Pleomorphic adenoma with extensive squamous and mucinous metaplasia and a novel MALAT1::PLAG1 fusion gene.

Cases of metaplastic pleomorphic adenoma can be diagnostically challenging. Many of these cases fall into the Milan system's SUMP category, and some may be misdiagnosed. The author shows a case of pleomorphic adenoma with extensive squamous and mucinous metaplasia and a novel MALAT1::PLAG1 fusion.

Primary pulmonary epithelioid hemangioendothelioma metastatic to the pleura and mediastinal lymph node with a prominent rhabdoid cytomorphology showing CAMTA1::WWTR1 fusion and novel PRDM1 and TNFRSF14 mutations.

Cases of epithelioid hemangioendothelioma with WWTR1::CAMTA1 fusion can show rhabdoid cytomorphology. Lack of intracytoplasmic luminal spaces, marked rhabdoid cytomorphology, and variability in the expression of vascular markers makes the diagnosis of EHE challenging. Therefore, a high level of suspicion and ancillary studies (immunohistochemistry and next generation sequencing) help reach a definitive diagnosis in these cases.

Integrating indicator-based and event-based surveillance data for risk mapping of West Nile virus, Europe, 2006 to 2021.

BackgroundWest Nile virus (WNV) has an enzootic cycle between birds and mosquitoes, humans being incidental dead-end hosts. Circulation of WNV is an increasing public health threat in Europe. While detection of WNV is notifiable in humans and animals in the European Union, surveillance based on human case numbers presents some limitations, including reporting delays.AimWe aimed to perform risk mapping of WNV circulation leading to human infections in Europe by integrating two types of surveillance systems: indicator-based and event-based surveillance.MethodsFor indicator-based surveillance, we used data on human case numbers reported to the European Centre for Disease Prevention and Control (ECDC), and for event-based data, we retrieved information from news articles collected through an automated biosurveillance platform. In addition to these data sources, we also used environmental data to train ecological niche models to map the risk of local WNV circulation leading to human infections.ResultsThe ecological niche models based on both types of surveillance data highlighted new areas potentially at risk of WNV infection in humans, particularly in Spain, Italy, France and Greece.ConclusionAlthough event-based surveillance data do not constitute confirmed occurrence records, integrating both indicator-based and event-based surveillance data proved useful. These results underscore the potential for a more proactive and comprehensive strategy in managing the threat of WNV in Europe by combining indicator- and event-based and environmental data for effective surveillance and public health response.

Hyalinising clear cell carcinoma with a novel fusion gene: Insights into the diagnosis.

Hyalinising clear cell carcinoma (HCCC) is a rare salivary gland neoplasm characterised by an EWSR1::ATF1 fusion. Rare cases showing EWSR1::CREB1 rearrangements have been reported. This article presents a case of HCCC with a novel EWSR1-CREB1 fusion, diffuse eosinophilic appearance, novel cytomorphological findings, PAS-negativity, and late regional and distant lymph node metastases.

First wave of COVID-19 in Venezuela: Epidemiological, clinical, and paraclinical characteristics of first cases.

The coronavirus disease 2019 (COVID-19) pandemic has particularly affected countries with weakened health services in Latin America, where proper patient management could be a critical step to address the epidemic. In this study, we aimed to characterize and identify which epidemiological, clinical, and paraclinical risk factors defined COVID-19 infection from the first confirmed cases through the first epidemic wave in Venezuela. A retrospective analysis of consecutive suspected cases of COVID-19 admitted to a sentinel hospital was carried out, including 576 patient cases subsequently confirmed for severe acute respiratory syndrome coronavirus 2 infection. Of these, 162 (28.1%) patients met the definition criteria for severe/critical disease, and 414 (71.2%) were classified as mild/moderate disease. The mean age was 47 (SD 16) years, the majority of which were men (59.5%), and the most frequent comorbidity was arterial hypertension (23.3%). The most common symptoms included fever (88.7%), headache (65.6%), and dry cough (63.9%). Severe/critical disease affected mostly older males with low schooling (p < 0.001). Similarly, higher levels of glycemia, urea, aminotransferases, total bilirubin, lactate dehydrogenase, and erythrocyte sedimentation rate were observed in severe/critical disease patients compared to those with mild/moderate disease. Overall mortality was 7.6% (44/576), with 41.7% (28/68) dying in hospital. We identified risk factors related to COVID-19 infection, which could help healthcare providers take appropriate measures and prevent severe clinical outcomes. Our results suggest that the mortality registered by this disease in Venezuela during the first epidemic wave was underestimated. An increase in fatalities is expected to occur in the coming months unless measures that are more effective are implemented to mitigate the epidemic while the vaccination process is ongoing.

