Factors leading to dissemination of cutaneous anthrax: an international ID-IRI study.

Background: Although anthrax is a rare zoonotic infection, it still causes significant mortality and morbidity. In this multicenter study, which is the largest anthrax case series ever reported, we aimed to describe the factors leading to dissemination of cutaneous anthrax. Methods: Adult patients with cutaneous anthrax from 16 referral centers were pooled. The study had a retrospective design, and included patients treated between January 1, 1990 and December 1, 2019. Probable, and confirmed cases based upon CDC anthrax 2018 case definition were included in the study. A descriptive statistical analysis was performed for all variables. Results: A total of 141 cutaneous anthrax patients were included. Of these, 105 (74%) patients had probable and 36 (26%) had confirmed diagnosis. Anthrax meningitis and bacteremia occurred in three and six patients, respectively. Sequelae were observed in three patients: cicatricial ectropion followed by ocular anthrax (n = 2) and movement restriction on the left hand after surgical intervention (n = 1). One patient had gastrointestinal anthrax. The parameters related to poor outcome (p < 0.05) were fever, anorexia, hypoxia, malaise/fatigue, cellulitis, fasciitis, lymphadenopathy, leukocytosis, high CRP and creatinine levels, longer duration of antimicrobial therapy, and combined therapy. The last two were seemingly the consequences of dissemination rather than being the reasons. The fatality rate was 1.4%. Conclusions: Rapid identification of anthrax is crucial for prompt and effective treatment. Systemic symptoms, disseminated local infection, and high inflammatory markers should alert the treating physicians for the dissemination of the disease.

RELATION OF APELIN, TUMOR NECROSIS FACTOR ALPHA AND CLAUDIN-5 TO BODY MASS INDEX IN CHOLECYSTECTOMIES.

Objective: The aim of this study was to investigate the relationship of Claudin-5, Apelin, Tumor Necrosis Factor Alpha (TNF-α) expression, and body mass index (BMI) of cholecystectomies. Materials and methods: Sixty-eight paraffin embedded cholecystectomy specimens diagnosed as chronic cholecystitis were collected in the Pathology Department of the Training and Research Hospital between 2015-2017. The samples were stained with Apelin, Claudin-5 and TNF-α. The immunohistochemical study was carried out using the system in an automatic staining machine. Results: There was a significant positive correlation between BMI and TNF-α staining (p=0.010). This result indicated that the degree of staining increased together with BMI. When age, BMI, and the other biochemical parameters were evaluated, a significant correlation was found between BMI and blood glucose only (p=0.029); correlations of BMI with the other parameters were not statistically significant. Conclusion: Although there is no relationship between inflammation and BMI with Claudin-5 and Apelin in this study, there is a significant relationship between BMI and TNF-α.

Differences in SUV39H1 and androgen receptor distribution in adenomyomatous hyperplasia and prostatic adenocarcinoma.

Background: Androgen receptor (AR) contributes to the growth of both early- and late-stage prostate cancer. Overexpression of suppressor of variegation 3-9 homolog 1 (SUV39H1) increases migration of prostate cancer cells, while depletion of SUV39H1 suppresses migration of prostate cancer cells. Aim: In this study, the aim was to show the relationships of AR and SUV39H1 with adenomyomatous hyperplasia (AH) and prostate adenocarcinoma (PCa). Materials and Methods: 70 AH and 70 PCa preparations in Pathology Department from 2013 to 16 were retrospectively investigated. Samples with immunohistochemical staining for AR and SUV39H1 were evaluated with a light microscope. After pathologic investigation of samples, AR and SUV39H1 expressions were scored. The changes in the frequencies of the obtained scores in the AH and PCa groups were analyzed statistically. Results: AR expression was observed to be greater in AH compared to PCa. This difference was found to be statistically significant (p = 0.003). SUV39H1 expression was identified to be greater in PCa compared to AH and this showed statistical significance (p = 0.031). PCa samples were identified to have nearly 1.5 times more SUV39H1 mild staining compared to AH samples and this increase was two times for SUV39H1 strong staining. Conclusion: In our study, AR expression was greater in AH compared to PCa samples. This situation is inverse to the known mechanism and cannot be clearly explained. It needs to be supported with large series and other prognostic parameters. This study observed increased SUV39H1 values in PCa compared to AH and from this aspect, it may be considered an important poor prognosis parameter.

