Preoperative cardiac assessment in liver transplant candidates

New and extended indications, older age, higher cardiovascular risk, and the long-standing cirrhosis-associated complications mandate specific skills for an appropriate preoperative assessment of the liver transplant (LT) candidate. The incidence of cardiac diseases (dysrhythmias, cardiomyopathies, coronary artery disease, valvular heart disease) are increasing among LT recipients: however, no consensus exists among clinical practice guidelines for cardiovascular screening and risk stratification. In spite of different "transplant center-centered protocols", basic "pillars" are common (electrocardiography, baseline echocardiography, functional assessment). Owing to intrinsic limitations, yields and relevance of noninvasive stress tests, under constant scrutiny even if used, are discussed, focusing the definition of the "high risk" candidate and exploring noninvasive imaging and new forms of stress imaging. The aim is to find an appropriate and rational stepwise algorithm. The final commitment is to select the right candidate for a finite resource, the graft, able to save (and change) lives

Darolutamide in hormone-sensitive and castration-resistant prostate cancer

Introduction: Important changes in the treatment of prostate cancer have taken place in recent years. Non-metastatic castration-resistant prostate cancer (nmCRPC) has been clinically delineated. In this setting, three drugs have been approved in high-risk disease: apalutamide, enzalutamide and darolutamide.Areas covered:This manuscript aims to profile darolutamide, its clinical development, pharmacologic properties, efficacy and safety. We presented the results of published clinical studies, but we also investigated ongoing ones.Expert opinion: An indirect comparison with the other two aforementioned drugs emerged. While the clinical efficacy is comparable, the toxicity profile is different for darolutamide, resulting in greater tolerance. We must wait for the results of the trials that study darolutamide in hormone-sensitive disease, both in the metastatic phase and in the localized phase. Clinical experience will also be important to determine ever more personalized treatments for patients.</p

TRK fusion positive cancers:From first clinical data of a TRK inhibitor to future directions

Genetic alterations of neurotrophic tropomyosin or tyrosine receptor kinase (NTRK) 1/2/3 genes generate TRK fusion proteins have been reported in a variety of adult and child cancers from diverse cell/tissue lineages. Larotrectinib, a tumour-agnostic TRK inhibitor, has shown remarkable efficacy in a novel "basket" study which has enrolled patients from infants to elderly with different TRK fusion-positive cancers. In this review, we focus on the challenges and expectations on the development of "tumour-agnostic" targeted therapies in rare malignancies.</p

Ataxia with oculomotor apraxia type 2: a clinical, pathologic, and genetic study

BACKGROUND: Ataxia with oculomotor apraxia type 2 (AOA2) is characterized by onset between age 10 and 22 years, cerebellar atrophy, peripheral neuropathy, oculomotor apraxia (OMA), and elevated serum alpha-fetoprotein (AFP) levels. Recessive mutations in SETX have been described in AOA2 patients. OBJECTIVE: To describe the clinical features of AOA2 and to identify the SETX mutations in 10 patients from four Italian families. METHODS: The patients underwent clinical examination, routine laboratory tests, nerve conduction studies, sural nerve biopsy, and brain MRI. All were screened for SETX mutations. RESULTS: All the patients had cerebellar features, including limb and truncal ataxia, and slurred speech. OMA was observed in two patients, extrapyramidal symptoms in two, and mental impairment in three. High serum AFP levels, motor and sensory axonal neuropathy, and marked cerebellar atrophy on MRI were detected in all the patients who underwent these examinations. Sural nerve biopsy revealed a severe depletion of large myelinated fibers in one patient, and both large and small myelinated fibers in another. Postmortem findings are also reported in one of the patients. Four different homozygous SETX mutations were found (a large-scale deletion, a missense change, a single-base deletion, and a splice-site mutation). CONCLUSIONS: The clinical phenotype of oculomotor apraxia type 2 is fairly homogeneous, showing only subtle intrafamilial variability. OMA is an inconstant finding. The identification of new mutations expands the array of SETX variants, and the finding of a missense change outside the helicase domain suggests the existence of at least one more functional region in the N-terminus of senataxin

Avelumab in gastric cancer

Gastric cancer (GC) is the fifth most common malignancy and the third cause of cancer-related deaths worldwide. Currently, surgery and chemotherapy remain the main therapeutic options and the prognosis of the disease is still poor in the metastatic setting. Avelumab is a human IgG1 antibody directed against PD-L1 approved for Merkel cell carcinoma and urothelial carcinoma that could be useful also for the treatment of GC. This review describes the chemical structure, the pharmacologic properties and the current knowledge of the efficacy of avelumab in the treatment of GC from the data available on the first and later phase clinical trials. The ongoing studies testing this drug either alone or in combination with other drugs are also described