Outpatient prescription patterns of COVID-19 drugs in the metropolitan area of Mexico City.

BACKGROUND: We aimed to describe the use of drugs with apparent efficacy in ambulatory patients with confirmed COVID-19 and the relationship of Google Trends searches with prescriptions and the total number of COVID-19 cases in Mexico City. METHODS: Between March 2020 and February 2021, we surveyed 350 patients confirmed to have COVID-19 across 3 hospitals in Mexico City for their ambulatory prescriptions. We analysed the correlation between prescription patterns of 4 drugs with apparent efficacy against COVID-19, Google Trends searches for these drugs, and the overall number of confirmed COVID-19 cases in Mexico City. RESULTS: We included 350 patients, of whom 59% were women with a median age of 38 years (interquartile range, 29-51), and 72% had a bachelor's degree or higher. There were ambulatory medical prescriptions in 172 (49%) patients, and self-prescriptions were reported in 99 (28%) patients. The prescription rate was high for hydroxychloroquine/azithromycin (19%) and dexamethasone (25%). There was a decrease in the prescription of hydroxychloroquine (P < 0.001) and a strong positive correlation between hydroxychloroquine (r = 0.66; 95% confidence interval, 0.11-0.90; P = 0.02) prescription and online searches for hydroxychloroquine. There was a strong positive correlation between online searches for azithromycin, dexamethasone, ivermectin, and vitamin D and the number of confirmed COVID-19 cases. CONCLUSIONS: During the COVID-19 pandemic, there was a high proportion of prescriptions for hydroxychloroquine/azithromycin and dexamethasone despite their unproven efficacy. Analysis of Google Trends showed a strong correlation between the overall number of confirmed COVID-19 cases and searches for such drugs, suggesting a higher rate of prescriptions. Analysis of online searches could thus help to actively survey public health behaviours in the future.

Spatially regulated editing of genetic information within a neuron.

In eukaryotic cells, with the exception of the specialized genomes of mitochondria and plastids, all genetic information is sequestered within the nucleus. This arrangement imposes constraints on how the information can be tailored for different cellular regions, particularly in cells with complex morphologies like neurons. Although messenger RNAs (mRNAs), and the proteins that they encode, can be differentially sorted between cellular regions, the information itself does not change. RNA editing by adenosine deamination can alter the genome's blueprint by recoding mRNAs; however, this process too is thought to be restricted to the nucleus. In this work, we show that ADAR2 (adenosine deaminase that acts on RNA), an RNA editing enzyme, is expressed outside of the nucleus in squid neurons. Furthermore, purified axoplasm exhibits adenosine-to-inosine activity and can specifically edit adenosines in a known substrate. Finally, a transcriptome-wide analysis of RNA editing reveals that tens of thousands of editing sites (>70% of all sites) are edited more extensively in the squid giant axon than in its cell bodies. These results indicate that within a neuron RNA editing can recode genetic information in a region-specific manner.

Solitary fibrous tumour of the submandibular gland: Novel insights from clinical practice on a close mimicker of pleomorphic adenoma and a diagnostic challenge for the cytopathologist.

Spindle cell lesions of the salivary glands are rare and account for less than 3% of the salivary gland aspirates. A definitive classification of salivary gland neoplasms by fine needle aspiration is possible for the most common lesions but remains a challenge for the less common entities. We present a case of a 72-year-old male with a solitary fibrous tumour (SFT) of the submandibular gland mimicking a myoepithelial-rich pleomorphic adenoma (PA). In this article, we discuss novel insights that help differentiate SFT from PA and other spindle cell lesions.

Stereotactic body radiation therapy for liver metastases: Clinical outcomes and literature review.

