Identifying risk factors for blood culture negative infective endocarditis: An international ID-IRI study.

Background: Blood culture-negative endocarditis (BCNE) is a diagnostic challenge, therefore our objective was to pinpoint high-risk cohorts for BCNE. Methods: The study included adult patients with definite endocarditis. Data were collected via the Infectious Diseases International Research Initiative (ID-IRI). The study analysing one of the largest case series ever reported was conducted across 41 centers in 13 countries. We analysed the database to determine the predictors of BCNE using univariate and logistic regression analyses. Results: Blood cultures were negative in 101 (11.65 %) of 867 patients. We disclosed that as patients age, the likelihood of a negative blood culture significantly decreases (OR 0.975, 95 % CI 0.963-0.987, p < 0.001). Additionally, factors such as rheumatic heart disease (OR 2.036, 95 % CI 0.970-4.276, p = 0.049), aortic stenosis (OR 3.066, 95 % CI 1.564-6.010, p = 0.001), mitral regurgitation (OR 1.693, 95 % CI 1.012-2.833, p = 0.045), and prosthetic valves (OR 2.539, 95 % CI 1.599-4.031, p < 0.001) are associated with higher likelihoods of negative blood cultures. Our model can predict whether a patient falls into the culture-negative or culture-positive groups with a threshold of 0.104 (AUC±SE = 0.707 ± 0.027). The final model demonstrates a sensitivity of 70.3 % and a specificity of 57.0 %. Conclusion: Caution should be exercised when diagnosing endocarditis in patients with concurrent cardiac disorders, particularly in younger cases.

Latent Tuberculosis Infection Management in Solid Organ Transplantation Recipients: A National Snapshot.

OBJECTIVE:  Latent tuberculosis infection (LTBI) screening is strongly recommended in the pre-transplant evaluation of solid organ transplant (SOT) recipients, although it remains inadequate in many transplant centers. We decided to investigate pre-transplant TB risk assessment, LTBI treatment, and registry rates in Turkey. MATERIAL AND METHODS:  Adult SOT recipients who underwent tuberculin skin test (TST) and/or interferon-gamma release test (IGRA) from 14 centers between 2015 and 2019 were included in the study. An induration of ≥5 mm on TST and/or probable/positive IGRA (QuantiFERON-TB) was considered positive for LTBI. Demographic features, LTBI screening and treatment, and pre-/post-transplant TB history were recorded from the electronic database of transplantation units across the country and pooled at a single center for a unified database. RESULTS:  TST and/or IGRA were performed in 766 (33.8%) of 2266 screened patients most of whom were kidney transplant recipients (n = 485, 63.4%). LTBI screening test was positive in 359 (46.9%) patients, and isoniazid was given to 203 (56.5%) patients. Of the patients treated for LTBI, 112 (55.2%) were registered in the national registry, and 82 (73.2%) completed the treatment. Tuberculosis developed in 6 (1.06%) of 563 patients who were not offered LTBI treatment. CONCLUSION:  We determined that overall, only one-third of SOT recipients in our country were evaluated in terms of TB risk, only 1 of the 2 SOT recipients with LTBI received treatment, and half were registered. Therefore, we want to emphasize the critical importance of pretransplant TB risk stratification and registration, guided by revised national guidelines.

Infections after musculoskeletal injuries in earthquake survivors.