Daptomycin versus teicoplanin in the treatment of osteomyelitis: Results of the Göztepe retrospective cohort study.

OBJECTIVES: Daptomycin is highly effective against Gram-positive multidrug-resistant bacteria. Publications on daptomycin in osteomyelitis treatment are limited. PATIENTS AND METHODS: In this multicenter retrospective cohort study, the aim was to evaluate the outcomes of osteomyelitis cases having received daptomycin or teicoplanin. This multicenter retrospective cohort study gathered data from seven centers located in five cities of Turkey. Study inclusion criteria were as follows: (a) magnetic resonance imaging and/or direct X-ray revealed osteomyelitis or biopsy pathologic examination results concomitant with osteomyelitis. Chi-squareand Student t-tests were used for statistical comparison. RESULTS: A total of 72 patients, 38 cases in the daptomycin group and 34 cases in the teicoplanin group diagnosed with osteomyelitis fulfilling the study inclusion criteria, were included in the study. Clinical success at the end of induction therapy was achieved in 32/38 cases in the daptomycin cohort vs. 30/34 cases in the teicoplanin cohort (p: 0.73). CONCLUSION: Although this is a limited experience in a small but well-defined cohort, our data suggest that daptomycin may be a safe alternative to glycopeptides in osteomyelitis treatment. A randomized controlled clinical study involving larger cohorts may increase the available evidence.

An eight-case 1q21 region series: novel aberrations and clinical variability with new features.

BACKGROUND: Rearrangement of the 1q21 region of chromosome 1 manifests as multiple phenotypes, including microcephaly, intellectual disability, dysmorphic facial features, eye abnormalities, cardiac defects, genitourinary anomalies, autism spectrum disorder, psychiatric conditions and seizures. Herein, we describe eight patients with 1q21 deletion and duplication syndromes, and novel deletions and findings. METHODS: Chromosomal microarray analysis was performed to identify the existence of copy number variation. Quantitative polymerase chain reaction was applied using specific primers for the control and 1q21 region of chromosome 1. Mutational analysis was performed in case 5 using direct genomic sequencing for exons 1-6 in RBM8A. RESULTS: Copy number variation analysis identified seven deletions and one duplication of the 1q21 region in the eight patients. In addition, four variations were de novo, and two deletions are reported here for the first time. One of the cases (case 7) presents moderate intellectual disability and dysmorphic facial findings, whereas chromosomal microarray analysis showed that case 7 had an 889-kb deletion in the 1q21 proximal region (GPR89A, PDZK1, CD160, POLR3C and NBPF12). CONCLUSION: Although the deletion in case 5 did not include the thrombocytopenia-absent radius syndrome critical region or the RBM8A gene, he had pectoral muscle hypoplasia, radius and humerus hypoplasia and short curved ribs, which are indicative of a potential thrombocytopenia-absent radius region modifier. The findings in case 7 suggest that the proximal part of the 1q21 microdeletion syndrome region might be very important for the onset of clinical manifestations. Some novel findings were observed in the presented cases, such as radius and humerus hypoplasia and brain stem hypoplasia. The presented findings expand the spectrum of 1q21 aberrations and provide evidence of genotype-phenotype correlations for this region.

Infection control bundles in intensive care: an international cross-sectional survey in low- and middle-income countries.

