Encephalitis lethargica. What is still wrong?

Encephalitis lethargica developed in epidemic from 1919 to 1926 in Europe and throughout the world. From the clinical point of view, the disturbances of consciousness and alertness and the possible outcomes of a postencephalitic Parkinsonism has attracted much attention. For a long time, it was thought that such a disease may still occur sporadically. In this review, the authors examined historical and current pictures of epidemics that may be related to Encephalitis lethargica. The previous Nona and Russian Influenza exhibited frequent neurological symptoms. The Spanish flu, formerly related to Encephalitis lethargica, would appear an epidemic that had its development in a partially overlapping period. The current pandemic linked to COVID-19 sometimes has aspects that can resemble Encephalitis lethargica. Based on historical analysis and the more recent immunological data, it could be suggested that Encephalitis lethargica was an autoimmune encephalitis that arose in a secondary form to the action of a viral agent. It cannot be ruled out that this agent was a coronavirus. From the nosological point of view, the term Encephalitis lethargica should be abolished in designating autoimmune encephalitis pictures that run sporadically.

Author Correction: Titanium-carbide MXenes for work function and interface engineering in perovskite solar cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Titanium-carbide MXenes for work function and interface engineering in perovskite solar cells.

To improve the efficiency of perovskite solar cells, careful device design and tailored interface engineering are needed to enhance optoelectronic properties and the charge extraction process at the selective electrodes. Here, we use two-dimensional transition metal carbides (MXene Ti3C2Tx) with various termination groups (Tx) to tune the work function (WF) of the perovskite absorber and the TiO2 electron transport layer (ETL), and to engineer the perovskite/ETL interface. Ultraviolet photoemission spectroscopy measurements and density functional theory calculations show that the addition of Ti3C2Tx to halide perovskite and TiO2 layers permits the tuning of the materials' WFs without affecting other electronic properties. Moreover, the dipole induced by the Ti3C2Tx at the perovskite/ETL interface can be used to change the band alignment between these layers. The combined action of WF tuning and interface engineering can lead to substantial performance improvements in MXene-modified perovskite solar cells, as shown by the 26% increase of power conversion efficiency and hysteresis reduction with respect to reference cells without MXene.

MiR-29b antagonizes the pro-inflammatory tumor-promoting activity of multiple myeloma-educated dendritic cells.

Dendritic cells (DCs) have a key role in regulating tumor immunity, tumor cell growth and drug resistance. We hypothesized that multiple myeloma (MM) cells might recruit and reprogram DCs to a tumor-permissive phenotype by changes within their microRNA (miRNA) network. By analyzing six different miRNA-profiling data sets, miR-29b was identified as the only miRNA upregulated in normal mature DCs and significantly downregulated in tumor-associated DCs. This finding was validated in primary DCs co-cultured in vitro with MM cell lines and in primary bone marrow DCs from MM patients. In DCs co-cultured with MM cells, enforced expression of miR-29b counteracted pro-inflammatory pathways, including signal transducer and activator of transcription 3 and nuclear factor-κB, and cytokine/chemokine signaling networks, which correlated with patients' adverse prognosis and development of bone disease. Moreover, miR-29b downregulated interleukin-23 in vitro and in the SCID-synth-hu in vivo model, and antagonized a Th17 inflammatory response. All together, these effects translated into strong anti-proliferative activity and reduction of genomic instability of MM cells. Our study demonstrates that MM reprograms the DCs functional phenotype by downregulating miR-29b whose reconstitution impairs DCs ability to sustain MM cell growth and survival. These results underscore miR-29b as an innovative and attractive candidate for miRNA-based immune therapy of MM.

Innate immunity in cutaneous melanoma.

The skin immune system is composed of a vast network of immune cells, including lymphocytes, macrophages, neutrophils, dendritic cells and Langerhans cells, which not only are involved in inflammatory responses but also contribute to homeostatic function and may participate in the various steps of carcinogenesis. Many studies support the notion that innate immunity has a key role in the development, growth and prognosis of cutaneous malignant melanoma (MM), through the release of pro- and/or anti-inflammatory cytokines and tumour growth factors. The tumour environment in a major subset of cutaneous MM shows evidence of a T cell-infiltrated phenotype, but there is less known about the presence and the phenotype of other immune system cells. Response to immunotherapy is largely correlated with the presence of T cells in the tumour microenvironment, while the regulation exerted by stromal components such as macrophages and mast cells has been less investigated. In the current report, we review the recent literature, focusing our attention on the role of macrophages, dendritic cells, mast cells and natural killer cells in orchestrating MM progression, to better understand tumour immunobiology. The identification of new therapeutic targets and the application of approaches aimed at modulating crosstalk between immune and tumour cells, could have a crucial impact on immunotherapy and result in better clinical outcome. We hope this review will be helpful in cutaneous MM research.

