Many animals display a capacity to regenerate tissues or even a complete body. One of the main goals of regenerative biology is to identify the genes and genetic networks necessary for this process. ...Drosophila offers an ideal model system for such studies. The wide range of genetic and genomic approaches available for use in flies has helped in initiating the deciphering of the mechanisms underlying regeneration, and the results may be applicable to other organisms, including mammals. Moreover, most models of regeneration require experimental manipulation, whereas in Drosophila discrete domains can be ablated by genetically induced methods. Here, we present a summary of current research into imaginal disc regeneration and discuss the power of this tissue as a tool for understanding the genetics of regeneration.
The success of direct-acting antivirals (DAA) against hepatitis C is a major breakthrough in hepatology. Until now, however, there are very few data on the effect of hepatitis C virus (HCV) ...eradication in patients who have already developed hepatocellular carcinoma.
The study included patients with HCV infection and prior history of treated hepatocellular carcinoma who achieved complete response and lacked ‘non-characterized nodules’ at the time they underwent anti-HCV treatment with all-oral DAAs in 4 hospitals. Patients receiving interferon as part of the antiviral regimen were excluded. The baseline characteristics, laboratory and radiologic tumor response were registered in all patients before starting antiviral therapy and during the follow-up according to the clinical practice policy.
Between 2014 and 2015, 103 patients with prior hepatocellular carcinoma received DAA, 58 of them met the inclusion criteria. After a median follow-up of 5.7months, 3 patients died and 16 developed radiologic tumor recurrence (27.6%). The pattern of recurrence was: intrahepatic growth (3 patients), new intrahepatic lesion (1 nodule in 5 patients, up to 3 nodules less or equal to 3cm in 4 cases and multifocal in one patient) and infiltrative ill-defined hepatocellular carcinoma and/or extra-hepatic lesions in 3 patients.
Our data show an unexpected high rate and pattern of tumor recurrence coinciding with HCV clearance and, although based in a very small cohort of patients, should be taken as a note of caution and prime a large scale assessment that exceeds the individual investigators capacity.
High rate of cancer recurrence after DAA treatment in patients with prior hepatocellular carcinoma. Disruption of immune surveillance may facilitate the emergence of metastatic clones.
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•The risk of HCC in patients with HCV cirrhosis treated with DAAs persists despite viral cure.•The presence of indeterminate nodules before starting DAA is associated with a 3 times ...greater risk of HCC.•A time association between DAA therapy and developing HCC reflects increased short-term HCC risk.•DAA therapy elicits a mechanism that primes the emergence of HCC early during follow-up.
Despite direct-acting antivirals being highly effective at eradicating hepatitis C virus infection, their impact on the development of hepatocellular carcinoma (HCC) remains controversial. We analyzed the clinical and radiological outcome of cirrhotic patients treated with interferon-free regimens to estimate the risk of developing HCC.
This was a retrospective multicenter study focusing on cirrhotic patients treated with direct-acting antivirals until December 2016. Clinical and radiologic characteristics were collected before the start of antiviral therapy, at follow-up and at HCC development. Diagnosis of HCC was centrally validated and its incidence was expressed as HCC/100 person-years.
A total of 1,123 patients were included (60.6% males, 83.8% Child-Pugh A) and 95.2% achieved a sustained virologic response. Median time of follow-up was 19.6 months. Seventy-two patients developed HCC within a median of 10.3 months after starting antiviral treatment. HCC incidence was 3.73 HCC/100 person-years (95% CI 2.96–4.70). Baseline liver function, alcohol intake and hepatic decompensation were associated with a higher risk of HCC. The relative risk was significantly increased in patients with non-characterized nodules at baseline 2.83 (95% CI 1.55–5.16) vs. absence of non-characterized nodules. When excluding these patients, the risk remained increased.
These data expose a clear-cut time association between interferon-free treatment and HCC. The mechanisms involved in the increased risk of HCC emergence in the short term require further investigation.
In this cohort of cirrhotic patients, interferon-free therapies achieved a high rate of sustained virologic response (>95%); however, we reported a risk of de novo hepatocellular carcinoma of 3.73 per 100 person-years and a clear-cut time association with antiviral therapy. The time association between starting direct-acting antivirals and developing hepatocellular carcinoma, together with the association with the presence of non-characterized nodules at baseline ultrasound, suggests that antiviral therapy elicits a mechanism (probably immune-related) that primes the growth and clinical recognition of hepatocellular carcinoma early during follow-up. As a result, short-term liver cancer risk is significantly increased.
Recognition of non-characterized liver nodules (NCLN) prior to direct-acting antivirals (DAAs) is associated with increased hepatocellular carcinoma (HCC) risk in patients with HCV. The risk of HCC ...has not been defined in F3/F4 patients in whom NCLN have been ruled-out before starting DAAs and at sustained virological response (SVR). This study aimed to estimate HCC incidence in this population.
We performed a prospective study including HCV-infected patients with F3/F4 fibrosis, without a history of HCC, and who achieved SVR after DAAs. Patients were only included if they had undergone ultrasound imaging that excluded the presence of HCC/NCLN within 30 days after SVR. All patients were evaluated every 6 months until developing primary liver cancer, death or withdrawal of informed consent. HCC incidence was expressed per 100 patient-years (/100PY). Adherence to screening program was calculated every 6 months for the first 48 months.