BACKGROUND: In low- and middle-income countries (LMICs), the burden of healthcare-associated infections (HCAIs) is not known due to a lack of national surveillance systems, standardized infection definitions, and paucity of infection prevention and control (IPC) organizations and legal infrastructure. AIM: To determine the status of IPC bundle practice and the most frequent interventional variables in LMICs. METHODS: A questionnaire was emailed to Infectious Diseases International Research Initiative (ID-IRI) Group Members and dedicated IPC doctors working in LMICs to examine self-reported practices/policies regarding IPC bundles. Responding country incomes were classified by World Bank definitions into low, middle, and high. Comparison of LMIC results was then made to a control group of high-income countries (HICs). FINDINGS: This survey reports practices from one low-income country (LIC), 16 middle-income countries (MICs) (13 European), compared to eight high-income countries (HICs). Eighteen (95%) MICs had an IPC committee in their hospital, 12 (63.2%) had an annual agreed programme and produced an HCAI report. Annual agreed programmes (87.5% vs 63.2%, respectively) and an annual HCAI report (75.0% vs 63.2%, respectively) were more common in HICs than MICs. All HICs had at least one invasive device-related surveillance programme. Seven (37%) MICs had no invasive device-related surveillance programme, six (32%) had no ventilator-associated pneumonia prevention bundles, seven (37%) had no catheter-associated urinary tract infection prevention bundles, and five (27%) had no central line-associated bloodstream infection prevention bundles. CONCLUSION: LMICs need to develop their own bundles with low-cost and high-level-of-evidence variables adapted to the limited resources, with further validation in reducing infection rates.

Mitochondrial DNA copy number alterations in familial mediterranean fever patients.

OBJECTIVES AND BACKGROUND: Familial Mediterranean Fever (FMF) is characterized by recurrent fever episodes as a result of inflammation of serous membranes. Changes in the number of different mtDNA copy number variations, detected in FMF patients, who developed amyloidosis, might be an important parameter in the understanding of the pathophysiology of the disease. METHODS: Changes in the mtDNA copy number between 50 patients with FMF, who had M694V homozygote mutation and amyloidosis, and 50 healthy controls, who had not any MEFV mutation or FMF clinical finding, were examined. The 22 MEFV mutations were analyzed by Pyromark Q24 system. Quantitative analysis was performed on RT-PCR. The level of mtDNA was calculated using the delta Ct (ΔCt) of average Ct of mtDNA and nDNA (ΔCt = Ct mtDNA-Ct nDNA) in the same well as an exponent of 2 (2ΔCt). RESULTS: A significant decrease in the amount of mtDNA was detected in FMF patients with M694V homozygous mutation carriers, who developed amyloidosis compared to the control group (p < 0.001). CONCLUSION: In this study, mitochondrial dysfunction, which has been identified through changes in the mitochondrial genome in many diseases, was identified by showing that the copy number variations of mtDNA in leukocytes also decreased for FMF disease (Tab. 3, Fig. 1, Ref. 21).

Correction to: Prediction of unfavorable outcomes in cryptococcal meningitis: results of the multicenter infectious Diseases International Research Initiative (ID-IRI) cryptococcal meningitis study.

In the original version of this article, Mustafa Sunbul was not included in the list of authors for this article. The name has been added accordingly.

Prediction of unfavorable outcomes in cryptococcal meningitis: results of the multicenter Infectious Diseases International Research Initiative (ID-IRI) cryptococcal meningitis study.

Cryptococcal meningitis (CM) is mostly seen in immunocompromised patients, particularly human immunodeficiency virus (HIV)-positive patients, but CM may also occur in apparently immunocompetent individuals. Outcome analyses have been performed in such patients but, due to the high prevalence of HIV infection worldwide, CM patients today may be admitted to hospitals with unknown HIV status, particularly in underdeveloped countries. The objective of this multicenter study was to analyze all types of CM cases in an aggregate cohort to disclose unfavorable outcomes. We retrospectively reviewed the hospitalized CM patients from 2000 to 2015 in 26 medical centers from 11 countries. Demographics, clinical, microbiological, radiological, therapeutic data, and outcomes were included. Death, neurological sequelae, or relapse were unfavorable outcomes. Seventy (43.8%) out of 160 study cases were identified as unfavorable and 104 (65%) were HIV infected. On multivariate analysis, the higher Glasgow Coma Scale (GCS) scores (p = 0.021), cerebrospinal fluid (CSF) leukocyte counts > 20 (p = 0.038), and higher CSF glucose levels (p = 0.048) were associated with favorable outcomes. On the other hand, malignancy (p = 0.026) was associated with poor outcomes. Although all CM patients require prompt and rational fungal management, those with significant risks for poor outcomes need to be closely monitored.

The burden and epidemiology of community-acquired central nervous system infections: a multinational study.

