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Burkholderia mallei is a gram-negative bacterium that causes glanders disease, which primarily affects equids. B. mallei can infect humans and cause clinical manifestations ranging from subclinical infections to severe conditions [...]

IntroductionMalignant pleural mesothelioma (MPM) is a poor-prognosis disease. Owing to the recent availability of new therapeutic options, there is a need to better assess prognosis. The initial clinical response could represent a useful parameter.MethodsWe proposed a transfer learning approach to predict an initial treatment response starting from baseline CT scans of patients with advanced/unresectable MPM undergoing first-line systemic therapy. The therapeutic response has been assessed according to the mRECIST criteria by CT scan at baseline and after two to three treatment cycles. We used three slices of baseline CT scan as input to the pre-trained convolutional neural network as a radiomic feature extractor. We identified a feature subset through a double feature selection procedure to train a binary SVM classifier to discriminate responders (partial response) from non-responders (stable or disease progression).ResultsThe performance of the prediction classifiers was evaluated with an 80:20 hold-out validation scheme. We have evaluated how the developed model was robust to variations in the slices selected by the radiologist. In our dataset, 25 patients showed an initial partial response, whereas 13 patients showed progressive or stable disease. On the independent test, the proposed model achieved a median AUC and accuracy of 86.67% and 87.50%, respectively.ConclusionsThe proposed model has shown high performance even by varying the reference slices. Novel tools could help to improve the prognostic assessment of patients with MPM and to better identify subgroups of patients with different therapeutic responsiveness.

Background: The treatment of non-small-cell lung cancer (NSCLC) patients with reduced respiratory function represents a challenge for thoracic surgeons. Minimally invasive surgery seems to be beneficial for these patients because it reduces tissue trauma and its impact on respiratory mechanics. Application of the robotic technique, the use of CO2 insufflation and longer surgical time are factors that could influence the outcomes of marginal pulmonary function patients. The objective of this study was to evaluate the impact of the robotic technique on the postoperative outcomes of patients with poor lung function. Methods: We retrospectively collected and analyzed data from consecutive marginal respiratory function patients who underwent robotic or open lobectomy for NSCLC. Data regarding clinical, operative and postoperative details were compared between the open and robotic approaches. Results: The outcomes of 100 patients with reduced respiratory function were evaluated, of whom 59 underwent open lobectomies and 41 underwent robotic lobectomies. Robotic lobectomy was characterized by a longer operative time, a reduced hospital stay and a lower incidence of postoperative complications (22% vs. 33.9%), when compared to the open approach. Conclusion: Robotic lobectomy is a safe and feasible procedure for patients with marginal pulmonary function.

Locally advanced non-small cell lung cancer (NSCLC) consists of a heterogeneous group, with different pulmonary extension and lymph nodal involvement. Robotic surgery can play a key role in these tumours thanks to its technological features, although open surgery is still considered the gold-standard approach. Our study aims to evaluate the surgical and oncological outcomes of locally advanced NSCLC patients who underwent robotic surgery in a high-volume centre. Data from consecutive patients with locally advanced NSCLC who underwent robotic lobectomy were retrospectively analysed and compared with patients treated with open surgery. Clinical characteristics and surgical and oncological information were evaluated. From 2010 to 2020, 131 patients underwent anatomical lung resection for locally advanced NSCLC. A total of 61 patients were treated with robotic surgery (46.6%); the median hospitalization time was 5.9 days (range 2–27) and the postoperative complication rate was 18%. Open surgery was performed in 70 patients (53.4%); the median length of stay was 9 days (range 4–48) and the postoperative complication rate was 22.9%. The median follow-up time was 70 months. The 5-year overall survival was 34% in the robotic group and 31% in the thoracotomy group. Robotic surgery can be considered safe and feasible not only for early stages but also for the treatment of locally advanced NSCLC.