BACKGROUND AND AIM: The role of stereotactic body radiation therapy (SBRT) in the management of liver metastasis is increasing, using ablative doses with the goal of local control and ultimately improving survival. The aim of this study is to evaluate our initial results regarding local control, overall survival and toxicity in patients with liver metastases treated with this technique, due to the lack of evidence reported in Latin America. MATERIALS/METHODS: We performed a retrospective chart review from November 2012 to June 2018 of 24 patients with 32 liver metastases. Kaplan-Meier curves were constructed for local control and overall survival. Clinical and prognostic factors were further analyzed by independent analysis. Median follow-up period was 22 months (range, 1-65 months). RESULTS: Median age was 62 years (range, 40-84 years). Colorectal carcinoma was the most common primary cancer. Overall 1-year and 2-years local control rates were 82% (95% Confidence Interval [CI], 70-98%) and 76.2% (95% CI, 45-90%), respectively. Median overall survival rate was 35 months (95%, CI 20.5-48 months). Overall 1-year and 2-year survival rates were 85.83% (95% CI, 64-99%) and 68% (95% CI, 45-84%), respectively. No acute or late grade 3 or 4 toxicity was observed during the follow-up period. CONCLUSIONS: SBRT achieves excellent local control and overall survival rates with low toxicity in patients with liver metastases. Based on our literature review, our results are consistent with larger reports. Further randomized trials are required to compare with other local therapies.

CyberKnife Stereotactic Radiosurgery in brain metastases: A report from Latin America with literature review.

BACKGROUND AND AIM: Stereotactic radiosurgery is increasingly being employed for the treatment of brain metastases, both as an adjuvant to surgical resection, and also as a primary treatment modality. The aim of this study is to evaluate overall survival and local control in patients with brain metastases treated with CyberKnife Stereotactic Radiosurgery (CKRS), due to the lack of evidence reported in Latin America. MATERIALS AND METHODS: We performed a retrospective chart review from October 2011 to January 2017 of 49 patients with 152 brain metastases. Clinical and prognostic factors were further analyzed by independent analysis. Kaplan-Meier curves were constructed for overall survival and local control. The median follow-up period was 12 months (range, 1-37 months). RESULTS: The median age was 61 years (range, 27-85 years) and Karnofsky performance status >70 in 96% of the patients. The median overall survival rate was 15.5 months (95% confidence interval [CI], 10.23-24.3 months). Overall 3-month, 6-month and 1-year local control rates were 98% (95% CI, 85-99%), 96% (95% CI, 82-99%), and 90% (94% IC, 76-96%), respectively. Local failure (LF) was observed in 6 patients (18 lesions). No late complications, such as radiation necrosis, were observed during the follow-up period. CONCLUSIONS: CKRS achieves excellent overall survival and local control rates with low toxicity in patients with brain metastases.

Cyberknife stereotactic radiosurgery and denosumab for giant cell tumour of the skull base: Case report.

Giant cell tumours (GCT) of the skull is a rare entity with only small number of cases reported in literature and optimal treatment is yet to be determined. These tumours have shown high recurrence rates after incomplete surgery, usually occurring during the first year. Even with new surgical techniques a complete resection in skull base tumours is not always possible without functional compromise. Therefore, adjuvant therapy is essential to enhance local control and quality of life. We report a rare case of a 34-year-old male with giant cell tumour (GCT) of the skull base involving the petrous bone, clivus and sphenoid body. The patient received Cyberknife stereotactic radiosurgery (CK SRS) and denosumab after surgery. This combined therapy allowed local control and tumour reduction with secondary neurological improvement during a 4-year follow up.

Evaluating handedness measures in spider monkeys.

Despite long-standing interest and a vast body of literature, there is still disagreement as to how handedness should be measured in nonhuman primates. The primary goal of this study was to evaluate two common measures of handedness in nonhuman primates using the spider monkey, a unique study species due to its lack of a thumb and limited dexterity. Contrary to our predictions and previous findings in Ateles, there was no evidence for group-level hand biases on either the coordinated bimanual TUBE task or a unimanual reaching task. At the individual level, monkeys exhibited preferences on both tasks. There was a leftward trend on the bimanual task and a rightward trend on the unimanual task. Monkeys that were strongly lateralized on the bimanual task showed a comparable hand preference on the unimanual task, whereas monkeys with a moderate preference on the bimanual task shifted to the opposite hand on the unimanual task. Comparing across measures, the two hand-use patterns reported (consistent and shift) might have obscured group-level findings, given the available sample size. Overall, these data reaffirm that task type influences hand use in primates, and multiple measures are needed to fully characterize the construct of handedness. Consideration should be given to the difficulty required between tasks as well as between species.

