Clear cell carcinoma of the ovary: Clues for radiologists to perform a correct diagnosis.

Ovarian clear cell carcinoma (OCCC) is an uncommon high-grade primary epithelial ovarian cancer, covering about 10-12 % of all ovarian malignancies. It has a strong association with endometriosis. OCCC diagnosis, at advanced stages, has an aggressive biological behaviour, and the therapeutic strategies for ovarian OCCC are somehow different from other ovarian carcinomas. Therefore, early diagnosis of these tumours is of extreme importance. As some ovarian tumours subtypes have distinguishing features, it is possible to differentiate them based on their imaging characteristics, which can guide patient management and help the clinicians and pathologists in their diagnosis. A large mass on one side of the ovary that is mostly cystic, with a focal or multifocal irregular eccentric growing solid mural nodules or projections protruding into the cystic space, may suggest clear cell carcinoma of the ovary diagnosis. The solid nodules usually have an intermediate signal on T2-weighted images. The cystic component can be either single or multilocular, and the contents may contain protein or blood. CT scanning is still the preferred method for preoperative staging and postoperative restaging, and radiologists are crucial in identifying this type of tumour. We reviewed the imaging files of patients with surgically proven clear cell carcinoma at the specimens, and our findings agree with previous studies. This paper aims to perform a comprehensive revision of OCCC's radiological and clinic-pathological features and assist radiologists in recognizing OCCC and narrowing down the possibilities of differential diagnosis.

Improving primary prophylaxis of variceal bleeding by adapting therapy to the clinical stage of cirrhosis. A competing-risk meta-analysis of individual participant data.

BACKGROUND & AIMS: Non-selective ß-blockers (NSBBs) and endoscopic variceal-ligation (EVL) have similar efficacy preventing first variceal bleeding. Compensated and decompensated cirrhosis are markedly different stages, which may impact treatment outcomes. We aimed to assess the efficacy of NSBBs vs EVL on survival in patients with high-risk varices without previous bleeding, stratifying risk according to compensated/decompensated stage of cirrhosis. METHODS: By systematic review, we identified RCTs comparing NSBBs vs EVL, in monotherapy or combined, for primary bleeding prevention. We performed a competing-risk, time-to-event meta-analysis, using individual patient data (IPD) obtained from principal investigators of RCTs. Analyses were stratified according to previous decompensation of cirrhosis. RESULTS: Of 25 RCTs eligible, 14 failed to provide IPD and 11 were included, comprising 1400 patients (656 compensated, 744 decompensated), treated with NSBBs (N = 625), EVL (N = 546) or NSBB+EVL (N = 229). Baseline characteristics were similar between groups. Overall, mortality risk was similar with EVL vs. NSBBs (subdistribution hazard-ratio (sHR) = 1.05, 95% CI = 0.75-1.49) and with EVL + NSBBs vs either monotherapy, with low heterogeneity (I2 = 28.7%). In compensated patients, mortality risk was higher with EVL vs NSBBs (sHR = 1.76, 95% CI = 1.11-2.77) and not significantly lower with NSBBs+EVL vs NSBBs, without heterogeneity (I2 = 0%). In decompensated patients, mortality risk was similar with EVL vs. NSBBs and with NSBBs+EVL vs. either monotherapy. CONCLUSIONS: In patients with compensated cirrhosis and high-risk varices on primary prophylaxis, NSBBs significantly improved survival vs EVL, with no additional benefit noted adding EVL to NSBBs. In decompensated patients, survival was similar with both therapies. The study suggests that NSBBs are preferable when advising preventive therapy in compensated patients.

A 15-Year Retrospective Review of Ciguatera in the Madeira Islands (North-East Atlantic, Portugal).

