Association of Immune Semaphorins with COVID-19 Severity and Outcomes.

Semaphorins have recently been recognized as crucial modulators of immune responses. In the pathogenesis of COVID-19, the activation of immune responses is the key factor in the development of severe disease. This study aimed to determine the association of serum semaphorin concentrations with COVID-19 severity and outcomes. Serum semaphorin concentrations (SEMA3A, -3C, -3F, -4D, -7A) were measured in 80 hospitalized adult patients with COVID-19 (moderate (n = 24), severe (n = 32), critical, (n = 24)) and 40 healthy controls. While SEMA3C, SEMA3F and SEMA7A serum concentrations were significantly higher in patients with COVID-19, SEMA3A was significantly lower. Furthermore, SEMA3A and SEMA3C decreased with COVID-19 severity, while SEMA3F and SEMA7A increased. SEMA4D showed no correlation with disease severity. Serum semaphorin levels show better predictive values than CRP, IL-6 and LDH for differentiating critical from moderate/severe COVID-19. SEMA3F and SEMA7A serum concentrations were associated with the time to recovery, requirement of invasive mechanical ventilation, development of pulmonary thrombosis and nosocomial infections, as well as with in-hospital mortality. In conclusion, we provide the first evidence that SEMA3A, SEMA3C, SEMA3F and SEMA7A can be considered as new biomarkers of COVID-19 severity.

Emergence of Echinococcus multilocularis in Central Continental Croatia: A Human Case Series and Update on Prevalence in Foxes.

Human alveolar echinococcosis (HAE), caused by the metacestode stage of Echinococcus multilocularis, has emerged in many European countries over the last two decades. Here, we report the first data on the new HAE focus with increasing incidence in central Croatia, describe its clinical presentation and outcomes in diagnosed patients, and provide an update on the prevalence and geographic distribution of Echinococcus multilocuaris in red foxes. After the initial case in 2017 from the eastern state border, from 2019 to 2022, five new autochthonous HAE cases were diagnosed, all concentrated in the Bjelovar-Bilogora County (the county incidence in 2019 and 2021: 0.98/105, in 2022: 2.94/105/year; prevalence for 2019-2022: 4.91/105). The age range among four female and two male patients was 37-67 years. The patients' liver lesions varied in size from 3.1 to 15.5 cm (classification range: P2N0M0-P4N1M0), and one patient had dissemination to the lungs. While there were no fatalities, postoperative complications in one patient resulted in liver transplantation. In 2018, the overall prevalence of red foxes was 11.24% (28/249). A new focus on HAE has emerged in central continental Croatia, with the highest regional incidence in Europe. Screening projects among residents and the implementation of veterinary preventive measures following the One Health approach are warranted.

Endoscopic Endonasal Surgery for a Pterygopalatine Fossa Hydatid Cyst.

Background: Cystic echinococcosis is a manifestation of a zoonosis caused by larvae of the tapeworm Echinococcus granulosus sensu lato and pterygopalatine fossa cases are extremely rare. Clinical Presentation and Findings: A 45-year-old Caucasian female with a history of repeated surgeries for HC was referred to our center for treatment of a cystic mass of the pterygopalatine fossa. Multiorgan dissemination was noted on preoperative imaging. Interventions: An endonasal endoscopic procedure was carried over under general anesthesia and the CE completely removed. Etiology was confirmed by molecular diagnostics. Three weeks after the skull base procedure, the patient underwent a combined abdominal/urological procedure for treatment of other cysts. Conclusion: This case shows that the pterygopalatine fossa HC are amenable to surgical treatment using the endonasal endoscopic approach. Extensive preoperative workup is essential to assess the extent of the disease.

Is strongyloidiasis currently autochthonous in Croatia? A retrospective study.

BACKGROUND: Autochthonous human infections with Strongyloides stercoralis have been well documented in many European regions. By exploring patients' data, we aimed to find elements for its current endemicity in Croatia. METHODS: This retrospective descriptive study analysed epidemiological and clinical data of patients treated for strongyloidiasis from January 2010 to May 2019 at a teaching hospital in Zagreb, Croatia. The diagnosis was made by direct methods using light microscopy and/or serology. RESULTS: Among 65 patients with strongyloidiasis, 60% were men, and 78.5% were 50-79 y of age. The sensitivity of the examination of three stool samples after concentration, saline provocation and serology was 26.2, 80.7 and 86.2%, respectively. Clinical presentation included asymptomatic patients with eosinophilia (41.5%), chronic symptomatic infection (33.8%), acute infection (18.5%) and hyperinfection (6.2%). Twenty patients (30.8%) were immunosuppressed; among four of whom developed hyperinfection, two died. Initially 71.7% of patients were treated with albendazole and 13.3% with ivermectin, with an equal parasitological cure rate (72.2% and 75%; p=0.09). In 11 patients, acute infection was autochthonous in its origin. CONCLUSIONS: Strongyloidiasis is currently endemic in Croatia and immunosuppressed travellers to this region should be advised to take precautions. Patients undergoing immunosuppression and organ donors from Croatia should be screened.

Unusual presentations of actinomycosis: a case series and literature review.