Toxicity outcome in patients treated with modulated arc radiotherapy for localized prostate cancer.

AIM: This study evaluates the acute toxicity outcome in patients treated with RapidArc for localized prostate cancer. BACKGROUND: Modern technologies allow the delivery of high doses to the prostate while lowering the dose to the neighbouring organs at risk. Whether this dosimetric advantage translates into clinical benefit is not well known. MATERIALS AND METHODS: Between December 2009 and May 2012, 45 patients with primary prostate adenocarcinoma were treated using RapidArc. All patients received 1.8 Gy per fraction, the median dose to the prostate gland, seminal vesicles, pelvic lymph nodes and surgical bed was 80 Gy (range, 77.4-81 Gy), 50.4 Gy, 50.4 Gy and 77.4 Gy (range, 75.6-79.2 Gy), respectively. RESULTS: The time between the last session and the last treatment follow up was a median of 10 months (range, 3-24 months). The incidence of grade 3 acute gastrointestinal (GI) and genitourinary (GU) toxicity was 2.2% and 15.5%, respectively. Grade 2 acute GI and GU toxicity occurred in 30% and 27% of patients, respectively. No grade 4 acute GI and GU toxicity were observed. Older patients (>median) or patients with V60 higher than 35% had significantly higher rates of grade ≥2 acute GI toxicity compared with the younger ones. CONCLUSIONS: RapidArc in the treatment of localized prostate cancer is tolerated well with no Grade >3 GI and GU toxicities. Older patients or patients with higher V60 had significantly higher rates of grade ≥2 acute GI toxicity. Further research is necessary to assess definitive late toxicity and tumour control outcome.

Spatial and temporal trends of dengue infections in Curaçao: A 21-year analysis.

Dengue viruses are a significant global health concern, causing millions of infections annually and putting approximately half of the world's population at risk, as reported by the World Health Organization (WHO). Understanding the spatial and temporal patterns of dengue virus spread is crucial for effective prevention of future outbreaks. By investigating these patterns, targeted dengue surveillance and control measures can be improved, aiding in the management of outbreaks in dengue-affected regions. Curaçao, where dengue is endemic, has experienced frequent outbreaks over the past 25 years. To examine the spatial and temporal trends of dengue outbreaks in Curaçao, this study employs an interdisciplinary and multi-method approach. Data on >6500 cases of dengue infections in Curaçao between the years 1995 and 2016 were used. Temporal and spatial statistics were applied. The Moran's I index identified the presence of spatial autocorrelation for incident locations, allowing us to reject the null hypothesis of spatial randomness. The majority of cases were recorded in highly populated areas and a relationship was observed between population density and dengue cases. Temporal analysis demonstrated that cases mostly occurred from October to January, during the rainy season. Lower average temperatures, higher precipitation and a lower sea surface temperature appear to be related to an increase in dengue cases. This effect has a direct link to La Niña episodes, which is the cooling phase of El Niño Southern Oscillation. The spatial and temporal analyses conducted in this study are fundamental to understanding the timing and locations of outbreaks, and ultimately improving dengue outbreak management.

Systemic oxidative stress associates with the development of post-COVID-19 syndrome in non-hospitalized individuals.

