Risk factors for nonidiopathic and idiopathic facial nerve palsies: findings of a retrospective study.

BACKGROUND: Idiopathic (IF) and nonidiopathic facial (NIF) nerve palsies are the most common forms of peripheral facial nerve palsies. Various risk factors for IF palsies, such as weather, have been explored, but such associations are sparse for NIF palsies, and it remains unclear whether certain diagnostic procedures, such as contrast agent-enhanced cerebral magnetic resonance imaging (cMRI), are helpful in the differential diagnosis of NIF vs. IF. METHODS: In this retrospective, monocentric study over a five-year period, the medical reports of 343 patients with peripheral facial nerve palsy were analysed based on aetiology, sociodemographic factors, cardiovascular risk factors, consultation time, diagnostic procedures such as cMRI, and laboratory results. We also investigated whether weather conditions and German Google Trends data were associated with the occurrence of NIF. To assess the importance of doctors' clinical opinions, the documented anamneses and clinical examination reports were presented and rated in a blinded fashion by five neurology residents to assess the likelihood of NIF. RESULTS: A total of 254 patients (74%) had IF, and 89 patients (26%) had NIF. The most common aetiology among the NIF patients was the varicella zoster virus (VZV, 45%). Among the factors analysed, efflorescence (odds ratio (OR) 17.3) and rater agreement (OR 5.3) had the highest associations with NIF. The day of consultation (Friday, OR 3.6) and the cMRI findings of contrast enhancement of the facial nerve (OR 2.3) were also risk factors associated with NIF. In contrast, the local weather, Google Trends data, and cardiovascular risk factors were not associated with NIF. CONCLUSION: The findings of this retrospective study highlight the importance of patient history and careful inspections to identify skin lesions for the differential diagnosis of acute facial nerve palsy. Special caution is advised for hospital physicians during the tick season, as a surge in NIF cases can lead to a concomitant increase in IF cases, making it challenging to choose adequate diagnostic methods.

Sterile protection against human malaria by chemoattenuated PfSPZ vaccine.

A highly protective malaria vaccine would greatly facilitate the prevention and elimination of malaria and containment of drug-resistant parasites. A high level (more than 90%) of protection against malaria in humans has previously been achieved only by immunization with radiation-attenuated Plasmodium falciparum (Pf) sporozoites (PfSPZ) inoculated by mosquitoes; by intravenous injection of aseptic, purified, radiation-attenuated, cryopreserved PfSPZ ('PfSPZ Vaccine'); or by infectious PfSPZ inoculated by mosquitoes to volunteers taking chloroquine or mefloquine (chemoprophylaxis with sporozoites). We assessed immunization by direct venous inoculation of aseptic, purified, cryopreserved, non-irradiated PfSPZ ('PfSPZ Challenge') to malaria-naive, healthy adult volunteers taking chloroquine for antimalarial chemoprophylaxis (vaccine approach denoted as PfSPZ-CVac). Three doses of 5.12 × 104 PfSPZ of PfSPZ Challenge at 28-day intervals were well tolerated and safe, and prevented infection in 9 out of 9 (100%) volunteers who underwent controlled human malaria infection ten weeks after the last dose (group III). Protective efficacy was dependent on dose and regimen. Immunization with 3.2 × 103 (group I) or 1.28 × 104 (group II) PfSPZ protected 3 out of 9 (33%) or 6 out of 9 (67%) volunteers, respectively. Three doses of 5.12 × 104 PfSPZ at five-day intervals protected 5 out of 8 (63%) volunteers. The frequency of Pf-specific polyfunctional CD4 memory T cells was associated with protection. On a 7,455 peptide Pf proteome array, immune sera from at least 5 out of 9 group III vaccinees recognized each of 22 proteins. PfSPZ-CVac is a highly efficacious vaccine candidate; when we are able to optimize the immunization regimen (dose, interval between doses, and drug partner), this vaccine could be used for combination mass drug administration and a mass vaccination program approach to eliminate malaria from geographically defined areas.

Internet searching on the head louse in the UK since the COVID-19 pandemic.