LiNiO2 remains a target for layered oxide Li‐ion cathode development as it can theoretically deliver the highest energy density of this materials class. In practice, LiNiO2 suffers from poor capacity retention due to electrochemically‐induced structural changes. While the impact of Ni off‐stoichiometry on the electrochemical performance has been extensively studied, that of planar defects present in the as‐synthesized cathode is not well understood. Advanced ex situ and operando structure probes are used to identify and quantify point and planar defects present in as‐synthesized Li1‐yNi1+yO2 cathodes and monitor their evolution during the first cycle. Specifically, a 7Li nuclear magnetic resonance (NMR) signature characteristic of Li environments near twin boundaries is identified; an assignment supported by first‐principles calculations and scanning transmission electron microscopy (STEM) images of twin boundary defects. The NMR results suggest that the concentration of twin boundaries depends on the amount of Ni excess. Moreover, operando magnetometry and ex situ synchrotron X‐ray diffraction and NMR demonstrate that these planar defects impede Li reinsertion into the bulk cathode at reasonable discharge rates and contribute to the first cycle irreversible capacity. These findings provide new design rules for Li1‐yNi1+yO2 cathodes, whereby a reduced concentration of twin boundaries in the pristine material leads to reduced kinetic limitations and improved cathode utilization. [ABSTRACT FROM AUTHOR]

We report a case of Burkholderia mallei causing glanders in a 73-year-old patient from the Northeast Region of Brazil. The patient was hospitalized with severe pneumonia. PCR and genomic sequencing confirmed B. mallei in pleural drainage. Genotyping revealed a novel genotype, emphasizing the need for genetic surveillance in zoonotic infections. [ABSTRACT FROM AUTHOR]

Ni‐rich LiNixCoyMnzO2 cathode materials offer high practical capacities and good rate capability, but are notorious for being unstable at high state of charge. Here, a series of such layered oxides with nickel contents ranging from 88 to 100 mol% is fabricated by sodium‐to‐lithium ion exchange, yielding materials devoid of NiLi•${\mathrm{Ni}}_{{\mathrm{Li}}}^ \bullet $ substitutional defects. Examining the initial charge/discharge cycle reveals effects that are specifically caused by transition‐metal substitution, which would otherwise be obscured by changes in lithium‐site defect concentration. Lowering the nickel content helps to stabilize the high‐voltage regime, while simultaneously negatively affecting lithium diffusion. Operando X‐ray diffraction indicates mitigation of volume variation during cycling and transition toward solid‐solution behavior with sufficiently high cobalt and manganese contents, thus providing an explanation for the increased stability. The interplay between transition‐metal substitution, kinetic hindrance, and solid‐solution behavior may be a result of local inhomogeneities due to lithium‐vacancy pinning, which is further elucidated through density functional theory calculations. Overall, this work sheds new light on the effects of manganese and cobalt incorporation into the transition‐metal layer and their conjunction with NiLi•${\mathrm{Ni}}_{{\mathrm{Li}}}^ \bullet $ defects. [ABSTRACT FROM AUTHOR]

Introduction: Malignant pleural mesothelioma (MPM) is a poor-prognosis disease. Owing to the recent availability of new therapeutic options, there is a need to better assess prognosis. The initial clinical response could represent a useful parameter. Methods: We proposed a transfer learning approach to predict an initial treatment response starting from baseline CT scans of patients with advanced/ unresectable MPM undergoing first-line systemic therapy. The therapeutic response has been assessed according to the mRECIST criteria by CT scan at baseline and after two to three treatment cycles. We used three slices of baseline CT scan as input to the pre-trained convolutional neural network as a radiomic feature extractor. We identified a feature subset through a double feature selection procedure to train a binary SVM classifier to discriminate responders (partial response) from non-responders (stable or disease progression). Results: The performance of the prediction classifiers was evaluated with an 80:20 hold-out validation scheme. We have evaluated how the developed model was robust to variations in the slices selected by the radiologist. In our dataset, 25 patients showed an initial partial response, whereas 13 patients showed progressive or stable disease. On the independent test, the proposed model achieved a median AUC and accuracy of 86.67% and 87.50%, respectively. Conclusions: The proposed model has shown high performance even by varying the reference slices. Novel tools could help to improve the prognostic assessment of patients with MPM and to better identify subgroups of patients with different therapeutic responsiveness. [ABSTRACT FROM AUTHOR]

Primary pulmonary leiomyosarcomas (PPLs) are incredibly rare tumors, characterized by an often-aggressive clinical behavior. Diagnosis is frequently incidental. Whenever present, symptoms are nonspecific, thus PPLs are usually misdiagnosed as other more common respiratory diseases or lung cancer subtypes. Surgery is the best treatment choice and in the therapeutic strategy, timeliness and radicality are of major importance. We report the case of a huge left PPL, successfully treated with salvage surgery after a careful multidisciplinary preoperative assessment, which permitted a prompt diagnostic path and surgery.