BACKGROUND: Post-COVID-19 syndrome (PCS) remains a major health issue worldwide, while its pathophysiology is still poorly understood. Systemic oxidative stress (OS) may be involved in PCS, which is reflected by lower circulating free thiols (R-SH, sulfhydryl groups), as they are receptive to rapid oxidation by reactive species. This study aimed to investigate the longitudinal dynamics of serum R-SH after SARS-CoV-2 infection and its association with the development of PCS in individuals with mild COVID-19. METHODS: Baseline serum R-SH concentrations were measured and compared between 135 non-hospitalized COVID-19 subjects and 82 healthy controls (HC). In COVID-19 subjects, serum R-SH concentrations were longitudinally measured during the acute disease phase (up to 3 weeks) and at 3, 6, and 12 months of follow-up, and their associations with relevant clinical parameters were investigated, including the development of PCS. RESULTS: Baseline albumin-adjusted serum R-SH were significantly reduced in non-hospitalized COVID-19 subjects as compared to HC (p = 0.041), reflecting systemic OS. In mild COVID-19 subjects, trajectories of albumin-adjusted serum R-SH levels over a course of 12 months were longitudinally associated with the future presence of PCS 18 months after initial infection (b = -9.48, p = 0.023). CONCLUSION: Non-hospitalized individuals with COVID-19 show evidence of systemic oxidative stress, which is longitudinally associated with the development of PCS. Our results provide a rationale for future studies to further investigate the value of R-SH as a monitoring biomarker and a potential therapeutic target in the development of PCS.

The gut microbiota as an early predictor of COVID-19 severity.

Several studies reported alterations of the human gut microbiota (GM) during COVID-19. To evaluate the potential role of the GM as an early predictor of COVID-19 at disease onset, we analyzed gut microbial samples of 315 COVID-19 patients that differed in disease severity. We observed significant variations in microbial diversity and composition associated with increasing disease severity, as the reduction of short-chain fatty acid producers such as Faecalibacterium and Ruminococcus, and the growth of pathobionts as Anaerococcus and Campylobacter. Notably, we developed a multi-class machine-learning classifier, specifically a convolutional neural network, which achieved an 81.5% accuracy rate in predicting COVID-19 severity based on GM composition at disease onset. This achievement highlights its potential as a valuable early biomarker during the first week of infection. These findings offer promising insights into the intricate relationship between GM and COVID-19, providing a potential tool for optimizing patient triage and streamlining healthcare during the pandemic.IMPORTANCEEfficient patient triage for COVID-19 is vital to manage healthcare resources effectively. This study underscores the potential of gut microbiota (GM) composition as an early biomarker for COVID-19 severity. By analyzing GM samples from 315 patients, significant correlations between microbial diversity and disease severity were observed. Notably, a convolutional neural network classifier was developed, achieving an 81.5% accuracy in predicting disease severity based on GM composition at disease onset. These findings suggest that GM profiling could enhance early triage processes, offering a novel approach to optimizing patient management during the pandemic.

Investigating COVID-19 Vaccine Impact on the Risk of Hospitalisation through the Analysis of National Surveillance Data Collected in Belgium.

The national vaccination campaign against SARS-CoV-2 started in January 2021 in Belgium. In the present study, we aimed to use national hospitalisation surveillance data to investigate the recent evolution of vaccine impact on the risk of COVID-19 hospitalisation. We analysed aggregated data from 27,608 COVID-19 patients hospitalised between October 2021 and February 2022, stratified by age category and vaccination status. For each period, vaccination status, and age group, we estimated risk ratios (RR) corresponding to the ratio between the probability of being hospitalised following SARS-CoV-2 infection if belonging to the vaccinated population and the same probability if belonging to the unvaccinated population. In October 2021, a relatively high RR was estimated for vaccinated people > 75 years old, possibly reflecting waning immunity within this group, which was vaccinated early in 2021 and invited to receive the booster vaccination at that time. In January 2022, a RR increase was observed in all age categories coinciding with the dominance of the Omicron variant. Despite the absence of control for factors like comorbidities, previous infections, or time since the last administered vaccine, we showed that such real-time aggregated data make it possible to approximate trends in vaccine impact over time.

The COVID HOME study research protocol: Prospective cohort study of non-hospitalised COVID-19 patients.