OBJECTIVES: This study aimed to investigate the infections following musculoskeletal injuries in earthquake survivors, offering a future clinical point of reference for the handling of musculoskeletal injuries resulting from earthquakes. PATIENTS AND METHODS: In this single-center retrospective observational study, 225 earthquake survivors (120 females, 105 males; median: 39 years; range, 18 to 94 years) admitted between February 2023 and April 2023 were evaluated. Patients with musculoskeletal injuries and patients who had at least one month of follow-up data were included in the study. Diagnosis of healthcare-associated infections was verified by an infection control physician in accordance with the Centers for Disease Control and Prevention. RESULTS: Among all cultures, the most isolated pathogen was Acinetobacter baumannii (49.4%), followed by enterococci (28.6%). Colistin sensitivity of A. baumannii was 36 (94.7%). However, sensitivity rate was 5.3% for ciprofloxacin, 10.5% for piperacillin-tazobactam, and 26.4% for carbapenems, which are frequently used for skin and soft tissue infections. Among all, 76% of the microorganisms isolated from wound culture and 58% of the microorganisms isolated from deep tissue culture were found to be multidrug-resistant pathogens. During the follow-up, 12 (5.3%) patients had hospital-acquired urinary tract infections, 13 (5.7%) patients had hospitalacquired bloodstream infections, one (0.4%) patient had hospital-acquired pneumonia, and 74 (32.8%) patients had surgical site infections. Eighty (35.6%) of the patients were followed up in the intensive care unit, and the overall mortality rate was 2.7%. CONCLUSION: While gram-positive microorganisms are frequently the causative microorganisms in infections after traumatic injuries, this study revealed that gram-negative microorganisms could be observed more frequently in postearthquake traumatic injuries. Most causative microorganisms are resistant to commonly prescribed antibiotics in clinical settings, which makes them more challenging to treat.

Causative Microorganisms in Community-Acquired Urinary Tract Infections and Risk Factors for the Development of Infection with Extended-Spectrum ß-Lactamase-Producing Species.

Objective: This study aimed to determine the microorganisms grown in the urine cultures of patients followed up with the diagnosis of community-acquired urinary tract infection (CA-UTI), their antibiotic susceptibility, and the risk factors that cause extended-spectrum ß-lactamase (ESBL) production in microorganisms. Materials and Methods: Patients diagnosed with CA-UTI in the Yildirim Beyazit University City Hospital Infectious Diseases and Clinical Microbiology Clinic between February 2019 and February 2020 were prospectively analyzed. The microorganisms grown in the urine cultures and antibiotic susceptibility rates were examined. The clinical and demographic characteristics of the patients were compared in terms of the isolated agent producing ESBL. Results: Escherichia coli (63.8%) and Klebsiella pneumoniae (22.0%) were the most common microorganisms detected in the urine cultures; the rate of those producing ESBL was 46.6%. Antibiotics with high resistance rates were ampicillin (74.2%), cefuroxime (49.6%), and ceftriaxone (49%). Male gender, complicating factors, immunosuppression, kidney transplantation and history of antibiotic use were determined as significant risk factors for ESBL production. Male gender, immunosuppression, and history of antibiotic use were also independent risk factors. ROC analysis of risk factors showed ESBL-producing bacteria were isolated at a high rate in patients having ≥3 risk factors. Conclusion: The resistance rates in our study are quite high. Male gender, history of antibiotic use and immunosuppression status were found to be independent risk factors for ESBL positivity in patients with CA-UTI, and the more risk factors a patient has, the higher the risk of ESBL positivity.

Analysis of peripheral lymphocyte subsets and T-cell exhaustion in SARS-CoV-2 Infection.