BACKGROUND: Wide-ranging restrictions on social and educational activities were imposed in 2020 in response to the COVID-19 pandemic. These likely influenced the population dynamics of the head louse. Close physical contact between human hosts is required for transmission of this ectoparasite. METHOD: Pre- and post-pandemic internet interest in the head louse in the UK was compared using Google Trends data from March 2017 to March 2022 and modeling using the Meta Prophet package. The influence of school holidays and school attendance was also investigated. RESULTS: There was a sharp decline in internet searching of the term "head louse" from March 2020 onwards coinciding with COVID-19 restrictions, and a large difference between pre- and post-pandemic search volumes. No influence of school holidays or attendance on internet searching on the head louse was found. CONCLUSION: The results suggest pandemic restrictions have had a large effect on head louse incidence.

Social mobility and gonorrhoea in Germany during 2020.

OBJECTIVES: The incidence of STIs is likely to be related to levels of social activity and mobility. Novel datasets detailing levels of social activity were made widely available during the COVID-19 pandemic. These allow the relationship between activity and STI incidence to be examined. METHODS: The correlation between social activities and the reported number of gonorrhoea cases between March and December 2020 in Germany was studied. Regression through Autoregressive Integrated Moving Average (ARIMA) time series modelling identified those activities associated with case numbers. RESULTS: ARIMA regression identified a significant association with 'transit' activity within the Apple data and 'parks' within Google. CONCLUSIONS: This study illustrates the potential newly available measures of social activity provided for STI research. Reductions in STI incidence are likely to have occurred due to COVID-19 social restrictions. Although other studies report reductions in infectious diseases during this period, few examine the potential social factors mediating this. The results illustrate the continual need for sexual health services throughout the pandemic.

Withholding or withdrawing life support in long-term neurointensive care patients: a single-centre, prospective, observational pilot study.

PURPOSE: Scarce evidence exists regarding end-of-life decision (EOLD) in neurocritically ill patients. We investigated the factors associated with EOLD making, including the group and individual characteristics of involved healthcare professionals, in a multiprofessional neurointensive care unit (NICU) setting. MATERIALS AND METHODS: A prospective, observational pilot study was conducted between 2013 and 2014 in a 10-bed NICU. Factors associated with EOLD in long-term neurocritically ill patients were evaluated using an anonymised survey based on a standardised questionnaire. RESULTS: 8 (25%) physicians and 24 (75%) nurses participated in the study by providing their 'treatment decisions' for 14 patients at several time points. EOLD was 'made' 44 (31%) times, while maintenance of life support 98 (69%) times. EOLD patterns were not significantly different between professional groups. The individual characteristics of the professionals (age, gender, religion, personal experience with death of family member and NICU experience) had no significant impact on decisions to forgo or maintain life-sustaining therapy. EOLD was patient-specific (intraclass correlation coefficient: 0.861), with the presence of acute life-threatening disease (OR (95% CI): 18.199 (1.721 to 192.405), p=0.038) and low expected patient quality of life (OR (95% CI): 9.276 (1.131 to 76.099), p=0.016) being significant and independent determinants for withholding or withdrawing life-sustaining treatment. CONCLUSIONS: Our findings suggest that EOLD in NICU relies mainly on patient prognosis and not on the characteristics of the healthcare professionals.

First-in-human, Randomized, Double-blind Clinical Trial of Differentially Adjuvanted PAMVAC, A Vaccine Candidate to Prevent Pregnancy-associated Malaria.

