Nivolumab plus ipilimumab combination therapy in patients with advanced hepatocellular carcinoma previously treated with sorafenib: 5-year results from CheckMate 040.

BACKGROUND: Nivolumab plus ipilimumab demonstrated promising clinical activity and durable responses in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC) in the CheckMate 040 study at 30.7-month median follow-up. Here, we present 5-year results from this cohort. PATIENTS AND METHODS: Patients were randomized 1 : 1 : 1 to arm A [nivolumab 1 mg/kg plus ipilimumab 3 mg/kg Q3W (four doses)] or arm B [nivolumab 3 mg/kg plus ipilimumab 1 mg/kg Q3W (four doses)], each followed by nivolumab 240 mg Q2W, or arm C (nivolumab 3 mg/kg Q2W plus ipilimumab 1 mg/kg Q6W). The primary objectives were safety, tolerability, investigator-assessed objective response rate (ORR), and duration of response (DOR) per RECIST version 1.1. RESULTS: A total of 148 patients were randomized across treatment arms. At 60-month minimum follow-up (62.6-month median follow-up), the ORR was 34% (n = 17), 27% (n = 13), and 29% (n = 14) in arms A, B, and C, respectively. The median DOR was 51.2 months [95% confidence interval (CI) 12.6 months-not estimable (NE)], 15.2 months (95% CI 7.1 months-NE), and 21.7 months (95% CI 4.2 months-NE), respectively. The median overall survival (OS) was 22.2 months (34/50; 95% CI 9.4-54.8 months) in arm A, 12.5 months (38/49; 95% CI 7.6-16.4 months) in arm B, and 12.7 months (40/49; 95% CI 7.4-30.5 months) in arm C; 60-month OS rates were 29%, 19%, and 21%, respectively. In an exploratory analysis of OS by response (6-month landmark), the median OS was meaningfully longer for responders versus nonresponders for all arms. No new safety signals were identified with longer follow-up. There were no new discontinuations due to immune-mediated adverse events since the primary analysis. CONCLUSIONS: Consistent with the primary analysis, the arm A regimen of nivolumab plus ipilimumab continued to demonstrate clinically meaningful responses and long-term survival benefit, with no new safety signals in patients with advanced HCC following sorafenib treatment, further supporting its use as a second-line treatment in these patients.

Unveiling the HER2-low phenomenon: exploring immunohistochemistry and gene expression to characterise HR-positive HER2-negative early breast cancer.

PURPOSE: HER2-low breast cancer (BC) is a novel entity with relevant therapeutic implications, especially in hormone receptor (HR) positive BC. This study examines whether HER2 mRNA through the 21-gene assay, Oncotype DX (ODX), can refine the diagnosis of HER2-low and HER2-zero, obtained by immunohistochemistry (IHC). METHODS: Between Jan 2021 and Jan 2023, 229 consecutive HR-positive HER2-negative early BC (T1-3 N0-1) have been characterised by IHC and ODX. HER2 status by IHC was either zero (IHC-0) or low (IHC-1 + and IHC-2 + /ISH-negative) while HER2-zero was further divided into HER2-null (IHC-0) and HER2-ultralow (IHC-1-10%). HER2 gene expression by ODX was negative if lower 10.7. RESULTS: The distribution of HER2 IHC was as follows: 53.3% HER2-0, 29.25% HER2-1 + , and 17.5% HER2-2 + . The clinicopathological characteristics were similar in the three groups, with higher PgR-negative rate in HER2-zero (13.9% vs 3% vs 5%). The distribution of RS was homogeneous in the three groups with the median HER2 gene expression of 9.20 [IQR: 8.70-9.60]. HER2 gene expression gradually increased as the IHC score, with substantial overlap. After adjusting for confounders, HER2-1 + and HER2 2 + had a significant positive correlation between HER2 gene expression and IHC [OR 1.42, 95% CI 1.21 to 1.68, p < 0.001; OR 1.96, 95% CI 1.61 to 2.37, p < 0.001] compared to the HER2-zero group. HER2 gene expression did not differ between HER2-null and HER2-ultralow subgroups. CONCLUSION: Due to the substantial overlap, the HER2 gene expression is unable to properly distinguish HER2-low and HER2-zero IHC whose accurate identification is critical in the context of HER2-negative BC.