Introduction: : Immune responses against Coronavirus (SARS-CoV-2) may be highly complex. It has been suggested that T-cell fatigue develops due to continuous stimulation of T-cells by SARS-CoV-2 in Coronavirus disease-2019 (COVID-19). It was aimed to assess peripheral lymphocyte subsets and T-cell exhaustion in various clinical courses of the disease in patients diagnosed with COVID-19. Materials and Methods: This study included 150 patients who were assigned into the "mild-to-moderate disease" group, or "severe disease" group based on their clinical and laboratory characteristics. Peripheral lymphocyte subsets and T-cell exhaustion markers [programmed cell death protein 1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3)] were determined in the peripheral blood using flow cytometry. Result: Mean (±SD) age was 53.3 ± 14.5 years, and female to male ratio was 55/95. In the mild-to-moderate disease (MMD) group, 55 patients had pneumonia and 20 patients had COVID-19 without pneumonia. In the severe disease (SD) group, 43 patients had severe pneumoniae and 32 patients were in critical condition. Lymphocyte counts were less than 1.0 x 109/L in 69.3% of the patients in the SD group, and the difference between the MMD group and SD group was statistically significant (p= 0.001). Total T cells, CD4+ and CD8+ T-cell counts were significantly lower in the SD group vs. MMD group (p< 0.001, p< 0.001, p< 0.001, respectively). PD-1 expression by CD8+ and CD4 T+ cells was higher (p= 0.042, p= 0.029, respectively) and Tim-3 expression from CD4 T+ cells was lower (p= 0.000) in the SD group vs. MMD group. Serum IFN-γ levels were not statistically different in the MMD and SD groups (p= 0.2). Conclusions: T-cell counts may be significantly reduced along with an increased expression of the T-cell exhaustion marker PD-1 in severe COVID-19, but Tim-3 expression was not increased in our study patients.

Iatrogenic botulism cases after gastric and axillary application of botulinum toxin and review of literature.

INTRODUCTION: Iatrogenic botulism is a rare, serious disease that progresses with descending paralysis and develops after cosmetic or therapeutic botulinum toxin-A (BoNT-A) application. CASE PRESENTATIONS: In this case series; six cases of iatrogenic botulism followed up in our center are presented. Four of these developed after gastric BoNT-A and two after axillary BoNT-A application. RESULTS: The most important cause for the disease was the use of unlicensed products and high-dose toxin applications. The first symptoms were blurred vision, double vision, difficulty in swallowing, and hoarseness. Symptoms appeared within 4-10 days after the application of BoNT-A. Symptoms progressed in the course of descending paralysis in the following days with fatigue, weakness in extremities and respiratory distress. Diagnosis was based on patient history and clinical findings. The main principles of foodborne botulism therapy were applied in the treatment of iatrogenic botulism. If clinical worsening continued, regardless of the time elapsed after BoNT-A application, the use of botulinum antitoxin made a significant contribution to clinical improvement and was recommended. CONCLUSIONS: Routine and new indications for BoNT-A usage are increasing and, as a result, cases of iatrogenic botulism will be encountered more frequently. Physicians should be alert for iatrogenic botulism in the follow-up after BoNT-A applications and in the differential diagnosis of neurological diseases that are presented with similar findings.

Investigation of polypharmacy, antimicrobial-related potential drug-drug interactions in patients with hematological malignancies.

PURPOSE: Drug-drug interactions (DDIs) occur when one drug interferes with the pharmacological activity of another and can lead to increased side effects. The purpose of this study was to examine potential interactions between antimicrobials and other drugs in patients with hematological malignancies (HMs). METHOD: The medications used by 233 patients with HMs before and during hospitalization in Ankara City Hospital Hematology Clinic services between January 2021 and July 2021 were examined. Potential DDIs (pDDIs) were identified through UptoDate, Drugs.com, and MedScape databases. The effects of major antimicrobial-related pDDIs on patients were examined. Agreement between the two interaction systems was judged based on the kappa test. SPSS R Version 4.0.2 was used in the statistical analysis of the data, p<.05 was considered significant. RESULTS: The prevalence of polypharmacy before hospitalization was determined as 22.7%. Diagnosed with acute leukemia and multiple myeloma, more antimicrobial-related pDDIs were detected during hospitalization (p<.001). A total of 758 antimicrobial-related pDDIs, which were in the major category in at least one of the three databases, were detected in 72.5% (169/233) of the participants. It was determined that the total hospitalization period of patients with major antimicrobial-related pDDIs was longer (p<.001). There was negligible agreement between UptoDate and Dugs.com and between Drugs.com and MedScape (kappa: 0.008 for both). There was no compatibility between UptoDate and MedScape (kappa<0). CONCLUSION: Interactions between antimicrobials and other drugs are undesirable problems. Further studies are required to evaluate the clinical and economic effects of the interactions on patients with HMs.

