Yasemin Heper

Background/Objectives: The risk factors for the severe presentation (severe sepsis or septic shock) are not fully understood in ICU-acquired candidaemia. The primary objective of this study was to evaluate risk factors for the severe presentation (severe sepsis or septic shock) and mortality in patients with candidaemia in ICUs. Secondarily, we compared 28-day mortality between patients treated with fluconazole and those treated with an echinocandin. Methods: A retrospective cohort design was employed in a single-center ICU setting, encompassing a study period from 2004 to 2023. Adult patients who had Candida growth in blood cultures taken 48 h after admission to the ICU were included in the study. Risk factors for the severe presentation (severe sepsis and septic shock) and mortality were evaluated in the 141 patients included in the study. The treatment comparison between fluconazole and echinocandins was performed in 113 patients (with 48-h rules) and 125 patients (without 48-h rules). Results: Among 141 patients, 77 (54.6%) died within 28 days. We found that in the multivariable model, APACHE II score, TPN use, steroid use, and concomitant bacteremia were associated with severe presentation. Each one-point increase in APACHE II score was associated with higher risk of severe presentation (adjusted OR 1.146, 95% CI 1.056–1.242; p = 0.001). TPN use and steroid use were also associated with higher risk (adjusted OR 3.297, 95% CI 1.265–8.590; p = 0.015; and adjusted OR 6.067, 95% CI 1.486–24.768; p = 0.012, respectively). Concomitant bacteraemia was associated with lower odds of severe presentation. Patients with severe presentation (severe sepsis or septic shock) had a higher risk of 28-day mortality than patients with sepsis (adjusted OR 8.06, 95% CI 2.60–25.00; p < 0.001). In the primary cohort (n = 113; overlap weights), 28-day mortality was 49.2% with fluconazole and 52.1% with echinocandin (OR 1.12, 95% CI 0.37–3.45; p = 0.838). Results were consistent in the 125-patient cohort without the 48-h rule (OR 1.40, 95% CI 0.51–3.81; p = 0.508). Conclusions: Each one-point increase in APACHE II score on admission, TPN use, and steroid use was associated with severe presentation in ICU-acquired candidaemia. The severity of the clinical presentation at the onset of candidaemia (presence of severe sepsis or septic shock) was strongly associated with 28-day mortality. No difference in 28-day mortality was detected between fluconazole and echinocandin treatment, but this comparison was imprecise and cannot inform antifungal choice.

Purpose Despite established protocols, the global resurgence of syphilis remains a public health challenge, with outcomes influenced by disease stage and host factors. This study described 18-year epidemiological trends and identified predictors of serological treatment response and long-term seroreversion. Methods We retrospectively analyzed 503 adults diagnosed with syphilis between 2005 and 2022 and classified disease stages according to CDC criteria. Treatment response was defined as a ≥ 4-fold decline in rapid plasma reagin (RPR) titers within 12 months for early-stage and 24 months for late-stage syphilis, while seroreversion was defined as a non-reactive RPR. Overall, 157 patients were included in the treatment-response analysis and 159 in the seroreversion analysis, the latter including two additional patients who achieved seroreversion before treatment-response assessment. Independent predictors were identified using multivariable logistic regression. Results Syphilis cases increased significantly after 2015, with late-stage disease accounting for 75.7% (n = 381) of diagnoses. Early syphilis rose from 10.5% (2005–2015) to 30.2% after 2015 (p < 0.001). Among patients with available HIV test results, 29.4% (134/456) of cases were in people with HIV. Early-stage syphilis was more frequent in people living with HIV (PLWH) than in HIV-negative individuals (32% vs. 20.1%). Among patients with follow-up, 75.2% (118/157) achieved a serological response. In multivariate analysis, late-stage syphilis was a negative predictor of response (OR 0.22, 95% CI 0.07–0.76; p = 0.016), while baseline RPR titers ≥ 1:8 were a strong positive predictor (OR 8.18, 95% CI 1.72–38.85; p = 0.008). HIV status was not independently associated with response (p > 0.05). Seroreversion occurred in 35.8%, with no independent predictors identified. Conclusions The syphilis burden has grown, driven by delayed diagnosis and late-stage predominance despite recent trends toward earlier detection. In this cohort, disease stage and baseline RPR titers were stronger predictors of serological response than HIV status. The higher frequency of early-stage diagnosis in PLWH is consistent with the potential impact of intensified screening and may reflect differences in healthcare engagement and testing practices compared with the general population.