BACKGROUND: Malaria in pregnancy has major impacts on mother and child health. To complement existing interventions, such as intermittent preventive treatment and use of impregnated bed nets, we developed a malaria vaccine candidate with the aim of reducing sequestration of asexual "blood-stage" parasites in the placenta, the major virulence mechanism. METHODS: The vaccine candidate PAMVAC is based on a recombinant fragment of VAR2CSA, the Plasmodium falciparum protein responsible for binding to the placenta via chondroitin sulfate A (CSA). Healthy, adult malaria-naive volunteers were immunized with 3 intramuscular injections of 20 µg (n = 9) or 50 µg (n = 27) PAMVAC, adjuvanted with Alhydrogel or glucopyranosyl lipid adjuvant in stable emulsion (GLA-SE) or in a liposomal formulation with QS21 (GLA-LSQ). Allocation was random and double blind. The vaccine was given every 4 weeks. Volunteers were observed for 6 months following last immunization. RESULTS: All PAMVAC formulations were safe and well tolerated. A total of 262 adverse events (AEs) occurred, 94 (10 grade 2 and 2 grade 3) at least possibly related to the vaccine. No serious AEs occurred. Distribution and severity of AEs were similar in all arms. PAMVAC was immunogenic in all participants. PAMVAC-specific antibody levels were highest with PAMVAC-GLA-SE. The antibodies inhibited binding of VAR2CSA expressing P. falciparum-infected erythrocytes to CSA in a standardized functional assay. CONCLUSIONS: PAMVAC formulated with Alhydrogel or GLA-based adjuvants was safe, well tolerated, and induced functionally active antibodies. Next, PAMVAC will be assessed in women before first pregnancies in an endemic area. CLINICAL TRIALS REGISTRATION: EudraCT 2015-001827-21; ClinicalTrials.gov NCT02647489.

Co-infections in Visceral Pentastomiasis, Democratic Republic of the Congo.

Snakeborne Armillifer pentastomiasis is an emerging human parasitic infection in rural tropical areas where snake meat is eaten. After a series of severe ocular A. grandis larval infections and anecdotal abdominal infection in Sankuru District, Democratic Republic of the Congo, during 2014-2015, we systematically investigated possible pentastomid etiology in patients who underwent surgery in the region. Histologic and molecular analyses by established pentastomid 18S rDNA- and newly developed Armillifer-specific cytochrome oxidase PCRs revealed larval pentastomid lesions in 3.7% of patients. Some persons had A. armillatus and A. grandis co-infections. Another pentastomid larva, Raillietiella sp., was molecularly detected in 1 patient who had concomitant A. grandis and A. armillatus infection. The PCRs used were suitable for detecting pentastomid species even in highly necrotic tissues. Phylogenetic analyses of Armillifer cytochrome oxidase genes detected multiple local strains.

Molecular Diagnosis of Abdominal Armillifer grandis Pentastomiasis in the Democratic Republic of Congo.

Pentastomiasis is an emerging snake-borne parasitic zoonosis in the tropics. We describe a molecular and morphological study to diagnose a cluster of asymptomatic abdominal human infections caused by Armillifer grandis. The findings may indicate a silent epidemic in a rural area where severe symptomatic ocular cases with the same parasite species have recently surfaced. Molecular diagnostics are of increasing importance when patient material from remote areas cannot be thoroughly examined locally for logistic reasons.

Burden of serious fungal diseases in Hungary.

Valid data on the prevalence of serious fungal diseases are difficult to derive as in most countries these conditions are not reportable infections. To assess the burden of these infections in Hungary prevalence estimates from international peer-reviewed papers and population statistics were utilised. In the intensive care unit (ICU) population at least 370 cases of serious yeast and 52 mould infections can be expected yearly. The total number of candidaemia cases may be as high as 1110 annually. In patients with acute leukaemia and recipients of haematopoietic stem cell and solid organ transplants the predicted incidence is more than 55 every year. Recurrent vulvovaginal candidiasis--though not a life-threatening condition--can adversely affect the quality of life of more than 177,000 Hungarian women. According to organisation for economic co-operation and development (OECD), 4.7% of total population older than 15 will suffer from chronic obstructive pulmonary disease (COPD) and 4.4% from asthma, adding another very broad risk group to the aforementioned categories susceptible for mycotic complications. Here more than 17,000 can have severe asthma with fungal sensitisation (SAFS) and more than 13,000 are at risk for developing allergic bronchopulmonary aspergillosis (ABPA). The incidence of dermatomycoses and other superficial fungal infections is even more difficult to assess but--according to international estimations--can affect around 14.3% of the total population. More than 1.6 million Hungarians may suffer from fungal diseases annually, with 33,000 cases being life threatening or very serious. This is an under-recognised problem of special importance for public health.

