Simultaneous ovarian and endometrial osseous metaplasia: a case report

BACKGROUND: Endometrial ossification is a rare disease. More than 80% of cases occur after pregnancy, but it has been observed in patients with a history of endometritis, dilation and curettage, and metabolic disorders. CASE: A 42-year-old woman presented with osseous metaplasia of both the endometrium and ovaries. At laparoscopy both adnexa were covered with adhesions and were adherent to the posterior wall of the uterus. Following adhesiolysis, calcified nodules were removed from both ovaries with biopsy forceps. Endometrial bone tissue was removed by hysteroscopic resection. CONCLUSION: To our knowledge, this is the first reported case of osseous metaplasia of both the endometrium and ovaries since all cases described to date in the literature involved only the uterine cavity. Conservative management with endoscopic surgery is effective.     

Die sympathischen Ganglien des Magens bei einigen experimentellen und spontanen Magenkrankheiten

Ohne ZusammenfassungHierzu Tafel V.Die Anregung, Leitung und Redaktion der Arbeit ging von Dr. d'Amato aus, die technische Ausführung von Dr. Macrì.     

Dual IGF1R/IR inhibitors in combination with GD2-CAR T-cells display a potent anti-tumor activity in diffuse midline glioma H3K27M-mutant

BackgroundDiffuse midline gliomas (DMG) H3K27M-mutant, including diffuse intrinsic pontine glioma (DIPG), are pediatric brain tumors associated with grim prognosis. Although GD2-CAR T-cells demonstrated significant anti-tumor activity against DMG H3K27M-mutant in vivo, a multimodal approach may be needed to more effectively treat patients. We investigated GD2 expression in DMG/DIPG and other pediatric high-grade gliomas (pHGG) and sought to identify chemical compounds that would enhance GD2-CAR T-cell anti-tumor efficacy.MethodsImmunohistochemistry in tumor tissue samples and immunofluorescence in primary patient-derived cell lines were performed to study GD2 expression. We developed a high-throughput cell-based assay to screen 42 kinase inhibitors in combination with GD2-CAR T-cells. Cell viability, western blots, flow-cytometry, real time PCR experiments, DIPG 3D culture models, and orthotopic xenograft model were applied to investigate the effect of selected compounds on DIPG cell death and CAR T-cell function.ResultsGD2 was heterogeneously, but widely, expressed in the tissue tested, while its expression was homogeneous and restricted to DMG/DIPG H3K27M-mutant cell lines. We identified dual IGF1R/IR antagonists, BMS-754807 and linsitinib, able to inhibit tumor cell viability at concentrations that do not affect CAR T-cells. Linsitinib, but not BMS-754807, decreases activation/exhaustion of GD2-CAR T-cells and increases their central memory profile. The enhanced anti-tumor activity of linsitinib/GD2-CAR T-cell combination was confirmed in DIPG models in vitro, ex vivo, and in vivo.ConclusionOur study supports the development of IGF1R/IR inhibitors to be used in combination with GD2-CAR T-cells for treating patients affected by DMG/DIPG and, potentially, by pHGG.     

COVID-19 and Guillain-Barré syndrome: A single-center prospective case series with a 1-year follow-up

Single reports of Guillain-Barré syndrome (GBS) have been reported worldwide during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. While case reports are likely to be biased toward uncommon clinical presentations, systematic assessment of prospective series can highlight the true clinical features and spectrum. In this prospective, observational study, we included all consecutive patients who developed GBS. In patients with SARS-CoV-2 infection as antecedent, the time-gap between the infection and GBS onset had to be ≤30 days. The referral was a neurological University Research Hospital, in the Italian Region more severely involved by the pandemic, and hospitalizing both COVID+ and non-COVID neurological diseases. Clinical, laboratory, cerebrospinal fluid, and electromyographic features of GBS diagnosed between March 2020 and March 2021 were compared to a retrospective series of GBS diagnosed between February 2019 and February 2020 (control population). Nasopharyngeal swab was still positive at GBS onset in 50% of patients. Mild-to-moderate COVID-related pneumonia, as assessed by X-ray (6 patients) or X-ray plus computerized tomography (2 patients) co-occurred in 6 of 10 patients. GBS diagnosed during the pandemic period, including 10 COVID-GBS and 10 non–COVID-GBS, had higher disability on admission (P = .032) compared to the GBS diagnosed between February 2019 and 2020, possibly related to later hospital referral in the pandemic context. Compared to non–COVID-GBS (n = 10) prospectively diagnosed in the same period (March 2020–2021), post–COVID-GBS (n = 10) had a higher disability score on admission (P = .028), lower sum Medical Research Council score (P = .022) and lymphopenia (P = .025), while there were no differences in GBS subtype/variant, severity of peripheral involvement, prognosis and response to treatment. Cerebrospinal fluid search for SARS-CoV-2 RNA and antiganglioside antibodies were negative in all COVID+ patients. Temporal clustering of cases, coinciding with the waves of the pandemic, and concomitant reduction of the incidence of COVID-negative GBSs may indicate a role for SARS-CoV-2 infection in the development of GBS, although the association may simply be related to a bystander effect of systemic inflammation; lack of prevalence of specific GBS subtypes in post–COVID-GBS also support this view. GBS features and prognosis are not substantially different compared to non–COVID-GBS.     

