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Background and study aims Artificial Intelligence (AI) systems could make the optical diagnosis (OD) of diminutive colorectal polyps (DCPs) more reliable and objective. This study was aimed at prospectively evaluating feasibility and diagnostic performance of AI-standalone and AI-assisted OD of DCPs in a real-life setting by using a white light-based system (GI Genius, Medtronic Co, Minneapolis, Minnesota, United States). Patients and methods Consecutive colonoscopy outpatients with at least one DCP were evaluated by 11 endoscopists (5 experts and 6 non-experts in OD). DCPs were classified in real time by AI (AI-standalone OD) and by the endoscopist with the assistance of AI (AI-assisted OD), with histopathology as the reference standard. Results Of the 480 DCPs, AI provided the outcome "adenoma" or "non-adenoma" in 81.4% (95% confidence interval [CI]: 77.5-84.6). Sensitivity, specificity, positive and negative predictive value, and accuracy of AI-standalone OD were 97.0% (95% CI 94.0-98.6), 38.1% (95% CI 28.9-48.1), 80.1% (95% CI 75.2-84.2), 83.3% (95% CI 69.2-92.0), and 80.5% (95% CI 68.7-82.8%), respectively. Compared with AI-standalone, the specificity of AI-assisted OD was significantly higher (58.9%, 95% CI 49.7-67.5) and a trend toward an increase was observed for other diagnostic performance measures. Overall accuracy and negative predictive value of AI-assisted OD for experts and non-experts were 85.8% (95% CI 80.0-90.4) vs. 80.1% (95% CI 73.6-85.6) and 89.1% (95% CI 75.6-95.9) vs. 80.0% (95% CI 63.9-90.4), respectively. Conclusions Standalone AI is able to provide an OD of adenoma/non-adenoma in more than 80% of DCPs, with a high sensitivity but low specificity. The human-machine interaction improved diagnostic performance, especially when experts were involved., Competing Interests: Conflict of Interest Paggi S and Amato A: speaker honoraria from Fujifilm Co. Rondonotti E: speaker honoraria from Fujifilm Co., Medtronic Co. consultancy. Radaelli F: Speaker honoraria from Fujifilm Co; research grant from Fujifilm Co; endoscopy equipment loan from Medtronic Co. Hassan C: Medtronic Co, Fujifilm Co and Odin Co. consultancy. All the other authors declare no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Optical diagnosis of colonic polyps is poorly reproducible outside of high volume referral centers. The present study aimed to assess whether real-time artificial intelligence (AI)-assisted optical diagnosis is accurate enough to implement the leave-in-situ strategy for diminutive (≤ 5 mm) rectosigmoid polyps (DRSPs)., Methods: Consecutive colonoscopy outpatients with ≥ 1 DRSP were included. DRSPs were categorized as adenomas or nonadenomas by the endoscopists, who had differing expertise in optical diagnosis, with the assistance of a real-time AI system (CAD-EYE). The primary end point was ≥ 90 % negative predictive value (NPV) for adenomatous histology in high confidence AI-assisted optical diagnosis of DRSPs (Preservation and Incorporation of Valuable endoscopic Innovations [PIVI-1] threshold), with histopathology as the reference standard. The agreement between optical- and histology-based post-polypectomy surveillance intervals (≥ 90 %; PIVI-2 threshold) was also calculated according to European Society of Gastrointestinal Endoscopy (ESGE) and United States Multi-Society Task Force (USMSTF) guidelines., Results: Overall 596 DRSPs were retrieved for histology in 389 patients; an AI-assisted high confidence optical diagnosis was made in 92.3 %. The NPV of AI-assisted optical diagnosis for DRSPs (PIVI-1) was 91.0 % (95 %CI 87.1 %-93.9 %). The PIVI-2 threshold was met with 97.4 % (95 %CI 95.7 %-98.9 %) and 92.6 % (95 %CI 90.0 %-95.2 %) of patients according to ESGE and USMSTF, respectively. AI-assisted optical diagnosis accuracy was significantly lower for nonexperts (82.3 %, 95 %CI 76.4 %-87.3 %) than for experts (91.9 %, 95 %CI 88.5 %-94.5 %); however, nonexperts quickly approached the performance levels of experts over time., Conclusion: AI-assisted optical diagnosis matches the required PIVI thresholds. This does not however offset the need for endoscopists' high level confidence and expertise. The AI system seems to be useful, especially for nonexperts., Competing Interests: E. Rondonotti has received speakerʼs honoraria from Fujifilm Co., is a member of the Fujifilm Co. expert group, and has provided consultancy to Medtronic Co. C. Hassan has equipment on loan from Fujifilm Co. S. Paggi, A. Amato, and R. Maselli have received speakerʼs honoraria from Fujifilm Co. A. Repici has provided consultancy and has received research grants, not related to the present study, from Fujifilm Co., Medtronic, and Boston Scientific Co. and has provided consultancy to Cosmo Pharmaceuticals S.p.A. and Erbe Elektromedizin GmbH. F. Radaelli has received speakerʼs honoraria and a research grant, not related to the present study, from Fujifilm Co. The remaining authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Glucocorticoid treatment is the standard initial therapy for patients with immune thrombocytopenia (ITP). Despite a rate of 60-80% of initial remissions, only 30 to 50% of adults have a sustained response after discontinuation. Second line options are splenectomy, thrombopoietin-receptor agonists (TPO-RAs), rituximab and intravenous immunoglobulin. Third line treatments include a mix of immunosuppressive drugs (e.g. azathioprine, ciclosporin, etc.). Recently international guidelines have proposed a treatment algorithm formalizing TPO-RAs and splenectomy as second and third line respectively, confirming splenectomy as second line choice only in emergency. Here we present a single center observational retrospective study of eltrombopag as second line treatment. We evaluated 48 adult primary chronic ITP patients since 2003. Forty-four out of 48 patients received a first line treatment with glucocorticoids. Twenty-two (61%) patients needed a second line treatment: 18 received eltrombopag, 3 a second course of steroid and one patient underwent splenectomy. Every patient before starting eltrombopag or receiving splenectomy underwent bone marrow examination. Overall response rate to eltrombopag was 94% with a CR rate of 76% and a PR of 23%; only one patient was non responder, underwent splenectomy and received subsequent treatment with rituximab, romiplostim and cyclosporin obtaining CR. One patient developed an autoimmune pancytopenia about a month after starting TPO-RA and in addition to eltrombopag received steroid and rituximab with blood count improvement. After a median follow up of 21,1 months (range 0,4-64,7 months) 16 patients (89%) are still on therapy maintaining response. As regards safety, gastrointestinal side effects were rare and low grade; only one patient discontinued eltrombopag after few weeks, because of dizziness. One patient had a relapse of deep venous thrombosis while no major bleeding complications were observed. Our real-life single center experience confirms efficacy and safety of eltrombopag as second line treatment in chronic ITP patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Medication of acute episodes of mood disorders has changed over the last decades following the results of randomized clinical trials., Objective: The aim of this study was to analyze medication prescribed at discharge from two psychiatric wards. We focused on hospitalization as one of the best opportunities to start prophylaxis., Methods: We examined retrospectively the clinical records of 357 patients hospitalized for mood episodes in two psychiatric wards in the Cagliari area (SPDC-1 and SPDC-2) between 1 January and 31 December 2016. We focused on the psychotropic medication prescribed at discharge from the hospital., Results: Most patients were discharged with antipsychotics (86%) and/or benzodiazepines (89%). Combined medication was frequent, including various co-administration of first-generation and/or second-generation antipsychotics (26% of patients), or antipsychotics combined with mood-stabilizers (51% of patients). There was a preferential prescription of first-generation antipsychotics in SPDC-1, and of second-generation antipsychotics in SPDC-2. Prescription of lithium was significantly more frequent in SPDC-1., Conclusion: Although the treatment was in line with randomized clinical trials, the choice of individual psychotropic agents differed significantly between the two wards. Different prescription attitudes can have consequences on the long-term outcome of patients discharged from the hospital after an acute mood episode.