The first ciguatera fish poisoning (CFP) in Portugal dates from 2008 when 11 people reported CFP symptoms after consuming a 30 kg amberjack caught around the Selvagens Islands (Madeira Archipelago). Since then, 49 human poisonings have been reported. The emergence of a new threat challenged scientists and regulators, as methods for toxic microalgae analyses and ciguatoxin (CTX) detection were not implemented. To minimise the risk of ciguatera, the Madeira Archipelago authorities interdicted fisheries in Selvagens Islands and banned the capture of amberjacks weighing more than 10 kg in the entire region of Madeira Archipelago. The accurate identification and quantification of the benthic toxin-producing algae species spreading to new areas require efforts in terms of both microscopy and molecular techniques. Two ciguatera-causing dinoflagellates, Gambierdiscus excentricus and Gambierdiscus australes, were identified in the Madeira Island and Selvagens sub-archipelago, respectively. Regarding the CTX analysis (N2a cell-based assay and LC-MS) in fish, the results indicate that the Selvagens Islands are a ciguatera risk area and that fish vectoring CTX are not limited to top predator species. Nevertheless, advances and improvements in screening methods for the fast detection of toxicity in seafood along with certified reference material and sensitive and selective targeted analytical methods for the determination of CTX content are still pending. This study aims to revise the occurrence of ciguatera cases in the Madeira Archipelago since its first detection in 2008, to discuss the risk management strategy that was implemented, and to provide a summary of the available data on the bioaccumulation of CTX in marine fish throughout the marine food web, taking into consideration their ecological significance, ecosystem dynamics, and fisheries relevance.

Transjugular intrahepatic portosystemic shunt in patients with hepatocellular carcinoma: A systematic review.

BACKGROUND/AIMS: Transjugular intrahepatic portosystemic shunts (TIPS) in patients with hepatocellular carcinoma (HCC) may improve access to curative therapies, treat portal hypertension (PH)-related complications without worsening liver function, and increase overall survival. Data on the efficacy and safety of TIPS to treat PH complications in HCC patients, as well as the HCC treatment response, were evaluated. METHODS: Studies reporting efficacy in controlling bleeding/ascites or response to HCC therapy, safety, and survival in patients with HCC and TIPS were searched systematically on PubMed and Embase. An extraction of articles using predefined data fields and quality indicators was used. RESULTS: We selected 19 studies and found 937 patients treated for ascites/bleeding and 177 evaluating HCC treatment response. Over half were under 5 cm and solitary lesions, and most studies included tumours with portal vein thrombosis. Regarding PH studies, TIPS resolved bleeding/ascites in >60% of patients, more effective for bleeding. There were no lethal complications reported and procedural bleeding occurred in <5%. Hepatic encephalopathy occurred in 15%-30% within three months. In the HCC treatment-response studies, major complication rates were low with no mortality. In the studies that evaluated the response to transarterial chemoembolization, complete response rate of patients with TIPS varied from 16% to 75%. Liver transplantation rate varied from 8% to 80%, with >40% rate in half of the studies. CONCLUSIONS: In the published studies, TIPS is effective in treating PH complications in patients with HCC. Prospective studies on TIPS placement in patients with HCC are urgently needed to evaluate the efficacy and safety of TIPS in this setting.

Alcohol-related liver disease phenotype impacts survival after an acute variceal bleeding episode.

BACKGROUND & AIMS: Alcohol-related hepatitis (AH) encompasses a high mortality. AH might be a concomitant event in patients with acute variceal bleeding (AVB). The current study aimed to assess the prevalence of AH in patients with AVB and to compare the clinical outcomes of AH patients to other alcohol-related liver disease (ALD) phenotypes and viral cirrhosis. METHODS: Multicentre, observational study including 916 patients with AVB falling under the next categories: AH (n = 99), ALD cirrhosis actively drinking (d-ALD) (n = 285), ALD cirrhosis abstinent from alcohol (a-ALD) (n = 227) and viral cirrhosis (n = 305). We used a Cox proportional hazards model to calculate adjusted hazard ratio (HR) of death adjusted by MELD. RESULTS: The prevalence of AH was 16% considering only ALD patients. AH patients exhibited more complications. Forty-two days transplant-free survival was worse among AH, but statistical differences were only observed between AH and d-ALD groups (84 vs. 93%; p = 0.005), when adjusted by MELD no differences were observed between AH and the other groups. At one-year, survival of AH patients (72.7%) was similar to the other groups; when adjusted by MELD mortality HR was better in AH compared to a-ALD (0.48; 0.29-0.8, p = 0.004). Finally, active drinkers who remained abstinent presented better survival, independently of having AH. CONCLUSIONS: Contrary to expected, AH patients with AVB present no worse one-year survival than other patients with different alcohol-related phenotypes or viral cirrhosis. Abstinence influences long-term survival and could explain these counterintuitive results.

Studying the Influence of Multisensory Stimuli on a Firefighting Training Virtual Environment.