How to deal with low-flow low-gradient aortic stenosis and reduced left ventricle ejection fraction: from literature review to tips for clinical practice.

Low-flow low-gradient aortic stenosis (LFLG AS) with reduced left ventricle ejection fraction (LVEF) is still a diagnostic and therapeutic challenge. The aim of this paper is to review the latest evidences about the assessment of the valvular disease, usually difficult because of the low-flow status, and the therapeutic options. Special emphasis is given to the available diagnostic tools for the characterization of LFLG AS without functional reserve at stress echocardiography and to the factors that clinicians should evaluate to choose between surgical aortic valve repair, transcatheter aortic valve implantation, or medical therapy.

Construct Validity Supports Use of a Novel, Tablet-Based Neurocognitive Assessment for Adolescents and Young Adults Affected by Perinatal HIV from Vulnerable Communities in the United States.

Construct validity of novel tablet-based neurocognitive tests (in the NeuroScreen app) measuring processing speed, working memory, and executive functioning in adolescents and young adults (AYA) living with perinatally-acquired HIV (PHIV) and perinatal HIV-exposure without infection (PHEU) was examined. Sixty-two AYA (33 PHIV, 29 PHEU) were recruited from an ongoing longitudinal study (CASAH) in New York City. Medium to large and statistically significant correlations were found between NeuroScreen and gold standard, paper-and-pencil tests of processing speed, working memory, and executive functioning. Results provide partial support for NeuroScreen as an alternative to cumbersome paper-and-pencil tests for assessing neurocognition among HIV-affected AYA.

Significant chronic airway abnormalities in never-smoking HIV-infected patients.

OBJECTIVES: The aim of the study was to describe chronic lung disease in HIV-infected never-smokers by looking at clinical, structural and functional abnormalities. METHODS: This comparative cross-sectional study included 159 HIV-infected never-smoking patients [mean (± standard deviation) age 54.6 ± 9.1 years; 13.2% female; 98.1% with undetectable viral load] and 75 nonmatched never-smoking controls [mean (± standard deviation) age 52.6 ± 6.9 years; 46.7% female]. We examined calcium scoring computer tomography (CT) scans or chest CT scans, all with a lung-dedicated algorithm reconstruction, to assess emphysema and airway disease (respiratory bronchiolitis and/or bronchial wall thickening), tested pulmonary function using spirometry, lung volumes and the diffusion lung capacity of carbon monoxide (DLCO), and assessed respiratory symptoms using the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT). RESULTS: Twenty-five (17.2%) of the HIV-infected patients versus two (2.7%) of the controls had a CAT score > 10. Only 5% of the HIV-infected patients showed FEV1% < 80%, and 25% had DLCO < 75% of the predicted value. Based on the CT scans, they had increased prevalences, compared with the controls, of airway disease (37% versus 7.9%, respectively) and emphysema (18% versus 4%, respectively), with more severe and more frequent centrilobular disease. After correction for age, sex and clinical factors, HIV infection was significantly associated with CAT > 10 [odds ratio (OR) 7.7], emphysema (OR 4), airway disease (OR 4.5) and DLCO < 75% of predicted (OR 4). CONCLUSIONS: Although comparisons were limited by the different enrolment methods used for HIV-infected patients and controls, the results suggest that never-smoking HIV-infected patients may present with chronic lung damage characterized by CT evidence of airway disease. A minority of them showed respiratory symptoms, without significant functional abnormalities.

Frozen section accurately allows pathological characterization of endometrial cancer in patients with a preoperative ambiguous or inconclusive diagnoses: our experience.