Implementing deep learning models for the classification of Echinococcus multilocularis infection in human liver tissue.

BACKGROUND: The histological diagnosis of alveolar echinococcosis can be challenging. Decision support models based on deep learning (DL) are increasingly used to aid pathologists, but data on the histology of tissue-invasive parasitic infections are missing. The aim of this study was to implement DL methods to classify Echinococcus multilocularis liver lesions and normal liver tissue and assess which regions and structures play the most important role in classification decisions. METHODS: We extracted 15,756 echinococcus tiles from 28 patients using 59 whole slide images (WSI); 11,602 tiles of normal liver parenchyma from 18 patients using 33 WSI served as a control group. Different pretrained model architectures were used with a 60-20-20% random splitting. We visualized the predictions using probability-thresholded heat maps of WSI. The area-under-the-curve (AUC) value and other performance metrics were calculated. The GradCAM method was used to calculate and visualize important spatial features. RESULTS: The models achieved a high validation and test set accuracy. The calculated AUC values were 1.0 in all models. Pericystic fibrosis and necrotic areas, as well as germinative and laminated layers of the metacestodes played an important role in decision tasks according to the superimposed GradCAM heatmaps. CONCLUSION: Deep learning models achieved a high predictive performance in classifying E. multilocularis liver lesions. A possible next step could be to validate the model using other datasets and test it against other pathologic entities as well, such as, for example, Echinococcus granulosus infection.

L1-CAM in Mucinous Ovarian Carcinomas and Borderline Tumors: Impact on Tumor Recurrence and Potential Role in Tumor Progression.

Mucinous ovarian carcinoma (MOC) is a rare histotype of primary ovarian carcinoma. Frequent pathogenic molecular alterations include mutations in KRAS , TP53 , and overexpression of human epidermal growth factor receptor 2, but without having prognostic relevance. As L1-CAM (cell adhesion molecule) has previously shown prognostic relevance in other epithelial tumors of the female genital tract, we analyzed whether L1-CAM expression affected MOC prognosis. In addition, we investigated L1-CAM expression in mucinous borderline tumors (MBOTs) with and without adjacent MOC to identify its potential role in the pathogenesis of MOC. We examined a well-characterized collective of 39 MOCs by immunohistochemistry and compared their expression with clinicopathologic data. L1-CAM positivity was defined as any (even single-cell) positivity. Furthermore, we compared the L1-CAM expression in 20 MBOT regions adjacent to a MOC with that of 15 pure MBOTs. L1-CAM expression in MOC was significantly associated with recurrence, independent of tumor stage. Overall, 7/20 positive cases recurred versus 0/19 L1-CAM-negative cases ( P =0.032), showing a significant difference in time to progression. Furthermore, the presence of at least 1 defined molecular alteration (L1-CAM, aberrant p53, or human epidermal growth factor receptor 2) was found more frequently in the MBOT regions adjacent to a MOC (14/20) than in pure MBOTs (3/15) ( P =0.024). Expression of the tumor marker L1-CAM is frequent (51%) in MOC and is associated with tumor recurrence. The lack of L1-CAM may serve to characterize cases with a low risk of recurrence. Furthermore, the presence of specific molecular alterations in MBOTs is associated with adjacent carcinomas and may define potential pathways in tumor progression.

Time perception at resting state and during active motion: The role of anxiety and depression.

BACKGROUND: Time perception and motion intensity are interrelated factors that may influence symptom expression and severity in case of various psychiatric conditions, including anxiety and depression. AIMS: The present study aimed to 1) explore the associations between the intensity of physical activity, time perception, impulsivity, anxiety and depressive symptoms, and to 2) investigate the extent to which resting state motion intensity can be used to identify the assessed psychiatric conditions. METHODS: 20 healthy controls and 20 psychiatric patients (with either anxiety or depression-related diagnoses) were included in the study and filled out a questionnaire consisting of validated anxiety, depression and impulsivity measures. Time perception was measured by a computerized time production task, whereas motion intensity was analyzed by a motion capture and analysis software. Respondents were randomly assigned to an experimental (with active motion task) and non-experimental group (resting state conditions). Both subgroups were repeatedly assessed, in order to explore changes in motion intensity, time perception and psychiatric symptom levels. RESULTS: Random forest regression analysis identified the level of impulsivity, depression and anxiety as the strongest predictors of resting state motion intensity, while a path analysis model indicated that controls and psychiatric patients show different pathways regarding the connection between motion intensity changes, time production ratio alterations and symptom reduction. CONCLUSIONS: Our study implies the importance of distinguishing between clinical and subclinical severity of psychiatric symptoms when considering the association between motion intensity, time perception, anxiety and depression. Potential transdiagnostic relevance of resting state motion intensity is also addressed.

