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In September 2023, a patient in Italy who had never traveled abroad was referred for testing for suspected hepatic cystic echinococcosis. Lesions were incompatible with cystic echinococcosis; instead, autochthonous alveolar echinococcosis was confirmed. Alveolar echinococcosis can be fatal, and awareness must be raised of the infection's expanding distribution.

PurposeHuman alveolar echinococcosis (AE) is a potentially lethal zoonosis caused by the cestode Echinococcus multilocularis. The aim of this systematic review is to establish a comprehensive global AE literature overview taking into account the epidemiologically relevant AE research of the twenty-first century.MethodsWe systematically searched the global literature published from 2001 through 2018 via MEDLINE, EMBASE, the Russian databases eLIBRARY.RU, CyberLeninka, the Chinese databases CNKI, VIP, Journals.research.ac.ir (Farsi language-based), Jordan E-Library (Arab language-based) and supplementary Google Scholar, in accordance with the PRISMA guidelines. QGIS software was used for the mapping of the affected countries.ResultsWe have listed 154 relevant publications in the final literature synopsis in consideration of our quality assessment. Including non-autochthonous cases, human AE was reported in 36 countries within the northern hemisphere from 2001 to 2018. The first publication of AE in Tajikistan, Pakistan, South Korea, Belgium, the Netherlands, Slovakia, Hungary, Lithuania, Latvia, Slovenia and Morocco occurred in this century; further first cases in Taiwan, Thailand, and Denmark were considered to be non-autochthonous by the authors. The highest total case numbers (n ≥ 100 in a single article) were reported in France, Germany, Switzerland, Poland, and Lithuania, including China and Kyrgyzstan with by far the highest prevalence figures.ConclusionsOur paper emphasises the increasing spread of reported cases and the rise in its numbers in the literature of the twenty-first century, especially in western, northern and eastern Europe, as well as in central Asia. Epidemiological studies on human infections are lacking in many parts of the world.

Positron emission tomography-computed tomography (PET-CT) with 18F-fluorodesoxyglucose (FDG) is the imaging modality of choice for assessing inflammation surrounding hepatic alveolar echinococcosis (AE) lesions. This study is the first to evaluate FDG uptake in hepatic AE (n = 51) based on the standardized uptake value (SUV) and to correlate the SUVs with primary morphology and calcification patterns, based on the Echinococcus multilocularis Ulm Classification for Computed-Tomography (EMUC-CT). Our results show that the SUVs were increased for lesions with EMUC-CT types I-IV primary morphology, compared to the surrounding healthy liver tissue (SUV = 2.5 ± 0.4; p < 0.05). Type IV lesions included, by far, the highest number of PET-negative lesions. A comparison of lesions with different primary morphologies showed clear differences. The highest SUVs were found for types I and III, and the lowest was found for type IV. Type IV lesions (SUV, 3.8 ± 1.5) showed significantly lower uptake compared to type I (SUV, 6.9 ± 3.5; p = 0.030) and type III (SUV, 7.4 ± 3.9; p = 0.031) lesions. For type II lesions, the results showed only a statistical trend (SUV, 6.1 ± 3.1; p = 0.073). Due to the small number of cases, an evaluation of type V (n = 1) lesions was not possible. The different SUVs of lesions with different primary morphologies, particularly the lower FDG uptake observed in type IV lesions, suggested that these SUVs might reflect different stages of the disease.

Introduction In humans, alveolar echinococcosis (AE) is a serious helminthic disease. Additionally to a long-term medical treatment, in all suitable cases a complete surgical resection with a 20-mm safe distance (minimal distance of larval tissue to resection margin) is recommended. We analyzed the influence of the safe distance and the effect of the postoperative anthelmintic prophylaxis on the long-term outcome of patients who underwent surgery with curative intent. Objective Ninety-two operated patients were evaluated regarding the safe distance, the duration of medical therapy with benzimidazole derivates, and the further course of AE. Results Median follow-up after surgical procedure was 8.3 years. Twelve patients had a safe distance of 20 mm or more, 16 patients between 10 and 19 mm, 21 patients between 1 and 10 mm, and 10 patients 1 mm. In a further 33 patients, the affected liver was resected without any safe distance. Recurrence of AE was seen in 15 patients between 4 months and 24 years after initial operation. Safe distances of patients with recurrent disease were: 13 ×  no safe distance, one patient with 1-mm and one patient with 13-mm safe distance. In all patients except one with recurrent AE, postoperative therapy with benzimidazole derivates was stopped. Conclusion A safe distance of at least 1 mm in combination with medical anthelmintic treatment continuing for two years might offer a good chance of being disease-free long term, but the exact period of medical treatment needed is not defined. The therapy regime should be determined through an interdisciplinary approach in specialized centers.