How we perceive and experience the world around us is inherently multisensory. Most of the Virtual Reality (VR) literature is based on the senses of sight and hearing. However, there is a lot of potential for integrating additional stimuli into Virtual Environments (VEs), especially in a training context. Identifying the relevant stimuli for obtaining a virtual experience that is perceptually equivalent to a real experience will lead users to behave the same across environments, which adds substantial value for several training areas, such as firefighters. In this paper, we present an experiment aiming to assess the impact of different sensory stimuli on stress, fatigue, cybersickness, Presence and knowledge transfer of users during a firefighter training VE. The results suggested that the stimulus that significantly impacted the user's response was wearing a firefighter's uniform and combining all sensory stimuli under study: heat, weight, uniform, and mask. The results also showed that the VE did not induce cybersickness and that it was successful in the task of transferring knowledge.

Bivalve Shellfish Safety in Portugal: Variability of Faecal Levels, Metal Contaminants and Marine Biotoxins during the Last Decade (2011-2020).

Bivalves are a high-value product whose production has markedly increased, reaching 9863 tonnes in Portugal in 2021. Bivalves' habitats-lagoons, estuaries and coastal waters-are exposed to biological and anthropogenic contaminants, which can bioaccumulate in these organisms and pose a significant public health risk. The need to obtain a safe product for human consumption led to the implementation of standardised hygiene regulations for harvesting and marketing bivalve molluscs, resulting in routine monitoring of bivalve production areas for microbial quality, metal contaminants, and marine biotoxins. While excessive levels of biotoxins and metal contamination lead to temporary harvesting bans, high faecal contamination leads to area reclassification and impose post-harvest treatments. In this study, the seasonal and temporal variability of these parameters were analysed using historical data generated by the monitoring programme during the last decade. Moreover, the impact of the monitoring program on bivalve harvesting from 2011 to 2020 was assessed. This program presented a considerable improvement over time, with an increase in the sampling effort and the overall program representativeness. Finally, contamination risk, revising control measures, and defining recommendations for risk mitigation measures are given in the light of ten years' monitoring.

Non-invasive tools for compensated advanced chronic liver disease and portal hypertension after Baveno VII - an update.

Non-invasive tests (NITs) and liver stiffness measurement (LSM) in particular, have entered clinical practice over 20 years ago as point-of-care tests to diagnose liver fibrosis in patients with compensated chronic liver disease. Since then, NITs use has evolved thanks to a large number of studies in all major etiologies of liver disease, and they have become important tools to stratify the risk of portal hypertension and liver-related events. The Baveno VII consensus workshop provided several novel recommendations regarding the use of well-established and novel NITs in the specific setting of portal hypertension screening, diagnosis and follow-up. The Baveno VII expert panels paid special attention to summarizing the existing data into simple clinical rules able to guide clinicians in their practice. The "rule of five" for LSM is a tool to stratify the risk of liver-related events, and LSM alone or in combination with platelet count, can be used now to rule-in and rule-out compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension, as well as to rule-out high-risk varices. Use of NITs in obese subjects with non-alcoholic fatty liver disease (NAFLD) and patients with viral hepatitis C that has been successfully treated, require specific knowledge. This review will update the reader on these aspects.

Hepatic encephalopathy is not a contraindication to pre-emptive TIPS in high-risk patients with cirrhosis with variceal bleeding.

BACKGROUND: A pre-emptive transjugular intrahepatic portosystemic shunt (pTIPS) reduces mortality in high-risk patients with cirrhosis (Child-Pugh C/B+active bleeding) with acute variceal bleeding (AVB). Real-life studies point out that <15% of patients eligible for pTIPS ultimately undergo transjugular intrahepatic portosystemic shunt (TIPS) due to concerns about hepatic encephalopathy (HE). The outcome of patients undergoing pTIPS with HE is unknown. We aimed to (1) assess the prevalence of HE in patients with AVB; (2) evaluate the outcome of patients presenting HE at admission after pTIPS; and (3) determine if HE at admission is a risk factor for death and post-TIPS HE. PATIENTS AND METHODS: This is an observational study including 2138 patients from 34 centres between October 2011 and May 2015. Placement of pTIPS was based on individual centre policy. Patients were followed up to 1 year, death or liver transplantation. RESULTS: 671 of 2138 patients were considered at high risk, 66 received pTIPS and 605 endoscopic+drug treatment. At admission, HE was significantly more frequent in high-risk than in low-risk patients (39.2% vs 10.6%, p<0.001). In high-risk patients with HE at admission, pTIPS was associated with a lower 1-year mortality than endoscopic+drug (HR 0.374, 95% CI 0.166 to 0.845, p=0.0181). The incidence of HE was not different between patients treated with pTIPS and endoscopic+drug (38.2% vs 38.7%, p=0.9721), even in patients with HE at admission (56.4% vs 58.7%, p=0.4594). Age >56, shock, Model for End-Stage Liver Disease score >15, endoscopic+drug treatment and HE at admission were independent factors of death in high-risk patients. CONCLUSION: pTIPS is associated with better survival than endoscopic treatment in high-risk patients with cirrhosis with variceal bleeding displaying HE at admission.

