable side effect that may potentiate viral replication.

Clinical and pathological predictors for FDG-PET/CT avidity in patients with marginal zone lymphoma-a retrospective cohort study.

BACKGROUND: The clinical value of FDG-PET/CT for staging and monitoring treatment response in patients with aggressive lymphoma is well established. Conversely, its role in the assessment and management of marginal zone lymphoma (MZL) is less conclusive. We aimed to assess clinical, laboratory, and pathological predictors for FDG uptake in these patients, in an attempt to identify MZL patients whose management will benefit from this imaging modality. METHODS: In this single-center, retrospective cohort study, we included all adult patients diagnosed with MZL at the Rabin Medical Center between January 2006 and December 2020 who underwent FDG-PET/CT at the time of diagnosis. Primary outcomes were FDG avidity (defined as a visual assessment of at least moderate intensity), SUVmax, and SUVliver. Variables such as advanced clinical stage, primary disease site, hemoglobin level (Hb), platelet count (Plt), serum albumin, LDH level, ß-2 microglobulin, and Ki 67 index were evaluated univariate and multivariate analysis using logistic and linear regression models. Association between FDG avidity and progression-free and overall survival was evaluated using Kaplan-Meier curves and Cox regression analysis. RESULTS: A total of 207 MZL patients were included in this study, 76 of whom (36.7%) had FDG-avid disease. Baseline patients' characteristics such as age, gender, and comorbid conditions were similar between patients with and without significant FDG uptake. In a multivariate logistic regression model, non-gastric MALT (OR 4.2, 95% CI 1.78-10), Ki 67 index ≥ 15% (OR 3.64, 95% CI 1.36-9.76), and elevated LDH level (OR 8.6, 95% CI 3.2-22.8) were all associated with positive FDG avidity. In a multivariate linear regression model, a combination of advanced clinical stage, specific disease subtypes, LDH level, and Ki 67 index predicted the value of SUVmax (P value < 0.001; adjusted R2 = 33.8%) and SUVmax/SUVliver (P value < 0.001; adjusted R2 = 27%). Baseline FDG avidity was associated to PFS and OS only in univariate analyses. CONCLUSIONS: In this retrospective cohort study, we present prediction models for positive FDG uptake and SUVmax in MZL patients. These models aim to help clinicians choose patients suitable for incorporation of FDG-PET/CT for staging and monitoring disease and reduce the costs of redundant tests.

ß-Blockers, Tachycardia, and Survival Following Sepsis: An Observational Cohort Study.

BACKGROUND: Sepsis is associated with excessive release of catecholamines, which causes tachycardia and is correlated with poor clinical outcome. ß-Blockers (BBs) may blunt this effect on heart rate (HR). The objective of this study is to assess whether long-term BB therapy is associated with better clinical outcomes in patients with sepsis admitted to internal medicine wards. METHODS: We performed a single-center, observational cohort study. We included adult patients who were hospitalized in medicine departments due to sepsis. A propensity score model for BB therapy was used to match patients. The primary outcome was the 30-day all-cause mortality rate. A multivariate analysis was performed to identify risk factors for an adverse outcome. Patients were stratified according to absolute tachycardia (HR ≥100/min) or relative tachycardia at presentation (tachycardia index above the third quartile, with tachycardia index defined as the ratio of HR to temperature). RESULTS: A total of 1186 patients fulfilled the inclusion criteria. In the propensity-matched cohort patients given BB treatment were younger (median age [interquartile range], 74 [62-82] vs 81 [68-87] years; P ≤ .001). BB treatment was associated with reduction in 30-day mortality rates for patients with absolute tachycardia (odds ratio, 0.406; 95% confidence interval, .177-.932). Final model with interaction variable of BB treatment with HR was associated with short-term survival (odds ratio, 0.38; 95% confidence interval, .148-.976). Selective BB therapy had a stronger protective effect than nonselective BB therapy. CONCLUSIONS: Long-term BB therapy was associated with decreased mortality rate in patients hospitalized with sepsis in internal medicine wards exhibiting absolute and relative tachycardia.

Natural History and Risk Stratification in Andersen-Tawil Syndrome Type 1.

BACKGROUND: Andersen-Tawil Syndrome type 1 (ATS1) is a rare arrhythmogenic disorder, caused by loss-of-function mutations in the KCNJ2 gene. We present here the largest cohort of patients with ATS1 with outcome data reported. OBJECTIVES: This study sought to define the risk of life-threatening arrhythmic events (LAE), identify predictors of such events, and define the efficacy of antiarrhythmic therapy in patients with ATS1. METHODS: Clinical and genetic data from consecutive patients with ATS1 from 23 centers were entered in a database implemented at ICS Maugeri in Pavia, Italy, and pooled for analysis. RESULTS: We enrolled 118 patients with ATS1 from 57 families (age 23 ± 17 years at enrollment). Over a median follow-up of 6.2 years (interquartile range: 2.7 to 16.5 years), 17 patients experienced a first LAE, with a cumulative probability of 7.9% at 5 years. An increased risk of LAE was associated with a history of syncope (hazard ratio [HR]: 4.54; p = 0.02), with the documentation of sustained ventricular tachycardia (HR 9.34; p = 0.001) and with the administration of amiodarone (HR: 268; p < 0.001). The rate of LAE without therapy (1.24 per 100 person-years [py]) was not reduced by beta-blockers alone (1.37 per 100 py; p = 1.00), or in combination with Class Ic antiarrhythmic drugs (1.46 per 100 py, p = 1.00). CONCLUSIONS: Our data demonstrate that the clinical course of patients with ATS1 is characterized by a high rate of LAE. A history of unexplained syncope or of documented sustained ventricular tachycardia is associated with a higher risk of LAE. Amiodarone is proarrhythmic and should be avoided in patients with ATS1.