BACKGROUND: The aim of this study was to assess the agreement rate between intraoperative evaluation (IOE) and final diagnosis (FD) in a series of surgically resected endometrial carcinoma (EC), with a preoperative ambiguous or inconclusive diagnosis by endometrial biopsies and imaging. METHODS: A retrospective study was performed selecting patients who underwent surgery with IOE for suspected EC at our institution from 2012 to 2018. A K coefficient was determined with respect to the histotype, tumor grade, myometrial infiltration and cervical involvement. RESULTS: Data analysis has been performed on 202 women. The IOE evaluation was distributed as Endometrioid (n = 180) and Non-Endometrioid (n = 22). The comparison between the frozen section (FS) and the definitive histological subtype showed an overall agreement rate of 93,07% (k = 0.612) and an agreement of 97.2% for Endometrioid vs 59% for Non-Endometrioid tumors. The FIGO system grading was the same in 91,1% of patients, none was upgraded and in 8,9% downgraded. Observed agreements were 89,11% and 95,54% for myometrial and cervical involvement, respectively. CONCLUSIONS: The good agreement between intraoperative grading, myometrial invasion and their histological definition on permanent sections highlights that FS is a good predictor for surgical outcome, in particular in presence of a preoperative ambiguous or inconclusive diagnostic evaluation.

Hemangioma of the umbilical cord with associated amnionic inclusion cyst: two uncommon entities occurring simultaneously.

This corrects the article DOI: 10.32074/1591-951X-26-17.

Hemangioma of the umbilical cord with associated amnionic inclusion cyst: two uncommon entities occurring simultaneously.

Umbilical cord hemangioma is an uncommon benign vascular neoplasm arising from the free segment of the umbilical cord, distinct from placental and fetal insertion, and is thought to originate from endothelial cells of the umbilical vessels. Cystic changes in the umbilical cord rarely occur as a consequence of the damage to the amnionic surface of the cord caused by the presence of the hemangioma. Until now, a total of 8 cases of umbilical cord hemangioma associated with cystic changes in the umbilical cord have been reported in the literature, however, among these cases, only one showed an associated cyst derived from inclusion of the amniotic epithelium, and the remaining seven cases consisted of hemangiomas with associated pseudocyst of the umbilical cord. We herein report a case of umbilical cord hemangioma with an associated amnionic epithelial inclusion cyst. Clinicopathological features and differential diagnostic considerations are also discussed.

Colocutaneous fistula through ulcerative colitis and cancer to the pyoderma gangrenosum: a never-ending story for a single patient. Case report.

BACKGROUND: Inflammatory bowel diseases may be associated with many extraintestinal complications, that in some cases can represent the first onset of these disorders. In particular during the course of the disease, Ulcerative Colitis develops extraintestinal manifestations very frequently. One of the rarest is pyoderma gangrenosum, a noninfectious neuthrophilic dermatosis, that can involve most commonly legs but also other parts of the skin or mucosas. It can be idiopathic or associated with gammopathies, vasculitis, chronic arthritis or, like in our case, with inflammatory bowel disease and malignancies. CASE PRESENTATION: A 38-year-old man was referred to our Department with a colo-cutaneous fistula in the left quadrant of abdominal wall. In the anamnesis he reported a trauma during a soccer match three weeks before. Through a CT scan and endoscopy with biopsy an inflammatory bowel disease with a segmental colitis and stenosis was diagnosed. After medical therapy, an initial radiological drainage and a period of parenteral nutrition, he underwent a left hemicolectomy. Despite the previous endoscopic biopsy the histopathological examination put in evidence not only inflammatory disease (in particular Ulcerative Colitis) but also a colorectal tumor pT4pN0. After the full recovery before chemotherapy he has developed on the chest and on the abdomen some painful nodules, with central necrosis, one of those in contact with one of the ribs. Through TC and RM it was impossible to understand the precise nature of these skin lesions. With biopsy a pyoderma gangrenosum was diagnosed and treated until complete resolution. DISCUSSION AND CONCLUSION: Management of inflammatory bowel diseases can be a true challenge, not only for the intestinal manifestations, but also for all the other features not related to gut. In some cases the same patient can develop many complications, such as malignancies or rare cutaneous diseases. Despite the initial surprise for such a weird evolution in a same patient, from fistula to inflammatory disease to cancer and finally to pyoderma gangrenosum, to face every single complication following consolidated diagnostic and pathological paths has been the correct strategy for controlling the disease.