Point prevalence of antibiotic usage in major referral hospital in Turkey.

INTRODUCTION: The most important and undesirable consequence of inappropriate antibiotic use is the spread of antibiotic resistance, increased adverse effects, increased mortality and healthcare costs. We aimed to assess antibiotic usage characteristics in inpatient setting in our center. MATERIALS AND METHODS: A one-day, single center point-prevalence study was carried out on June 9th 2021, in Ankara City Hospital in Turkey. Data of antibiotic consumption, appropriateness of usage and predictors of inappropriate use in adult patients were evaluated. RESULTS: Out of 2640 adult patients, 893 (33.8%) were receiving at least one antibiotic. A total of 1212 antibiotic prescriptions with an average of 1.44±0.64 were found. Antibiotics were most commonly used for therapeutic purpose (84.7%), followed by surgical prophylaxis (11.6%). Majority of therapeutically used antibiotics were empirical (67.9%). Infectious diseases consultation was present in 68.3% with a compliance rate of 95.7%. Rate of inappropriate use was 20%. The most frequent cause of inappropriateness was unnecessary use (52.5%). Most commonly and most inappropriately used antibiotics were carbapenems (17.5%) and first generation cephalosporins (38.7%), respectively. Most of the inappropriateness observed in first-generation cephalosporins was due to inappropriate longer surgical prophylaxis. While age is an independent risk factor for inappropriate antibiotic use (p = 0.042), COVID-19 unit admission, use for therapeutic purpose and infectious diseases consultation were protective factors (p<0.001, p<0.001, p<0.001). CONCLUSION: Rate of inappropriate use was low, but inappropriate surgical prophylaxis remains an important problem in surgical units. There is a considerable need to implement an antimicrobial stewardship program that focuses on surgical prophylaxis practices.

Impact of Inflammation-Related Genes on COVID-19: Prospective Study at Turkish Cohort.

The pandemic coronavirus disease 2019 (COVID-19) has caused a high mortality rate and poses a significant threat to the population. The disease may progress with mild symptoms or may cause the need for intensive care, depending on many factors. In this study, it was aimed to determine if there is a tendency due to genetic factors in COVID-19 patients. Ninety-four of 188 patients with mild clinical and 94 with severe clinical symptoms were included in the study. The targeted panel including coagulopathy (F2, F5), viral invasion (ACE2), and inflammation (CXCL8, IFNAR2, IFNL4, IL10, IL2, IL6, IRF7, TLR3, TLR7, TNF) related genes was performed sequenced by the next generation sequencing (NGS). The variants found were classified and univariate analyses were performed to select candidate variables for logistic model. Risk factors and variants were compared. It was revealed that the presence of 2 or more risk factors caused the disease to progress severely (p < 0.001). Heterozygous IRF7:c.1357-23dup variant had a 2.5 times higher risk for mild disease compared to severe disease. Other variants were found to be more significant in mild disease. Since polymorphic variants were not evaluated in the literature, the findings of our study could not be compared with the literature. However, as variants that may be effective in the severity of infections may differ according to ethnicity. This study has the feature of being a guide for subsequent studies to be carried out especially in Turkish population. Clinical course of the COVID-19 is likely to depend on a variety of risk factors, including age, sex, clinical status, immunology and genetic factors.

Effect of 2 Different High-Dose Methylprednisolone Treatments on Clinical Outcomes in Severe COVID-19 Patients.