A total of 185 patients (63/122, F3/F4) were included. Among those with cirrhosis, 92% were Child-Pugh A and 42.7% had clinically significant portal hypertension (CSPH). Albumin-bilirubin score was 1 in 84.9% and 2 in 15.1% of patients, respectively. The median clinical and radiologic follow-up was 52.4 months and 48 months, respectively. Ten patients developed HCC: HCC incidence was 1.46/100PY (95% CI 0.79-2.71) in the whole cohort, 2.24/100PY (95% CI 1.21-4.17) in F4 only and 3.63/100PY (95% CI 1.95–6.74) in patients with CSPH. No HCC was registered in patients with F3. Median time between SVR and HCC occurrence was 28.1 months; 12 non-primary liver cancers were also identified.
Patients with cirrhosis without NCLN at SVR remain at risk of HCC development. The absence of HCC in patients with F3 reinforces their marginal cancer risk, but prospective studies are needed to exclude them from screening programs.
Patients with HCV-related cirrhosis, without non-characterized liver nodules at sustained virologic response, remain at risk of hepatocellular carcinoma despite viral cure. However, the cancer risk after successful direct-acting antiviral treatment is marginal in patients with F3 fibrosis without non-characterized liver nodules. If confirmed in larger prospective studies, current screening recommendations may need to be revisited in this group of patients.
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•F4 patients without non-characterized liver nodules remained at risk of HCC after HCV cure.•All cases of HCC were observed in patients with a history of decompensation and/or clinically significant portal hypertension.•None of the 63 F3 cured patient without non-characterized nodules developed HCC.•Larger studies are needed to define the HCC risk in F3 cured patients.
The study of thoracic injuries and biomechanics during CPR requires detailed studies that are very scarce. The role of the heart in CPR biomechanics has not been determined. This study aimed to ...determine the risk factors importance for serious ribcage damage due to CPR.
Data were collected from a prospective registry of out-of-hospital cardiac arrest between April 2014 and April 2017. This study included consecutive out-of-hospital CPR attempts undergoing an autopsy study focused on CPR injuries. Cardiac mass ratio was defined as the ratio of real to expected heart mass. Pearson’s correlation coefficient was used to select clinically relevant variables and subsequently classification tree models were built. The Gini index was used to determine the importance of the associated serious ribcage damage factors. The LUCAS® chest compressions device forces and the cardiac mass were analyzed by linear regression.
Two hundred CPR attempts were included (133 manual CPR and 67 mechanical CPR). The mean age of the sample was 60.4 ± 13.5, and 56 (28%) were women. In all, 65.0% of the patients presented serious ribcage damage. From the classification tree build with the clinically relevant variables, age (0.44), cardiac mass ratio (0.26), CPR time (0.22), and mechanical CPR (0.07), in that order, were the most influential factors on serious ribcage damage. The chest compression forces were greater in subjects with higher cardiac mass.
The heart plays a key role in CPR biomechanics being cardiac mass ratio the second most important risk factor for CPR injuries.
There is no consensus on the imaging tests that should be performed at the initial staging of melanoma patients.
To evaluate the diagnostic accuracy of 4 imaging studies for the initial staging of ...melanoma patients.
Cross-sectional study with prospectively collected data, from January 2011 to April 2017, including patients with clinical stage T2b to T4b according to 2009 American Joint Committee on Cancer, without evidence of metastasis.
Initial staging of 308 patients detected 16.6% of metastases and 5.8% false-positive results, overall. Regional lymph node ultrasonography showed a metastasis detection rate (MDR) of 12.8%, false-positive rate of 0.8%, and accuracy of 96.0%. Computed tomography (CT) and positron emission tomography-CT had the highest detection rates at stage T4b: MDR, 13.3%; false-positive rate, 8.9%; accuracy, 91.1%; and MDR, 6.9%; false-positive rate, 0%; and accuracy, 93.1%, respectively. Brain magnetic resonance imaging showed a MDR of 2.0% in T4b.
Single-center study.
Performing ultrasound scans for assessing lymph node metastasis in patients with American Joint Committee on Cancer T2b stage and above is advisable. In patients with stage T4b, CT or positron emission tomography-CT are suitable for the detection of metastasis. Brain magnetic resonance imaging at T4b deserves further discussion, considering the ultimate clinical benefit in management and therapeutic options for asymptomatic patients.
This randomized, controlled trial assessed the effect of transarterial embolization (TAE) (without associated chemotherapy) on the survival of patients with nonsurgical hepatocellular carcinoma ...(HCC). Eighty consecutive patients were randomized to treatment with embolization (Group A, n = 40), or to symptomatic treatment (Group B, n = 40), there being no differences between both groups regarding the degree of liver function impairment and tumor stage. Eighty‐two percent of the patients presented a self‐limited postembolization syndrome, without treatment‐related mortality. Fifty‐five percent of the treated cases exhibited a partial response, which resulted in a lower probability of tumor progression during follow‐up (57% vs. 77% at 1 year; P < .005). However, after a median follow‐up of 24 months (30 deaths in each group), there are no differences in survival (Group A: 49% and 13%; Group B: 50% and 27%, at 2 and 4 years, respectively; P = .72). The absence of differences was maintained even when dividing patients according to Child‐Pugh's grade, Okuda stage, or performance status test (PST). Furthermore, there were no differences in the probability of complications or in the need of hospital admissions. In conclusion, TAE has a marked antitumoral effect associated to a slower growth of the tumor, but it does not improve the survival of patients with nonsurgical HCC.
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