Risk assessment of central nervous system (CNS) infection patients is of key importance in predicting likely pathogens. However, data are lacking on the epidemiology globally. We performed a multicenter study to understand the burden of community-acquired CNS (CA-CNS) infections between 2012 and 2014. A total of 2583 patients with CA-CNS infections were included from 37 referral centers in 20 countries. Of these, 477 (18.5%) patients survived with sequelae and 227 (8.8%) died, and 1879 (72.7%) patients were discharged with complete cure. The most frequent infecting pathogens in this study were Streptococcus pneumoniae (n = 206, 8%) and Mycobacterium tuberculosis (n = 152, 5.9%). Varicella zoster virus and Listeria were other common pathogens in the elderly. Although staphylococci and Listeria resulted in frequent infections in immunocompromised patients, cryptococci were leading pathogens in human immunodeficiency virus (HIV)-positive individuals. Among the patients with any proven etiology, 96 (8.9%) patients presented with clinical features of a chronic CNS disease. Neurosyphilis, neurobrucellosis, neuroborreliosis, and CNS tuberculosis had a predilection to present chronic courses. Listeria monocytogenes, Staphylococcus aureus, M. tuberculosis, and S. pneumoniae were the most fatal forms, while sequelae were significantly higher for herpes simplex virus type 1 (p < 0.05 for all). Tackling the high burden of CNS infections globally can only be achieved with effective pneumococcal immunization and strategies to eliminate tuberculosis, and more must be done to improve diagnostic capacity.

Tetanus in adults: results of the multicenter ID-IRI study.

Tetanus is an acute, severe infection caused by a neurotoxin secreting bacterium. Various prognostic factors affecting mortality in tetanus patients have been described in the literature. In this study, we aimed to analyze the factors affecting mortality in hospitalized tetanus patients in a large case series. This retrospective multicenter study pooled data of tetanus patients from 25 medical centers. The hospitals participating in this study were the collaborating centers of the Infectious Diseases International Research Initiative (ID-IRI). Only adult patients over the age of 15 years with tetanus were included. The diagnosis of tetanus was made by the clinicians at the participant centers. Izmir Bozyaka Education and Research Hospital's Review Board approved the study. Prognostic factors were analyzed by using the multivariate regression analysis method. In this study, 117 adult patients with tetanus were included. Of these, 79 (67.5%) patients survived and 38 (32.5%) patients died. Most of the deaths were observed in patients >60 years of age (60.5%). Generalized type of tetanus, presence of pain at the wound area, presence of generalized spasms, leukocytosis, high alanine aminotransferase (ALT) and C-reactive protein (CRP) values on admission, and the use of equine immunoglobulins in the treatment were found to be statistically associated with mortality (p < 0.05 for all). Here, we describe the prognostic factors for mortality in tetanus. Immunization seems to be the most critical point, considering the advanced age of our patients. A combination of laboratory and clinical parameters indicates mortality. Moreover, human immunoglobulins should be preferred over equine sera to increase survival.

Is choroidal thickness related with disease activity and joint damage in patient with rheumatoid arthritis.

OBJECTIVE: Aim of the study was to evaluate the choroidal thickness (CT) in patients with RA and detect the relation with disease activity and joint damage in patients with rheumatoid arthritisBACKGROUND: Rheumatoid arthritis (RA) is a systemic inflammatory disease associated with various extra-articular organ manifestations including ocular manifestationsMATERIALS AND METHODS: We included 59 eyes of 59 patients with RA and 59 eyes of 59 controls without RA in the study. Subfoveal and perifoveal CT were measured using enhanced depth imaging optic coherence tomography. Disease activity score 28 (DAS 28) and Larsen score were calculated for each patient with RA and compared with measurements of CT. RESULTS: CT was statistically thinner in patients with RA than controls, at subfoveal CT (p = 0.008), at 500 µm temporal to the fovea (p = 0.004), at 1000 µm temporal to the fovea (p = 0.010), at 1500 µm temporal to the fovea (p = 0.005), at 500 µm nasal to the fovea (p = 0.035). Additionally there was no correlation measurements of CT with disease activity and joint damage. CONCLUSIONS: Subfoveal and perifoveal CT was significantly thinner in patients with RA than in healthy controls but there was no correlation detected between CT measurements and DAS 28 or Larsen scores (Tab. 5, Ref. 33).