Reporting of melanoma cell densities in the sentinel node refines outcome prediction.

INTRODUCTION: Sentinel node biopsy is a key procedure to predict prognosis in melanoma. In a prospective study we compare reporting on melanoma cell densities in cytospin preparations with semiquantitative histopathology for predicting outcome. PATIENTS AND METHODS: Sentinel nodes from 900 melanoma patients were bisected. One half of each node was disaggregated mechanically. The melanoma cell density (number of HMB45 positive cells per million lymphocytes with at least one cell showing morphological features of a melanoma cell) was recorded after examining two cytospins. For the second half the maximum diameter of metastasis was determined after haematoxylin and eosin (H&E) and immunohistological staining of three slides. RESULTS: Cytospins were positive for melanoma in 218 of 900 patients (24%). Routine pathology was positive in 111 of 900 (12%) patients. A more extensive pathological workup in cytospin-only positive patients led to a revised diagnosis (from negative to positive) in 23 of 101 patients (22.7%). We found a moderate but significant correlation between melanoma cell densities (determined in cytospins) and the maximum diameter of metastasis (determined by pathology) (rho = 0.6284, p < 0.001). At a median follow-up of 37 months (IQR 25-53 months) melanoma cell density (cytospins) (p < 0.001), thickness of melanoma (p = 0.008) and ulceration status (p = 0.026) were significant predictors for melanoma specific survival by multivariable testing and were all confirmed as key predictive factors by the random forest model. Maximum diameter of metastases, age and sex were not significant by multivariable testing (all p > 0.05). CONCLUSION: Recording melanoma cell densities by examining two cytospins accurately predicts melanoma outcome and outperforms semiquantitative histopathology.

Delirium in hospitalized COVID-19 patients: Predictors and implications for patient outcome.

INTRODUCTION: Delirium is recognized as a severe complication of coronavirus-disease-2019 (COVID-19). COVID-19-associated delirium has been linked to worse patient outcomes and is considered to be of multifactorial origin. Here we sought to evaluate the incidence and risk factors of delirium in hospitalized COVID-19 patients, along with its impact on clinical outcome. METHODS: Consecutive adult COVID-19 patients admitted to a tertiary academic referral hospital between March 1st and December 31st, 2020 were included. Potential risk factors for delirium were evaluated, including: age, gender, disease severity (as per the highest WHO grading reached during admission), laboratory parameters for infection and renal function (as per their most extreme values), and presence of comorbidities. To assess the relative strength of risk factors for predicting the occurrence of delirium, we performed a random-forest survival analysis. RESULTS: 347 patients with positive COVID-19 PCR test and median age 68.2 [IQR 55.5, 80.5] years were included. Of those, 79 patients (22.8%) developed delirium, 81 (23.3%) were transferred to ICU, 58 (16.7%) died. 163 (73.8%) patients were discharged home, 13 (5.9%) to another hospital, 32 (14.5%) to nursing homes, 13 (5.9%) to rehabilitation with an overall median admission-to-discharge time of 53 [IQR 14, 195] days. The strongest predictors for the occurrence of delirium were blood urea nitrogen (minimal depth value (MD): 3.33), age (MD: 3.75), disease severity (as captured by WHO grading; MD: 3.93), leukocyte count (MD: 4.22), the presence of a neurodegenerative history (MD: 4.43), ferritin (MD: 4.46) and creatinine (MD: 4.59) levels. CONCLUSION: The risk of delirium in COVID-19 can be stratified based on COVID-19 disease severity and-similar to delirium associated with other respiratory infections-the factors advanced age, neurodegenerative disease history, and presence of elevated infection and renal-retention parameters. Screening for these risk factors may facilitate early identification of patients at high-risk for COVID-19-associated delirium.

