Isolated Aortitis: a Rare Cause of Febrile Illness

Febrile illness often presents a challenge for the clinician. The main causes of febrile illness are infections, solid or haematological malignancies and connective tissue disorders, including vasculitis. A 49-year-old woman sought medical attention because of intermittent fever that lasted 2 weeks. She presented no further symptoms or physical signs to suggest the aetiology. The epidemiological context was irrelevant. Analyses revealed anaemia of chronic disease and significant elevations of inflammatory parameters. A comprehensive study was performed, which revealed presence of an aortitis. Investigation of infectious and immunological causes was negative. We arrived at the definitive diagnosis of isolated aortitis. She was treated with corticosteroid and methotrexate, with resolution of symptoms and clinical abnormalities.info:eu-repo/semantics/publishedVersio

Functional Outcome of Endovascular Treatment in Patients With Acute Ischemic Stroke With Large Vessel Occlusion: Mothership Versus Drip-and-Ship Model in a Portuguese Urban Region

Introduction Endovascular treatment (EVT) with mechanical thrombectomy and acute carotid stenting has become an integral part of the treatment of acute ischemic stroke with large vessel occlusion. Despite being included in the most recent stroke guidelines, only comprehensive centers can offer EVT and thus patients frequently need to be transferred from primary hospitals. We aimed to assess which pre-hospital model of care - direct admission to a comprehensive stroke center (mothership) or transfer to a comprehensive stroke center after the first admission to the nearest hospital (drip-and-ship) - had the most benefit in stroke patients in a Portuguese urban region. Methods We selected patients admitted to a comprehensive stroke center who underwent EVTs between January 2018 and December 2020, in Lisbon, Portugal. We used data from the Safe Implementation of Treatments in Stroke (SITS) International registry on stroke severity, previous modified Rankin Scale (mRS), time from symptom onset to the first admission, time from symptom onset to the procedure, and mRS three months post stroke. We defined an unfavorable outcome as having an mRS >2 at three months post stroke. For patients with previous mRS >2, an unfavorable outcome was defined as any increase in mRS at three months post stroke. Results We analyzed the data of 1154 patients, of which 407 were admitted through a mothership approach and 747 through a drip-and-ship approach. Both groups were similar regarding sociodemographic characteristics, stroke risk factors, previous disability, and stroke severity. Median onset-to-door time was higher (126 vs 110 minutes, p-value=0.002) but onset-to-procedure time was lower (199 vs 339 minutes, p-value<0.001) in the mothership group. The mothership group had a higher proportion of patients with mRS <3 at three months post stroke than the drip-and-ship group (41.3% vs 34.9%, p-value=0.035). Mortality was similar in both groups. A multivariate logistic regression model confirmed a lower probability of unfavorable outcomes with the mothership approach (OR = 0.677, 95% CI 0.514-0.892, p-value=0.006). Surprisingly, onset-to-procedure time did not have an impact on functional outcomes. Conclusion Our findings show that the mothership model results in better functional outcomes for patients with acute ischemic stroke with large vessel occlusion. Further studies are needed to better define patient selection for this strategy and the impact of a mothership model in comprehensive stroke centers.info:eu-repo/semantics/publishedVersio

Single-cell functional and chemosensitive profiling of combinatorial colorectal therapy in zebrafish xenografts.

Cancer is as unique as the person fighting it. With the exception of a few biomarker-driven therapies, patients go through rounds of trial-and-error approaches to find the best treatment. Using patient-derived cell lines, we show that zebrafish larvae xenotransplants constitute a fast and highly sensitive in vivo model for differential therapy response, with resolution to reveal intratumor functional cancer heterogeneity. We screened international colorectal cancer therapeutic guidelines and determined distinct functional tumor behaviors (proliferation, metastasis, and angiogenesis) and differential sensitivities to standard therapy. We observed a general higher sensitivity to FOLFIRI [5-fluorouracil(FU)+irinotecan+folinic acid] than to FOLFOX (5-FU+oxaliplatin+folinic acid), not only between isogenic tumors but also within the same tumor. We directly compared zebrafish xenografts with mouse xenografts and show that relative sensitivities obtained in zebrafish are maintained in the rodent model. Our data also illustrate how KRAS mutations can provide proliferation advantages in relation to KRASWT and how chemotherapy can unbalance this advantage, selecting for a minor clone resistant to chemotherapy. Zebrafish xenografts provide remarkable resolution to measure Cetuximab sensitivity. Finally, we demonstrate the feasibility of using primary patient samples to generate zebrafish patient-derived xenografts (zPDX) and provide proof-of-concept experiments that compare response to chemotherapy and biological therapies between patients and zPDX. Altogether, our results suggest that zebrafish larvae xenografts constitute a promising fast assay for precision medicine, bridging the gap between genotype and phenotype in an in vivo setting.info:eu-repo/semantics/publishedVersio

Path Tracing vs. Volume Rendering Technique in Post-Surgical Assessment of Bone Flap in Oncologic Head and Neck Reconstructive Surgery: A Preliminary Study