Open in new tab Download slide OBJECTIVES To assess the current practice of pulmonary metastasectomy at 15 European Centres. Short- and long-term outcomes were analysed. METHODS Retrospective analysis on patients ≥18 years who underwent curative-intent pulmonary metastasectomy (January 2010 to December 2018). Data were collected on a purpose-built database (REDCap). Exclusion criteria were: previous lung/extrapulmonary metastasectomy, pneumonectomy, non-curative intent and evidence of extrapulmonary recurrence at the time of lung surgery. RESULTS A total of 1647 patients [mean age 59.5 (standard deviation; SD = 13.1) years; 56.8% males] were included. The most common primary tumour was colorectal adenocarcinoma. The mean disease-free interval was 3.4 (SD = 3.9) years. Relevant comorbidities were observed in 53.8% patients, with a higher prevalence of metabolic disorders (32.3%). Video-assisted thoracic surgery was the chosen approach in 54.9% cases. Wedge resections were the most common operation (67.1%). Lymph node dissection was carried out in 41.4% cases. The median number of resected lesions was 1 (interquartile range 25–75% = 1–2), ranging from 1 to 57. The mean size of the metastases was 18.2 (SD = 14.1) mm, with a mean negative resection margin of 8.9 (SD = 9.4) mm. A R0 resection of all lung metastases was achieved in 95.7% cases. Thirty-day postoperative morbidity was 14.5%, with the most frequent complication being respiratory failure (5.6%). Thirty-day mortality was 0.4%. Five-year overall survival and recurrence-free survival were 62.0% and 29.6%, respectively. CONCLUSIONS Pulmonary metastasectomy is a low-risk procedure that provides satisfactory oncological outcomes and patient survival. Further research should aim at clarifying the many controversial aspects of its daily clinical practice. [ABSTRACT FROM AUTHOR]

ObjectivesThe host DNA sensor proteins TLR9, STING, IFI16 are central signaling molecules that control the innate immune response to cytosolic nucleic acids. Here we propose to investigate how Natural killer (NK) cell infection by human herpesvirus (HHV)-6A, HHV-6B or HHV-7 is able to modify DNA sensor signaling in NK cells.MethodsWe infected the NK92 cell line and primary NK cells with cell-free inocula of HHV-6A, HHV-6B or HHV-7 and evaluated TLR9, STING, and IFI16 pathway expression by Real-Time PCR, Western Blot, immunofluorescence and flow cytometry for 1, 2, 3, and 6 days post-infection. We evaluated NK cell cytokine-producing by Real-Time PCR and enzyme immunosorbent assay.ResultsNK92 and primary NK cells were promptly infected by three viruses, as demonstrated by virus presence (DNA) and transcription (RNA) analysis. Our data show STING/STAT6 up-modulation in HHV-6A infected NK cells. NK cells infected with HHV-6B and HHV-7 up-regulated CCL3, IFN-alpha, TNF-alpha, IL-8 and IFN-gamma and slightly induced IL-4, and CCL4. HHV-6A infected NK cells up-regulated IL-4 and IL-13 and slightly induced IL-10, TNF-alpha, IFN-alpha, and IFN-gamma.ConclusionFor the first time, we demonstrate that HHV-6A, HHV-6B, and HHV-7 infections have a differential impact on intracellular DNA sensors. HHV-6B and HHV-7 mainly lead to the active control of in vivo viral spreading by pro-inflammatory cytokine secretion via TLR9. HHV-6A infected NK cells conversely induced STING/STAT6 pathway, as a mechanism of anti-viral activation, but they were characterized by a Th2 type response and a non-cytotoxic profile, suggesting a potential novel mechanism of HHV-6A-mediated immunosuppression.