Managing atypical and typical herpetic central nervous system infections: results of a multinational study.

There have been many studies pertaining to the management of herpetic meningoencephalitis (HME), but the majority of them have focussed on virologically unconfirmed cases or included only small sample sizes. We have conducted a multicentre study aimed at providing management strategies for HME. Overall, 501 adult patients with PCR-proven HME were included retrospectively from 35 referral centres in 10 countries; 496 patients were found to be eligible for the analysis. Cerebrospinal fluid (CSF) analysis using a PCR assay yielded herpes simplex virus (HSV)-1 DNA in 351 patients (70.8%), HSV-2 DNA in 83 patients (16.7%) and undefined HSV DNA type in 62 patients (12.5%). A total of 379 patients (76.4%) had at least one of the specified characteristics of encephalitis, and we placed these patients into the encephalitis presentation group. The remaining 117 patients (23.6%) had none of these findings, and these patients were placed in the nonencephalitis presentation group. Abnormalities suggestive of encephalitis were detected in magnetic resonance imaging (MRI) in 83.9% of the patients and in electroencephalography (EEG) in 91.0% of patients in the encephalitis presentation group. In the nonencephalitis presentation group, MRI and EEG data were suggestive of encephalitis in 33.3 and 61.9% of patients, respectively. However, the concomitant use of MRI and EEG indicated encephalitis in 96.3 and 87.5% of the cases with and without encephalitic clinical presentation, respectively. Considering the subtle nature of HME, CSF HSV PCR, EEG and MRI data should be collected for all patients with a central nervous system infection.

Infections in travellers returning to Turkey from the Arabian peninsula: a retrospective cross-sectional multicenter study.

Mass gatherings pooling people from different parts of the world-the largest of which is to Mecca, Saudi Arabia, for Hajj-may impose risks for acquisition and dissemination of infectious diseases. A substantial number of pilgrims to Hajj and Umrah are Turkish citizens (456,000 in 2014) but data are lacking on scale of the problem. We did a retrospective cross-sectional multicenter study in Turkey to explore the range of infections among inpatients who had recently returned from the Arabian Peninsula. Our inclusion criteria were patients who had acquired an infection during their trip to an Arabian Peninsula country, or who became symptomatic within 1 week of their return. The data were collected retrospectively for January 1, 2013 and March 1, 2015. 185 Turkish patients were recruited to the study across 15 referral centers with travel associated infectious diseases after returning from Arabian Peninsula countries (predominantly Saudi Arabia 163 [88.1 %] for religious purposes 162 [87.5 %]). Seventy four (40.0 %) of them were ≥ 65 years old with numerous comorbidities including diabetes (24.3 %) and COPD (14.1 %). The most common clinical diagnosis was respiratory tract infections (169 [91.5 %]), followed by diarrheal diseases (13 [7 %]), and there was one case of MERS-CoV. Patients spent a median of 5 (3-7) days as hospital inpatients and overall mortality was 1.1 %. Returning travellers from the Arabian Peninsula present as inpatients with a broad range of infectious diseases similar to common community acquired infections frequently seen in daily medical practices in Turkey.

Management of septic shock and severe infections in migrants and returning travelers requiring critical care.

During the past decade, global human movement created a virtually "borderless world". Consequently, the developed world is facing "forgotten" and now imported infectious diseases. Many infections are observed upon travel and migration, and the clinical spectrum is diverse, ranging from asymptomatic infection to severe septic shock. The severity of infection depends on the etiology and timeliness of diagnosis. While assessing the etiology of severe infection in travelers and migrants, it is important to acquire a detailed clinical history; geography, dates of travel, places visited, type of transportation, lay-overs and intermediate stops, potential exposure to exotic diseases, and activities that were undertaken during travelling and prophylaxis and vaccines either taken or not before travel are all important parameters. Tuberculosis, malaria, pneumonia, visceral leishmaniasis, enteric fever and hemorrhagic fever are the most common etiologies in severely infected travelers and migrants. The management of severe sepsis and septic shock in migrants and returning travelers requires a systematic approach in the evaluation of these patients based on travel history. Early and broad-spectrum therapy is recommended for the management of septic shock comprising broad spectrum antibiotics, source control, fluid therapy and hemodynamic support, corticosteroids, tight glycemic control, and organ support and monitoring. We here review the diagnostic and therapeutic routing of severely ill travelers and migrants, stratified by the nature of the infectious agents most often encountered among them.