Endovascular and surgical approaches of ethmoidal dural fistulas: a multicenter experience and a literature review.

Ethmoidal dural arteriovenous fistulae are rare vascular malformations associated with a high risk of bleeding. We present a multicenter contemporary series of patients treated with microsurgical and endovascular techniques. Sixteen consecutive patients were evaluated and/or treated between 2008 and 2015 at four centers with large experience in the endovascular and surgical treatment of cerebrovascular diseases. We analyzed demographic and clinical data, risk factors for dural fistulas, treatment type, peri- and post-operative morbidity, clinical and radiological outcomes, rates of occlusion, and long-term neurological outcome. Sixteen patients (81 % men, mean age of 58 years) with ethmoidal dural fistulas were included in the analysis. Seven patients had suffered an intracranial hemorrhage; the remaining presenting with neurological signs and symptoms or the fistula was an incidental finding. Three patients were managed conservatively. Among patients who underwent intervention (n = 13), 46.1 % were treated with endovascular therapy and 53.9 % were treated surgically. Complete angiographic obliteration was achieved in 100 % immediately after treatment and at last follow-up evaluation. All patients experienced a favorable neurological recovery (mRS 0-2) at the last follow-up visit (12 months). Ethmoidal dural AVFs are found mostly in male patients. Nowadays, due to wider use of non-invasive imaging, AVFs are discovered with increasing frequency in patients with minimal or no symptoms. Traditionally, these fistulas were considered "surgical." However, in the modern endovascular era, selected patients can be effectively and safely treated with embolization although surgical ligation continues to have an important role in their management.

Complex Aneurysm: The Unpredictable Pathological Entity.

BACKGROUND: Surgical treatment of complex aneurysms often requires the execution of a revascularization procedure. Even if avoiding the concomitant trapping of the aneurysm during the bypass procedure (waiting for the subsequent endovascular or spontaneous closure) permits one to verify the graft's patency and patient's adaptation to increased flow, the hemodynamic changes induced by the bypass may cause the aneurysmal rupture. Whether or not to perform the concomitant trapping of the aneurysm still remains a dilemma. Here we illustrate our management protocol through the critical analysis of some illustrative cases of our series. MATERIALS AND METHODS: Between 1990 and 2016, 48 of 157 patients affected by complex aneurysms underwent a revascularization procedure. In 19 cases (1990-1997) only a bypass procedure was performed. Spontaneous or endovascular closure was obtained within the first postoperative week once the graft patency had been verified (staged revascularization strategy). In the remaining 29 cases. The total amount of cases is 48. 19 cases staged revascularization strategy. 29 cases single stage revascularization strategy. RESULTS: In the staged revascularization era, one patient died because of the rupture of the aneurysm before its closure.In the single-stage era no further cases of rebleeding were observed. Neurologic status of this group was unvaried or improved. CONCLUSIONS: Given the unpredictable response of complex aneurysms to the hemodynamic changes induced by the revascularization, in our opinion it is always preferable to perform complete or at least incomplete trapping of the aneurysm during the bypass procedure.

Childhood adversity, health and quality of life in adults with intellectual and developmental disabilities.