Background/Objectives: Transfusion-Related Immunomodulation (TRIM) is a complex biological phenomenon that develops following allogeneic blood transfusions. Exosomes released from stored red blood cell concentrates (RBC) may be a potential mediator of TRIM. This study aims to analyze the effects of exosomes on T cell proliferation and regulatory T cell (Treg) differentiation. Methods: RBC concentrates obtained from six healthy donors were divided into non-leukoreduced (NR) and leukoreduced (LR) units. Exosomes were isolated from these RBCs by ultracentrifugation. Allogeneic and autologous exosome pools were prepared. Peripheral blood mononuclear cells (PBMCs) were cultured with exosome pools (with 0.2, 1, or 5 μg doses) under allogeneic or autologous conditions. T-cell proliferation and Tregs were assessed by flow cytometry. Results: Total exosomal protein content increased during storage, with significantly higher levels in NR-RBC derived exosomes (NR-Exo) than LR-RBC derived exosomes (LR-Exo). NR-Exos significantly enhanced both CD4⁺ and CD8⁺ T cell proliferation, predominantly in allogeneic cultures. The proliferative effect was observed at different doses. In contrast, exosome treatment did not promote expansion of Treg populations. Instead, autologous cultures demonstrated reduced frequencies of CD8⁺ Tregs and CD39-expressing Tregs, whereas allogeneic cultures showed minimal changes. Moreover, leukoreduction attenuated exosome-mediated T-cell proliferation. Conclusions: RBC-Exos preferentially enhance effector T cell proliferation under allogeneic conditions, particularly when isolated from NR-RBC units. Tregs tended to decrease in both the autologous and leukoreduced groups. These findings suggest that RBC-Exos support both immunosuppressive effects and immune activation. However, the characteristics of the RBC and the transfusion (allogeneic/autologous and leukoreduced/non-leukoreduced) are considered the key factors in observing these effects.

Background: Serology documents prior Toxoplasma gondii exposure in people living with HIV (PLWH), whereas peripheral-blood polymerase chain reaction (PCR) detects circulating DNA and can be difficult to interpret at low target levels. We evaluated serological profiles, buffy-coat PCR yield, and test agreement in a routine-care cohort. Methods: This cross-sectional study included 135 PLWH attending Bursa Uludağ University from March 2021 to August 2022. Anti- T. gondii immunoglobulin G (IgG), immunoglobulin M (IgM), and IgG avidity were measured using VIDAS. Buffy-coat DNA was tested by real-time PCR targeting the 529-bp repetitive element. Samples with cycle-threshold (Ct) values >35 were retested; positivity required reproducible Ct ≤40. Results: IgG seropositivity was 28.1% (38/135; 95% confidence interval [CI], 21.2%-36.3%), and IgM positivity was 1.5% (2/135). Of 37 samples with avidity results, 29 (78.4%) had high avidity. PCR detected DNA in 2 participants (1.5%; 95% CI, 0.4%-5.2%); both were IgG/IgM seronegative with Ct values of 37.2 and 38.5. Raw IgG-PCR agreement was 70.4%, but Cohen's kappa was -0.03 (p=0.37). Age ≥36 years was associated with IgG seropositivity (unadjusted odds ratio, 3.99; 95% CI, 1.61-9.94). Conclusions: Serology identified prior exposure, whereas buffy-coat PCR produced two rare high-Ct signals. These data do not estimate diagnostic accuracy or establish active infection. High-Ct peripheral-blood results require confirmation and clinical correlation.