AimsSARS-CoV-2 infection is associated with adverse outcomes in patients with cardiovascular disease. Here, we analyzed whether specific biomarkers predict the clinical course of COVID-19 in patients with cardiovascular comorbidities.Methods and resultsWe enrolled 2147 patients with SARS-CoV-2 infection which were included in the Lean European Open Survey on SARS-CoV‑2 (LEOSS)-registry from March to June 2020. Clinical data and laboratory values were collected and compared between patients with and without cardiovascular comorbidities in different clinical stages of the disease. Predictors for mortality were calculated using multivariate regression analysis. We show that patients with cardiovascular comorbidities display significantly higher markers of myocardial injury and thrombo-inflammatory activation already in the uncomplicated phase of COVID-19. In multivariate analysis, elevated levels of troponin [OR 1.54; (95% CI 1.22–1.96), p < 0.001)], IL-6 [OR 1.69 (95% CI 1.26–2.27), p < 0.013)], and CRP [OR 1.32; (95% CI 1.1–1.58), p < 0.003)] were predictors of mortality in patients with COVID-19.ConclusionPatients with cardiovascular comorbidities show elevated markers of thrombo-inflammatory activation and myocardial injury, which predict mortality, already in the uncomplicated phase of COVID-19. Starting targeted anti-inflammatory therapy and aggressive anticoagulation already in the uncomplicated phase of the disease might improve outcomes after SARS-CoV-2 infection in patients with cardiovascular comorbidities.Graphic abstractElevated markers of thrombo-inflammatory activation predict outcome in patients with cardiovascular comorbidities and COVID-19 disease: insights from the LEOSS registry

Cystic (CE) and alveolar (AE) echinococcosis are chronic, neglected parasitic diseases burdened by high morbidity and, for AE, by high mortality, if left untreated. CE and AE have a widespread distribution, including Europe. Albendazole (ABZ), a broad-spectrum benzimidazole drug widely used to treat parasitic infections, is the drug of choice for the management of CE and AE, and is parasitostatic on echinococcal metacestodes. In Europe, ABZ is licensed for interrupted \"cyclic\" treatment, for a maximum of 3 cycles. However, better efficacy with no increased side effects has been shown when the drug is administered continuously and for longer periods. Current international recommendations, on the basis of clinical, pharmacological, and biological studies, recommend continuous administration of ABZ for months to years for the treatment of CE and AE, and this schedule has been widely in use for the past 20 years. However, in Europe this internationally recommended schedule, with the exception of France, is technically \"off-label\", and, as such, requires an informed consent by the patient and, in some countries, even precludes the reimbursement of the drug cost. Adding to the very high cost of the drug, frequent \"out-of-stock\" situation, and packaging format impractical for long therapies, these conditions put patients with CE and AE regularly at risk of treatment discontinuation and disease progression. European regulations envisage variations to marketing authorization, but postauthorization studies should be carried out by the holder of the license of the drug, in the form of randomized controlled trials. While such studies do not seem feasible and would probably not be ethically justified for CE and AE, European regulations envisage other possibilities in particular situations, which apply to CE and AE, but there is limited interest to invest in this perspective. We urge a coordination between stakeholders to find effective and feasible ways to take action to revise the benzimidazole dosage regimens for CE and AE and to ensure a fair, regular, and easy access to the appropriate treatment to those suffering from these serious diseases.

Alveolar (AE) and cystic echinococcosis (CE) in humans are caused by the metacestode of the tapeworms Echinococcus multilocularis and Echinococcus granulosus sensu lato (s.l.). Immunohistochemistry with the monoclonal antibodies (mAb) Em2G11, specific for AE, and the mAb EmG3, specific for AE and CE, is an important pillar of the histological diagnosis of these two infections. Our aim was to further evaluate mAb EmG3 in a diagnostic setting and to analyze in detail the localization, distribution, and impact of small particles of Echinococcus multilocularis (spems) and small particles of Echinococcus granulosus s.l. (spegs) on lymph nodes. We evaluated the mAb EmG3 in a cohort of formalin-fixed, paraffin embedded (FFPE) specimens of AE (n = 360) and CE (n = 178). These samples originated from 156 AE-patients and 77 CE-patients. mAb EmG3 showed a specific staining of the metacestode stadium of E. multilocularis and E. granulosus s.l. and had a higher sensitivity for spems than mAb Em2G11. Furthermore, we detected spegs in the surrounding host tissue and in almost all tested lymph nodes (39/41) of infected patients. 38/47 lymph nodes of AE showed a positive reaction for spems with mAb EmG3, whereas 29/47 tested positive when stained with mAb Em2G11. Spegs were detected in the germinal centers, co-located with CD23-positive follicular dendritic cells, and were present in the sinuses. Likewise, lymph nodes with spems and spegs in AE and CE were significantly enlarged in size in comparison to the control group. mAb EmG3 is specific for AE and CE and is a valuable tool in the histological diagnosis of echinococcosis. Based on the observed staining patterns, we hypothesize that the interaction between parasite and host is not restricted to the main lesion since spegs are detected in lymph nodes. Moreover, in AE the number of spems-affected lymph nodes is higher than previously assumed. The enlargement of lymph nodes with spems and spegs points to an immunological interaction with the small immunogenic particles (spems and spegs) of Echinococcus spp.