Immune-mediated neurological syndromes in SARS-CoV-2-infected patients

Journal of Neurology - Evidence of immune-mediated neurological syndromes associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is limited. We therefore...     

Shape Memory Alloy—Polymer Composites: Static and Fatigue Pullout Strength under Thermo-Mechanical Loading

This work was carried out within the context of an R&D project on morphable polymer matrix composites (PMC), actuated by shape memory alloys (SMA), to be used for active aerodynamic systems in automotives. Critical issues for SMA–polymer integration are analyzed that are mostly related to the limited strength of metal–polymer interfaces. To this aim, materials with suitable thermo-mechanical properties were first selected to avoid premature activation of SMA elements during polymer setting as well as to avoid polymer damage during thermal activation of SMAs. Nonstandard samples were manufactured for both static and fatigue pullout tests under thermo-mechanical loading, which are made of SMA wires embedded in cylindrical resin blocks. Fully coupled thermo-mechanical simulations, including a special constitutive model for SMAs, were also carried out to analyze the stress and temperature distribution in the SMA–polymer samples as obtained from the application of both mechanical loads and thermal activation of the SMA wires. The results highlighted the severe effects of SMA thermal activation on adhesion strength due to the large recovery forces and to the temperature increase at the metal–polymer interface. Samples exhibit a nominal pullout stress of around 940 MPa under static mechanical load, and a marked reduction to 280 MPa was captured under simultaneous application of thermal and mechanical loads. Furthermore, fatigue run-out of 5000 cycles was achieved, under the combination of thermal activation and mechanical loads, at a nominal stress of around 200 MPa. These results represent the main design limitations of SMA/PMC systems in terms of maximum allowable stresses during both static and cyclic actuation.     

Disclosing incidental findings in brain research: The rights of minors in decision‐making

MRI is used routinely in research with children to generate new knowledge about brain development. The detection of unexpected brain abnormalities (incidental findings; IFs) in these studies presents unique challenges. While key issues surrounding incidence and significance, duty of care, and burden of disclosure have been addressed substantially for adults, less empirical data and normative analyses exist for minors who participate in minimal risk research. To identify ethical concerns and fill existing gaps, we conducted a comprehensive review of papers that focused explicitly on the discovery of IFs in minors. The discourse in the 21 papers retrieved for this analysis amply covered practical issues such as informed consent and screening, difficulties in ascertaining clinical significance, the economic costs and burden of responsibility on researchers, and risks (physical or psychological). However, we found little discussion about the involvement of minors in decisions about disclosure of IFs in the brain, especially for IFs of low clinical significance. In response, we propose a framework for managing IFs that integrates practical considerations with explicit appreciation of rights along the continuum of maturity. This capacity‐adjusted framework emphasizes the importance of involving competent minors and respecting their right to make decisions about disclosure. J. Magn. Reson. Imaging 2013;38:1009–1013. © 2013 Wiley Periodicals, Inc.     

Cancer Risk Associated with Residential Proximity to Industrial Sites: A Review

In this study, the authors sought to review available epidemiologic studies of cancer risk and its association with residence in a neighborhood characterized by industrial sites and to discuss options for future study design. The authors attempted to identify all case-control studies published from January 1980 through July 1997 in which investigators examined exposure resulting from residential proximity to an industrial site neighborhood relative to an increased risk of lung, urinary tract, and lymphohematopoietic malignancies. During these years, some authors reported significant associations between lung cancer risk and residential proximity to (a) smelters, (b) complex industrial areas, and (c) other localized emission sources. There was some evidence that leukemia and lymphomas occurred in the neighborhoods that contained industrial sites.