This study aims to compare a relatively novel three-dimensional rendering called Path Tracing (PT) to the Volume Rendering technique (VR) in the post-surgical assessment of head and neck oncologic surgery followed by bone flap reconstruction. This retrospective study included 39 oncologic patients who underwent head and neck surgery with free bone flap reconstructions. All exams were acquired using a 64 Multi-Detector CT (MDCT). PT and VR images were created on a dedicated workstation. Five readers, with different expertise in bone flap reconstructive surgery, independently reviewed the images (two radiologists, one head and neck surgeon and two otorhinolaryngologists, respectively). Every observer evaluated the images according to a 5-point Likert scale. The parameters assessed were image quality, anatomical accuracy, bone flap evaluation, and metal artefact. Mean and median values for all the parameters across the observer were calculated. The scores of both reconstruction methods were compared using a Wilcoxon matched-pairs signed rank test. Inter-reader agreement was calculated using Spearman’s rank correlation coefficient. PT was considered significantly superior to VR 3D reconstructions by all readers (p &lt; 0.05). Inter-reader agreement was moderate to strong across four out of five readers. The agreement was stronger with PT images compared to VR images. In conclusion, PT reconstructions are significantly better than VR ones. Although they did not modify patient outcomes, they may improve the post-surgical evaluation of bone-free flap reconstructions following major head and neck surgery

Eumycetoma caused by Diaporthe phaseolorum (Phomopsis phaseoli): a case report and a mini-review of Diaporthe/Phomopsis spp invasive infections in humans

AbstractDiaporthe phaseolorum (syn. Phomopsis phaseoli) is a frequent fungal parasite of plants, present on all continents around the world. It has rarely been involved in human diseases. We report a case of eumycetoma with osteomyelitis of the forefoot caused by this fungus and diagnosed by molecular biology. The patient had positive HTLV-1 serology and was a farmer from French Guiana who walked barefoot. He was successfully treated with long-term oral itraconazole (400 mg/day). A review of the literature underlines the essential roles of plants and host immunosuppression in this infection and the favourable outcome with a triazole antifungal treatment

A 10-year experience in preoperative ultrasound imaging for parotid glands’ benign neoformations

Salivary gland neoplasms represent less than 4% of all head and neck lesions, being 80% in the parotid gland and usually benign. Imaging plays a key role in the evaluation of parotid gland masses. Ultrasound is cheap, with an excellent resolution and a safe real time assessment making it an ideal first evaluation option. Conversely, MRI is considered a second-line pre-surgery exam used to determine the location, the extension and the signal features of a parotid lesion. Both US and MRI are poorly reliable for predicting histology, therefore a fine-needle aspiration cytology (FNAC) is usually needed. In our retrospective study, we examined 263 patients with parotid diseases and a FNAC positive for a benign neoplasm, who underwent surgery between 2010 and 2020, in the departments of Otorhinolaryngology and Maxillofacial surgery in Verona. We compared a group of 126 patients preoperatively evaluated with ultrasound and a control group of 137 patients studied through third level imaging (usually MRI). In our case series, both third level imaging and US were used in equal measure, despite the lesion size. We found the recurrence rate to be almost the same between the two diagnostic methods and we saw that the patients studied through third level preoperative imaging had a higher complication rate and a worse facial nerve outcome. In our opinion, for patients with a FNAC positive for benign lesion the exclusive use of ultrasound imaging provides enough information to study the neoplasm while allowing for a faster and cheaper preoperative evaluation

An Initial In Vitro Investigation into the Potential Therapeutic Use of SupT1 Cells to Prevent AIDS in HIV-Seropositive Individuals

HIV infection usually leads to a progressive decline in number and functionality of CD4+ T lymphocytes, resulting in AIDS development. In this study, I investigated the strategy of using inoculated SupT1 cells to move infection from HIV-1 X4 strains toward the inoculated cells, which should theoretically prevent infection and depletion of normal CD4+ T cells, preventing the development of AIDS-related pathologies. Interestingly, the persistent in vitro replication in SupT1 cells renders the virus less cytopathic and more sensitive to antibody-mediated neutralization, suggesting that replication of the virus in the inoculated SupT1 cells may have a vaccination effect in the long run. In order to mimic the scenario of a therapy in which SupT1 cells are inoculated in an HIV-seropositive patient, I used infected SupT1/PBMC cocultures and a series of control experiments. Infections were done with equal amounts of the wild type HIV-1 LAI virus. The SupT1 CD4+CD8+ T cell population was distinguished from the PBMC CD4+CD8− T cell population by FACS analysis. The results of this study show that the virus-mediated killing of primary CD4+ T cells in the SupT1/PBMC cocultures was significantly delayed, suggesting that the preferential infection of SupT1 cells can induce the virus to spare primary CD4+ T cells from infection and depletion. The preferential infection of SupT1 cells can be explained by the higher viral tropism for the SupT1 cell line. In conclusion, this study demonstrates that it's possible in an in vitro system to use SupT1 cells to prevent HIV infection of primary CD4+ T cells, suggesting that further exploration of the SupT1 cell line as a cell-based therapy against HIV-1 may prove worthwhile

Cyclin D1 promotes neurogenesis in the developing spinal cord in a cell cycle-independent manner

Neural stem and progenitor cells undergo an important transition from proliferation to differentiation in the G1 phase of the cell cycle. The mechanisms coordinating this transition are incompletely understood. Cyclin D proteins promote proliferation in G1 and typically are down-regulated before differentiation. Here we show that motoneuron progenitors in the embryonic spinal cord persistently express Cyclin D1 during the initial phase of differentiation, while down-regulating Cyclin D2. Loss-of-function and gain-offunction experiments indicate that Cyclin D1 (but not D2) promotes neurogenesis in vivo, a role that can be dissociated from its cell cycle function. Moreover, reexpression of Cyclin D1 can restore neurogenic capacity to D2-expressing glial-restricted progenitors. The neurogenic function of Cyclin D1 appears to be mediated, directly or indirectly, by Hes6, a proneurogenic basic helic-loop-helix transcription factor. These data identify a cell cycle-independent function for Cyclin D1 in promoting neuronal differentiation, along with a potential genetic pathway through which this function is exerted