Background: Cancer had never been considered as a relevant problem in patients treated with lithium until 2015, when a document published by the European Medicine Agency concluded that long-term use of lithium might induce renal tumors. A few months later, we observed the case of a woman treated with lithium for 18 years who was diagnosed with both thyroid and renal tumors., Methods: This study aimed to investigate the correlation between lithium treatment and thyroid or renal tumors. We analyzed clinical records in our lithium clinic database, causes of death of patients who had been visited at least once at the lithium clinic, reports of lithium adverse reactions in the European and WHO pharmacovigilance databases, and published cases of thyroid and renal tumors in long-term lithium-treated patients., Results: Of the 1871 lithium patients who had been visited at least once between 1980 and 2013, eight had been diagnosed with thyroid papillary carcinoma and two with clear-cell renal-cell carcinoma. No cases of thyroid cancer and only one case of renal tumor were the cause of death according to the 375 available death certificates. VigiAccess database contained a total of 29 and 14 cases of renal and thyroid tumors, respectively. EudraVigilance database contained 21 cases of renal and 8 of thyroid neoplasms. Literature search yielded 6 published cases of thyroid papillary carcinoma and 25 cases of various renal tumors. However, two population-based studies did not find any increased risks of cancer in patients exposed to lithium, whereas two nationwide studies did not find any excess of renal tumors., Conclusion: So far it has not been possible epidemiologically to confirm an increased risk of thyroid or renal cancers associated with lithium. Such a conclusion is supported by the findings of low rates and mortalities of thyroid or renal cancers from the present lithium clinic data.

