Classical fever of unknown origin in 21 countries with different economic development: an international ID-IRI study.

Fever of unknown origin (FUO) is a serious challenge for physicians. The aim of the present study was to consider epidemiology and dynamics of FUO in countries with different economic development. The data of FUO patients hospitalized/followed between 1st July 2016 and 1st July 2021 were collected retrospectively and submitted from referral centers in 21 countries through ID-IRI clinical research platform. The countries were categorized into developing (low-income (LI) and lower middle-income (LMI) economies) and developed countries (upper middle-income (UMI) and high-income (HI) economies). This research included 788 patients. FUO diagnoses were as follows: infections (51.6%; n = 407), neoplasms (11.4%, n = 90), collagen vascular disorders (9.3%, n = 73), undiagnosed (20.1%, n = 158), miscellaneous diseases (7.7%, n = 60). The most common infections were tuberculosis (n = 45, 5.7%), brucellosis (n = 39, 4.9%), rickettsiosis (n = 23, 2.9%), HIV infection (n = 20, 2.5%), and typhoid fever (n = 13, 1.6%). Cardiovascular infections (n = 56, 7.1%) were the most common infectious syndromes. Only collagen vascular disorders were reported significantly more from developed countries (RR = 2.00, 95% CI: 1.19-3.38). FUO had similar characteristics in LI/LMI and UMI/HI countries including the portion of undiagnosed cases (OR, 95% CI; 0.87 (0.65-1.15)), death attributed to FUO (RR = 0.87, 95% CI: 0.65-1.15, p-value = 0.3355), and the mean duration until diagnosis (p = 0.9663). Various aspects of FUO cannot be determined by the economic development solely. Other development indices can be considered in future analyses. Physicians in different countries should be equally prepared for FUO patients.

Discordance between Serum Neutralizing Antibody Titers and the Recovery from COVID-19.

The recent pandemic of COVID-19 has caused a tremendous alarm around the world. Details of the infection process in the host have significant bearings on both recovery from the disease and on the correlates of the protection from the future exposures. One of these factors is the presence and titers of neutralizing Abs (NAbs) in infected people. In the current study, we set out to investigate NAbs in the recovered subjects discharged from the hospital in full health. Serum samples from a total of 49 documented consecutive COVID-19 subjects were included in the study. All the subjects were adults, and serum samples collected during the discharge were tested in viral neutralization, enzyme immunoassay (EIA), and Western immunoblot tests against viral Ags. Even though a majority of the recovered subjects had raised significant NAb titers, there is a substantial number of recovered patients (10 out of 49) with no or low titers of NAbs against the virus. In these cohorts as well as in patients with high NAb titers, viral Ag binding Abs were detectable in EIA tests. Both NAb titers and EIA detectable Abs are increased in patients experiencing a severe form of the disease, and in older patients the Ab titers were heightened. The main conclusion is that the recovery from SARS-CoV-2 infection is not solely dependent on high NAb titers in affected subjects, and this recovery process is probably produced by a complex interplay between many factors, including immune response, age of the subjects, and viral pathology.

Tocilizumab treatment in severe COVID-19: a multicenter retrospective study with matched controls.

Coronavirus disease-2019 (COVID-19) associated pneumonia may progress into acute respiratory distress syndrome (ARDS). Some patients develop features of macrophage activation syndrome (MAS). Elevated levels of IL-6 were reported to be associated with severe disease, and anti-IL-6R tocilizumab has been shown to be effective in some patients. This retrospective multicenter case-control study aimed to evaluate the efficacy of tocilizumab in hospitalized COVID-19 patients, who received standard of care with or without tocilizumab. Primary outcome was the progression to intubation or death. PSMATCH (SAS) procedure was used to achieve exact propensity score (PS) matching. Data from 1289 patients were collected, and study population was reduced to 1073 based on inclusion-exclusion criteria. The composite outcome was observed more frequently in tocilizumab-users, but there was a significant imbalance between arms in all critical parameters. Primary analyses were carried out in 348 patients (174 in each arm) after exact PS matching according to gender, ferritin, and procalcitonin. Logistic regression models revealed that tocilizumab significantly reduced the intubation or death (OR 0.40, p = 0.0017). When intubation is considered alone, tocilizumab-users had > 60% reduction in odds of intubation. Multiple imputation approach, which increased the size of the matched patients up to 506, provided no significant difference between arms despite a similar trend for intubation alone group. Analysis of this retrospective cohort showed more frequent intubation or death in tocilizumab-users, but PS-matched analyses revealed significant results for supporting tocilizumab use overall in a subset of patients matched according to gender, ferritin and procalcitonin levels.