Candidozyma auris (formerly Candida auris) is an emerging multidrug-resistant fungal pathogen associated with healthcare-associated infections and high mortality. This study evaluated the clinical characteristics, antifungal susceptibility profiles, and risk factors for candidemia and mortality in patients with C. auris isolation. This retrospective cohort study included patients with at least one clinical specimen positive for C. auris between May 2023 and June 2025. Patients were classified as having colonization or infection based on clinical and microbiological criteria. Trend analysis evaluated changes across colonization, non-bloodstream infection, and candidemia, and risk factors for candidemia and mortality were assessed using Firth penalized logistic regression. Forty-nine patients were included (median age, 67 years), of whom 63.3% were in the intensive care unit at the time of isolation. Colonization and infection were identified in 55.1% and 44.9% of patients, respectively, with candidemia being the most common presentation (68.2% of infections). The frequencies of intensive care unit stay, central venous catheter use, and total parenteral nutrition increased significantly from colonization to candidemia (p for trend <0.05). In multivariable analysis, intensive care unit stay (aOR 4.2, p=0.03) and total parenteral nutrition (aOR 6.9, p=0.04) were independently associated with candidemia. All isolates were resistant to fluconazole, echinocandins showed high in vitro activity, and amphotericin B MICs were ≥2 μg/mL in 64.3% of isolates. Overall, in-hospital mortality was 46.9%. Charlson Comorbidity Index, total parenteral nutrition, and clinically significant infection were independently associated with in-hospital mortality.

Background: Durable virological suppression is achieved in the majority of people living with HIV (PLWH) receiving contemporary antiretroviral therapy (ART). However, a subset of patients experience persistent low-level viremia (LLV), the clinical relevance and underlying determinants of which remain incompletely understood. Methods: Adult PLWH followed between 1 January 2005 and 31 December 2025 were retrospectively evaluated. LLV was defined as detectable HIV-1 RNA < 200 copies/mL on at least two consecutive measurements during follow-up in individuals receiving ART for at least 6 months. Patients with sustained virological suppression served as controls. Propensity score matching (1:1) was performed using variables associated with LLV in univariate analyses. Multivariable logistic regression analysis was applied to identify factors independently associated with LLV, and a p value < 0.05 was considered statistically significant. Results: Among 880 PLWH, 45 patients with LLV and 113 virologically suppressed controls were included. LLV was associated with lower baseline CD4+ T-cell counts, higher baseline HIV-1 RNA levels, delayed virological suppression at weeks 8 and 24, increased frequency of AIDS-defining illnesses and a higher prevalence of metabolic comorbidities, including hypertension, diabetes mellitus or dyslipidemia in univariate analysis. After propensity score matching, 32 patients remained in each group, with no clear association between low-level viremia and antiretroviral regimen class. Multivariable regression analysis showed baseline CD4+ T-cell count < 200 cells/µL, and the presence of ≥1 metabolic comorbidity (hypertension, diabetes mellitus or dyslipidemia) remained independently associated with LLV. Conclusions: Our findings suggest that LLV is associated with host-related factors rather than antiretroviral regimen failure. The coexistence of immunological impairment and metabolic comorbidities in patients with LLV underscores the importance of comprehensive clinical evaluation.