Background: The treatment of non-small-cell lung cancer (NSCLC) patients with reduced respiratory function represents a challenge for thoracic surgeons. Minimally invasive surgery seems to be beneficial for these patients because it reduces tissue trauma and its impact on respiratory mechanics. Application of the robotic technique, the use of CO2 insufflation and longer surgical time are factors that could influence the outcomes of marginal pulmonary function patients. The objective of this study was to evaluate the impact of the robotic technique on the postoperative outcomes of patients with poor lung function. Methods: We retrospectively collected and analyzed data from consecutive marginal respiratory function patients who underwent robotic or open lobectomy for NSCLC. Data regarding clinical, operative and postoperative details were compared between the open and robotic approaches. Results: The outcomes of 100 patients with reduced respiratory function were evaluated, of whom 59 underwent open lobectomies and 41 underwent robotic lobectomies. Robotic lobectomy was characterized by a longer operative time, a reduced hospital stay and a lower incidence of postoperative complications (22% vs. 33.9%), when compared to the open approach. Conclusion: Robotic lobectomy is a safe and feasible procedure for patients with marginal pulmonary function. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is a Gram-negative bacterium that commonly infects subjects with weakened immune system causing deadly infections above all at pulmonary level. During infection, P. aeruginosa produces a well-organized bacterial structure, called biofilm, activating the quorum-sensing (QS) signaling, a mechanism of gene regulation. In this work, we synthesized already known QS inhibitors (QSi) designed on the scaffold of the N-(3-oxododecanoyl) homoserine lactone (3O-C12-HSL) QS molecule and conjugated them with ciprofloxacin to inhibit P. aeruginosa biofilm formation and increase the antibiotic susceptibility of clinical strains. We identified, for the first time, a QSi conjugated with ciprofloxacin (ET37), that is able to reduce the formation of biofilm and the onset of tolerant clones in P. aeruginosa clinical strains. This compound could have a wide application in clinical setting. The possibility to affect biofilm formation in chronically infected patients, such as patients affected by cystic fibrosis, and to reduce the onset of ciprofloxacin resistance would improve patient healing and allow to decrease antibiotic drug dosage.

Background: We have recently reported the presence of Human herpesvirus-6A (HHV-6A) DNA in the 43% of endometrial epithelial cells from primary idiopathic infertile women, with no positivity in fertile women. To investigate the possible effect of HHV-6A infection in endometrial (e)NK cells functions, we examined activating/inhibitory receptors expressed by eNK cells and the corresponding ligands on endometrial cells during HHV-6A infection.Methods: Endometrial biopsies and uterine flushing samples during the secretory phase were obtained from 20 idiopathic infertile women and twenty fertile women. HHV-6A infection of endometrial epithelial cells was analyzed by Real-Time PCR, immunofluorescence and flow cytometry. eNKs receptors and endometrial ligands expression were evaluated by immunofluorescence and flow cytometry.Results: We observed the presence of HHV-6A infection (DNA, protein) of endometrial epithelial cells in the 40% of idiopathic infertile women. The eNK from all the subgroups expressed high levels of NKG2D and NKG2A receptors. Functional studies showed that NKG2D activating receptor and FasL are involved in the acquired cytotoxic function of eNK cells during HHV-6A infection of endometrial epithelial cells. In the presence of HHV-6A infection, eNK cells increased expression of CCR2, CXCR3 and CX3CR1 chemokine receptors (p = 0.01) and endometrial epithelial cells up-modulated the corresponding ligands: MCP1 (Monocyte chemotactic protein 1, CCL2), IP-10 (Interferon gamma-induced protein 10, CXCL10) and Eotaxin-3 (CCL26).Conclusion: Our results, for the first time, showed the implication of eNK cells in controlling HHV-6A endometrial infection and clarify the mechanisms that might be implicated in female idiopathic infertility.

Francesco Margari,1 Michele Sicolo,1 Lucia Spinelli,1 Franco Mastroianni,2 Adriana Pastore,1 Francesco Craig,3 Maria Giuseppina Petruzzelli31Psychiatry Unit, Department of Neuroscience and Sense Organs, Hospital Polyclinic of Bari, University of Bari “Aldo Moro”, 2Geriatrics Unit, Hospital “Miulli”, Acquaviva delle Fonti; 3Child Neuropsychiatry Unit, Department of Neuroscience and Sense Organs, University of Bari “Aldo Moro,” Bari, ItalyAbstract: Patients with dementia often have neuropsychiatric symptoms. The objective of this study was to evaluate the relationship between neuropsychiatric symptoms and progressive cognitive decline by assessing cognitive impairment, depressive symptoms, and aggressive behavior in a sample of elderly subjects. The study sample consisted of 201 subjects admitted to nursing homes. For the purpose of the present study each subject was evaluated using the Mini-Mental State Examination, the Geriatric Depression Scale, and the Modified Overt Aggression Scale. The results show that aggressive behavior and depressive symptoms are associated with progressive cognitive decline in elderly subjects. Early assessment of these conditions can promote rational therapeutic strategies that may improve the quality of life and delay institutionalization for elderly patients.Keywords: neuropsychiatric symptoms, dementia, behavioral and psychological syndromes of dementia (BPSD), progressive cognitive decline