Nested defects on the boundary of topological superconductors

Helical Majorana edge states at the 2D boundaries of 3D topological superconductors can be gapped by a surface Zeeman field. Here we study the effect nested defects imprinted on the Zeeman field can have on the edge states. We demonstrate that depending on the configuration of the field, we can induce dimensional reduction of gapless Majorana modes from 2D to 1D or quasi-0D at magnetic domain walls. We determine the nature of the Majorana localization on these defects as a function of the magnitude and configuration of the Zeeman field. Finally, we observe a generalization of the index theorem governing the number of gapless modes at the interface between topologically nontrivial systems with partial Chern numbers

Biostimulation as a Means for Optimizing Fruit Phytochemical Content and Functional Quality of Tomato Landraces of the San Marzano Area

The effect of plant biostimulation on fruits of traditional tomato germplasm is largely unknown. We examined how a tropical plant-derived biostimulant impacts the nutritional, functional, and compositional characteristics of tomato fruits from four landraces, collected in the San Marzano (SM) tomato Protected Designation of Origin (PDO) region, by profiling primary and secondary metabolites. Biostimulation was not able to completely reshuffle the morpho-physiological and nutritional profile of the four landraces. Their distinct phytochemical profile indicated a genotype specific tuning of the analyzed traits, which also included an improved yield and fruit quality. Biostimulation of SM1 and SM3 increased photosynthetic accumulation of carbohydrate reserves, improved mineral nutrient use efficiency and consequently, yield (+21% and 34%, respectively). Moreover, biostimulation augmented the nutraceutical properties of the SM2 landrace. Interestingly, the plant-derived product increased in all genotypes lycopene, but not polyphenol accumulation in fruits. Our results show the potential of biostimulatory applications towards optimizing the fruit quality of the acclaimed SM landraces, which is suitable to satisfy both the rising consumer demand for premium traditional tomatoes and the technological needs of the food industry

Implementing a robotic liver resection program does not always require prior laparoscopic experience

Background: Preliminary experience in laparoscopic liver surgery is usually suggested prior to implementation of a robotic liver resection program. Methods: This was a retrospective cohort analysis of patients undergoing robotic (RLR) versus laparoscopic liver resection (LLR) for hepatocellular carcinoma at a center with concomitant initiation of robotic and laparoscopic programs RESULTS: A total of 92 consecutive patients operated on between May 2014 and February 2019 were included: 40 RLR versus 52 LLR. Median age (69 vs. 67; p = 0.74), male sex (62.5% vs. 59.6%; p = 0.96), incidence of chronic liver disease (97.5% vs.98.1%; p = 0.85), median model for end-stage liver disease (MELD) score (8 vs. 9; p = 0.92), and median largest nodule size (22 vs. 24&nbsp;mm) were similar between RLR and LLR. In the LLR group, there was a numerically higher incidence of nodules located in segment 4 (20.0% vs. 16.6%; p = 0.79); a numerically higher use of Pringle's maneuver (32.7% vs. 20%; p = 0.23), and a shorter duration of surgery (median of 165.5 vs. 217.5&nbsp;min; p = 0.04). Incidence of complications (25% vs.32.7%; p = 0.49), blood transfusions (2.5% vs.9.6%; p = 0.21), and median length of stay (6 vs. 5; p = 0.54) were similar between RLR and LLR. The overall (OS) and recurrence-free (RFS) survival rates at 1 and 5&nbsp;years were 100 and 79 and 95 and 26% for RLR versus 96.2 and 76.9 and 84.6 and 26.9% for LLR (log-rank p = 0.65 for OS and 0.72 for RFS). Conclusions: Based on our results, concurrent implementation of a robotic and laparoscopic liver resection program appears feasible and safe, and is associated with similar oncologic long-term outcomes

Induced Topological Phases at the Boundary of 3D Topological Superconductors

We present tight-binding models of 3D topological superconductors in class DIII that support a variety of winding numbers. We show that gapless Majorana surface states emerge at their boundary in agreement with the bulk-boundary correspondence. At the presence of a Zeeman field, the surface states become gapped and the boundary behaves as a 2D superconductor in class D. Importantly, the 2D and 3D winding numbers are in agreement, signifying that the topological phase of the boundary is induced by the phase of the 3D bulk. Hence, the boundary of a 3D topological superconductor in class DIII can be used for the robust realization of localized Majorana zero modes