Investigation of the changing etiology and risk factors of prosthetic joint infections : a university hospital surveillance study from 2011-2017.

We sought to characterize the causative pathogens of prosthetic joint infections (PJIs), evaluate the trends in microbial etiologies, and identify potential risk factors for PJI. This was a retrospective study analyzing 70 patients with PJI following 3,253 total joint arthroplasties between 2011 and 2017. Staphylococci were the most common cause of infection (52.9%). There was a significant trend in the percentage of carbapenem-resistant gram-negative bacilli (GNB) (increased to 66.7% in 2016 from 0.0% in 2011) (p=0.021). GNB and polymicrobial etiology were found at significantly high levels in cases involving early PJIs (p=0.005 and p=0.048, respectively). While staphylococci were significantly higher in PJIs after total knee arthroplasty (75%), GNB were significantly higher in PJIs after total hip arthroplasty (49.1%) (p<0.001 and p=0.001, respectively). Binary logistic regression analysis showed that the risk of PJI was significantly higher in cases with fracture and diabetes mellitus (odds ratio [OR], 4.3, 95% confidence interval [CI], 1.78-10.5 ; OR, 4.1, 95% CI, 1.66-10.5, respectively). These results suggest that the empirical and targeted antimicrobial treatment of PJIs may become more difficult in the future.

Transforming a U.S. scholarly concentrations program internationally: lessons learned.

BACKGROUND: Scholarly Concentrations programs in U.S. medical schools aim to instill passion for critical thinking and promote careers in academic medicine. The rise of these programs has seen variable goals, structure, and outcomes. Transformation of these programs internationally is in its infancy. METHODS: We describe implementation of the Johns Hopkins School of Medicine Scholarly Concentrations program, offering Basic Science, Clinical Science, Medical Ethics/Healing Arts, History of Medicine, and Public Health/Community Service, at Bezmiâlem Vakif University in Istanbul, Turkey. Over six modules in the preclinical years, students develop a faculty-mentored experience which encourages the acquisition of attitudes and skills for self-directed, lifelong learning and scholarship. This culminates in abstract and project presentation. We report program characteristics (context and logistics) and outcomes (student engagement and experiences). RESULTS: The Scholarly Concentrations program at Bezmiâlem began in 2014, with nearly two completed cohorts of students. In comparison to Johns Hopkins, students at Bezmiâlem begin at an earlier age (thus do not have as much prior research experience) and are subsequently evaluated for residency in terms of test scores rather than scholarship and publications, but have a similar level of intellectual curiosity and desire to take ownership of their project. Eighty-two percent of Bezmiâlem students stated the project they pursued was either their own idea or was an idea they formed after meeting with their mentor. Students at Bezmialem were more likely to choose Clinical Science projects (p = 0.009). Only 5% of Bezmiâlem students in end-of-course survey felt dissatisfied with the level of ownership they experienced with their project, a frequency similar to that seen by Johns Hopkins students (2%). CONCLUSIONS: Scholarly Concentrations programs play an important role in U.S. medical schools, and these programs can be successfully implemented internationally. The Scholarly Concentrations program at Johns Hopkins has been transformed to a program at Bezmiâlem in Istanbul, the first program outside North America or the European Union. When designing these programs, one must consider the context, logistics, student engagement, and outcomes. While long-term outcomes are needed, this can serve as a model for implementation elsewhere.