Background: Concerns about the adverse effects of long-term treatment with lithium include reduced renal function. In the present study, we examined comorbidities which may be associated with chronic kidney disease in a cohort of patients treated with lithium for up to 41 years., Methods: We studied 394 patients who were treated with lithium for ≥ 5 years. The potential role of comorbidities (diabetes, concurrent antihypertensive medication, treatment with L-thyroxine, and presence of antithyroid peroxidase/microsomes, anti-thyroglobulin, and/or anti-thyrotropin-receptor antibodies) was analysed. We focused on the categories of patients with an estimated glomerular filtration rate (eGFR) lower than 60 or 45 mL/min/1.73 m 2 as calculated from serum creatinine according to the Modification of Diet in Renal Disease Study Group. We applied multivariate regression analysis and Cox survival analysis to study the effects exerted by sex, age, duration of lithium treatment, and comorbidities using eGFR categories as the dependent variable. Kaplan-Meier curves were generated to measure the time to decline to an eGFR lower than 45 mL/min/1.73 m 2 in patients with positive or negative thyroid antibodies., Results: Age was associated with a decline to an eGFR lower than 60 mL/min/1.73 m 2 after controlling for sex, duration of lithium treatment, and comorbidities. Circulating thyroid antibodies were associated with a decline to an eGFR lower than 45 mL/min/1.73 m 2 ., Conclusions: The present study is the first to suggest a potential role of circulating thyroid antibodies in the severe decline of eGFR in lithium-treated patients.

As shown by genomic studies, colorectal cancer (CRC) is a highly heterogeneous disease, where copy number alterations (CNAs) may greatly vary among different patients. To explore whether CNAs may be present also in histologically normal tissues from patients affected by CRC, we performed CGH + SNP Microarray on 15 paired tumoral and normal samples. Here, we report for the first time the occurrence of CNAs as a common feature of the histologically normal tissue from CRC patients, particularly CNAs affecting different oncogenes and tumor-suppressor genes, including some not previously reported in CRC and others known as being involved in tumor progression. Moreover, from the comparison of normal vs paired tumoral tissue, we were able to identify three groups: samples with an increased number of CNAs in tumoral vs normal tissue, samples with a similar number of CNAs in both tissues, and samples with a decrease of CNAs in tumoral vs normal tissue, which may be likely due to a selection of the cell population within the tumor. In conclusion, our approach allowed us to uncover for the first time an unexpected frequency of genetic alteration in normal tissue, suggesting that tumorigenic genetic lesions are already present in histologically normal colonic tissue and that the use in array comparative genomic hybridization (CGH) studies of normal samples as reference for the paired tumors can lead to misrepresented genomic data, which may be incomplete or limited, especially if used for the research of target molecules for personalized therapy and for the possible correlation with clinical outcome., Competing Interests: Compliance with ethical standards Conflicts of interest None

A 63-year-old woman was admitted because of sudden ischemic hemyplegia promptly cleared up by intravenous (IV) recombinant tissue plasminogen activator. On subsequent 2-dimensional echocardiogram, we observed an extremely mobile homogeneous mass attached by a short stalk to ventricular insertion of anterolateral papillary muscle chordae tendineae. The mass was surgically removed. Gross anatomy showed a mass with a gelatinoids appearance formed on histology by a lining of hyperplastic endocardial cells covering a hypocellular stroma consistent with papillary fibroelastoma. Given the prompt clinical improvement with IV thrombolytic therapy, we postulate that cerebral artery occlusion was at least in part because of thrombotic material., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

The Authors report a rare case of bladder diverticulum with radiological findings compatible with infiltrating bladder cancer and left ureterohydronephrosis. The definitive diagnosis was possible only after surgical intervention with mass removal and histological examination that resulted compatible with bladder diverticulum producing an inflammatory pseudotumor of the wall.