OBJECTIVE: The present study aimed to evaluate and compare the use of 2 different high-dose methylprednisolone posology in treating severe coronavirus disease 2019 pneumonia regarding mortality and recovery time between themselves and against steroidal/ non-steroidal treatment. MATERIAL AND METHODS: Severe coronavirus disease 2019 patients followed up between March 2020 and January 2021 were included. The steroid-free treatment protocol was applied before August 2020 (non-pulse group) and a treatment algorithm containing normal and high doses of methylprednisolone was applied after August 2020 (pulse group). Patients with clinical deterioration under the normal dose of methylprednisolone were administered 250 mg or 1000 mg of methylprednisolone for 3 days. We compared the pulse and non-pulse groups, in addition to pulse subgroups with each other, for clinical outcomes. RESULTS: A total of 138 patients were included, including 36 patients in the non-pulse group and 102 in the pulse group. In the pulse group, 70 patients received 1000 mg/day and 32 received 250 mg/day of high-dose methylprednisolone therapy. In the comparison of pulse and non-pulse patient groups, mortality rate was lower in the pulse group (P < .001), and the time to discharge without oxygen support was shorter. Although the patients in the 250 mg subgroup were older, there was no difference between the 250 mg and 1000 mg subgroups in terms of end of oxygen requirement, discharge with oxygen support, and mortality. In addition, the required time to reach the oxygen-free period in patients discharged without oxygen support was similar in the 2 subgroups, and the majority of patients in both subgroups reached the oxygen-free period on the 20th day after initiating methylprednisolone. CONCLUSION: Since there was no difference in clinical improvement between the use of 250 mg or 1000 mg methylprednisolone in patients with severe coronavirus disease 2019 infection, 1000 mg methylprednisolone was not required.

BNT162b2 or CoronaVac as the Third Dose against Omicron: Neutralizing Antibody Responses among Transplant Recipients Who Had Received Two Doses of CoronaVac.

We evaluated neutralizing antibodies against the Omicron variant and Anti-Spike IgG response in solid organ (SOT) or hematopoietic stem cell (HSTC) recipients after a third dose of BNT162b2 (BNT) or CoronaVac (CV) following two doses of CV. In total, 95 participants underwent SOT (n = 62; 44 liver, 18 kidney) or HSCT (n = 27; 5 allogeneic, 22 autologous) were included from five centers in Turkey. The median time between third doses and serum sampling was 154 days (range between 15 to 381). The vaccine-induced antibody responses of both neutralizing antibodies and Anti-Spike IgGs were assessed by plaque neutralizing assay and immunoassay, respectively. Neutralizing antibody and Anti-Spike IgG levels were significantly higher in transplant patients receiving BNT compared to those receiving CV (Geometric mean (GMT):26.76 vs. 10.89; p = 0.03 and 2116 Au/mL vs. 172.1 Au/mL; p < 0.001). Solid organ transplantation recipients, particularly liver transplant recipients, showed lower antibody levels than HSCT recipients. Thus, among HSCT recipients, the GMT after BNT was 91.29 and it was 15.81 in the SOT group (p < 0.001). In SOT, antibody levels after BNT in kidney transplantation recipients were significantly higher than those in liver transplantation recipients (GMT: 48.32 vs. 11.72) (p < 0.001). Moreover, the neutralizing antibody levels after CV were very low (GMT: 10.81) in kidney transplantation recipients and below the detection limit (<10) in liver transplant recipients. This study highlights the superiority of BNT responses against Omicron as a third dose among transplant recipients after two doses of CV. The lack of neutralizing antibodies against Omicron after CV in liver transplant recipients should be taken into consideration, particularly in countries where inactivated vaccines are available in addition to mRNA vaccines.

Knowledge and attitudes of orthopedic surgeons regarding prosthesis joint infection.

