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.

Non-Immunotherapy Approaches for Relapsed or Refractory AML: An Update for 2024.

BACKGROUND: Relapsed or refractory (R/R) acute myeloid leukemia (AML) is a challenging, high-risk, clinical scenario with a dismal outcome. Recent insights on the genetic, epigenetic, and metabolic events that drive clonal progression and the advent of novel therapies resulted in the incorporation of several new targeted therapies, alone or in combination, in the R/R setting with the aim of improving response rates and survival. Herein, we review current challenges and future opportunities with non-immunotherapeutic approaches to treat R/R AML. SUMMARY: Inhibitors of FLT3 and IDH 1/2 are now FDA approved for patients with R/R disease and corresponding mutations. These agents are also used in combination with intensive and low-intensity platforms in an attempt to improve response and survival. Several targeted agents are currently being tested alone or in combination in early-phase trials. These include drugs that target apoptotic pathways, drugs that interfere with key survival pathways of the R/R leukemic cell as well as therapies aimed toward the leukemia marrow microenvironment. Menin inhibitors are a promising class of active drugs in NPM1 and KMT2A-rearranged AML. KEY MESSAGES: Several new targeted therapies are being studied and are moving through pre-clinical and clinical pipelines. Significant remaining challenges include the development of synergistic combination therapies tailored to the specific biology and clinical context of the patient, and re-defining the role and timing of allogeneic transplantation in patients with R/R disease.

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.

Predictors for spontaneous resolution of classical FUO in patients undergoing PET-CT.

Spontaneous resolution is common in patients with classic fever of unknown origin (FUO). Identifying predictors of spontaneous resolution could reduce the usage of unnecessary, invasive tests or empirical therapy, and furthermore reduce patient anxiety. Identify predictors associated with spontaneous resolution of FUO. A single center, retrospective, cohort study. All hospitalized patients who underwent an [18F] FDG PET-CT scan for the investigation of classical FUO between 1/2012 and 1/2020 were included. We compared patients with spontaneous resolution of fever and clinical symptoms, to those who were diagnosed with a specific etiology of FUO (subdivided to infectious diseases, non-infectious inflammatory diseases (NIID), and malignancies). Epidemiologic characteristics as well as laboratory and PETCT study results were compared. Variables that were found to be associated with spontaneous resolution of FUO on univariate analysis (p < 0.1) were entered into a multivariable regression analysis. The results are reported as odds ratios (OR) and 95% confidence intervals (CI). A total of 303 patients were hospitalized for the investigation of classical FUO and underwent complete assessment. Fever resolved without a diagnosis in 84/303 patients (28%). Variables that were associated with spontaneous resolution of FUO on multivariable analysis included: no anemia, no hypoalbuminemia and no pathological FDG uptake on PET-CT. In 17.8% (15/84) of studies, PET-CT yielded false-positive results that led to additional unnecessary, invasive investigation. Patients without anemia or hypoalbuminemia, and those without uptake on PET-CT are more likely to have spontaneous resolution of classical FUO.

Intravenous Iron Supplementation for the Treatment of Chemotherapy-Induced Anemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The pathophysiology of cancer-related anemia is multifactorial, including that of chemotherapy-induced anemia (CIA). The guidelines are not consistent in their approach to the use of intravenous (IV) iron in patients with cancer as part of the clinical practice. Materials and methods: All randomized controlled trials that compared IV iron with either no iron or iron taken orally for the treatment of CIA were included. We excluded trials if erythropoiesis-stimulating agents (ESAs) were used. The primary outcome was the percentage of patients requiring a red blood cell (RBC) transfusion during the study period. The secondary outcomes included the hematopoietic response (an increase in the Hb level by more than 1 g/dL or an increase above 11 g/dL), the iron parameters and adverse events. For the dichotomous data, risk ratios (RRs) with 95% confidence intervals (Cis) were estimated and pooled. For the continuous data, the mean differences were calculated. A fixed effect model was used, except in the event of significant heterogeneity between the trials (p < 0.10; I2 > 40%), in which we used a random effects model. Results: A total of 8 trials published between January 1990 and July 2021 that randomized 1015 patients fulfilled the inclusion criteria. Of these, 553 patients were randomized to IV iron and were compared with 271 patients randomized to oral iron and 191 to no iron. IV iron decreased the percentage of patients requiring a blood transfusion compared with oral iron (RR 0.72; 95% CI 0.55−0.95) with a number needed to treat of 20 (95% CI 11−100). IV iron increased the hematopoietic response (RR 1.23; 95% CI 1.01−1.5). There was no difference with respect to the risk of adverse events (RR 0.97; 95% CI 0.88−1.07; 8 trials) or severe adverse events (RR 1.09; 95% CI 0.76−1.57; 8 trials). Conclusions: IV iron resulted in a decrease in the need for RBC transfusions, with no difference in adverse events in patients with CIA. IV iron for the treatment of CIA should be considered in clinical practice.

A Systematic Review Assessing the Underrepresentation of Cancer Patients in COVID-19 Trials.