Efficacy, T cell activation and antibody responses in accelerated Plasmodium falciparum sporozoite chemoprophylaxis vaccine regimens.

Repeated direct venous inoculation of Plasmodium falciparum sporozoites (PfSPZ) together with antimalarial chemoprophylaxis (PfSPZ-CVac) is the most potent way to induce sterile immunity against P. falciparum infection in malaria-naive volunteers. However, established schedules are complex and long. Here, we tested two accelerated three-dose schedules (28- and 10-day regimen) assessing efficacy by controlled human malaria infection (CHMI) against placebo, comparing vaccine-specific T cell and antibody responses by antigen-reactive T cell enrichment (ARTE) and protein microarray, respectively. Both regimens were similarly efficacious (67 and 63% vaccine efficacy) but different in the induction of vaccine-specific T cells and antibodies. The 10-day regimen resulted in higher numbers of antigen-specific CD4+ effector memory pro-inflammatory T cells and a broader antibody response compared with the 28-day regimen. Usually in nature, P. falciparum liver stage lasts about 6.5 days. The short vaccination-interval of the 10-day regimen prolongs the time of continuous exposure to liver-stage parasites, which may explain the stronger response. Besides dose and number of vaccinations, duration of liver-stage exposure is a factor to optimize PfSPZ-CVac immunogenicity.

A PfSPZ vaccine immunization regimen equally protective against homologous and heterologous controlled human malaria infection.

Immunization with radiation-attenuated Plasmodium falciparum (Pf) sporozoites (SPZ) in PfSPZ Vaccine, has provided better vaccine efficacy (VE) against controlled human malaria infection (CHMI) with the same parasites as in the vaccine (homologous) than with genetically distant parasites (heterologous). We sought to identify an immunization regimen that provided similar VE against CHMI with homologous and heterologous Pf for at least 9 weeks in malaria-naïve adults. Such a regimen was identified in part 1 (optimization), an open label study, and confirmed in part 2 (verification), a randomized, double-blind, placebo-controlled study in which VE was assessed by cross-over repeat CHMI with homologous (PfNF54) and heterologous (Pf7G8) PfSPZ at 3 and 9-10 weeks. VE was calculated using Bayesian generalized linear regression. In part 1, vaccination with 9 × 105 PfSPZ on days 1, 8, and 29 protected 5/5 (100%) subjects against homologous CHMI at 3 weeks after the last immunization. In part 2, the same 3-dose regimen protected 5/6 subjects (83%) against heterologous CHMI at both 3 and 9-10 weeks after the last immunization. Overall VE was 78% (95% predictive interval: 57-92%), and against heterologous and homologous was 79% (95% PI: 54-95%) and 77% (95% PI: 50-95%) respectively. PfSPZ Vaccine was safe and well tolerated. A 4-week, 3-dose regimen of PfSPZ Vaccine provided similar VE for 9-10 weeks against homologous and heterologous CHMI. The trial is registered with ClinicalTrials.gov, NCT02704533.

Mobility and COVID-19 mortality across Scandinavia: A modeling study.

BACKGROUND: In response to COVID-19, the Swedish government imposed few travel and mobility restrictions. This contrasted with its Scandinavian neighbours which implemented stringent restrictions. The influence these different approaches had on mobility, and thus on COVID-19 mortality was investigated. METHODS: Datasets indicating restriction severity and community mobility were examined; Google's 'Community Movement Reports' (CMR) show activity at key location categories; the Oxford COVID-19 Government Response Tracker collates legislative restrictions into a 'Stringency Index' (SI). RESULTS: CMR mobility categories were negatively correlated with COVID-19 mortality. The strongest correlations were obtained by negatively time lagging mortality data, suggesting restrictions had a delayed influence. During the 'first wave' a model using SI (AIC 632.87) proved favorable to one using contemporaneous CMR data and SI (AIC 1193.84), or lagged CMR data and SI (AIC 642.35). Validation using 'second wave' data confirmed this; the model using SI solely again being optimal (RMSE: 0.2486 vs. 0.522 and 104.62). Cross-country differences were apparent in all models; Swedish data, independent of SI and CMR, proved significant throughout. There was a significant association for Sweden and the death number across models. CONCLUSION: SI may provide a broader, more accurate, representation of changes in movement in response to COVID-19 restrictions.