Using Heart Rate Variability for Comparing the Effectiveness of Virtual vs Real Training Environments for Firefighters.

The use of Virtual Reality (VR) technology to train professionals has increased over the years due to its advantages over traditional training. This paper presents a study comparing the effectiveness of a Virtual Environment (VE) and a Real Environment (RE) designed to train firefighters. To measure the effectiveness of the environments, a new method based on participants' Heart Rate Variability (HRV) was used. This method was complemented with self-reports, in the form of questionnaires, of fatigue, stress, sense of presence, and cybersickness. An additional questionnaire was used to measure and compare knowledge transfer enabled by the environments. The results from HRV analysis indicated that participants were under physiological stress in both environments, albeit with less intensity on the VE. Regarding reported fatigue and stress, the results showed that none of the environments increased such variables. The results of knowledge transfer showed that the VE obtained a significant increase while the RE obtained a positive but non-significant increase (median values, VE: before - 4 after - 7, p = .003; RE: before - 4 after - 5, p = .375). Lastly, the results of presence and cybersickness suggested that participants experienced high overall presence and no cybersickness. Considering all results, the authors conclude that the VE provided effective training but that its effectiveness was lower than that of the RE.

Mycophenolate mofetil as second line treatment in autoimmune hepatitis - A retrospective single center analysis.

Background: Most patients with autoimmune hepatitis respond to standard treatment with steroids and azathioprine. While the disease is usually fatal if untreated, patients who respond well to therapy have an excellent prognosis. Nevertheless, second-line treatment is necessary in approximately 20% of patients, due to either intolerance or insufficient response to first line treatment.While data for mycophenolate mofetil (MMF) in patients intolerant to azathioprine is encouraging, MMF seems of less benefit in patients with insufficient response to first line treatment, but analyzed data on this issue is limited. Aim: To evaluate the efficacy and safety of MMF as a second-line therapy in patients with AIH. Methods: Retrospective analysis of a monocentric database of AIH patients who received medical care from 2000 to 2022. Clinical, immunological and biochemical parameters were assessed at different time points including last follow-up. Results: Overall, 144 patients with AIH were identified. Fifty out of 144 (35%) AIH patients received MMF. Forty (80%) received MMF due to first line treatment intolerance, while ten (20%) due to insufficient response to first line treatment.Remission with MMF monotherapy was 81.5% in the intolerance group versus 30% in the insufficient response group. Patients switched to MMF because of an insufficient response, more often needed additional prednisolone doses higher than 5 mg/day, a switch to third-line treatment or combination regiments, to achieve disease control. Conclusions: Patients treated with MMF because of intolerance to first line treatment show a good disease control under MMF in the majority of cases. Efficacy is considerably lower in the patients switched to MMF because of an insufficient response to first line treatment.

Liver Abscess Complicated with an Inflammatory Myofibroblastic Tumor.

Inflammatory myofibroblastic tumors have a wide spectrum of biological behaviour and are composed of inflammatory cells and myofibroblastic spindle cells. Tumors may infrequently involve the liver. Imaging findings are non-specific. Teaching Point: Radiologists should be familiar with inflammatory myofibroblastic tumors as a diagnostic consideration to avoid unnecessary surgery.

Potential vascular damage by posterior dislocation of sternoclavicular joint.