BACKGROUND: Associations between childhood adversity and negative health outcomes are well documented within the general population; however, this relationship has yet to be confirmed in adults with intellectual and developmental disabilities (I/DD). Bridging the gap between public health and I/DD research is critical in order to better understand the ways in which the health of people with I/DD are compromised by adversity and social disadvantage and to develop preventative care frameworks and health-promoting practices specifically for adults with I/DD. The aim of this exploratory study was to examine the relationships among adversity, physical health and quality of life in a sample of adults with I/DD. METHOD: Participants were adults with I/DD currently residing within campus-based residences. Demographic data, psychiatric and medical diagnoses, adverse childhood experiences scores and quality of life scores were aggregated from participants' electronic medical records. A health history form was completed for each participant based on a review of participants' medical records. RESULTS: Results indicated childhood adversity was significantly associated with number of chronic medical conditions (r = .35, P < .001, 95% BCa CI [.13, .53]). Childhood adversity was not significantly related to quality of life. After controlling for demographic variables, childhood adversity remained a significant predictor of health history (B = .32, P < .005, 95% BCa CI [.10, .52]), with greater adversity predicting greater medical illness. CONCLUSION: Participants demonstrated higher rates of childhood adversity compared with the general population, suggesting that individuals with I/DD may be particularly vulnerable to experiencing adversity during development. Childhood adversity was a significant predictor of physical illness in adults with I/DD. These findings emphasise the importance of screening for childhood adversity histories in adults with I/DD. Additionally, results demonstrate the importance of offering preventative interventions geared at preventing physical illness and promoting health in adults with I/DD with adversity and trauma backgrounds.

Comparison of outcomes following intersphincteric resection vs low anterior resection for low rectal cancer: a systematic review.

BACKGROUND: Low Rectal Anterior Resection (LAR) is challenging when anal canal mucosa and/or internal sphincter are involved by very low tumors. In these cases, Intersphincteric resection (ISR) with the removal of the internal sphincter is designed to increase the distal margin of resection, thus preserving the external sphincter and pubo-rectalis muscle complex. Aim is to compare results after ISR with those of LAR, including subgroup analysis of open, laparoscopic and robotic ISR. METHODS: Studies published from January 1991 to January 2017 describing ISR and comparing results with LAR in adults were included irrespective of the technique. Tumor and surgical characteristics, clinical, functional and oncological results were collected. RESULTS: 25 non-randomized studies were included. Postoperative mortality ranged between 0% and 2.3%. The hospital stay ranged from 5 days to 40 days, lower in robotic ISR group if compared with laparoscopic ISR. Patients avoiding permanent stoma with ISR accept a lower continence level as satisfactory. Furthermore, anorectal function after ISR often tends to improve. ISR and LAR presented not statistically significant differences. Oncological outcomes were not statistically different Morbidity, blood loss and need for blood transfusions were lower in the laparoscopic ISR if compared with open approach. CONCLUSIONS: Morbidity could more frequently affect open ISR if compared with laparoscopic ISR. Functional outcomes were influenced by neoadjuvant CRT, but not by the surgical approach of reconstruction, while were positively influenced by partial ISR with respect to total ISR.

Laparoscopic cholecystectomy for acute cholecystitis: are intended operative approach, timing and outcome affected by BMI? A multicenter retrospective study.