BACKGROUND: Periprosthetic joint infection (PJI) is a critical complication after joint arthroplasty and is accompanied by increasing rates of morbidity and mortality. Several studies have aimed at preventing PJI. AIM: To research the knowledge level and attitudes of orthopedic surgeons, who play a key role in both preventing and managing PJI. METHODS: We conducted a web-based survey to evaluate orthopedic surgeons' knowledge level and attitudes regarding PJI. The Likert scale survey utilized consisted of 30 questions which were prepared based on the "Proceedings of the International Consensus on Periprosthetic Joint Infection". RESULTS: A total of 264 surgeons participated in the survey. Their average age was 44.8, and 173 participants (65.5%) had more than 10 years of experience. No statistically significant relationship was found between the PJI knowledge of the surgeons and their years of experience. However, participants who worked in training and research hospitals demonstrated higher levels of knowledge than the ones in the state hospitals. It was also noticed that surgeons' knowledge concerning the duration of antibiotic therapy and urinary infections was not consistent with their attitudes. CONCLUSION: Even though orthopedic surgeons have adequate knowledge about preventing and managing PJI, their attitudes might contradict their knowledge. Future studies are required to examine the causes and solutions of the contradictions between orthopedic surgeons' knowledge and attitudes.

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.

Development and validation of COVID-19 associated candidemia score (CAC-Score) in ICU patients.

BACKGROUND: The development of candidemia is a highly fatal condition in severe COVID-19 infection. OBJECTIVES: This study aimed to develop a candidemia prediction score in COVID-19 patient based on the patient's clinical characteristics, and healthcare-related factors during intensive care units (ICU) follow-up. PATIENTS/METHODS: Severe COVID-19 patients hospitalised in ICU in Ankara City Hospital during the one-year period (August 15, 2020, and August 15, 2021) were included. After univariate analysis, multivariate analysis was applied using variable selection approach to investigate the effects of variables together and to create a score model for candidemia. Statistically significant factors were included in the development process of candida prediction score. RESULTS: Of 1305 COVID-19 ICU patients, 139 had a candidemia episode. According to the final model, four variables, presence of central venous catheter (CVC) (OR 19.07, CI 8.12-44.8, p < .0001), multifocal colonisation (OR 2.28, CI 1.39-3.72, p 0.001), length of ICU stays ≥14 days (OR 3.62, CI 2.42-5.44, p < .0001) and corticosteroids (OR 0.51, CI 0.34-0.76, p 0.0011) were the only statistically significant independent risk factors for candidemia. Score model was demonstrated by a nomogram, and the risk for candidemia was calculated to be high in patients who scored ≥56 points by using the criteria [CVC = 51, multifocal colonisation = 14, prolonged hospitalisation = 23, no steroid use = 12 points]. The AUC of the score is 0.84 (CI 0.81-0.87). CONCLUSION: We developed and validated an easy-to-use clinical prediction score for candidemia in severe COVID-19 infection. In COVID-19 ICU patients, the risk of candidemia is high if one of the other risk factors is present together with CVC.

Pathobiological alterations affecting the distinct clinical courses of pediatric versus adult COVID-19 syndrome.

Background/aim: The clinical presentation of pediatric coronavirus disease 2019 (COVID-19) is associated with a milder disease course than the adult COVID-19 syndrome. The disease course of COVID-19 has three clinicobiological phases: initiation, propagation, and complication. This study aimed to assess the pathobiological alterations affecting the distinct clinical courses of COVID-19 in pediatric age groups versus the adult population. We hypothesized that critical biogenomic marker expressions drive the mild clinical presentations of pediatric COVID-19. Materials and methods: Blood samples were obtained from 72 patients with COVID-19 hospitalized at Ankara City Hospital between March and July 2021. Peripheral blood mononuclear cells were isolated using Ficoll-Paque and density-gradient sedimentation. The groups were compared using a t-test and limma analyses. Mean standardized gene expression levels were used to hierarchically cluster genes employing Euclidean Gene Cluster 3.0. The expression levels of identified genes were determined using reverse transcription-polymerase chain reaction. Results: This study found that ANPEP gene expression was significantly downregulated in the pediatric group (p < 0.05, FC: 1.57) and IGF2R gene expression was significantly upregulated in the adult group (p < 0.05, FC: 2.98). The study results indicated that the expression of critical biogenomic markers, such as the first-phase (ACE2 and ANPEP) and second-phase (EGFR and IGF2R) receptor genes, was crucial in the genesis of mild clinical presentations of pediatric COVID-19. ANPEP gene expression was lower in pediatric COVID-19. Conclusion: The interrelationship between the ANPEP and ACE2 genes may prevent the progression of COVID-19 from initiation to the propagating phase in pediatric patients. High IGF2R gene expression could potentially contribute to a protective effect and may be a contributing factor for the mild clinical course observed in pediatric patients.