PARTIAL TRISOMY 5p12-q 11.2 RESULTING FROM A MARKER CHROMOSOME: A NEW CASE REPORT WITH ATTENTION DEFICIT HYPERACTIVITY DISORDER.

Partial trisomy of chromosome 5 was first described by Lejeune et al. in 1964 on the short arm (12). The vast majority of the partial trisomy 5 cases include 5p duplications; however we reported a small supernumerary marker chromosome. General symptoms include developmental delay, mental retardation, seizures, respiratory difficulties, congenital heart defects, abdominal muscle hypoplasia and dysmorphic features such as macrocephaly, enlarged anterior fontanelle, dolichocephaly, upslanting palpebral fissures, epicanthal folds, hypertelorism, abnormal ears, midface hypoplasia, short nose, broad nasal bridge and microretrognathia. Arachnodactyly and club foot may be seen as cytoskeletal abnormalities and, hypotonia may be determined in neurological exam. Here we reported a case with developmental delay, attention deficit hyperactivity disorder, mild mental retardation and dysmorphic features, caused by a new small supernumerary marker chromosome, generating partial trisomy 5pI 2-q 11.2. To our knowledge, this small supernumerary marker chromosome has not been reported before. Severe type of partial trisomy 5 includes seizures, congenital heart defects, hypotonia and failure to thrive. Previously reported partial trisomy 5 cases, who showed severe phenotype, had usually duplicated 5p13 region. Therefore, patients, who do not have duplicated 5p13, showed mild phenotype. Also, duplication of the long arm of chromosome 5, may contribute to the milder phenotype and the longer survival in partial trisomy 5 patients. Attention deficit hyperactivity disorder, which we described in the present case, may be a result of partial trisomy 5, because it includes ADHD4 gene. This case may help better understanding the karyotype/phenotype correlation related to partial trisomy 5.

The course of spinal tuberculosis (Pott disease): results of the multinational, multicentre Backbone-2 study.

We aimed to describe clinical, laboratory, diagnostic and therapeutic features of spinal tuberculosis (ST), also known as Pott disease. A total of 314 patients with ST from 35 centres in Turkey, Egypt, Albania and Greece were included. Median duration from initial symptoms to the time of diagnosis was 78 days. The most common complications presented before diagnosis were abscesses (69%), neurologic deficits (40%), spinal instability (21%) and spinal deformity (16%). Lumbar (56%), thoracic (49%) and thoracolumbar (13%) vertebrae were the most commonly involved sites of infection. Although 51% of the patients had multiple levels of vertebral involvement, 8% had noncontiguous involvement of multiple vertebral bodies. The causative agent was identified in 41% of cases. Histopathologic examination was performed in 200 patients (64%), and 74% were consistent with tuberculosis. Medical treatment alone was implemented in 103 patients (33%), while 211 patients (67%) underwent diagnostic and/or therapeutic surgical intervention. Ten percent of the patients required more than one surgical intervention. Mortality occurred in 7 patients (2%), and 77 (25%) developed sequelae. The distribution of the posttreatment sequelae were as follows: 11% kyphosis, 6% Gibbus deformity, 5% scoliosis, 5% paraparesis, 5% paraplegia and 4% loss of sensation. Older age, presence of neurologic deficit and spinal deformity were predictors of unfavourable outcome. ST results in significant morbidity as a result of its insidious course and delayed diagnosis because of diagnostic and therapeutic challenges. ST should be considered in the differential diagnosis of patients with vertebral osteomyelitis, especially in tuberculosis-endemic regions. Early establishment of definitive aetiologic diagnosis and appropriate treatment are of paramount importance to prevent development of sequelae.