Mucormycosis ranks third among invasive mycoses after Candidiasis and Aspergillosis and is associated with high mortality. Its incidence has increased with the rising number of immunosuppressed patients. In developing countries, the most common predisposing factor is uncontrolled diabetes mellitus (DM), whereas in developed countries it is immunosuppressive conditions. To examine local epidemiological data, predisposing factors, diagnostic and therapeutic options and survival in our center eighty-six adult mucormycosis patients between 2000 and 2020 were retrospectively analyzed. Thirty-nine (45.35%) were male, 47 (54.65%) were female, and the median age was 52 years (IQR, 42.5–62). The most frequent clinical presentation was sinus involvement, observed in 77 cases (89.53%). Of these, 38 (44.18%) were sinonasal, 5 (5.81%) sinoorbital, 9 (10.47%) rhinocerebral, and 25 (29.07%) rhino-orbito-cerebral mucormycosis. The remaining 9 cases (10.47%) had pulmonary mucormycosis. Predisposing factors included hematologic diseases in 51 patients (59.30%), DM in 33 (38.37%), solid organ transplantation (SOT) in 7 (8.14%), and solid organ malignancy in 7 (8.14%). The most common symptoms were fever (70.93%), swelling around the eyes and face (51.16%), pain (40.7%), erythema (34.88%), nasal discharge (30.23%), and headache (25.58%). Most frequent physical examination findings were necrotic lesions in the oral cavity and sinuses (87.21%), ophthalmoplegia (29.07%), ptosis (26.74%), vision loss (25.58%), and proptosis (22.09%). In all cases, amphotericin B formulations were preferred as initial therapy. Patients who received combination therapy (n = 14), 13 used posaconazole (POS) + liposomal amphotericin B (L-AmB) and one patient used itraconazole (ITC) + L-AmB. POS was administered to 14 patients receiving sequential oral therapy. The median duration of amphotericin B therapy was 46.5 days (IQR, 14.7–84.5), and the median total duration of antifungal therapy was 46.5 days (IQR, 14.7–90.3). The most common adverse effect of amphotericin B formulations was hypokalemia [L-AmB 68.75%, amphotericin B deoxycholate (AmB-D) 54.84%, amphotericin B lipid complex (ABLC) 50%]. At least one surgical intervention was performed in 74.42% of cases. The 12-week mortality rate was 48.84%, overall mortality rate was 61.63%. In analysis advanced age [12-week: OR: 1.04 (95% CI: 1.01–1.07), p = 0.011; overall: OR: 1.04 (95% CI: 1.01–1.07), p = 0.026 respectively], coexistence of both hematologic disease and DM [12-week OR: 5.73 (95% CI: 1.16–28.33), p = 0.032] associated with mortality. No significant difference was observed in 12-week mortality between surgical and non-surgical patients ( p = 0.107). In contrast, overall mortality was significantly higher in the non-surgical group (81.8% vs. 54.7%, p = 0.024). In univariable logistic regression analysis, surgical intervention was associated with a 73.2% reduction in the odds of overall mortality (OR: 0.268, 95% CI: 0.082–0.882, p = 0.030). In the multivariable logistic regression analysis, age was the only variable significantly associated with 12-week and overall mortality (respectively, p = 0.004 and p = 0.026). Each one-year increase in age was associated with an OR of 1.05 (95% CI: 1.02–1.09) for 12-week mortality and 1.04 (95% CI: 1.01–1.07) for overall mortality. In conclusion; our study showed that despite advanced diagnostic methods and antifungals, mortality remained high, sinus involvement was the most frequent involvement, surgical debridement increased survival, but increasing age was associated with poor prognosis.

Objective: Neurosyphilis is a severe manifestation of syphilis characterized by heterogeneous clinical presentations. Diagnosis and assessment of treatment response are challenging due to variable findings and limitations in interpreting serological tests. This study evaluates the clinical characteristics, laboratory findings, and treatment outcomes of neurosyphilis cases diagnosed at a single center over an 18-year period. Methods: Medical records of patients aged 18 years or older with positive syphilis serology who were diagnosed with neurosyphilis between 2005 and 2022 were reviewed in this retrospective observational study. Diagnosis and classification followed Centers for Disease Control and Prevention (CDC) criteria were applied for diagnosis and classification. Demographic data, clinical features, serological and cerebrospinal fluid (CSF) findings, treatments, and post-treatment outcomes were analyzed. Results: Of 503 patients with positive syphilis serology, 23 (4.6%) were diagnosed with neurosyphilis. Three (13%) patients were female, and 3 (13%) had human immunodeficiency virus infection. All patients were symptomatic; 7 (30.4%) had ocular involvement, and 16 (69.5%) presented with neurological manifestations. Tabes dorsalis was the most common presentation, occurring in seven patients (30.4%). Based on CDC criteria, four cases (17.4%) were classified as possible, 13 (56.5%) as probable, and 6 (26.1%) as confirmed neurosyphilis. Fifteen (65%) patients were in the tertiary stage, and eight (35%) were in the secondary stage. Serum rapid plasma reagin titers ranged from 1:1 to 1:512. The mean CSF leukocyte count was 30/mm3, and CSF protein levels ranged from 24 to 544 mg/dL. CSF Venereal Disease Research Laboratory test results were positive in six patients, and Treponema pallidum hemagglutination assay results were positive in 15 patients. Among 22 patients with follow-up data, seven (32%) achieved full recovery, 14 (64%) developed sequelae, and 1 (4.5%) died during follow-up. Conclusion: Neurosyphilis exhibits diverse clinical features and remains challenging to diagnose. Patients with syphilis require careful evaluation for neurological and ocular involvement, and syphilis should be included in the differential diagnosis of retinitis and uveitis.