Acute severe hepatitis outbreak in children: A perfect storm. What do we know, and what questions remain?

During the first half of 2022, the World Health Organization reported an outbreak of acute severe hepatitis of unknown aetiology (AS-Hep-UA) in children, following initial alerts from the United Kingdom (UK) where a cluster of cases was first observed in previously well children aged <6 years. Sporadic cases were then reported across Europe and worldwide, although in most countries incidence did not increase above the expected baseline. There were no consistent epidemiological links between cases, and microbiological investigations ruled out known infectious causes of hepatitis. In this review, we explore the evidence for the role of viral infection, superimposed on a specific host genetic background, as a trigger for liver pathology. This hypothesis is based on a high prevalence of Human Adenovirus (HAdV) 41F in affected children, together with metagenomic evidence of adeno-associated virus (Adeno-associated viruses)-2, which is a putative trigger for an immune-mediated liver injury. Roles for superantigen-mediated pathology have also been explored, with a focus on the potential contribution of SARS-CoV-2 infection. Affected children also had a high frequency of the MHC allele HLA-DRB1*04:01, supporting an immunological predisposition, and may have been vulnerable to viral coinfections due to disruption in normal patterns of exposure and immunity as a result of population lockdowns during the COVID-19 pandemic. We discuss areas of ongoing uncertainty, and highlight the need for ongoing scrutiny to inform clinical and public health interventions for this outbreak and for others that may evolve in future.

Surveillance of hemodialysis related infections: a prospective multicenter study.

As in many countries, there is neither a surveillance system nor a study to reveal the hemodialysis (HD) related infection rates in Turkey. We aimed to investigate the infection rate among HD outpatients and implement CDC's surveillance system. A multicenter prospective surveillance study is performed to investigate the infection rate among HD patients. CDC National Healthcare Safety Network (NHSN) dialysis event (DE) protocol is adopted for definitions and reporting. During April 2016-April 2018, 9 centers reported data. A total of 199 DEs reported in 10,035 patient-months, and the overall DE rate was 1.98 per 100 patient-months. Risk of blood culture positivity is found to be 17.6 times higher when hemodialysis was through a tunneled catheter than through an arteriovenous fistula. DE rate was significantly lower in patients educated about the care of their vascular access site. Staphylococcus aureus was the most causative microorganism among mortal patients. Outcomes of DEs were hospitalization (73%), loss of vascular access (18.2%), and death (7.7%). This first surveillance study revealed the baseline status of HD related infections in Turkey and showed that CDC National Healthcare Safety Network (NHSN) DE surveillance system can be easily implemented even in a high workload dialysis unit and be adopted as a nationwide DE surveillance program.

Remdesivir treatment for patients with moderate to severe COVID-19.