Non-invasive real-time biopsy of intracranial lesions using short time expanded circulating tumor cells on glass slide: report of two cases.

BACKGROUND: Circulating Tumor Cells (CTCs) are promising biomarkers for monitoring solid cancer and were used to monitor brain tumors. Here we report two cases in which, for the first time, CTCs were used in cytological diagnostic evaluation to discriminate a space-occupying lesion of the brain. CASE PRESENTATION: Two cases of focal intracranial lesions, unclassified for diagnosis, untreated and apparently symptomatic, were examined after high-contrast resolution Magnetic Resonance Imaging and/or Computed Tomography scans. CTCs were seeded on chamber slides and short-time expanded under the optimized conditions as we previously reported. The first case was a focal lesion localized in the parietal-occipital area in a 67-year-old woman. The second case was a 31-year-old man with an expansive intracerebral lesion localized in the left peri-trigonal area. Both patients underwent excisional biopsy. Histopathological evaluation of the biopsy confirmed the previous cytological diagnoses, and the analysis of the clinical outcomes retrospectively validated both diagnoses. CONCLUSIONS: The cases here reported illustrate the potential for using expanded CTCs as non-invasive, real-time biopsy. Moreover, non-invasive real-time biopsy can represent an alternative diagnostic tool to be used when a functional area of the brain is at risk of injury from excisional biopsy procedures.

Elastofibroma dorsi: a histochemical and immunohistochemical study.

Elastofibroma dorsi (ED) is considered a member of a heterogeneous group of benign fibrous (fibroblastic or myofibroblastic) soft-tissue tumors, frequently localized in the periscapular region in middle aged or older individuals. However, the pathogenesis of ED is still unclear and many authors believe that ED results from a reactive hyperproliferation of fibroblastic tissue, while others suggest that it may be a consequence of a mechanical friction. In our study, we examined 11 cases of ED using histochemical and immunohistochemical methods, in order to extend the knowledge about extracellular matrix composition and histopathogenesis of ED. From the results it appeared that stroma and interspersed spindle cells of ED were positive for both periostin and tenascin-C. Mast cells tryptase-positive were also abundant throughout the lesion. The perivascular distribution of periostin and tenascin-C, associated with the CD34 positivity, suggest that endothelial-mesenchymal transition events can account for neovascularization and production of fibroelastic tissue characteristic of elastofibroma. Our data obtained in endothelial cells cultures demonstrated that elastin production is higher when the status of confluence of the cells is low. So, we can assume that such a phenomenon is a characteristic of mesenchymal/endothelial cells CD34 positive, in which elastin production results to be inversely proportional to the vascular differentiation of cellular elements. In the light of these considerations, we think that a cancerous nature of ED is unlikely. Overall, our study report, for the first time, a detailed description of extracellular matrix composition in ED, suggesting that a mechanical strain-dependent reactivation of periostin and tenascin-C expression, as well as of elastin deposition, could be responsible for development of ED.

Functional properties of the three hemoglobin phenotypes of Nelore cattle

Blood and stripped hemoglobin from Nelore cattle individuals were submitted to oxygen equilibrium experiments in both gasometric and spectrophotometric methods. No difference was detected in oxygen affinity and Bohr effect among Hb A, Hb B and Hb AB in experiments with both blood and stripped hemoglobin, in the presence and absence of the chloride ion. However, n values (Hill plots) were higher in Hb B and Hb AB (>2) than in Hb A (<2)

[Boerhaave syndrome. A case report and review of the literature]. / La sindrome di Boerhaave. Descrizione di un caso e revisione della Letteratura.

Spontaneous esophageal perforation (Boerhaave's syndrome) remains a difficult diagnostic and management problem with controversial recommendations regarding its treatment. The clinical manifestations of the disease are variable, and may be misleading, thus delaying accurate recognition. On the other hand, in view of the rapid onset of severe complications, particularly mediastinitis, a prompt diagnosis is essential to a better prognosis, successful operative outcome and potential survival. A case of spontaneous perforation of the thoracic esophagus penetrating the left pleural space treated within 4 hours from admission to the Emergency Room, with minimal surgical intervention is presented. Despite negative chest X-ray, a thoracic TC showed a small right sided effusion with left sided hydropneumothorax, and the definitive diagnosis was obtained by contrast study with a water soluble medium which showed the leak communicating freely with the left pleural space. The patient underwent repair by thoracic approach, the rupture was closed with a primary suture without flap reinforcement and the pleural space drained with the placement of single chest thoracostomy tube. The recovery was uneventful. The analysis of this case report and of the appropriate literature reveals that a poor prognosis is correlated with the time elapsed between the perforation and treatment. In conclusion the importance of an early aggressive surgical treatment for the Boerhaave's syndrome is emphasized, because any perforation treated more than 24 hours after the onset of symptoms, irrespective of the procedure used, is associated with a significantly higher morbility and mortality.