Fundic gland polyps (FGPs) are tiny multiple sessile polyps of the acid-secreting gastric mucosa. They have been described both in a sporadic form, mainly in middle-aged females, and in a syndromic form, associated with familial adenomatous polyposis (FAP)-Gardner's syndrome and attenuated variants (AFAP). They share the same histology, characterised by superficial and deep cystic dilatations, shortened gastric pits, with an inconspicuous lamina propria. They have been for a long time described as innocuous lesions, but some recent reports have shown that FGPs may harbour dysplastic foci and ultimately (particularly syndromic polyps) gastric cancer. Factors influencing their genesis are unknown. A circulating factor in FAP patients has been postulated and a role of female hormones has been suggested for sporadic FGPs. Whereas patients with sporadic FGPs have normal basal acid output, normal fast serum levels of gastrin and pepsinogen I, the role of gastrin seems crucial for the development of cystic changes in flat body-fundus mucosa, and for the appearance of FGPs in patients with Zollinger-Ellison syndrome. A role of H. pylori induced gastritis has been excluded. Actually, patients with both sporadic and syndromic FGPs appear consistently free from H. pylori colonisation, again for an unknown factor(s). Some recent reports have claimed a role for omeprazole in the genesis of FGPs, a highly controversial issue. Ultimately, the nature of FGPs is still debated: some have interpreted them as hamartomatous lesions, others as a peculiar form of hyperplastic polyp.

A case of clear cell renal carcinoma metastatic to the thyroid 5 years after surgical removal of the primary tumor is presented. The differential diagnosis related to cyto-histologic findings, the uncommon occurrence and the unpredictable behaviour of clear cell renal carcinoma are discussed.

The authors describe a case of undifferentiated rhabdomyosarcoma from unknown primary site, presenting as an acute hematologic malignancy with generalized lymphadenopathy, extensive bone marrow involvement and clinical and laboratory features of disseminated intravascular coagulation. Such a peculiar behaviour is known for rhabdomyosarcoma but is rare and can be a serious diagnostic problem for the clinician and the pathologist. The importance of a large spectrum immunohistochemistry as first diagnostic approach to any undifferentiated small-cell malignant tumor is stressed, together with the knowledge of the different immunoreactivity patterns. Desmin, MS-actin and myoglobin are the most reliable markers of this type of myogenic sarcoma.

The angiomyolipoma is a rare tumor of the kidney with benign clinical evolution which can be found in more than half of the female patients with tuberous sclerosis. An uncommon case of renal angiomyolipoma with extracapsular extension, inter-aortocaval lymph node involvement and pulmonary lymphangiomyomatosis with a clinical history of spontaneous recurrent pneumothorax but without the neurological signs of the tuberous sclerosis, is described. The natural history of this disease which has various clinical forms of presentations is still unclear. The role of the lymph-node dissection in the surgical treatment of this tumor is discussed.

The Authors describe a case of intranodal myofibroblastoma presenting in the submandibular region as a firm, indolent and freely mobile rounded nodule of about 3 cm. in diameter. The nature of this uncommon benign lesion is discussed. The observed histological features are partly different from the cases originally described. A proliferation of moderately pleomorphic spindle cells, which are vimentin and muscle specific actin positive, occupies a large part of a lymph node, sharply separated from the normal tissue. The so called "amianthoid fibres" are however absent and the inflammatory cells are almost exclusively eosinophils, mainly localized at the border between the lesion and the residual lymph node. Some spindle cells also show an unexplained positivity for the S-100 protein. In addition, extranodal extension of inflammation with few spindle cells is present. Such a complex picture has many features in common with the inflammatory pseudotumor of lymph node, another benign cause of lymphadenopathy. For this reason, the Authors suggest the possibility that myofibroblastoma is not a true neoplasm, but, together with the inflammatory pseudotumor, a peculiar type or a different stage of an abnormal lymph node reactivity.

A series of 60 gastric endocrine tumors comprised 44 body-fundus argyrophil carcinoids, of which 23 arose in a background of hypergastrinemia and type A chronic atrophic gastritis (A-CAG), mainly with histologic patterns suggestive of an autoimmune process. Only 22 percent (compared with 19 percent of 58 tumor-free A-CAG cases) of 36 carcinoids and 21 percent of 19 A-CAG carcinoids investigated had Helicobacter pylori (HP) colonization, against 50 percent of 14 CAG-associated neuroendocrine carcinomas or mixed endocrine-exocrine tumors, 84 percent of 150 cases with early gastric cancer (p < 0.001 versus carcinoids), mostly with B- or AB-type CAG, 76 percent of 97 tumor-free AB-CAG, and 95 percent of 151 tumor-free B-CAG cases. Secondary hypergastrinemia and local mechanisms activated by chronic autoimmune gastritis are among factors involved in the pathogenesis of relatively indolent CAG-associated carcinoids, whereas active HP gastritis in cooperation with environmental carcinogens may likely cause more severe epithelial transformation, leading to ordinary cancer and, possibly, to neuroendocrine carcinomas or mixed endocrine-exocrine tumors.