BACKGROUND: Remdesivir, which was first developed for the treatment of Ebola disease but failed to meet expectations, has become hope in the fight against the COVID-19 pandemic. This study aimed to evaluate risk factors for mortality and prognosis of adult moderate/severe COVID-19 patients treated with remdesivir, and safety and tolerability of 5 days of remdesivir treatment. METHODS: This multicenter prospective observational study was conducted in 14 centers in Turkey. Pregnancy or breastfeeding, multiorgan failure, or usage of vasopressors for septic shock, ALT > 5 × the upper limit of the normal range, or eGRF <30 mL/min or dialysis and receiving favipiravir were the exclusion criteria of the study. RESULTS: Among 500 patients, 494 patients were included in the study. On admission, 392 (79.3%) patients had moderate and 102 (20.6%) patients had severe COVID-19. The 28-day mortality was 10.1%. The median of the scores of the seven-category ordinal scale assessed on days 0, 3, 5, 7 were 4 and 3 on day 14. When the survival status of the patients was evaluated according to the time between the remdesivir start date and the end date of the symptoms, no statistically significant difference was found between the medians of the groups (p = 0.404). In multivariable analysis, age (OR, 1.05; 95%CI, 1.02-1.08; p = 0.003), SpO2 level on admission (OR, 3.03; 95%CI, 1.35-6.81; p = 0.007), heart rate (OR, 2.48; 95%CI, 1.01-6.07; p = 0.047), follow-up site at the hospital (clinic/ICU) (OR, 26.4; 95%CI, 11.6-60.17; p < 0.001) were independently associated with increased mortality. Grade 3 adverse event (AE) was observed in 4 (0.8%) patients. None of the patients experienced grade 4 or 5 AEs. DISCUSSION: Remdesivir is a safe and well-tolerated drug and older age, low SpO2 level on admission, tachycardia, and ICU admission are independently associated with increased mortality among patients with moderate/severe COVID-19 receiving remdesivir treatment.

Effect of chronic lung diseases on mortality of prevariant COVID-19 pneumonia patients.

Background: The aim of the study is to assess the effect of chronic lung disease on mortality in patients hospitalized with the diagnosis of prevariant COVID-19 Pneumonia compared to patients without chronic lung disease. Research design and methods: A cohort of 1,549 patients admitted to the pandemic clinic with a COVID-19 Pneumonia diagnosis was analyzed. Group 1 and Group 2 were compared in terms of the treatment they received, admission to intensive care, mortality and follow-up parameters. Results: The patient group with COVID-19 and lung disease consisted of 231 participants (14.91%) (Group 1). The patient group with COVID-19 but without lung disease had 1,318 participants (85.19%). Group 1 cases were found to receive more oxygen therapy and mechanical ventilation than Group 2 cases (p ≤ 0.001), Following univariate and multiple logistic regression analyses, it was determined that patients with chronic lung disease had a 25.76% higher mortality risk [OR: 25.763, 95% CI (Lower-Upper) (2.445-271.465), p = 0.007]. Conclusion: It was found that chronic lung disease contributed significantly to mortality in this study. Among chronic lung diseases, Chronic Obstructive Pulmonary Disease (COPD), lung cancer and interstitial lung diseases (ILDs) were shown to be more effective than other chronic lung diseases in patients with prevariant COVID-19 population.

COVID-19 patients with altered steroid hormone levels are more likely to have higher disease severity.

PURPOSE: This study aims to evaluate the correlations between the severity of the disease and serum steroid levels by analyzing the serum steroid levels in COVID-19 patients with different levels of disease progression and the control group. METHODS: Morning serum Aldosterone, 11-deoxycortisol, Androstenedione, 17-hydroxyprogesterone, Dihydrotestosterone (DHT), Dehydroepiandrosterone (DHEA), Corticosterone, Dehydroepiandrosterone sulfate (DHEAS), Estrone, Estradiol, Progesterone, 11-deoxycorticosterone, Cortisol, Corticosterone, Androsterone, Pregnenolone, 17-hydroxypregnenolone and 21-deoxycortisol levels were measured in 153 consecutive patients were grouped as mild, moderate, and severe based on the WHO COVID-19 disease severity classification and the control group. Steroid hormone levels were analyzed at once with a liquid chromatography-tandem mass spectrometric method (LC-MS/MS). RESULTS: In our study, nearly all steroids were statistically significantly higher in the patients' group than in the control group (p < 0.001). Also, DHEA was an independent indicator of the disease severity with COVID-19 CONCLUSIONS: Our study reveals that the alteration in steroid hormone levels was correlated with disease severity. Also, steroid hormone levels should be followed up during COVID-19 disease management.