BACKGROUND: The new severe acute respiratory syndrome coronavirus 2 has emerged as a global pandemic that threatens thousands around the world. Observational cohort studies have demonstrated that cancer patients have inferior outcomes due to underlying malignancy, treatment-related immunosuppression, or increased comorbidities. We aimed to examine the representation of cancer patients (hematological malignancies and solid tumors) in COVID-19 therapeutic and prophylactic interventional trials. METHODS: In this review, all randomized controlled trials (RCTs) published between December 2019 and August 2021 were included. We included only trials evaluating medications that were recommended by NIH guidelines: steroids, tocilizumab, remdesivir, and REGN-COV2. RESULTS: The search yielded 541 potentially relevant RCTs, 22 of which were considered suitable. All trials included patients with solid cancer and hematological malignancies in the formal reported inclusion criteria. However, only two trials reported the accurate number of cancer patients included. Ten trials excluded neutropenic patients and seven trials excluded thrombocytopenic patients. Eleven trials excluded patients that were treated with any immunosuppression treatment. None of the two trials that included cancer patients reported separate outcomes for this population. CONCLUSION: Our systematic review shows that cancer patients are underrepresented in COVID-19 interventional therapeutic trials, and evidence regarding outcomes are lacking.

Representation of women in editorial boards of infectious disease and microbiology journals-cross-sectional study.

OBJECTIVES: We aimed to assess whether there is an association between the proportion of female editors-in-chief and members of editorial boards in infectious disease (ID) and microbiology journals. METHODS: Our cross-sectional observational study included ID or microbiology journals according to the 2019 Clarivate Journal Citation Reports. Journals' Q ranking, open-access status, and number and gender of editors-in-chief and editorial board members were collected from the journals' official websites. We conducted a binary gender assignment for each editor using names, pictures, and other online descriptors. Journals with over 100 editorial board members and those with over 25% of board members for whom we could not determine gender were excluded. Editorial teams with >50% women were considered women dominant. Univariate and multivariable analyses for female editor dominance were performed. RESULTS: Overall, 167 journals were included, with total 6057 editorial members, 1655 (27.3%) of whom were women. Of 214 editors-in-chief, 48 (22%) were women, and only 25% (40 of 162) of journals had female editor-in-chief dominance. Factors associated with female dominance in the editor-in-chief role in univariate analysis were higher quartile rank, higher impact factor, and open access. Open-access journals remined significant in multivariable analysis (odds ratio (OR) 2.521; 95% CI, 1.140-5.576, p = 0.022). Larger editorial boards were less likely to have female dominance. Female editor-in-chief dominance was significantly associated with women-dominant editorial boards. DISCUSSION: ID and microbiology journals have significantly few women as editors-in-chief and editorial board members. Understanding the reasons for this inequality is required as an important step to confront and resolve it.

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.

Autoimmune and inflammatory manifestations associated with acute myeloid leukemia with Trisomy 8-Case series and review of the literature.

AML can be associated with autoimmune or inflammatory phenomena (AIP) occurring prior, concomitantly, or after its diagnosis. Trisomy 8 is one of the most common cytogenetic abnormalities associated with AML. We describe three patients with AML, trisomy 8, and associated AIP and review the known literature on this association. All of our patients had major symptomatic relief when treated with leukemia-directed therapy and corticosteroids. AIP in AML may be an underdiagnosed phenomenon, particularly in patients with trisomy 8.

The Importance of Abnormal Platelet Count in Patients with Clostridioides difficile Infection.

BACKGROUND: Clostridium difficile infection (CDI) causes morbidity and mortality. Platelets have been increasingly recognized as an important component of innate and adaptive immunity. We aimed to assess the incidence of thrombocytopenia and thrombocytosis in CDI and the effect of an abnormal platelet count on clinical outcomes. METHODS: This single-center, retrospective cohort study consisted of all adult patients hospitalized in Rabin Medical Center between 1 January 2013 and 31 December 2018 with laboratory confirmed CDI. 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. RESULTS: A total of 527 patients with CDI were included. Among them 179 (34%) had an abnormal platelet count: 118 (22%) had thrombocytopenia and 61 (11.5%) had thrombocytosis. Patients with thrombocytosis were similar to control patients other than having a significantly higher white blood cell count at admission. Patients with thrombocytopenia were younger than control patients and were more likely to suffer from malignancies, immunosuppression, and hematological conditions. In a multivariable analysis, both thrombocytosis (OR 1.89, 95% CI 1.01-3.52) and thrombocytopenia (OR 1.70, 95% CI 1.01-2.89) were associated with 30-days mortality, as well as age, hypoalbuminemia, acute kidney injury, and dependency on activities of daily living. A sensitivity analysis restricted for patients without hematological malignancy or receiving chemotherapy revealed increased mortality with thrombocytosis but not with thrombocytopenia. CONCLUSIONS: In this retrospective study of hospitalized patients with CDI, we observed an association between thrombocytosis on admission and all-cause mortality, which might represent a marker for disease severity. Patients with CDI and thrombocytopenia also exhibited increased mortality, which might reflect their background conditions and not the severity of the CDI. Future studies should assess thrombocytosis as a severity marker with or without the inclusion of the WBC count.