Background/Objectives: Our study was designed to explore the potential role of allogeneic CD8⁺ T lymphocytes present in red blood cell concentrates (RBCs) in the development of transfusion-related immunomodulation (TRIM) and the effect of storage time on these cells. Methods: From six units of whole blood, donated by volunteers, RBCs were obtained and each one was divided into three equal parts to provide the samples for storage days 0, 21, and 42. On related days, mononuclear cells (MNCs) were isolated from these RBC samples. MNCs were cultured, and phytohemagglutinin was added to half of the culture wells to stimulate the cells and achieve T cell division. Supernatants and MNCs were obtained from stimulated (STI) and unstimulated (US) wells. Supernatants were used for cytokine analyses, while MNCs were used to investigate the T cells and transcription factors. Results: The frequency of CD8⁺ T lymphocytes (Tc), their subgroups (Tc1, Tc2, and Tc17), specific transcription factors, and effector cytokines decreased during the storage time, but cell viability increased. CD3⁺CD8⁺TNF-α+ cells were significantly higher in the STI group on day 0 compared to the US group. Other cells did not respond to the mitogen (phytohemagglutinin) stimulation. Conclusions: During storage, the number of Tc cells and their ability to respond to mitogens decreased over time. The unresponsiveness was not recovered in ex vivo cell culture. Our findings suggest that transfused Tc cells are unlikely to be primary mediators of TRIM.

Toxoplasmosis infestation during pregnancy is typically asymptomatic however, the risk of vertical transmission increases with advancing gestational age. Due to the absence of overt clinical symptoms in most pregnant women, diagnosis relies on serological testing. Seroprevalence rates vary widely depending on geographical location and cultural practices. In the fetus, toxoplasmosis can result in a spectrum of outcomes, ranging from asymptomatic infection to severe neurological impairment. This study aimed to determine the seroprevalence of Toxoplasma gondii during pregnancy and to evaluate fetal transmission in seropositive pregnant women. For those diagnosed with acute toxoplasmosis, neonatal examination, serological tests, and transfontanel ultrasonography were conducted. This retrospective cohort study evaluated Anti-Toxoplasma IgM, IgG, and IgG avidity results of patients who presented to a tertiary medical center between 2015 and 2020. All maternal serological results, ultrasonographic evaluations, and neonatal data (e.g., serology, transfontanel ultrasonography) from births in the institution were obtained from hospital records. During the study period, 69 out of 2137 women (3.2%) had positive or borderline Toxoplasma IgM results. Seventeen patients were considered to have preconceptional infection, other 46 were suspected as acute toxoplasmosis during pregnancy. Three patients were lost to follow-up, and 5 pregnancies were terminated. Overall, 46 patients (2.1%) were started on spiramycin treatment by a mean gestational age of 14 weeks. Amniocentesis was performed in 14 cases, all of which had negative PCR results. Among neonates with available data, no findings suggestive of congenital toxoplasmosis were detected. The maternal seroprevalence of Toxoplasma gondii observed at our center aligns with findings from similar studies. 2 percent of 2137 women were suspected as acute toxoplasmosis and none of the 38 babies had neonatal intracranial abnormalities. However, the low acceptance rate (30%) for fetal diagnostic testing and the lack of complete neonatal serologic data may contribute to the observed low rate of congenital toxoplasmosis.