Diagnosis of adrenal adenoma: value of central spot of high-intensity hyperintense rim sign and homogeneous isointensity to liver on gadolinium-enhanced fat-suppressed spin-echo MR images.

Eighty-nine patients with 108 adrenal masses, either adenomas (n = 88) or malignant lesions (n = 20), underwent magnetic resonance imaging (MRI) of the abdomen at 0.5 T for the purpose of determining whether adrenal adenomas could be differentiated from malignant lesions on gadolinium-enhanced fat-suppressed T1-weighted spin-echo (SE) images (Gd-E FS T1WI) and on T2-weighted SE images. The imaging protocol included conventional unenhanced SE T1- and T2-weighted sequences and Gd-E FS T1WI. Three observers independently evaluated signal intensity on unenhanced and enhanced images and also the presence of structures of high signal intensity in the outer margin [hyperintense rim sign (HRS)] or in the center [hyperintense central spot (HCS)] of the adrenal masses. Forty-one (46.5%) of 88 adenomas were homogeneously isointense to liver in unenhanced and enhanced T1-weighted sequences and in T2WI. HCS and HRS were observed in 33/88 (37.5%) and 15/88 (17%) adenomas, respectively, on Gd-E FS T1WI; in contrast, these signs were never revealed in any case of malignant lesions. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy in classifying lesions as suggestive of adenoma were 93%, 90%, 98%, 75%, and 93%, respectively. Visual evaluation of details of tumor structures on Gd-E FS T1WI allows good characterization of adrenal masses. HCS, HRS, and homogeneous isointensity to liver are characteristic signs of adrenal adenomas.

[A rare case of a perforated diverticulum of the cecum]. / Un raro caso di diverticolo perforato del cieco.

A rare case of peritonitis by cecal perforated diverticulum which was diagnosed after surgery by histology is reported. Preoperative diagnosis is often ignored and, in rare cases, is not always clear at laparotomy. Clinical aspects, diagnostic procedures, histological picture and surgical treatment are described. In the literature diverticula are classified as "solitary" and "multiple", "congenital" and "acquired", "true" and "false" and finally "usual type" and "hidden variant". The treatment of cecal acute diverticulitis is, in the majority of patients, surgery. Simple resection of the diverticulum and suture of the breach in double layer is the elective operation of non-complicated diverticulum or with an inflamed projection from the cecal wall ("usual type"). Segmental resection of colon or "right hemicolectomy" is recommended when a precise diagnosis is not possible and in complicated diverticula ("hidden variant"). On the basis of personal experience it is underlined that diagnosis is rarely made preoperatively since the clinical picture suggests an acute appendicitis. If there are some doubts for appendicitis, a incidental tumor or possible perforated diverticulum of the cecum should be considered and urgent surgery is mandatory.

Incidentally discovered adrenal masses: evaluation with gadolinium enhancement and fat-suppressed MR imaging at 0.5 T.

The purpose of the study is to evaluate the ability of Gd-enhancement and fat-suppressed MR imaging operating at midfield strength to characterize incidentally discovered adrenal masses. Sixty patients with 72 adrenal masses incidentally discovered during US or CT exams were studied with a 0.51 MR unit following clinical and laboratory evaluation. After Gd-DTPA intravenous administration a modified three-point Dixon technique was performed in all patients. This technique provided three images sets: conventional T1-weighted SE images, fat-suppressed T1-weighted images and water-suppressed T1-weighted images. Diagnosis was established by means of surgery (11 lesions), fine-needle biopsy (21 lesions) and stability on ultrasonographic follow-up for at least 1 year (range, 12-87 months) from adrenal lesion discovery (40 masses). In most of adenomas (n = 55) an homogeneous enhancement was observed on postcontrast T1WI; however, 15 out of these lesions showed a small focal spot of high intensity in Gd-enhanced fat-suppressed images. On the contrary, malignant conditions (n = 6) and pheochromocytoma (n = 1), all had inhomogeneous signal intensities which were relatively higher after Gadolinium injection as compared with the liver. The fat suppression technique demonstrated areas of bright signal intensity related to high vascularity. The performance of three observers in order to differentiate malignant from benign conditions showed sensitivity, specificity, diagnostic accuracy, positive and negative predictive values of 100, 88.5, 90, 50 and 100% on the basis of gadolinium enhancement only, by utilizing the Dixon technique. In conclusion, although Gd-enhancement and fat-suppressed sequence helped correctly differentiate among the groups of incidentally discovered adrenal masses, the degree of overlap suggests that it is still difficult to characterize individual patients. However, the modified three-point Dixon technique after contrast material administration appears to be a further capability of midfield MRI in the characterization of adrenal tissue.