PurposeThe ongoing pandemic caused by the novel severe acute respiratory coronavirus 2 (SARS-CoV-2) has stressed health systems worldwide. Patients with chronic kidney disease (CKD) seem to be more prone to a severe course of coronavirus disease (COVID-19) due to comorbidities and an altered immune system. The study’s aim was to identify factors predicting mortality among SARS-CoV-2-infected patients with CKD.MethodsWe analyzed 2817 SARS-CoV-2-infected patients enrolled in the Lean European Open Survey on SARS-CoV-2-infected patients and identified 426 patients with pre-existing CKD. Group comparisons were performed via Chi-squared test. Using univariate and multivariable logistic regression, predictive factors for mortality were identified.ResultsComparative analyses to patients without CKD revealed a higher mortality (140/426, 32.9% versus 354/2391, 14.8%). Higher age could be confirmed as a demographic predictor for mortality in CKD patients (> 85 years compared to 15–65 years, adjusted odds ratio (aOR) 6.49, 95% CI 1.27–33.20, p = 0.025). We further identified markedly elevated lactate dehydrogenase (> 2 × upper limit of normal, aOR 23.21, 95% CI 3.66–147.11, p < 0.001), thrombocytopenia (< 120,000/µl, aOR 11.66, 95% CI 2.49–54.70, p = 0.002), anemia (Hb < 10 g/dl, aOR 3.21, 95% CI 1.17–8.82, p = 0.024), and C-reactive protein (≥ 30 mg/l, aOR 3.44, 95% CI 1.13–10.45, p = 0.029) as predictors, while renal replacement therapy was not related to mortality (aOR 1.15, 95% CI 0.68–1.93, p = 0.611).ConclusionThe identified predictors include routinely measured and universally available parameters. Their assessment might facilitate risk stratification in this highly vulnerable cohort as early as at initial medical evaluation for SARS-CoV-2.

The study was conducted in agreement with the Declaration of Helsinki and with the approval of the Ethics Committee of the University Hospital Ulm (AZ: 409/15), the authors certify that they have obtained all appropriate patient consent forms. Besides the EMUC-CT calcification pattern, the overall degree of calcification was rated as “none,” “slight,” “moderate,” or “considerable,” in order to assess the course of disease more comprehensively. Independent of the time course, the coefficient of determination (R2 = 0.5744) interestingly indicates a moderate to strong relationship between the mean number of lesions and the mean lesion size of the different primary morphological types: the more lesions there are present in one liver the smaller they are.

IntroductionReal-world data from multinational observational studies are required to better understand the role and performance of isavuconazole in real-world practice in Europe.MethodsA retrospective medical record review was conducted at 16 sites in Europe (France, Germany, Italy, Spain, and the United Kingdom). Eligible records were from patients aged ≥ 18 years at the time of isavuconazole initiation and received at least one dose of isavuconazole for suspected or confirmed invasive aspergillosis (IA) or invasive mucormycosis (IM) during the eligibility period (October 15, 2015 to June 30, 2019). Data were descriptively analysed. Success rates, overall survival, and times to these events were descriptively analysed.ResultsData were abstracted from 218 patients (201, IA; 17, IM) who received isavuconazole as monotherapy (initiated as infusion, 52%; oral, 46%). Isavuconazole was initiated as primary therapy in 92 patients (42.2%) and salvage therapy in 121 patients (55.5%) (unknown for five patients). Mean (standard deviation) age was 56.8 (15.6) years, 66% were men and 62% had at least three comorbidities, most frequently haematologic malignancy (62%). Estimated clinical response rate at week 24 was 54.5% (95% confidence interval [CI], 38.2–66.5%) for primary treatment and 73.5% (95% CI, 62.7–81.1%) for salvage therapy. Overall, 45 patients (21%) experienced at least one adverse event (AE). Serious AEs were experienced by 37 patients (17%), with seven related to isavuconazole; five patients (2.3%) discontinued isavuconazole monotherapy due to the serious AE. A total of 137 patients (63%) died, with 17 deaths (12.4%) related to their invasive fungal infection, 11 of whom initiated isavuconazole as salvage therapy.ConclusionsThis study adds to the growing body of evidence that whether used as first-line therapy or after the failure of other antifungal therapies, isavuconazole appears to have a promising clinical response and a good safety profile as an antifungal agent in patients with varied underlying conditions.