Analysis of infectious spondylodiscitis: 7-years data.

OBJECTIVE: Infectious spondylodiscitis (SD) is an infectious disease that is rare and difficult to diagnose due to its non-specific clinical features. In this study, we aimed to describe the clinical and diagnostic features of infectious spondylodiscitis. METHODS: All patients who were diagnosed with SD at our hospital during a 7-year period from January 1, 2011 through December 31, 2017 were included in the study. Spondylodiscitis is divided into the following three types: pyogenic, tuberculous, and brucellar. Clinical and laboratory data were collected retrospectively from the medical records of the patients. RESULTS: Of the 118 patients, 66 (55.9%) were female, 81 (68.6%) had pyogenic SD (PSD), 21 (17.8%) had tuberculous SD (TSD), and 16 (13.6%) had brucellar SD (BSD). The mean age was 59.3 ± 14.6 years. Leucocytosis was significantly higher in patients with PSD (p=0.01) than in patients with other types of SD. Thoracic involvement (47.6%) was significantly higher in patients with TSD (p=0.005) than in other patients. Sacral involvement (12.5%) was significantly higher in patients with BSD (p=0.01) than in other patients. Paravertebral abscess formation (42.8%) occurred most frequently in patients with TSD. Microbiologic agents were defined in 50% (18/36) of the surgical specimens and in 12.5% of the fine needle aspiration biopsy (FNAB) specimens. Staphylococcus aureus was the most common microbiological agent in patients with PSD. Spinal surgery was defined as a risk factor for PSD (p = 0.0001). Binary logistic regression analysis revealed that female gender, thoracic involvement and night sweats were the predictive markers for TSD (OR 4.5 [95% CI 1.3-15.3] and OR 5 [95% CI 1.7-14.6]). CONCLUSION: PSD is the most frequent form of SD. Leucocytosis is most common in patients with PSD. Thoracic involvement and paraspinal abscess were prominent in patients with TSD. Sacral involvement was most common in patients with BSD. Thoracic involvement, female gender and night sweats were the predictive markers for TSD. The microbiological culture positivity rate was higher in surgical specimens compared to FNAB specimens. The need for surgical treatment was most common in patients with TSD.

The Effect of Antiretroviral Therapy on IL-6, IL-1ß, TNF-α, IFN-γ Levels and their Relationship with HIV-RNA and CD4+ T Cells in HIV Patients.

BACKGROUND: Serum cytokine levels over the course of HIV infection usually increase with immunosuppression and decrease after antiretroviral treatment (ART). OBJECTIVES: The aim of the study is to compare cytokine levels between HIV-infected patients (HIP) and controls and investigate the relationship between CD4+T cell count, HIV-RNA levels, and cytokine levels. METHODS: The study subjects comprised ART-naive HIP (n=30) with no comorbidities and age-and sex-matched healthy controls. We measured levels of IL-6, IL-1ß, TNF-α, and IFN-γ in serum samples of HIP at the beginning and at month 6 of ART and in controls. RESULTS: The mean age of the study subjects was 38.7 ±10.3 years, with men making up 86.7% of the study subjects (n=26). IL-6, IL-1ß, and TNF-α levels were significantly higher in both ART-naive (p<0.001, p=0.002, p=0.001) and ART-experienced HIP (p<0.001) than controls. The IFN-γ level was lower in both ART-naive and ART-experienced HIP compared to controls (p=0.082 and p=0.002). There was a positive correlation between the CD4+T cell count and serum concentration of IFN- γ(r=0.320, p<0.05). While the serum IFN-γ concentration showed a negative correlation with the HIVRNA level(r=-0.412, p<0.001), the serum IL-1ß, IL-6, and TNF-α concentrations showed a positive correlation with the HIV-RNA level (r=0.349, p<0.001; r:0.54, p<0.001; r:0.438, p<0.00). CONCLUSION: Although serum concentrations of IL-6, IL-1ß and TNF-α showed a significant decrease after ART, they were still significantly higher than the controls. IFN-γ responded differently to ART compared to the other cytokines, indicating that it may play a distinct and important role in the pathogenesis of HIV infection.