INTRODUCTION: To review unusual actinomycosis cases that appeared as a diagnostic and therapeutic challenge at our institution and to present a literature review on the usual clinical presentations. METHODOLOGY: This retrospective review included all patients hospitalized for actinomycosis in a 10-year period at the University Hospital for Infectious Diseases "Dr. Fran Mihaljevic", Zagreb, Croatia. RESULTS: A total of 15 patients were hospitalized during the observed period, 9 (60%) females and 6 (40%) males. The localizations of actinomycosis were: pelvis (5), lungs (3), blood stream (2), colon (1), penis (1), stomach (1), skin (1), cervicofacial region (1). We present four unusual cases: subcutaneous actinomycotic abscess, actinomycosis of the stomach with underlying non-Hodgkin lymphoma, sepsis due to Actinomyces neslundii originated from chronic asymptomatic periapical tooth abscesses and actinomycosis of the distal part of the penile shaft. CONCLUSIONS: Actinomycosis was a very rare clinical problem in our clinical practice (0.032% of all hospitalizations and 0.0034% of all outpatients) but among those cases classical clinical presentations were also very rare.

Combined Albenazole-Praziquantel Treatment in Recurrent Brain Echinococcosis: Case Report.

We present a 40-year-old woman with a history of relapsing echinococcosis who had undergone a number of surgical procedures for cyst removal (right pulmectomy, cardiac surgery and 6 subsequent brain surgeries and two gamma knife procedures) and was admitted to University Hospital for Infectious Diseases "Fran Mihaljeviæ", Zagreb, Croatia in 2014 for pre-operative medical treatment of brain hydatidosis in the right parietal region. We aimed to attain a high cyst albendazole sulphoxide (ASO) concentration in order to achieve a more pronounced protoscolex inactivation and a high serum ASO concentration (reflecting the tissue concentrations) to reduce the risk of disease recurrence. The patient was treated with a higher dose of albendazole (15 mg/kg/day for 4 wk) that we had found effective in patients with liver hydatidosis, and combined with praziquantel over the last 14 d at a dose that is typically used to treat neurocysticercosis with an intention to improve ASO bioavailability. Neither serum nor cerebrospinal fluid concentrations on day 10 apparently differed from those on day 24 indicating a lack of an effect of praziquantel on ASO bioavailability. Intra-cystic ASO concentration was below the lower limit of quantification, but above the limit of detection. After the 7th episode of the disease and combined albendazole-praziquantel and surgery treatment, the patient achieved a 3-year remission. With the apparent lack of a meaningful pharmacokinetic praziquantel-albendazole interaction, this is most likely ascribable to the use of a higher albendazole dose than previously.

Repeated Percutaneous Treatment of Massive Hepatic Cystic Echinococcosis in a Child.

Because of mostly asymptomatic cyst growth and often-neglected nonspecific low-grade symptoms, many cases of cystic echinococcosis (CE) caused by Echinococcus granulosus in the pediatric population are diagnosed at school age, in an advanced and even complicated stage. In 2003, after 5 months of intermittent dull upper-right abdominal pain and nausea, a 13-year-old boy was diagnosed with massive liver CE, with ∼20 round-shaped double-walled medium-sized infective cysts, which permeated the whole liver. Because of their wide distribution across the liver tissue and the risky superficial position of some cysts, liver transplantation emerged as the optimal therapeutic option. Despite being described as only an exceptionally used method for CE, we subjected our patient on 4 occasions to a radiofrequency energy thermoablation (RFT) procedure similar to the one used for malignant neoplasms. In total, 9 superficially situated cysts were initially treated with RFT by using a 14-gauge outer needle and a temperature of 70°C for 8 minutes per cyst, and the remaining cysts were treated with the puncture-aspiration-instillation-reaspiration procedure, along with albendazole (15 mg/kg per day) therapy, for a period of 20 months. After 2 years of follow-up, 4 residual small-sized semisolidified cysts were seen in the liver, and the patient showed no signs of relapse. Although not routinely used, RFT, along with puncture-aspiration-instillation-reaspiration and prolonged albendazole therapy, has shown good tolerability and long-term efficacy in the treatment of multiple infective CE, which could suggest the usefulness of the RFT method beyond salvage situations in pediatric patients.

Relationship between age and intensive care unit-acquired bloodstream infections in infectious disease patients in Croatia.

INTRODUCTION: Intensive care unit-acquired bloodstream infections (ICU-BSI) belong to the most important nosocomial infections. Since there is scarce data available on their relationship with older age, we performed this study to estimate the age-related incidence of ICU-BSI and the odds of acquiring ICU-BSI in elderly critically ill infectious disease patients. METHODOLOGY: A retrospective observational analysis of prospectively collected demographic and clinical data of adult mechanically ventilated infectious disease patients, treated in a teaching hospital in Croatia between 1994 and 2008, using univariate, bivariate, and multivariate logistic regression analyses. RESULTS: Of the 1,093 included patients, 509 (46.6%) were ≥ 65 years old, among 256 (23.4%) of whom a total of 353 ICU-BSI episodes were recorded. No significant difference among ICU-BSI causative microorganisms between the observed age groups was found (P = 0.4940). The rate of patients with ICU-BSI was higher among elderly ones (26.1 vs. 21.1%, P = 0.048), and elderly patients used the ICU facilities (ICU stay, duration of mechanical ventilation and central venous catheter [CVC] use) significantly longer (P < 0.05). However, older age was not positively related with the development of ICU-BSI (OR 0.99, 95% CI: 0.71-1.38); as opposed to the duration of CVC use (OR 1.09, 95% CI: 1.07-1.10). CONCLUSION: It seems that among adult mechanically ventilated infectious disease patients, borderline significantly higher rate of ICU-BSI among those aged ≥ 65 years was related to longer use of ICU facilities, rather than to their older age itself. The duration of CVC use was identified as the only factor positively related to the development of ICU-BSI.