BACKGROUND: Laparoscopy is the gold-standard for cholecystectomy after acute cholecystitis, but the issue is controversial in obese subjects. PATIENTS AND METHODS: We reviewed 464 patients operated for acute cholecystitis (59 open and 405 laparoscopic) over the last five years at St Orsola University Hospital-Bologna and Umberto I University Hospital-Rome, comparing retrospectively: 1) BMI < 30 (397 patients) and BMI =/> 30 (67 patients) and moreover 2) BMI < 25 (207 patients) and BMI =/> 25 (257 patients). RESULTS: In the first comparison, obese patients showed higher cardiovascular co-morbidity (61.1% vs 44.5%, p=0.01), worse symptoms (Murphy's sign positive in 92.5% vs 80.8%, p=0.02; fever >38.5°C in 88.0% vs 76.0 %, p=0.02) and significant radiologic imaging (95.5% vs 85.1%, p=0.01) of acute cholecystitis. Laparoscopy was used in 83.6% of obese patients vs 87.9% without any difference, and operative time or conversion rate were similar. According to Tokyo Guidelines 2013, the number of patients who underwent surgery within 3 days or after 6 weeks was similar without statistical difference between the two groups. Hospital stay, morbidity and mortality were similar. Complications were seen in 25.4% of obese patients vs 15.9% (p= 0.03), mainly represented by wound infections. The second comparison did show no difference between two groups BMI =/>25 and BMI < 25. CONCLUSIONS: Our retrospective multicenter study showed no difference related to intended operative approach, timing and outcome in higher BMI versus lower BMI patients operated for acute cholecystitis.

Early versus delayed approach in cholecystectomy after admission to an emergency department. A multicenter retrospective study.

BACKGROUND: Discussion regarding the timing of cholecystectomy for acute cholecystitis is still ongoing. This study evaluates the outcomes of patients who underwent surgery for acute cholecystitis after emergency admission at St. Orsola University Hospital of Bologna and Umberto I Hospital La Sapienza University of Rome. PATIENTS AND METHODS: . We performed a retrospective study on 464 patients who underwent cholecystectomy for acute cholecystitis. We divided patients in three groups based on the time elapsed between the onset of symptoms and surgery: within 72 hours (Group A), between 72 hours and 6 weeks (Group B) and after 6 weeks (Group C). We performed both univariate and multivariate statistical analysis on the data collected. RESULTS: The best results were in Group C, with significant differences with the others two groups: higher rates of laparoscopic technique (93% of cases), no mortality, better morbidity and shorter hospital stay. On the contrary, no significant differences were observed between Groups A and B: laparoscopic cholecystectomy 67% vs 66%, morbidity (Clavien-Dindo III-IV) 5% vs 5%, mortality 2% vs 1%, hospital stay 6,6 vs 5,6 days. Conversion rate was 11% in Group A, 18% in Group B and 4% in Group C. CONCLUSION: Our experience shows better results for cholecystectomies performed after 6 weeks from the onset of symptoms, while earlier cholecystectomies have worse outcomes regardless if they are performed before or after 72 hours from the onset of symptoms.

Long-term Follow-up and Post-relapse Outcome of Patients with Localized Retroperitoneal Sarcoma Treated in the Italian Sarcoma Group-Soft Tissue Sarcoma (ISG-STS) Protocol 0303.

BACKGROUND: This study was designed to assess patterns of recurrence and long-term outcomes of patients undergoing surgery for localized retroperitoneal sarcoma (RPS) after neoadjuvant high dose long-infusion ifosfamide (HLI) and radiotherapy (RT). METHODS: Patients received three cycles of HLI (14 g/m2). RT was started in combination with II cycle up to a total dose of 50.4 Gy. Surgery was scheduled 4-6 weeks after the end of RT. The primary endpoint was relapse-free survival (RFS) after surgery. Secondary endpoints were overall survival (OS), crude cumulative incidence of local recurrence (CCI-LR), and distant metastases (CCI-DM). For patients who relapsed, progression-free survival (PFS) and post-relapse OS were estimated. The trial was registered with ITASARC_*II_2004_003. RESULTS: Between 2003 and 2010, 83 patients were recruited. At a median follow-up of 91.7 months, 42 (56%) of 75 operated patients developed LR (n = 27) or DM (n = 10) or both LR and DM (n = 5) relapse. Seven-year RFS was 46.6% [95% confidence interval (CI) 29.6-52.4]. Thirty-two patients died. Seven-year OS rate was 63.2% (95% CI 42.7-66.0). The corresponding CCI of LR and DM were 37.4% [standard error (SE) 5.5%] and 20.0% (SE 12.6%), respectively. The only factor significantly associated with LR was FNCLCC grading, whereas histological subtype resulted associated with DM. At recurrence, 24 patients (57%) underwent surgery. Two-year post-relapse PFS and OS rates for patients developing LR or DM were 14.8, 41.0, 27.3, and 63.6%, respectively. CONCLUSIONS: LR after neoadjuvant CT-RT for RPS were predominantly infield. While almost one half of relapsed patients underwent further surgery, prognosis was poor.