Clostridium difficile infection: Is there a change in the underlying factors? Inflammatory bowel disease and Clostridium difficile.

BACKGROUND / AIMS: Clostridium difficile is a Gram-positive, strict anaerobe, spore-forming bacterium. It can cause self-limiting mild diarrhea, severe diarrhea, pseudomembranous colitis, and fatal fulminant colitis. We aimed to investigate the changes in epidemiology and incidence of C. difficile infection in our hospital database. PATIENTS AND METHODS: Episodes of C. difficile toxin were identified in hospital database, and data such as age, sex, community versus hospital acquisition, intensive care follow-up, current or previous treatments with antibiotics within the past 3 months, medication with proton pump inhibitors, or immunosuppressive therapies were collected. RESULTS: Toxin-positive 78 individuals constituted the patient group. In univariate analyses, independent risk factors for toxin positivity were community versus hospital acquisition [odds ratio (OR), 5.49; 95% confidence interval (CI), 2.52-11.95; P = 0.0001], presence of inflammatory bowel diseases (IBDs) (OR, 21.5; 95% CI, 8.65-53.44; P = 0.0001), proton pump inhibitors' use (OR, 4.53; 95% CI, 1.97-10.43; P = 0.0001), immunosuppressive drug use (OR, 4.1; 95% CI, 2.01-8.3; P = 0.0001), and use of quinolone group of antibiotics (OR, 5.95; 95% CI, 1.92-18.46; P = 0.001). Antibiotic use was a protective risk factor (OR, 0.09; 95% CI, 0.01-0.78; P = 0.01) and presence of IBDs was an independent risk factor (OR, 6.8; 95% CI, 1.5-30.08; P = 0.01) in community-acquired group (OR, 0.09; 95% CI, 0.01-0.78; P = 0.01). CONCLUSION: In recent studies, C. difficile infections were demonstrated to be more frequent in younger individuals who did not have a history of hospitalization but had an underlying disease such as IBD. In our study, we showed the change in the epidemiological data with prominence of underlying diseases such as IBDs.

Epidemiological and molecular characteristics of meticillin-resistant Staphylococcus aureus in Turkey: A multicentre study.

The aim of this study was to investigate the epidemiological and molecular features of clinical meticillin-resistant Staphylococcus aureus (MRSA) isolates in Turkey. MRSA isolates were collected from six regions of Turkey. The mecA and nuc genes were detected by PCR. Antimicrobial susceptibilities were determined by the disk diffusion method. Staphylococcal cassette chromosome mec (SCCmec) and staphylococcal protein A (spa) typing were performed by the sequencing method for 270 randomly selected MRSA isolates. The US Centers for Disease Control and Prevention (CDC) definition was used for epidemiological diagnosis of community-associated MRSA (CA-MRSA). Resistance rates of MRSA to ciprofloxacin, gentamicin, clindamycin, erythromycin, rifampicin, trimethoprim/sulfamethoxazole and tetracycline were 93.4%, 81.2%, 38.5%, 57.8%, 93.9%, 1.1% and 93.1%, respectively. The most frequent SCCmec type was SCCmec III (91.1%). SCCmec type IV was found in 5.2% of the isolates. The most frequent spa type was t030 (81.1%). Five isolates were CA-MRSA if only the epidemiological definition was used (5/725; 0.7%). Two isolates were defined as CA-MRSA both by epidemiological features and SCCmec typing (2/270; 0.7%). Of 14 SCCmec type IV isolates, 12 were not defined as CA-MRSA by epidemiological features. In conclusion, this is the most comprehensive multicentre study in Turkey investigating MRSA using both epidemiological and genotypic features. The CA-MRSA rate is low in Turkey. Combined use of epidemiological and genotypic methods is the most accurate approach for the diagnosis of CA-MRSA.