Alveolar Echinococcosis-A Challenging Task for the Hepatobiliary Surgeon.

(1) Background: Alveolar echinococcosis (AE) is an ultimately fatal disease, whose only curative treatment is surgery. Due to its late presentation extended liver resections are often necessary. The true benefit of extensive surgery has yet to be established; (2) Methods: We present a single center experience of 33 cases of Echinococcus multilocularis that have been treated at a high-volume hepatobiliary surgery center between 2004 and 2021. (3) Results: Of the 33 patients 24 patients underwent major liver resection (73%). In addition to the liver resection patients frequently underwent complex extrahepatic procedures such as lymphadenectomy (n = 21, 61%), vascular resections and reconstructions (n = 9, 27%) or resections and reconstruction of the extrahepatic bile duct (n = 11, 33%). Seven patients suffered from ≥ grade III complications (21%). Complete resection was achieved in 17 patients. Fourteen patients had R1 resections and two had macroscopic parasitic remnant (R2). Progressive disease was reported in three patients (The two R2 patients and one R1 resected patient). At a median follow-up of 54 months no mortality has occurred in our cohort; (4) Conclusions: Liver resection remains the gold standard for AE. Even in extensive disease the combination of complex resection and perioperative benzimidazoles can achieve favorable long-term outcomes.

Google Trends Data and COVID-19 in Europe: Correlations and model enhancement are European wide.

The current COVID-19 pandemic offers a unique opportunity to examine the utility of Internet search data in disease modelling across multiple countries. Most such studies typically examine trends within only a single country, with few going beyond describing the relationship between search data patterns and disease occurrence. Google Trends data (GTD) indicating the volume of Internet searching on 'coronavirus' were obtained for a range of European countries along with corresponding incident case numbers. Significant positive correlations between GTD with incident case numbers occurred across European countries, with the strongest correlations being obtained using contemporaneous data for most countries. GTD was then integrated into a distributed lag model; this improved model quality for both the increasing and decreasing epidemic phases. These results show the utility of Internet search data in disease modelling, with possible implications for cross country analysis.

Forecasting the future number of pertussis cases using data from Google Trends.

BACKGROUND: Alternative methods could be used to enhance the monitoring and forecasting of re-emerging conditions such as pertussis. Here, whether data on the volume of Internet searching on pertussis could complement traditional modeling based solely on reported case numbers was assessed. METHODS: SARIMA models were fitted to describe reported weekly pertussis case numbers over a four-year period in Germany. Pertussis-related Google Trends data (GTD) was added as an external regressor. Predictions were made by the models, both with and without GTD, and compared with values within the validation dataset over a one-year and for a two-weeks period. RESULTS: Predictions of the traditional model using solely reported case numbers resulted in an RMSE (residual mean squared error) of 192.65 and 207.8, a mean absolute percentage error (MAPE) of 58.59 and 72.1, and a mean absolute error (MAE) 169.53 and 190.53 for the one-year and for the two-weeks period, respectively. The GTD expanded model achieved better forecasting accuracy (RMSE: 144.22 and 201.78), a MAPE 43.86, and 68.54 and a MAE of 124.46 and 178.96. Corrected Akaike Information Criteria also favored the GTD expanded model (1750.98 vs. 1746.73). The difference between the predictive performances was significant when using a two-sided Diebold-Mariano test (DM value: 6.86, p < 0.001) for the one-year period. CONCLUSION: Internet-based surveillance data enhanced the predictive ability of a traditionally based model and should be considered as a method to enhance future disease modeling.