BACKGROUND: Guidelines on COVID-19 management are developed as we learn from this pandemic. However, most research has been done on hospitalised patients and the impact of the disease on non-hospitalised and their role in transmission are not yet well understood. The COVID HOME study conducts research among COVID-19 patients and their family members who were not hospitalised during acute disease, to guide patient care and inform public health guidelines for infection prevention and control in the community and household. METHODS: An ongoing prospective longitudinal observational study of COVID-19 outpatients was established in March 2020 at the beginning of the COVID-19 pandemic in the Netherlands. Laboratory confirmed SARS-CoV-2 infected individuals of all ages that did not merit hospitalisation, and their household (HH) members, were enrolled after written informed consent. Enrolled participants were visited at home within 48 hours after initial diagnosis, and then weekly on days 7, 14 and 21 to obtain clinical data, a blood sample for biochemical parameters/cytokines and serological determination; and a nasopharyngeal/throat swab plus urine, stool and sperm or vaginal secretion (if consenting) to test for SARS-CoV-2 by RT-PCR (viral shedding) and for viral culturing. Weekly nasopharyngeal/throat swabs and stool samples, plus a blood sample on days 0 and 21 were also taken from HH members to determine whether and when they became infected. All participants were invited to continue follow-up at 3-, 6-, 12- and 18-months post-infection to assess long-term sequelae and immunological status.

Analysis of the risk of malignancy associated with the basaloid and oncocytic subtypes of the salivary gland neoplasm of unknown malignant potential (SUMP) category in the Milan system.

BACKGROUND: The salivary gland neoplasm of unknown malignant potential (SUMP) category reflects the cytomorphologic overlap and complexity of reporting salivary gland cytology in the Milan system. It includes neoplasms for which a diagnosis of a specific entity cannot be made and, more importantly, for which a carcinoma cannot be entirely excluded. For risk stratification, the subcategorization of SUMP based on the predominant cell type is recommended. This study was aimed at evaluating the risk of neoplasm (RON) and the risk of malignancy (ROM) of the basaloid and oncocytic subtypes of the SUMP category. METHODS: A retrospective analysis of 482 salivary gland fine-needle aspirations from 2012 to 2019 resulted in 48 SUMP cases. The cytology of these cases was reviewed and reclassified as the basaloid or oncocytic subtype. Surgical follow-up was available for 36 cases. The RON and ROM for each subtype were calculated. RESULTS: The RON and ROM were 100% and 23%, respectively, for monomorphic basaloid tumors and 88% and 58.8%, respectively, for monomorphic oncocytic tumors. The ROM for basaloid tumors was 8.3% without matrix/with minimal matrix and 60% with an nonfibrillary matrix. The ROM for oncocytic tumors was 50% without a cystic background and 60% with a cystic or mucinous background. The difference was not statistically significant for either of the subgroups. CONCLUSIONS: Even though statistically not significant in our study, the differential ROMs within the oncocytic and basaloid subgroups help in the risk stratification of SUMP cases. Further subcategorization based on the stroma and background helps in limiting the differential diagnosis but does not necessarily add to the value of the risk stratification.

Impact of the Milan System for Reporting Salivary Gland Cytology on risk assessment when used in routine practice in a real-time setting.

INTRODUCTION: Several retrospective studies across the world have validated the role of the Milan System for Reporting Salivary Gland Cytology (MSRSGC) in improving communication between pathologists and clinicians. In this study, we evaluated the applications of MSRSGC in a real-time setting for 2 years. MATERIALS AND METHODS: All salivary gland lesions that underwent fine-needle aspiration (FNA) from January 2018 to December 2020 were categorized according to MSRSGC guidelines. The risk of malignancy (ROM) was calculated for each category and compared with the ROM proposed by MSRSGC and recent retrospective studies. RESULTS: A total of 160 FNA of salivary gland lesions were categorized as: nondiagnostic (ND) 30 (18%), non-neoplastic (NN) 7 (10.6%), atypia of undetermined significance (AUS) 5 (3.1%), benign neoplasm (BN) 59 (36.8%), salivary gland of uncertain malignant potential (SUMP) 21 (13%), suspicious for malignancy (SM) 3 (1.84%), and malignant (M) 25 (15.6%). Histopathologic follow-up was available for 94 (57.5%) cases. The ROM for each category was ND 54%, NN 0%, AUS 66%, BN 0%, SUMP 37.56%, SM 100%, and M 100%. CONCLUSION: With strict adherence to the diagnostic criteria and MSRSGC guidelines, a ROM of 100% in SM and M categories and a ROM of 0% in NN can be achieved in a real-time setting. The high ROM in the ND category in our study highlights the value of repeat FNA/biopsy for this category. High ROM for AUS indicates the tendency to classify high-grade tumors as AUS, calling for refinement in its criteria.