[Adrenal myelolipomas: their magnetic resonance assessment]. / Mielolipomi del surrene: valutazione con risonanza magnetica.

Adrenal myelolipomas are rare nonfunctioning neoplasias consisting of a variable mixture of mature fat and bone marrow tissue. In the present study MRI appearances of six adrenal myelolipomas are presented. MR exams of six patients in which a conclusive diagnosis of adrenal myelolipomas was reached by means of surgery (1 case), US-guided fine-needle biopsy (3 cases) and typical diagnostic imaging in association with stability on US follow-up for at least two years (2 cases) were retrospectively evaluated. MR sequences protocol included pre- and post-contrast (Gd-DTPA) SE T1-weighted images and SE proton density and T2-weighted images. Five adrenal masses were examined by means of combination of gadolinium administration with a SE T1-weighted modified three-point Dixon technique. Three different MR structural patterns were pointed out: a) homogeneous hyperintense masses on T1-weighted images with intermediate signal on T2-weighted images, suggestive for predominantly fat-containing lesions (2 cases); b) heterogeneous masses with fat intensity areas and hyperintense areas on T2-weighted images and on post-contrast T1-weighted images, suitable for mixed fatty and myeloid elements (2 cases); c) nodules hypointense to the liver on T1-weighted images and hyperintense on T2-weighted images and after gadolinium administration, suggesting tumors primarily composed of myeloid cells (2 cases). A precise determination of fatty and myeloid elements within the lesions was observed by means of "water" and "fat" images provided by modified three-point Dixon technique. In conclusion, MRI allows to determine the various structural components of myelolipomas and therefore appears to be a very reliable technique in the diagnosis and characterization of the different structural patterns of this rare adrenal pathology.

Comparison between ethanol sclerotherapy and emptying with injection of saline in treatment of thyroid cysts.

We compared the results of ethanol sclerotherapy in thyroid cysts with emptying of cysts and instillation of saline. Twenty-six patients with recurrent thyroid cysts were treated with cyst aspiration and subsequent ethanol sclerotherapy. A control group of 44 patients was submitted to cyst aspiration and subsequent injection with isotonic saline; among them 20 had previously been treated with repeated aspirations of the cyst fluid. The patients were followed up clinically and ultrasonically 1 and 12 months after treatment. Cure was defined as the absence of any residual cystic lesion or an ultrasonic cyst volume less than 50% of basal after 12 months from the start of treatment. Cytological study showed all of the lesions to be benign. Of the 44 patients in the saline group 16 (36%) were cured, among whom 6 of 20 had previously been submitted to repeated aspirations. Among the 26 patients treated with ethanol sclerotherapy 20 (77%) were cured. Statistical analysis revealed a significantly higher effectiveness of treatment with ethanol than that with emptying and saline instillation (chi-square, P = 0.002) or with repeated aspiration and saline instillation (chi-square, P = 0.003). Slight pain was observed in two patients treated with saline and five treated with ethanol sclerotherapy. Three patients treated with ethanol sclerotherapy presented severe pain and one transitory hyperthyroidism. We conclude that ethanol sclerotherapy is effective and safe in the treatment of thyroid cysts.

[Review of a case series of cervical cysts and evaluation of the efficacy of sclerotherapy with tetracycline hydrochloride in thyroid cystic lesions]. / Revisione di una casistica di cisti della regione cervicale e valutazione dell'efficacia del trattamento sclerosante con tetraciclina cloridrato nelle lesioni cistiche tiroidee.

We have reexamined a series of 1119 patients consecutively submitted to fine needle aspiration of nodules of the neck. Among these in 166 cases ultrasonography combined with aspiration suggested the presence of cysts. 60 patients were submitted to cyst aspiration and 34 were aspirated and submitted to cyst injection with tetracycline hydrochloride. The patients were followed up clinically and ultrasonically 3 and 12 months after treatment. Cure was defined as the absence of any residual cystic lesion and an ultrasonic cyst volume less than 50% with respect to basal after 12 months from the start of treatment. 18 of the 60 (30%) patients only aspirated and 24 of the 34 patients (70%) in the tetracycline group were cured (statistically significant; p < 0.005). We conclude that tetracycline seems an effective sclerotherapy in treatment of thyroid cysts.

[Propanidid and trazodone in ultrashort anesthesia]. / Propanidide e trazodone nell'anestesia ultra-breve.

A brief general survey of the "anaesthesiological problem" is followed by the presentation of a method for use in ultra-short anaesthesia. Particular stress is laid on the importance that must be ascribed to premedication, even in situations of this type. The drug of choice is trazodone. An account is given of the main features of this synthetic molecule, and the details of its administration are described. Reference is also made to a series of 792 minor obstetric and gynaecological operations in which the method was employed. The size and range of this series are regarded as an outstanding aspect of the paper.