A 34-year-old man was admitted for surgical treatment following traumatic posterior sternoclavicular joint dislocation and anterior mediastinum hematoma with compression of brachiocephalic vein (A, B). Intra-operative positioning consid- ered access for possible sternotomy and control of upper vena cava territory in case of bleeding from venous confluent (C). Patient was submitted to open reduction of sternoclavicular joint through an oblique supraclavicular incision (D), fixation with high strength orthopedic suture (E), mediastinal drainage and closure with absorbable suture (F).

Carvedilol reduces the risk of decompensation and mortality in patients with compensated cirrhosis in a competing-risk meta-analysis.

BACKGROUND & AIMS: Whether non-selective ß-blockers can prevent decompensation of cirrhosis warrants clarification. Carvedilol might be particularly effective since its intrinsic vasodilatory activity may ameliorate hepatic vascular resistance, a major mechanism of portal hypertension in early cirrhosis. We assessed whether carvedilol may prevent decompensation and improve survival in patients with compensated cirrhosis and clinically significant portal hypertension (CSPH). METHODS: By systematic review we identified randomized-controlled trials (RCTs) comparing carvedilol vs. control therapy (no-active treatment or endoscopic variceal ligation [EVL]) in patients with cirrhosis and CSPH without previous bleeding. We performed a competing-risk time-to-event meta-analysis using individual patient data (IPD) obtained from principal investigators of RCTs. Only compensated patients were included. Primary outcomes were prevention of decompensation (liver transplantation and death were competing events) and death (liver transplantation was a competing event). Models were adjusted using propensity scores for baseline covariates with the inverse probability of treatment weighting (IPTW) approach. RESULTS: Among 125 full-text studies evaluated, 4 RCTs were eligible. The 4 provided IPD and were included, comprising 352 patients with compensated cirrhosis, 181 treated with carvedilol and 171 controls (79 received EVL and 92 placebo). Baseline characteristics were similar between groups. Standardized differences were <10% by IPTW. The risk of developing decompensation of cirrhosis was lower with carvedilol than in controls (subdistribution hazard ratio [SHR] 0.506; 95% CI 0.289-0.887; p = 0.017; I2 = 0.0%, Q-statistic-p = 0.880), mainly due to a reduced risk of ascites (SHR 0.491; 95% CI 0.247-0.974; p = 0.042; I2 = 0.0%, Q-statistic-p = 0.384). The risk of death was also lower with carvedilol (SHR 0.417; 95% CI 0.194-0.896; p = 0.025; I2 = 0.0%, Q-statistic-p = 0.989). CONCLUSIONS: Long-term carvedilol therapy reduced decompensation of cirrhosis and significantly improved survival in compensated patients with CSPH. This suggests that screening patients with compensated cirrhosis for CSPH to enable the prompt initiation of carvedilol could improve outcomes. PROSPERO REGISTRATION NUMBER: CRD42019144786. LAY SUMMARY: The transition from compensated cirrhosis to decompensated cirrhosis is associated with markedly reduced life expectancy. Therefore, preventing decompensation in patients with compensated cirrhosis would be associated with greatly improved patient outcomes. There has been controversy regarding the use of non-selective ß-blockers (portal pressure-lowering medications) in patients with cirrhosis and elevated portal blood pressure (portal hypertension). Herein, using a competing-risk meta-analysis to optimize sample size and properly investigate cirrhosis as a multistate disease and outcomes as time-dependent events, we show that carvedilol (a non-selective ß-blocker) is associated with a reduced risk of decompensating events and improved survival in patients with cirrhosis and portal hypertension.

Investigational drugs in early clinical development for portal hypertension.

INTRODUCTION: Advanced chronic liver disease is considered a reversible condition after removal of the primary etiological factor. This has led to a paradigm shift in which portal hypertension (PH) is a reversible complication of cirrhosis. The pharmacologic management of PH is centered on finding targets to modify the natural history of cirrhosis and PH. AREAS COVERED: This paper offers an overview of the use of pharmacological strategies in early clinical development that modify PH. Papers included were selected from searching clinical trial sites and PubMed from the last 10 years. EXPERT OPINION: A paradigm shift has generated a new concept of PH in cirrhosis as a reversible complication of a potentially curable disease. Decreasing portal pressure to prevent decompensation and further complications of cirrhosis that may lead liver transplantation or death is a goal. Therapeutic strategies also aspire achieve total or partial regression of fibrosis, thus eliminating the need for treatment or screening of PH.