Fourth cranial nerve: surgical anatomy in the subtemporal transtentorial approach and in the pretemporal combined inter-intradural approach through the fronto-temporo-orbito-zygomatic craniotomy. A cadaveric study.

Despite the recent progress in surgical technology in the last decades, the surgical treatment of skull base lesions still remains a challenge. The purpose of this study was to assess the anatomy of the tentorial and cavernous segment of the fourth cranial nerve as it appears in two different surgical approaches to the skull base: subtemporal transtentorial approach and pretemporal fronto-orbito-zygomatic approach. Four human cadaveric fixed heads were used for the dissection. Using both sides of each cadaveric head, we made 16 dissections: 8 with subtemporal transtentorial technique and 8 with pretemporal fronto-orbito-zygomatic approach. The first segment that extends from the initial point of contact of the fourth cranial nerve with the tentorium (point Q) to its point of entry into its dural channel (point D) presents an average length of 13.5 mm with an extremely wide range and varying between 3.20 and 9.3 mm. The segment 2, which extends from point D to the point of entry into the lateral wall of the cavernous sinus, presents a lesser interindividual variability (mean 10.4 mm, range 15.1-5.9 mm). A precise knowledge of the surgical anatomy of the fourth cranial nerve and its neurovascular relationships is essential to safely approach. The recognition of some anatomical landmarks allows to treat pathologies located in regions of difficult surgical access even when there is an important subversion of the anatomy.

Incidence, malignancy rates of diagnoses and cyto-histological correlations in the new Italian Reporting System for Thyroid Cytology: An institutional experience.

OBJECTIVE: FNA biopsy is considered as the most accurate method for the selection of patients with thyroid nodules that need for surgery or for the wait and see management. The aim of the present study is to clarify the risk of malignancy for the cytological data classified according to the 2014 Italian reporting system. METHODS: We report a retrospective analysis of 4043 patients in our institution's experience during the period April 2014 through December 2016 with the Italian reporting system for thyroid cytology. RESULTS: The diagnostic incidences of the 4043 cases were as follows: 9.8% TIR1; 1.3% TIR1C; 70% TIR2; 6.6% TIR3A; 4.5% TIR3B; 2.4% TIR4; 5.2% TIR5. A repeated aspiration was carried out in 68 out of 269 cases (25%) classified as TIR3A. A total of 407 cases with cytology underwent surgical resection. A malignant neoplasm was detected in 261 out of 407 (64%) cases. Regarding TIR3B, surgical excision was undertaken in 109 cases, which included 42 high-risk lesions and 67 Hürthle cell neoplasms. The risk of malignancy was significantly higher in the former compared to the latter (50% vs 9%; P<.05). CONCLUSIONS: This investigation emphasises the reliability of the 2014 Italian Reporting System concerning the mutual frequency of the diagnostic categories. The risk of malignancy is perfectly within the range of the estimated values.

Land use change impacts on floods at the catchment scale: Challenges and opportunities for future research.

Research gaps in understanding flood changes at the catchment scale caused by changes in forest management, agricultural practices, artificial drainage, and terracing are identified. Potential strategies in addressing these gaps are proposed, such as complex systems approaches to link processes across time scales, long-term experiments on physical-chemical-biological process interactions, and a focus on connectivity and patterns across spatial scales. It is suggested that these strategies will stimulate new research that coherently addresses the issues across hydrology, soil and agricultural sciences, forest engineering, forest ecology, and geomorphology.